Αρχειοθήκη ιστολογίου

Δευτέρα 17 Ιουλίου 2017

FtseMib future: spunti operativi per martedì 18 luglio - Milano Finanza

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Milano Finanza
FtseMib future: spunti operativi per martedì 18 luglio
Milano Finanza
Pericoloso invece il ritorno sotto 21.330 anche se, da un punto di vista grafico, solo il cedimento di quota 21.000 potrebbe annullare i recenti progressi e innescare una correzione di una certa consistenza. Difficile per adesso ipotizzare un ...

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Terry Cook: Vaccines protect Texas children - Austin American-Statesman

Austin American-Statesman
Terry Cook: Vaccines protect Texas children
Austin American-Statesman
According to the National Cancer Institute, virtually all cases of cervical cancer are caused by HPV, and about 70 percent of oropharyngeal (middle throat area, including the tongue, soft palate and tonsils) are cancers caused by HPV. The CDC ...



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Tedizolid inhibits MUC5AC production induced by methicillin-resistant Staphylococcus aureus in human airway epithelial cells

Publication date: Available online 17 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Kazuaki Takeda, Norihito Kaku, Yoshitomo Morinaga, Kosuke Kosai, Naoki Uno, Yoshifumi Imamura, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
The innate immune system plays an important role in early immunity against respiratory tract infection. Although airway epithelial cells produce mucus to eliminate pathogens and irritants, hypersecretion of mucus is harmful for the host as it may cause airway obstruction and inhibit influx of antimicrobial agents. It has been reported that several antimicrobial agents have an immunomodulatory effect in vitro and in vivo, but little is known about whether tedizolid, a novel oxazolidinone, can modulate immune responses. In this study, we evaluated whether tedizolid can suppress MUC5AC production in human airway epithelial cells stimulated by methicillin-resistant Staphylococcus aureus (MRSA). Compared with the control, tedizolid significantly inhibited MUC5AC protein production and mRNA overexpression at concentrations of both 2 and 10 μg/mL (representative of trough and peak concentrations in human epithelial lining fluid). Among the mitogen-activated protein kinase inhibitors tested, only extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation was inhibited by tedizolid as indicated by western blot analysis. These results indicate that tedizolid inhibits the overproduction of MUC5AC protein by inhibiting phosphorylation of ERK1/2. This study revealed that tedizolid suppresses excessive mucin production in human airway epithelial cells. The immunomodulatory effect of tedizolid may improve outcomes in patients with severe respiratory infectious diseases caused by MRSA.



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Inhibiting effects of fructanase on competence-stimulating peptide-dependent quorum sensing system in Streptococcus mutans

Publication date: Available online 17 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Yusuke Suzuki, Ryo Nagasawa, Hidenobu Senpuku
Streptococcus mutans produces glucosyltransferases encoded by the gtfB and gtfC genes, which synthesize insoluble glucan, and both insoluble and soluble glucans by conversion of sucrose, and are known as principal agents to provide strong biofilm formation and demineralization on tooth surfaces. S. mutans possess a Com-dependent quorum sensing (QS) system, which is important for survival in severe conditions. The QS system is stimulated by the interaction between ComD {Receptor to competence-stimulating peptide (CSP)} encoded by the comD and CSP encoded by the comC, and importantly associated with bacteriocin production and genetic competence. Previously, we found enzyme fructanase (FruA) as a new inhibitor for the glucan-dependent biofilm formation. In the present study, inhibiting effects by FruA on glucan-independent biofilm formation of S. mutans UA159, UA159.gtfB-, UA159.gtfC-, and UA159.gtfBC- were observed in sucrose and no sucrose sugars-supplemented conditions using the plate assay. The reduction of UA159.comC- and UA159.comD- biofilm formation were also observed as compared with UA159 in same conditions. These results suggested that inhibitions of glucan-independent and Com-dependent biofilm formation were involved in the inhibiting mechanism by FruA. To more thoroughly investigate effects by FruA on the QS system, we examined on CSP-stimulated and Com-dependent bacteriocin production and genetic transformation. FruA inhibited bacteriocin production in collaboration with CSP and genetic transformation in bacterial cell conditions treated with FruA. Our findings show that FruA has multiple effects that inhibit survival functions of S. mutans, including biofilm formation and CSP-dependent QS responses, indicating its potential use as an agent for prevention of dental caries.



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An infant with concurrent serotype 6C invasive pneumococcal disease and infectious mononucleosis

Publication date: Available online 17 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Naoko Nishikawa-Nakamura, Takafumi Okada, Keiko Nishimura, Tsuyako Iwai, Kimiko Ubukata, Satoshi Iwata, Asayuki Iwai
Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind.



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Resectable adenocarcinoma developing in the remnant pancreas 7 years after partial pancreatoduodenectomy for invasive ductal adenocarcinoma of the pancreas: a case report

Pancreatic adenocarcinoma still has an excessively high mortality rate and resection is the only potentially curative treatment. The postoperative 5-year survival rate is approximately 20% and recurrence devel...

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Terry Cook: Vaccines protect Texas children - Austin American-Statesman


Austin American-Statesman

Terry Cook: Vaccines protect Texas children
Austin American-Statesman
According to the National Cancer Institute, virtually all cases of cervical cancer are caused by HPV, and about 70 percent of oropharyngeal (middle throat area, including the tongue, soft palate and tonsils) are cancers caused by HPV. The CDC ...



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BMJ Open Gastroenterology

BMJ Open Gastroenterology, published by BMJ Publishing Group Ltd, last updated on 2017-07-17, available at http://ift.tt/2uDjuCb

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Evidence for plical support of the patella

Abstract

There is a consensus that there is no overt anterior joint capsule in the knee. However, other anterior structures act in lieu of a joint capsule: the quadriceps tendon and patellar retinacular fibres. In the absence of a capsule, the synovium forms the suprapatellar pouch. Other synovial structures, the plicae, are more controversial. They are often described as embryonic remnants with no function, despite surrounding the patella. We aimed to identify plical anatomy and histology on cadaveric dissection and to examine their embryology using the human virtual embryo website. Plicae were identified by two independent observers. Plical histology was examined using a panel of stains: H&E, Ab H&E, EVG and MSB trichrome. Embryonic knees were examined from Carnegie stages 20–23. Each knee had a suprapatellar plica and mediopatellar plica (MPP). The lateropatellar plica (LPP) appeared as a band in 5/10 cadavers, and as a ridge in the remainder. The overall impression, consistent across all specimens, was that the plicae formed a continuous band of synovial tissue around the proximal three-quarters of the patella. The infrapatellar fat pad (IFP) surrounded the remainder. Histologically, the plicae and IFP consisted of three layers (in order): a synovial layer, an undulated collagenous layer, and an adipose or areoloadipose layer. The subsynovial collagenisation is normally associated with the synovio-capsular boundary. Embryologically, plicae were not seen in either knee at any level for any given Carnegie stage. We suggest that plicae, along with the dynamic IFP, provide internal support to the patella mirroring the external support of retinacular fibres. Thus, the plicae complete the tissue complex acting in lieu of an anterior joint capsule. Evidence of plical functionality lends credence to the theory that the plicae are anatomical structures not functionless embryonic remnants.



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A 3D musculoskeletal model of the western lowland gorilla hind limb: moment arms and torque of the hip, knee and ankle

Abstract

Three-dimensional musculoskeletal models have become increasingly common for investigating muscle moment arms in studies of vertebrate locomotion. In this study we present the first musculoskeletal model of a western lowland gorilla hind limb. Moment arms of individual muscles around the hip, knee and ankle were compared with previously published data derived from the experimental tendon travel method. Considerable differences were found which we attribute to the different methodologies in this specific case. In this instance, we argue that our 3D model provides more accurate and reliable moment arm data than previously published data on the gorilla because our model incorporates more detailed consideration of the 3D geometry of muscles and the geometric constraints that exist on their lines-of-action about limb joints. Our new data have led us to revaluate the previous conclusion that muscle moment arms in the gorilla hind limb are optimised for locomotion with crouched or flexed limb postures. Furthermore, we found that bipedalism and terrestrial quadrupedalism coincided more regularly with higher moment arms and torque around the hip, knee and ankle than did vertical climbing. This indicates that the ability of a gorilla to walk bipedally is not restricted by musculoskeletal adaptations for quadrupedalism and vertical climbing, at least in terms of moment arms and torque about hind limb joints.



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IJMS, Vol. 18, Pages 1536: UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi

IJMS, Vol. 18, Pages 1536: UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi

International Journal of Molecular Sciences doi: 10.3390/ijms18071536

Authors: Gabriela Lando Letícia Marconatto Felipe Kessler William Lopes Augusto Schrank Marilene Vainstein Daniel Weibel

Synthetic polymers are the cause of some major environmental impacts due to their low degradation rates. Polyurethanes (PU) are widely used synthetic polymers, and their growing use in industry has produced an increase in plastic waste. A commercial polyether-based thermoplastic PU with hydrolytic stability and fungus resistance was only attacked by an entomopathogenic fungus, Metarhiziumanisopliae, when the films were pre-treated with Ultraviolet (UV) irradiation in the presence of reactive atmospheres. Water contact angle, Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR), scanning electron microscopy (SEM), and profilometer measurements were mainly used for analysis. Permanent hydrophilic PU films were produced by the UV-assisted treatments. Pristine polyether PU films incubated for 10, 30, and 60 days did not show any indication of fungal growth. On the contrary, when using oxygen in the UV pre-treatment a layer of fungi spores covered the sample, indicating a great adherence of the microorganisms to the polymer. However, if acrylic acid vapors were used during the UV pre-treatment, a visible attack by the entomopathogenic fungi was observed. SEM and FTIR-ATR data showed clear evidence of fungal development: growth and ramifications of hyphae on the polymer surface with the increase in UV pre-treatment time and fungus incubation time. The results indicated that the simple UV surface activation process has proven to be a promising alternative for polyether PU waste management.



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New imaging tools for an old disease: Secondary syphilis



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When is a sentinel node biopsy indicated for patients with primary melanoma? An update of the ‘Australian guidelines for the management of cutaneous melanoma’

Abstract

A sentinel lymph node biopsy is a surgical staging procedure performed for patients with primary cutaneous melanoma who are clinically lymph-node negative to determine whether there is low volume nodal metastasis in the draining lymph node field. A systematic review was recently performed to update the Australian clinical practice guidelines for the diagnosis and management of melanoma, addressing the question, 'When is a sentinel lymph node biopsy indicated?' This article discusses the findings of the systematic review and the evidence base for the updated guidelines.



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Plaque psoriasis is associated with subclinical atherosclerosis in a Chinese population



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Masthead



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Nutrients and host attributes modulate the abundance and functional traits of phyllosphere microbiome in rice

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Publication date: Available online 17 July 2017
Source:Microbiological Research
Author(s): Shobit Thapa, Radha Prasanna, Kunal Ranjan, Kulandaivelu Velmourougane, Balasubramanian Ramakrishnan
The abundance of phyllosphere bacterial communities of seven genotypes of rice −ADT- 38, ADT-43, CR-1009, PB-1, PS-5, P-44, and Pusa Basmati was investigated, in relation to nutrient dynamics of rhizosphere and leaves. P-44 genotype recorded highest pigment accumulation, while genotypes CR-1009 and P-44 exhibited most number of different bacterial morphotypes, Colony forming units in two media (Nutrient agar and R2A) varied significantly and ranged from 106-107 per g plant tissues. Among the selected 60 distinct morphotypes, IAA and siderophore producers were the dominant functional types. Biocontrol activity against Drechslera oryzae was shown by 38 isolates, while 17 and 9 isolates were potent against Rhizoctonia solani and Magnaporthe oryzae respectively. Principal Component Analysis (PCA) illustrated the significant effects of selected soil and leaf nutrients of seven rice varieties on the culturable phyllospheric population (log CFU), particularly in the R2A medium. Eigen values revealed that 83% of the variance observed could be assigned to Leaf-Fe, Leaf-Mn, chlorophyll b and soil organic carbon (OC). Quantitative PCR analyses of abundance of bacteria, cyanobacteria and archaebacteria revealed a host-specific response, with CR-1009 showing highest number of 16S rRNA copies of bacterial members, while both P-44 and PS-5 had higher cyanobacterial abundance, but lowest number of those belonging to archaebacteria. Nutritional aspects of leaf and soil influenced the abundance of bacteria and their functional attributes; this is of interest for enhancing the efficacy of foliar inoculants for improving plant growth and disease tolerance.



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The powerful hemostatic devices are one of the milestones for successful laparoscopic surgery

Uterine fibroids are the most common benign uterine tumors, and the choice of treatment depends on the patient's age, the reason for treatment, the issue of fertility preservation, and the patient's preference.1 Uterine fibroids, undoubtedly, are one of the most frequently used indications for surgery, especially laparotomy,2 and uterine fibroids also contributed to the most frequent cause of hysterectomy.3 However, organ-preservation concept has been widely accepted in the modern medicine4; therefore, there are many strategies developed for minimizing the invasiveness of surgery (robotic, laparoscopic surgery, hysteroscopic surgery, etc.)5,6 and minimizing the needs for operation (medicine treatment, uterine artery embolization, etc.).

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Linking arsenite- and cadmium-generated oxidative stress to microsatellite instability in vitro and in vivo

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Chang-Lin Wu, Li-Yan Huang, Christina L. Chang
Mismatch repair (MMR) corrects replicative errors and minimizes DNA damage that occurs frequently in microsatellites. MMR deficiency is manifested as microsatellite instability (MSI), which contributes to hypermutability and cancer pathogenesis. Genomic instability, including MSI and chromosomal instability, appears to be responsible for the carcinogenesis of arsenic and cadmium, common contaminants in our environment. However, few studies have addressed arsenic- or cadmium-induced MSI, especially its potential link with arsenic- or cadmium-generated oxidative stress, due to the lack of quantifiable MSI assays and cost-effective animal models. Here, using a dual-fluorescent reporter, we demonstrate that sub-lethal doses of cadmium or arsenite, but not arsenate, increased the MSI frequency in human colorectal cancer cells. Arsenite- and cadmium-induced MSI occurred concomitantly with increased levels of reactive species and oxidative DNA damage, and with decreased levels of MMR proteins. However, N-acetyl-l-cysteine (NAC) suppressed arsenite- and cadmium-induced MSI and oxidative stress while restoring the levels of MMR proteins in the cells. Similarly, MSI was induced separately by arsenite and cadmium, and suppressed by NAC, in zebrafish in a fluorescinated PCR-based assay with newly-developed microsatellite markers and inter-segmental comparisons. Of five selected antioxidants examined, differential effects were exerted on the MSI induction and cytotoxicity of both arsenite and cadmium. Compared to MMR-proficient cells, MMR-deficient cells were more resistant to arsenic-mediated and cadmium-mediated cytotoxicity. Our findings demonstrate a novel linkage between arsenite-generated and cadmium-generated oxidative stress and MSI induction. Our findings also caution that antioxidants must be individually validated before being used for preventing arsenite- and cadmium-induced MSI that is associated with cancer development.

Graphical abstract

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A case of acquired epidermodysplasia verruciformis in a renal transplant recipient clearing with multimodal treatment including HPV (Gardasil) vaccination



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Re: “Thyroglobulin as a Functional Biomarker of Iodine Status in a Cohort Study of Pregnant Women in the United Kingdom” by Bath et al. (Thyroid 2017;27:426–433)

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Thyroid , Vol. 0, No. 0.


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Fewer Cancer Cases, More Cancer Deaths in Rural America - Healthline


Healthline

Fewer Cancer Cases, More Cancer Deaths in Rural America
Healthline
Rural counties had lower incidence rates for breast, prostate, stomach, liver, uterus, bladder, and thyroid cancers. Rural counties have lower incidence rates than metropolitan counties — but similar to nonmetropolitan urban counties — for pancreatic ...



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Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species [Research]

Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca2+ handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptor (RyR)-1. We tested whether similar changes occur after mechanically demanding eccentric contractions. Human subjects performed 100 repeated drop jumps, which require eccentric knee extensor contractions upon landing. This exercise caused a major PLFFD, such that maximum voluntary and electrically evoked forces did not recover within 24 h. Drop jumps induced only minor signs of increased ROS, and RyR1 fragmentation was observed in only 3 of 7 elderly subjects. Also, isolated mouse muscle preparations exposed to drop-jump–mimicking eccentric contractions showed neither signs of increased ROS nor RyR1 fragmentation. Still, the free cytosolic [Ca2+] during tetanic contractions was decreased by ~15% 1 h after contractions, which can explain the exaggerated force decrease at low-stimulation frequencies but not the major frequency-independent force depression. In conclusion, PLFFD caused by mechanically demanding eccentric contractions does not involve any major increase in ROS or RyR1 fragmentation.—Kamandulis, S., de Souza Leite, F., Hernandez, A., Katz, A., Brazaitis, M., Bruton, J. D., Venckunas, T., Masiulis, N., Mickeviciene, D., Eimantas, N., Subocius, A., Rassier, D. E., Skurvydas, A., Ivarsson, N., Westerblad, H. Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species.



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Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice [Research]

Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type–dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.25 mg/kg of either 20-nm citrate-coated AgNPs or citrate buffer using oropharyngeal aspiration. Neutrophils in bronchoalveolar lavage fluid (BALF) served as markers of inflammation. We found significant strain- and treatment-dependent variation in neutrophils in BALF. GWA mapping identified 10 significant single-nucleotide polymorphisms (false discovery rate, 15%) in 4 quantitative trait loci on mouse chromosomes 1, 4, 15, and 18, and Nedd4l (neural precursor cell expressed developmentally downregulated gene 4-like; chromosome 18), Ano6 (anocatmin 6; chromosome 15), and Rnf220 (Ring finger protein 220; chromosome 4) were considered candidate genes. Quantitative RT-PCR revealed significant inverse associations between mRNA levels of these genes and neutrophil influx. Nedd4l, Ano6, and Rnf220 are candidate susceptibility genes for AgNP-induced lung inflammation that warrant additional exploration in future studies.—Scoville, D. K., Botta, D., Galdanes, K., Schmuck, S. C., White, C. C., Stapleton, P. L., Bammler, T. K., MacDonald, J. W., Altemeier, W. A., Hernandez, M., Kleeberger, S. R., Chen, L.-C., Gordon, T., Kavanagh, T. J. Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice.



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Dynamics and Energetics of the Mammalian Phosphatidylinositol Transfer Protein Phospholipid Exchange Cycle [Signal Transduction]

Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. Yet, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics (MD) simulations of the mammalian StART-like PtdIns/ phosphatidylcholine (PtdCho) transfer protein PITPα, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the MD simulations. These studies provided five key insights into the PITPα lipid exchange cycle: (1) interaction of PITPα with the membrane is spontaneous and mediated by four specific protein substructures, (2) the ability of PITPα to initiate closure around the phospholipid ligand is accompanied by loss of flexibility of two helix/loop regions as well as of the C-terminal helix, (3) the energy barrier of phospholipid extraction from the membrane is lowered by a network of hydrogen bonds between the lipid molecule and PITPα, (4) the trajectory of PtdIns or PtdCho into and through the lipid-binding pocket is chaperoned by sets of PITPα residues conserved throughout the StART-like PITP family, and (5) conformational transitions in the C-terminal helix have specific functional involvements in PtdIns transfer activity. Taken together, these findings provide the first mechanistic description of key aspects of the PITPα PtdIns/PtdCho exchange cycle, and offer a rationale for the high conservation of particular sets of residues across evolutionarily distant members of the metazoan StART-like PITP family.

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News and Announcements

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8





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An attempt at predicting blood β-hydroxybutyrate from Fourier-transform mid-infrared spectra of milk using multivariate mixed models in Polish dairy cattle

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): T.K. Belay, B.S. Dagnachew, Z.M. Kowalski, T. Ådnøy
Fourier transform mid-infrared (FT-MIR) spectra of milk are commonly used for phenotyping of traits of interest through links developed between the traits and milk FT-MIR spectra. Predicted traits are then used in genetic analysis for ultimate phenotypic prediction using a single-trait mixed model that account for cows' circumstances at a given test day. Here, this approach is referred to as indirect prediction (IP). Alternatively, FT-MIR spectral variable can be kept multivariate in the form of factor scores in REML and BLUP analyses. These BLUP predictions, including phenotype (predicted factor scores), were converted to single-trait through calibration outputs; this method is referred to as direct prediction (DP). The main aim of this study was to verify whether mixed modeling of milk spectra in the form of factors scores (DP) gives better prediction of blood β-hydroxybutyrate (BHB) than the univariate approach (IP). Models to predict blood BHB from milk spectra were also developed. Two data sets that contained milk FT-MIR spectra and other information on Polish dairy cattle were used in this study. Data set 1 (n = 826) also contained BHB measured in blood samples, whereas data set 2 (n = 158,028) did not contain measured blood values. Part of data set 1 was used to calibrate a prediction model (n = 496) and the remaining part of data set 1 (n = 330) was used to validate the calibration models, as well as to evaluate the DP and IP approaches. Dimensions of FT-MIR spectra in data set 2 were reduced either into 5 or 10 factor scores (DP) or into a single trait (IP) with calibration outputs. The REML estimates for these factor scores were found using WOMBAT. The BLUP values and predicted BHB for observations in the validation set were computed using the REML estimates. Blood BHB predicted from milk FT-MIR spectra by both approaches were regressed on reference blood BHB that had not been used in the model development. Coefficients of determination in cross-validation for untransformed blood BHB were from 0.21 to 0.32, whereas that for the log-transformed BHB were from 0.31 to 0.38. The corresponding estimates in validation were from 0.29 to 0.37 and 0.21 to 0.43, respectively, for untransformed and logarithmic BHB. Contrary to expectation, slightly better predictions of BHB were found when univariate variance structure was used (IP) than when multivariate covariance structures were used (DP). Conclusive remarks on the importance of keeping spectral data in multivariate form for prediction of phenotypes may be found in data sets where the trait of interest has strong relationships with spectral variables.



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Antioxidant status and gut microbiota change in an aging mouse model as influenced by exopolysaccharide produced by Lactobacillus plantarum YW11 isolated from Tibetan kefir

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): Jian Zhang, Xiao Zhao, Yunyun Jiang, Wen Zhao, Ting Guo, Yongqiang Cao, Junwei Teng, Xiaona Hao, Juan Zhao, Zhennai Yang
This study investigated the effect of exopolysaccharide (EPS) produced by Lactobacillus plantarum YW11 on the oxidative status and gut microbiota in an aging mouse model induced with d-galactose. The in vitro assay of the antioxidant activity of the EPS showed concentration-dependent (0.25–3.0 mg/mL) activities. At 3.0 mg/mL, the EPS reached the highest scavenging activities with half maximal inhibitory concentration values against hydroxyl radicals at 75.10% and 1.22 mg/mL, superoxide anion at 62.71% and 1.54 mg/mL, 2, 2-diphenyl-1-picrylhydrazyl at 35.11% and 0.63 mg/mL, and the maximal chelating rate on ferrous ion and the half-maximal chelating concentration of the EPS at 41.09% and 1.07 mg/mL, respectively. High doses of EPS (50 mg/kg per day) effectively relieved the oxidative stress in the aging mice with increased levels of glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity in mice serum by 21.55, 33.14, 61.09, and 38.18%, respectively, and decreased malondialdehyde level from 11.69 to 5.89 mmol/mL compared with those in the untreated aging mice model. The analysis of pyrosequencing sequence data from the gut microbiota revealed that the EPS could recover the microbiota diversity and phylotypes decreased or eliminated by the d-galactose treatment. The EPS could selectively decrease the abundance of Flexispira (37.5 fold), and increase the abundance of Blautia (36.5 fold) and Butyricicoccus (9.5 fold), which correspondingly decreased the content of nitrogen oxides to 9.87% and increased the content of short-chain fatty acids by 2.23 fold, thereby improving the oxidative and health conditions of the host intestinal tract. Further correlation analysis of core-microbiota variation induced by different treatments showed a strong correlation with oxidative phenotypes [catalase, goodness of prediction (Q2) = 0.49; total antioxidant capacity, Q2 = 0.45; nitrogen oxides, Q2 = 0.67; short-chain fatty acids, Q2 = 0.55]. The fermented milk with L. plantarum YW11 containing EPS also showed favorable antioxidant and gut microbiota regulating activities. The present finding provided new insights into the functional mechanism of probiotics bioactivity.



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The use of national-level data to describe trends in intramammary antimicrobial usage on Irish dairy farms from 2003 to 2015

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): Simon J. More, Tracy A. Clegg, Finola McCoy
In this study, we used national-level data to describe trends in on-farm intramammary antimicrobial usage in Ireland from 2003 to 2015. We calculated actual sales of intramammary tubes and the quantity of active substance sold, by year, product type [lactation or dry cow therapy (DCT)], antimicrobial group, World Health Organization antimicrobial classification, and from 2009 to 2015, prescribing route. We also estimated on-farm usage of lactation and dry cow intramammary antimicrobials using defined daily dose (DDDvet) and defined course dose (DCDvet) calculations, and dry cow coverage. Sales of tubes of antimicrobial for DCT have increased, and the estimated national dry cow coverage in 2015 was 1,022 DCDvet per 1,000 cows per year. An increase has also occurred in sales of teat sealant (2015 sales: 66.7 tubes with teat sealant for every 100 tubes with antimicrobial for DCT). In contrast, the number of tubes of antimicrobial sold for lactation use has decreased to 1,398 DDDvet and 466 DCDvet per 1,000 animals per year. Sales in intramammary tubes with at least one critically important antimicrobial (CIA) have either risen since 2007 (DCT) or fallen (lactation therapy). Increases were observed in both the number of dry cow and lactation tubes containing CIA considered of highest priority for human health. Differences between prescribing routes with respect to CIA usage were observed. This study provides detailed insight into on-farm usage of intramammary antimicrobials in Ireland. It demonstrates positive national progress but also highlights areas for review. In particular, blanket dry cow treatment in Ireland should be reconsidered. It is not possible to investigate farm-level variation in antimicrobial usage from national sales data. In several countries, measurement and benchmarking have been critical to progress in reducing antimicrobial usage in farm animal production. Central collation of data on farm-level antimicrobial use is also needed in Ireland to allow objective measurement and benchmarking of on-farm usage. More generally, standardized indicators to quantify antimicrobial usage in farm animals are urgently needed to allow country-level comparisons.



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Comparing the effect of homogenization and heat processing on the properties and in vitro digestion of milk from organic and conventional dairy herds

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): D.L. Van Hekken, M.H. Tunick, D.X. Ren, P.M. Tomasula
We compared the effects of homogenization and heat processing on the chemical and in vitro digestion traits of milk from organic and conventional herds. Raw milk from organic (>50% of dry matter intake from pasture) and conventional (no access to pasture) farms were adjusted to commercial whole and nonfat milk fat standards, and processed with or without homogenization, and with high-temperature-short-time or UHT pasteurization. The milk then underwent in vitro gastrointestinal digestion. Comparison of milk from organic and conventional herds showed that the milks responded to processing in similar ways. General composition was the same among the whole milk samples and among the nonfat milk samples. Protein profiles were similar, with intact caseins and whey proteins predominant and only minor amounts of peptides. Whole milk samples from grazing cows contained higher levels of α-linolenic (C18:3), vaccenic (C18:1 trans), and conjugated linoleic acids, and lower levels of palmitic (C16:0) and stearic (C18:0) acids than samples from nongrazing cows. Processing had no effect on conjugated linoleic acid and linolenic acid levels in milk, although homogenization resulted in higher levels of C8 to C14 saturated fatty acids. Of the 9 volatile compounds evaluated, milk from grazing cows contained lower levels of 2-butanone than milk from nongrazing cows, and milk from both farms showed spikes for heptanal in UHT samples and spikes for butanoic, octanoic, nonanoic, and N-decanoic acids in homogenized samples. At the start of in vitro digestion, nonfat raw and pasteurized milk samples formed the largest acid clots, and organic milk clots were larger than conventional milk clots; UHT whole milk formed the smallest clots. Milk digests from grazing cows had lower levels of free fatty acids than digests from nongrazing cows. In vitro proteolysis was similar in milk from both farms and resulted in 85 to 95% digestibility. Overall, milk from organic/grass-fed and conventional herds responded in similar ways to typical homogenization and heat processing used in United States dairy plants and showed only minor differences in chemical traits and in vitro digestion. Findings from this research enhance our knowledge of the effect of processing on the quality traits and digestibility of milk from organic/pasture-fed and confined conventional herds and will help health-conscious consumers make informed decisions about dairy selections.



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Interpretive Summaries, August 2017

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8





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Estimation of genetic parameters and heterosis for longevity in crossbred Danish dairy cattle

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): J.B. Clasen, E. Norberg, P. Madsen, J. Pedersen, M. Kargo
Crossbreeding has been shown to improve the longevity of dairy cattle in countries across the world. The aim of this study was to estimate heterosis, breed effects, and genetic parameters for longevity in crossbred dairy cattle among Danish Holstein (DH), Danish Red (DR), and Danish Jersey (DJ) breeds. Data were provided from 119 Danish commercial herds that use systematic crossbreeding (i.e., rotational crossbreeding). Additional data from 11 mixed-breed herds with DH and DJ were included to estimate reliable breed effects for DJ. Survival information on 73,741 cows was analyzed with a linear animal model using the artificial insemination–REML algorithm in the DMU package. Five longevity (L) traits were defined: days from first calving until the end of first lactation or culling (L1), days from first calving until the end of second lactation or culling (L2), days from first calving until the end of third lactation or culling (L3), days from first calving until the end of fourth lactation or culling (L4), and days from first calving until the end of fifth lactation or culling (L5). Heritabilities ranged between 0.022 and 0.090. Additive breed effects in units of days were estimated relative to DH for DR as −0.5 (L1), +10.5 (L2), +18.5 (L3), +11.9 (L4), and +28.6 (L5), and corresponding figures for DJ were +2.0, +0.5, +14.2, +27.7, and +44.0. Heterosis effects in L1 were low (1.2%) but favorable in crosses between DH and DR, whereas negative heterosis effects were estimated for crosses between DH and DJ (−2.5%) and DR and DJ (−1.2%). The largest heterosis effects for L2, L3, L4, and L5 were found in DH × DR and were favorable (+3.3, +5.7, +7.7, and +8.5%, respectively). Corresponding figures for heterosis effects in DH × DJ and DR × DJ were favorable as well: +2.3, +4.1, +5.6, and +6.2% in DH × DJ and +3.1, +7.3, +6.9, and +7.2% in DR × DJ. The favorable heterosis effects show that crossbreeding is an efficient tool for improving longevity in Danish dairy cattle.



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Technical note: At-line prediction of mineral composition of fresh cheeses using near-infrared technologies

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): C.L. Manuelian, S. Currò, G. Visentin, M. Penasa, M. Cassandro, C. Dellea, M. Bernardi, M. De Marchi
Milk and dairy products are important sources of macro- and trace elements for human health. However, fresh cheeses usually have a lower mineral content than other cheeses, and this makes mineral prediction more difficult. Although mineral prediction in several food matrices using infrared spectroscopy has been reported in the literature, very little information is available for cheeses. The present study was aimed at developing near-infrared reflectance (NIR, 866–2,530 nm) and transmittance (NIT, 850–1,050 nm) spectroscopy models to predict the major mineral content of fresh cheeses. We analyzed samples of mozzarella (n = 130) and Stracchino (n = 118) using reference methods and NIR and NIT spectroscopy. We developed prediction models using partial least squares regression analysis, and subjected them to cross- and external validation. Average Na content was 0.15 and 0.22 g/100 g for mozzarella and Stracchino, respectively. The NIR and NIT spectroscopy performed similarly, with few exceptions. Nevertheless, none of the prediction models was accurate enough to replace the current reference analysis. The most accurate prediction model was for the Na content of mozzarella cheese using NIT spectroscopy (coefficient of determination of external validation = 0.75). We obtained the same accuracy of prediction for P in Stracchino cheese with both NIR and NIT spectroscopy. Our results confirmed that mineral content is difficult to predict using NIT and NIR spectroscopy.



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Trained-user opinion about Welfare Quality measures and integrated scoring of dairy cattle welfare

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): S. de Graaf, B. Ampe, C. Winckler, M. Radeski, L. Mounier, M.K. Kirchner, M.J. Haskell, F.J.C.M. van Eerdenburg, A. de Boyer des Roches, S.N. Andreasen, J. Bijttebier, L. Lauwers, W. Verbeke, F.A.M. Tuyttens
The Welfare Quality (WQ) protocol for on-farm dairy cattle welfare assessment describes 27 measures and a stepwise method for integrating values for these measures into 11 criteria scores, grouped further into 4 principle scores and finally into an overall welfare categorization with 4 levels. We conducted an online survey to examine whether trained users' opinions of the WQ protocol for dairy cattle correspond with the integrated scores (criteria, principles, and overall categorization) calculated according to the WQ protocol. First, the trained users' scores (n = 8–15) for reliability and validity and their ranking of the importance of all measures for herd welfare were compared with the degree of actual effect of these measures on the WQ integrated scores. Logistic regression was applied to identify the measures that affected the WQ overall welfare categorization into the "not classified" or "enhanced" categories for a database of 491 European herds. The smallest multivariate model maintaining the highest percentage of both sensitivity and specificity for the "enhanced" category contained 6 measures, whereas the model for "not classified" contained 4 measures. Some of the measures that were ranked as least important by trained users (e.g., measures relating to drinkers) had the highest influence on the WQ overall welfare categorization. Conversely, measures rated as most important by the trained users (e.g., lameness and mortality) had a lower effect on the WQ overall category. In addition, trained users were asked to allocate criterion and overall welfare scores to 7 focal herds selected from the database (n = 491 herds). Data on all WQ measures for these focal herds relative to all other herds in the database were provided. The degree to which expert scores corresponded to each other, the systematic difference, and the correspondence between median trained-user opinion and the WQ criterion scores were then tested. The level of correspondence between expert scoring and WQ scoring for 6 of the 12 criteria and for the overall welfare score was low. The WQ scores of the protocol for dairy cattle thus lacked correspondence with trained users on the importance of several welfare measures.



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Seasonal and regional occurrence of heat-resistant spore-forming bacteria in the course of ultra-high temperature milk production in Tunisia

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): S. Kmiha, C. Aouadhi, A. Klibi, A. Jouini, A. Béjaoui, S. Mejri, A. Maaroufi
Spore-forming bacteria, principally Bacillus species, are important contaminants of milk. Because of their high heat resistance, Bacillus species spores are capable of surviving the heat treatment process of milk and lead to spoilage of the final product. To determine the factors influencing the contamination of milk, spore-forming bacteria occurrence throughout the UHT milk production line during winter, spring, and summer was studied. The obtained results confirm that the total viable rate decreases rapidly throughout the production line of UHT milk showing the efficiency of thermal treatments used. However, the persistent high rate of spore-forming bacteria indicates their high heat resistance, especially in spring and summer. In addition, a significant variation of the quality of raw milk according to the location of the collecting centers was revealed. The molecular identification showed a high degree of diversity of heat-resistant Bacillus species, which are isolated from different milk samples. The distribution of Bacillus species in raw milk, stored milk, bactofuged milk, pasteurized milk, and UHT milk were 28, 10, 16, 13, and 33%, respectively. Six Bacillus spp. including Bacillus licheniformis (52.38%), Bacillus pumilus (9.52%), Bacillus sp. (4.76%), Bacillus sporothermodurans (4.76%), Terribacillus aidingensis (4.76%), and Paenibacillus sp. (4.76%) were identified in different milk samples.



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A commercial immune modulating feed additive restores L-selectin and CCL5 expression following dexamethasone treatment of murine immune cells in a MyD88-dependent manner

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): R.J. Ortiz-Marty, A. Lewandowski, J.D. Chapman, I. Kanevsky-Mullarky
Bovine mastitis costs the dairy industry billions of dollars every year and presents a health challenge in dairy facilities. Immunosuppressive effects of the periparturient period increase the incidence of mastitis. During this time, cattle experience an elevation in circulating cortisol, which reduces polymorphonuclear cell function and ability to clear infection. OmniGen-AF (OMN; Phibro Animal Health, Teaneck, NJ) is an immunomodulatory feed additive that alters gene expression and is used to reduce rates of mastitis. We hypothesized that OMN restores gene expression during periods of immune stress through inhibiting the suppressive effects of glucocorticoid receptor signaling on Toll-like receptor signaling. To test our hypothesis, wild-type (WT) or MyD88 knockout mice were supplemented with OMN and challenged with lipopolysaccharide following dexamethasone (Dex) treatment. Polymorphonuclear cell and macrophage RNA was isolated from intraperitoneal lavages and analyzed for gene expression profiles. Treatment of mice with Dex suppressed expression of l-selectin and CCL5 as compared with phosphate-buffered saline treatment of WT mice. Expression of l-selectin and CCL5 was significantly reduced with Dex treatment in control-fed but not OMN-supplemented WT mice. The protective effect of OMN supplementation on l-selectin expression during Dex treatment was abolished in MyD88 knockout mice. These results suggest that OMN supplementation restores responses of certain genes suppressed by Dex in immune cells in a MyD88-dependent manner. Future research will determine the specific Toll-like receptors, transcription factors, and biochemical properties of OMN that restore gene expression in immunosuppressed cells.



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Rapid consumer-based sensory characterization of requeijão cremoso, a spreadable processed cheese: Performance of new statistical approaches to evaluate check-all-that-apply data

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): F.R. Torres, E.A. Esmerino, B. Thomas Carr, L.L. Ferrão, D. Granato, T.C. Pimentel, H.M.A. Bolini, M.Q. Freitas, A.G. Cruz
We investigated the performance of multidimensional alignment analysis and multidimensional scaling on phi coefficient values to evaluate check-all-that-apply questionnaire data. We evaluated 6 dairy foods belonging to the category of requeijão cremoso processed cheese (traditional, with starch, or with starch and vegetable fat). We obtained sensory descriptors using trained assessors in descriptive analysis for comparison. A check-all-that-apply questionnaire used with 121 consumers (77 women and 44 men; 18 to 57 yr old) proved to be a suitable alternative for sensory profiling, providing descriptions similar to descriptive analysis and discriminating between products. Multidimensional alignment analysis and multidimensional scaling were efficient and logical approaches for obtaining a deeper understanding of the data, allowing us to clarify the relationships between sensory descriptors and products and contribute to optimizing the different formulations of requeijão cremoso.



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Reformulating Minas Frescal cheese using consumers' perceptions: Insights from intensity scales and check-all-that-apply questionnaires

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): E.W. Oliveira, E.A. Esmerino, B. Thomas Carr, L.P.F. Pinto, H.L.A. Silva, T.C. Pimentel, H.M.A. Bolini, A.G. Cruz, M.Q. Freitas
We evaluated the performance of check-all-that-apply (CATA) questions and intensity scales to describe Minas Frescal cheese and its reformulation based on consumers' perceptions. Ten commercial samples with different formulations (full-fat, low-fat, or low-lactose) were evaluated by 200 consumers divided equally into 2 groups: 1 evaluated samples and described their ideal cheese using intensity scales and 1 did the same using CATA questions. Both methodologies provided similar information about the sensory characteristics of the Minas Frescal cheeses, the description of the ideal product, and directions for product reformulation. The ideal Minas Frescal cheese was characterized by high moisture, intense white color, homogeneous mass, typical Minas Frescal cheese aroma and flavor, softness, and juiciness. For the intensity scales, the recommendation was to increase the typical aroma and flavor, salty taste, and juiciness, and to decrease the bitter flavor; for the CATA questions, only increasing the typical Minas Frescal cheese flavor was important for all classes of cheeses. Even for a heterogeneous product with no defined manufacturing protocol, both methodologies presented satisfactory results that should be considered for use by cheese producers and the dairy industry.



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Drivers of choice for fluid milk versus plant-based alternatives: What are consumer perceptions of fluid milk?

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): K.S. McCarthy, M. Parker, A. Ameerally, S.L. Drake, M.A. Drake
Fluid milk consumption has declined for decades while consumption of nondairy alternatives has increased. A better understanding of why consumers purchase fluid milk or nondairy alternatives is needed to assist increased sales of milk or maintain sales without further decline. The objective of this study was to determine the extrinsic attributes that drive purchase within each product category. The second objective was to determine the personal values behind the purchase of each beverage type to give further understanding why particular attributes are important. An online conjoint survey was launched with 702 dairy consumers, 172 nondairy consumers, and 125 consumers of both beverages. Individual means-end chain interviews were conducted with fluid milk consumers (n = 75), plant-based alternative consumers (n = 68), and consumers of both beverages (n = 78). Fat content was the most important attribute for dairy milk followed by package size and label claims. Consumers of fluid milk preferred 1 or 2% fat content, gallon, or half-gallon packaging, conventionally pasteurized store-brand milk. Sugar level was the most important attribute for plant-based beverages, followed by plant source and package size. Almond milk was the most desirable plant source, and half-gallon packaging was the most preferred packaging. Means-end chain interviews results suggested that maintaining a balanced diet and healthy lifestyle was important to all consumer groups. Lactose free was an important attribute for plant-based alternative consumers and consumers of both dairy and nondairy. A distinguishing characteristic of those who only drank nondairy plant-based alternatives was that plant-based beverages contributed to a goal to consume less animal products, beliefs about animal mistreatment, and perceived lesser effect on the environment than fluid milk. Unique to fluid milk consumers was that fluid milk was perceived as a staple food item. These results suggest that the dairy industry should focus on the nutrition value of milk and educating consumers about misconceptions regarding dairy milk. Future beverage innovation should include the development of lactose-free milk that is also appealing to consumers in flavor.



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Genetic parameters of blood β-hydroxybutyrate predicted from milk infrared spectra and clinical ketosis, and their associations with milk production traits in Norwegian Red cows

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): T.K. Belay, M. Svendsen, Z.M. Kowalski, T. Ådnøy
The aim of this study was to estimate genetic parameters for blood β-hydroxybutyrate (BHB) predicted from milk spectra and for clinical ketosis (KET), and to examine genetic association of blood BHB with KET and milk production traits (milk, fat, protein, and lactose yields, and milk fat, protein, and lactose contents). Data on milk traits, KET, and milk spectra were obtained from the Norwegian Dairy Herd Recording System with legal permission from TINE SA (Ås, Norway), the Norwegian Dairy Association that manages the central database. Data recorded up to 120 d after calving were considered. Blood BHB was predicted from milk spectra using a calibration model developed based on milk spectra and blood BHB measured in Polish dairy cows. The predicted blood BHB was grouped based on days in milk into 4 groups and each group was considered as a trait. The milk components for test-day milk samples were obtained by Fourier transform mid-infrared spectrometer with previously developed calibration equations from Foss (Hillerød, Denmark). Veterinarian-recorded KET data within 15 d before calving to 120 d after calving were used. Data were analyzed using univariate or bivariate linear animal models. Heritability estimates for predicted blood BHB at different stages of lactation were moderate, ranging from 0.250 to 0.365. Heritability estimate for KET from univariate analysis was 0.078, and the corresponding average estimate from bivariate analysis with BHB or milk production traits was 0.002. Genetic correlations between BHB traits were higher for adjacent lactation intervals and decreased as intervals were further apart. Predicted blood BHB at first test day was moderately genetically correlated with KET (0.469) and milk traits (ranged from −0.367 with protein content to 0.277 with milk yield), except for milk fat content from across lactation stages that had near zero genetic correlation with BHB (0.033). These genetic correlations indicate that a lower BHB is genetically associated with higher milk protein and lactose contents, but with lower yields of milk, fat, protein, and lactose, and with lower frequency of KET. Estimates of genetic correlation of KET with milk production traits were from −0.333 (with protein content) to 0.178 (with milk yield). Blood BHB can routinely be predicted from milk spectra analyzed from test-day milk samples, and thereby provides a practical alternative for selecting cows with lower susceptibility to ketosis, even though the correlations are moderate.



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Use of milk fatty acids to estimate plasma nonesterified fatty acid concentrations as an indicator of animal energy balance

Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): J.R.R. Dórea, E.A. French, L.E. Armentano
Negative energy balance is an important part of the lactation cycle, and measuring the current energy balance of a cow is useful in both applied and research settings. The objectives of this study were (1) to determine if milk fatty acid (FA) proportions were consistently related to plasma nonesterified fatty acids (NEFA); (2) to determine if an individual cow with a measured milk FA profile is above or below a NEFA concentration, (3) to test the universality of the models developed within the University of Wisconsin and US Dairy Forage Research Center cows. Blood samples were collected on the same day as milk sampling from 105 Holstein cows from 3 studies. Plasma NEFA was quantified and a threshold of 600 µEq/L was applied to classify animals above this concentration as having high NEFA (NEFAhigh). Thirty milk FA proportions and 4 milk FA ratios were screened to evaluate their capacity to classify cows with NEFAhigh according to determined milk FA threshold. In addition, 6 linear regression models were created using individual milk FA proportions and ratios. To evaluate the universality of the linear relationship between milk FA and plasma NEFA found in the internal data set, 90 treatment means from 21 papers published in the literature were compiled to test the model predictions. From the 30 screened milk FA, the odd short-chain fatty acids (C7:0, C9:0, C11:0, and C13:0) had sensitivity slightly greater than the other short-chain fatty acids (83.3, 94.8, 80.0, and 85.9%, respectively). The sensitivities for milk FA C6:0, C8:0, C10:0, and C12:0 were 78.8, 85.3, 80.1, and 83.9%, respectively. The threshold values to detect NEFAhigh cows for the last group of milk FA were ≤2.0, ≤0.94, ≤1.4, and ≤1.8 g/100 g of FA, respectively. The milk FA C14:0 and C15:0 had sensitivities of 88.7 and 85.0% and a threshold of ≤6.8 and ≤0.53 g/100 g of FA, respectively. The linear regressions using the milk FA ratios C18:1 to C15:0 and C17:0 to C15:0 presented lower root mean square error (RMSE = 191 and 179 µEq/L, respectively) in comparison with individual milk FA proportions (RMSE = 194 µEq/L), C18:1 to even short-medium-chain fatty acid (C4:0–C12:0) ratio (RMSE = 220 µEq/L), and C18:1 to C14:0 (RMSE = 199 µEq/L). Models using milk FA ratios C18:1 to C15:0 and C17:0 to C15:0 had a better fit with the external data set in comparison with the other models. Plasma NEFA can be predicted by linear regression models using milk FA ratios.



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Processing characteristics of dairy cow milk are moderately heritable

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Publication date: August 2017
Source:Journal of Dairy Science, Volume 100, Issue 8
Author(s): G. Visentin, S. McParland, M. De Marchi, A. McDermott, M.A. Fenelon, M. Penasa, D.P. Berry
Milk processing attributes represent a group of milk quality traits that are important to the dairy industry to inform product portfolio. However, because of the resources required to routinely measure such quality traits, precise genetic parameter estimates from a large population of animals are lacking for these traits. Milk processing characteristics considered in the present study—rennet coagulation time, curd-firming time, curd firmness at 30 and 60 min after rennet addition, heat coagulation time, casein micelle size, and milk pH—were all estimated using mid-infrared spectroscopy prediction equations. Variance components for these traits were estimated using 136,807 test-day records from 5 to 305 d in milk (DIM) from 9,824 cows using random regressions to model the additive genetic and within-lactation permanent environmental variances. Heritability estimates ranged from 0.18 ± 0.01 (26 DIM) to 0.38 ± 0.02 (180 DIM) for rennet coagulation time; from 0.26 ± 0.02 (5 DIM) to 0.57 ± 0.02 (174 DIM) for curd-firming time; from 0.16 ± 0.01 (30 DIM) to 0.56 ± 0.02 (271 DIM) for curd firmness at 30 min; from 0.13 ± 0.01 (30 DIM) to 0.48 ± 0.02 (271 DIM) for curd firmness at 60 min; from 0.08 ± 0.01 (17 DIM) to 0.24 ± 0.01 (180 DIM) for heat coagulation time; from 0.23 ± 0.02 (30 DIM) to 0.43 ± 0.02 (261 DIM) for casein micelle size; and from 0.20 ± 0.01 (30 DIM) to 0.36 ± 0.02 (151 DIM) for milk pH. Within-trait genetic correlations across DIM weakened as the number of days between compared intervals increased but were mostly >0.4 except between the peripheries of the lactation. Eigenvalues and associated eigenfunctions of the additive genetic covariance matrix for all traits revealed that at least the 80% of the genetic variation among animals in lactation profiles was associated with the height of the lactation profile. Curd-firming time and curd firmness at 30 min were weakly to moderately genetically correlated with milk yield (from 0.33 ± 0.05 to 0.59 ± 0.05 for curd-firming time, and from −0.62 ± 0.03 to −0.21 ± 0.06 for curd firmness at 30 min). Milk protein concentration was strongly genetically correlated with curd firmness at 30 min (0.84 ± 0.02 to 0.94 ± 0.01) but only weakly genetically correlated with milk heat coagulation time (−0.27 ± 0.07 to 0.19 ± 0.06). Results from the present study indicate the existence of exploitable genetic variation for milk processing characteristics. Because of possible indirect deterioration in milk processing characteristics due to selection for greater milk yield, emphasis on milk processing characteristics is advised.



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PIM kinases 1, 2 and 3 in intracellular LIF signalling, proliferation and apoptosis in trophoblastic cells

Publication date: Available online 18 July 2017
Source:Experimental Cell Research
Author(s): Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R. Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M. Morales-Prieto, Udo R. Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3. Expression was analyzed by qPCR and immunochemical staining. Functions were evaluated by PIM inhibition followed by analysis of kinetics of cell viability as assessed by MTS assay, proliferation by BrdU assay, and apoptosis by Western blotting for BAD, BCL-XL, (cleaved) PARP, CASP3 and c-MYC. Apoptosis and necrosis were tested by flow cytometry (annexin V/propidium iodide staining). All analyzed PIM kinases are expressed in primary trophoblast cells and both cell lines and are regulated upon stimulation with LIF. Inhibition of PIM kinases significantly reduces viability and proliferation and induces apoptosis. Simultaneously, phosphorylation of c-MYC was reduced. These results demonstrate the involvement of PIM kinases in LIF-induced regulation in different trophoblastic cell lines which may indicate similar functions in primary cells.



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Annexin A2-modulated proliferation of pulmonary arterial smooth muscle cells depends on caveolae and caveolin-1 in hepatopulmonary syndrome

Publication date: Available online 17 July 2017
Source:Experimental Cell Research
Author(s): Lin Liao, Binwu Zheng, Bin Yi, Chang Liu, Lin Chen, Ziyang Zeng, Jing Gao
We have established that annexin A2 (ANXA2) is an important factor in the experimental hepatopulmonary syndrome (HPS) serum-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs). However, the detailed mechanism remains unclear. ANXA2 translocated to the caveolin-enriched microdomains (caveolae) in PASMCs upon HPS serum stimulation. The disruption of caveolae by Methyl-β-cyclodextrin (MβCD) alleviated the caveolae recruitment of ANXA2 and the ANXA2-mediated activation of ERK1/2 and NF-κB, so that ANXA2-modulated PASMC proliferation was suppressed. The over-expression of Cav-1 resulted in the relocation of ANXA2 from caveolae and negatively regulated ERK1/2 and NF-κB activation, which inhibited the ANXA2-modulated PASMC proliferative behavior. These data indicate that caveolae function as a signaling platform for ANXA2-induced proliferative behavior and Cav-1 participates upstream of ANXA2 in the activation of ERK1/2 and NF-κB.



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Effects of diets containing black-eyed beans and serotonin precursors on neuromuscular coordination in experimental mice

Aduema Wadioni, DI Izunwanne, AK Amah

International Journal of Clinical and Experimental Physiology 2017 4(2):97-100

Background and Aim: Black-eyed beans contain the neurotransmitter serotonin and its precursor, 5-hydroxytryptophan (5-HTP) which is known to have neurobehavioral effects on neuromuscular coordination. Therefore, the aim of this study was to find whether long-term consumption uncooked bean diet has effects on some neurobehavioral parameters notably; neuromuscular coordination using Swiss white mice as experimental animals. Methods: Thirty CD1 mice were randomly assigned into three groups, namely, control, uncooked beans diet (50% w/w), and serotonin precursor (5-HTP) diet (0.2 mg/50 g w/w) for 30 days. All the mice had access to clean drinking water ad libitum. Before the neurobehavioral parameters were assessed, the LD50of the beans and that of the serotonin precursor (5-HTP) was determined. Serotonin concentration was measured in beans using gas chromatography analysis. Neuromuscular coordination was investigated alongside food and water intake and body weight change. The involvement of serotonin pathway was investigated using the set of mice administered serotonin precursor for comparison with the beans diet-fed mice. Beam walking was used to assess neuromuscular coordination. Results: The results showed that beans and 5-HTP-fed mice showed better neuromuscular coordination when compared to control. This is because, decreased frequency of foot slips and longer latency of falls indicates a higher level of maneuverability in the beam, thus indicating better neuromuscular coordination. Conclusion: Long-term consumption of uncooked beans improves neuromuscular coordination.

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Cardioprotective effects of angiotensin converting Enzyme II

Leta Melaku, Andualem Mossie

International Journal of Clinical and Experimental Physiology 2017 4(2):57-68

To circumvent the major threats of low blood volume and low blood pressure, animals need powerful mechanisms for salt and water conservation, which is renin–angiotensin system (RAS). Activation of RAS is therefore a useful response in many demanding situations. However, an increased activity of the RAS, especially in combination with other cardiovascular risk factors, may lead to a cascade of deleterious effects such as hypertension, atherosclerosis, myocardial remodeling, heart failure, ischemic stroke, and diabetes mellitus. Many of these pathophysiological actions of angiotensin II (Ang II) may still be viewed as being homeostatic in principle but harmful if carried to excess. Numerous experimental studies have indicated that angiotensin-converting enzyme II (ACE II) efficiently hydrolyzes the potent vasoconstrictor Ang II to Ang 1–7. Thus, the axis formed by ACE II/Ang 1–7/Mas appears to represent an endogenous counter-regulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II, and Ang II Type 1 receptor (AT1R). Although most of the well-known cardiovascular and renal effects of RAS are attributed to ACE, an important enzyme in the generation of Ang II, much less is known about the functions of ACE II. This review summarizes recently published data on the basic properties of ACE II and Ang 1–7 and a summary of the evidence from experimental and clinical studies of various pathological conditions related to the biological roles of ACE II/Ang 1–7/Mas in the heart.

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The message of international yoga day

Gopal Krushna Pal

International Journal of Clinical and Experimental Physiology 2017 4(2):55-56



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A comparative study of the effect of ambient air pollution on ventilatory function tests in urban and rural population

Veeanna Hoovinahole Bhadranna, Christofer Thomas

International Journal of Clinical and Experimental Physiology 2017 4(2):69-74

Background and Aim: The particulate matter (PM10) is considered as the criteria parameter for assessing the quality of air that we respire as it is known to produce a significant impairment in ventilatory functions leading to respiratory diseases including bronchial asthma and chronic obstructive pulmonary disease. The aim of this study was to compare the lung function status in an urban population residing in an area with high ambient air pollutant with rural population with minimal concentration of air pollutant in their working environment. Methods: A cross sectional study was conducted with 144 exposed subjects and 148 control subjects. A computerised spirometer was used to assess the ventilatory function parameters. Ventilatory parameters like FVC, FEV1, FEV1/FVC, PEFR, FEF25, FEF50, FEF75, MVV was taken into consideration for the preset study which was also analysed with respect to the control and study group as well as with respect to the age group of the study subjects. Monitoring the concentration of the ambient air pollutants was done by the air monitoring stations of the Karnataka state pollution control board. Statistical analysis was done using SPSS package. Results: There was no significant differences in the anthropometric parameters of both study and control group. The results showed that the ventilatory function test of the urban study group was markedly declined when compared with the control group which was statistically significant. It was also found that the mean values of parameters like FVC, FEV1, PFF, FEV1/FVC%, FEF25-75%, V max 25%, 50%, 75% was statistically different in <30 years and >30 years among study and control group.Conclusion: Considering the fact that all the subjects participated in the study are from the same ethnic origin, residing at same altitude and non smokers, the significant reduction in the lung function parameters in the exposed group could be only due to the their exposure to the air pollutants.

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Problem-seeking learning in medical education

Sabyasachi Sircar

International Journal of Clinical and Experimental Physiology 2017 4(2):105-106



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Evaluation of anthropometric profile in obesity in nigerian females during pregnancy

WB Vidona, Aduema Wadioni, SN Okeke

International Journal of Clinical and Experimental Physiology 2017 4(2):75-81

Background and Aim: Excess body fat deposition is known to be unhealthy. There have been controversies on defined anthropometric parameters for the assessment of obesity during pregnancy. This is because certain cut-off values relating to it are influenced by age, sex, ethnicity, and trimesters of pregnancy. This study is aimed at investigating the use of anthropometric parameters to measure obesity and determine its prevalence in the different trimesters of pregnancy. Methods: The research is a prospective study of 460 pregnant women in the sample proportion of 110, 110, and 240 in the 1st, 2nd, and 3rd trimesters, respectively, chosen randomly from antenatal clinic of the Rivers State Primary Health care centre, Rumuepirikom, Obio-Akpor, Rivers State. Measurements of height, weight, waist circumference (WC), and hip circumference were obtained. Body mass index (BMI) was calculated from values of height and weight. Waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) were also calculated from waist and hiP values. Results: The result showed a BMI prevalence of 3.6%, 7.3%, and 0.8%; WC prevalence of 15.5%, 15.5%, and 3%; WHR prevalence of 43.6%, 35.5%, and 14.2%; WHtR prevalence of 56.4%, 51.8%, and 40% all in the 1st, 2nd, and 3rd trimesters, respectively. A negative linear correlation was shown between the other indices and BMI as an independent variable in 1st trimester with value (r = −0.015) against a (r = 0.085 and 0.165) in WC and WHtR, respectively. There was an association among the other anthropometric indices against BMI with no statistically significant difference at the level of 95% (P < 0.05). Conclusion: The results of this study are therefore recommended as a guide for clinical judgment in preventive and therapeutic health care services on obesity.

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Assessment of acute bronchodilator response in participants with or without airway obstruction in a tertiary care Hospital of West Bengal

Joyashree Banerjee, Ashmita Sengupta, Aloke Kumar Sinhababu, Anilbaran Singhamahapatra, Pranab Kumar Dey

International Journal of Clinical and Experimental Physiology 2017 4(2):92-96

Background and Aim: Acute bronchodilator response (BDR) during spirometry is very common in clinical studies. The response varies in different groups of participants. The aim of this study was to analyze the distribution of BDR in participants with or without airway obstruction. Methods: A retrospective analytical study of the spirometry results was undertaken. The spirometric values were analyzed for the present study. Among them, 1024 test results were included in our study. The values were estimated by an electronic spirometer, model-RMS Helios-702 in the Department of Physiology, R. G. Kar Medical College, Kolkata on 3200 participants. Results: Acute BDR was higher in chronic obstructive pulmonary disease (COPD) participants (45.4%) compared to other participants. Reversibility test was positive in 41.2% of asthma, 31% of allergic rhinitis, 32% of chronic cough, and 13.6% in apparently healthy participants. Conclusion: A good percentage of positive BDR is found not only in COPD and asthma but also in allergic rhinitis, chronic cough, apparently healthy participants which indicate its wider utility.

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Association of prehypertension status with sympathovagal imbalance in young first-degree relatives of Type 2 diabetics in Indian population is linked to body mass index

Gopal Krushna Pal, Pravati Pal, Balasubramanian Suchitra, Allampalli Sirisha, Nivedita Nanda

International Journal of Clinical and Experimental Physiology 2017 4(2):82-86

Background and Aim: As reports indicate that autonomic imbalance and hypertension in first-degree relatives (FDR) of type 2 diabetics predispose them to cardiovascular (CV) risks, in the present study, we have assessed contribution of body mass index (BMI) to sympathovagal imbalance (SVI) and prehypertension status in these patients. Methods: BMI, basal heart rate (BHR), blood pressure (BP), prehypertension status, rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in FDR of type 2 diabetics (Study group, n = 63) and in individuals with no family history of diabetes (Control group, n = 87). Results: BMI and low-frequency-high-frequency (LF-HF), the ratio of LF to HF power (LF-HF ratio) of HRV, a sensitive marker of SVI was significantly increased (P < 0.001) in the study group compared to control group. The SVI in the study group was due to concomitant sympathetic activation (increased LF) and vagal inhibition (decreased HF). In the study group, BMI was significantly correlated with LF-HF ratio, BHR, BP, and RPP. Multiple regression analysis demonstrated an independent contribution of BMI to prehypertension status and bivariate logistic regression revealed significant prediction of prehypertension status by LF-HF and BMI in the study group. Conclusion: BMI is more in FDR of type 2 diabetics and SVI in the form of increased sympathetic and decreased parasympathetic activity is present in them. Increased resting heart rate, elevated prehypertension status, decreased HRV, and increased RPP in these participants make them vulnerable to CV risks. BMI in these participants could be the link between SVI, prehypertension, and CV risks.

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Observation of various demographic, socio-economic and physical factors with Sthaulya (obesity) in individuals preferring day sleep: A cross sectional survey

Akhilesh Shukla, Anupama Shukla, AS Baghel, Mahesh Vyas

International Journal of Clinical and Experimental Physiology 2017 4(2):101-104

Background and Aim: Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Ayurveda has emphasized that the sleep pattern of the individual is equally responsible for obesity alike food. The aim of this study is to identify the association between day sleep and Sthaulya (Obesity) among patients aged between 20 and 60 years. Methods: A cross-sectional survey study was conducted among 250 Sthaulya (obesity) patients visiting the outpatient department. Sleep pattern questionnaire was used for the survey study. Results: The survey study revealed that habit of sleeping during daytime for more than 1 h, especially just after having lunch, waking up late after 6 AM in the morning, and sleeping for more than 8 h in a day is the important factors associated with Sthaulya (obesity). Conclusion: To prevent obesity, sleep after lunch and getting-up late in the morning should be avoided.

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Effect of physical activity and parameters of body stature and body composition on respiratory muscle strength in healthy young males: An observational study

Bhakti P Gadhavi, Jayesh Dalpatbhai Solanki, Hemant B Mehta, Amit H Makwana, Chinmay J Shah, Pradnya A Gokhale

International Journal of Clinical and Experimental Physiology 2017 4(2):87-91

Background and Aim: Obesity and physical inactivity affect respiratory functioning adversely. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) measure the strength of respiratory muscles. We studied the MIP and MEP in nonathletic young males in relation to adiposity and physical activity. Methods: We conducted a cross-sectional study on a consecutive sample of sixty young apparently healthy nonathletic males. Body mass index (BMI) and body composition were measured by Omron Karada Scan by tetra poplar bio-electrical impedance. We measured MIP and MEP by Ultima PFX real-time diffusion (RTD) (Medgraphic diagnostic company, USA), Breezesuite software, flow volume calibration, and guidelines laid by the American Thoracic Society. Results were analyzed further by comparing the actual value against the predicted value among the three patterns of subgrouping based on BMI, visceral fat (VF), and physical activity. Statistical significance was set at P< 0.05. Results: The study group had a mean age of 21 years, mean BMI of 22.5, and nearly half with BMI <22.5 and half were physically active. Better profile of body composition was present in males with BMI <22.5, VF <10%, and physical activity. MIP and MEP of the study participants were significantly lower than the predicted values, significantly better with physical activity and better without statistical significance with BMI or VF controlled. MIP and MEP correlated negatively but insignificantly with most other test parameters. Conclusion: Maximal respiratory pressures of young nonathletic males were less than predicted, more so with physical inactivity than adiposity. This indicates the importance of exercise and moderate physical activity to strengthen the respiratory muscle for optimal maximum respiration.

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News and Views



International Journal of Clinical and Experimental Physiology 2017 4(2):107-108



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Scientist to investigate how electrical charges help breast cancer spread

A leading scientist at the University of York has been awarded a grant worth almost £92,000 by research charity Breast Cancer Now to investigate – using innovative neuroscience techniques – whether a change in the electrical voltage of breast cancer...

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Computationally Driven Two-Dimensional Materials Design: What Is Next?

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b04327
ancac3?d=yIl2AUoC8zA


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Human Ribonuclease H1 resolves R loops and thereby enables progression of the DNA replication fork [Cell Biology]

Faithful DNA replication is essential for genome stability. To ensure accurate replication, numerous complex and redundant replication and repair mechanisms function in tandem with the core replication proteins to ensure DNA replication continues even when replication challenges are present that could impede progression of the replication fork. A unique topological challenge to the replication machinery is posed by RNA:DNA hybrids, commonly referred to as R-loops. While R-loops play important roles in gene expression and recombination at immunoglobulin sites, their persistence is thought to interfere with DNA replication by slowing or impeding replication fork progression. Therefore, it is of interest to identify DNA-associated enzymes that help resolve replication-impeding R-loops. Here, using DNA fiber analysis we demonstrate that human ribonuclease H1 (RNH1) plays an important role in replication fork movement in the mammalian nucleus by resolving R-loops. We found that RNH1 depletion results in accumulation of RNA:DNA hybrids, slowing of replication forks, and increased DNA damage. Our data uncovered a role for RNH1 in global DNA replication in the mammalian nucleus. Because accumulation of RNA:DNA hybrids is linked to various human cancers and neurodegenerative disorders, our study raises the possibility that replication fork progression might be impeded, adding to increased genomic instability and contributing to disease.

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Surface Toll-Like Receptor 3 Expression in Metastatic Intestinal Epithelial Cells induces Inflammatory Cytokine Production and Promotes Invasiveness [Signal Transduction]

Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells. In response to Poly(I:C) addition, the metastatic IECs also induced the chemokine CXCL10 in a TLR3-, TRIF- and IRF3- dependent manner, but failed to produce IFNβ. This was in contrast to healthy and non-metastatic IECs, which did not respond to Poly(I:C) stimulation. Endolysosomal acidification and the endosomal transporter protein UNC93B1 was required for the Poly(I:C)- induced CXCL10 production. However, TLR3- induced CXCL10 was triggered by immobilized Poly(I:C), was only modestly affected by inhibition of endocytosis, and could be blocked with an anti-TLR3 antibody, indicating that TLR3 still can signal from the cell surface of these cells. Furthermore, plasma membrane fractions from metastatic IECs contained both full-length and cleaved TLR3, demonstrating surface expression of both forms of TLR3. Our results imply that metastatic IECs express surface TLR3, allowing it to sense extracellular stimuli, which trigger chemokine responses, and promote invasiveness in these cells. We conclude that altered TLR3 expression and localization may have implications for cancer progression.

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The Cardiac Z-Disc Protein CEFIP Regulates Cardiomyocyte Hypertrophy By Modulating Calcineurin Signaling [Signal Transduction]

The z-disc is a structural component at the lateral borders of the sarcomere and is important for mechanical stability and contractility of both cardiac and skeletal muscles. Of note, the sarcomeric z-disc also represents a nodal point in cardiomyocyte function and signaling. Mutations of numerous z-disc proteins are associated with cardiomyopathies and muscle diseases. To identify additional z-disc proteins that might contribute to cardiac disease, we employed an in silico screen for cardiac-enriched cDNAs. This screen yielded a previously uncharacterized protein named cardiac enriched FHL2-interacting protein (CEFIP), which exhibited a heart and skeletal muscle-specific expression profile. Importantly, CEFIP was located at the z-disc and was upregulated in several models of cardiomyopathy. We also found that CEFIP overexpression induced the fetal gene program and cardiomyocyte hypertrophy. Yeast two-hybrid screens revealed that CEFIP interacts with the calcineurin-binding protein four and a half LIM domains 2 (FHL2). Since FHL2 binds calcineurin, a phosphatase controlling hypertrophic signaling, we examined the effects of CEFIP on the calcineurin/NFAT-pathway. These experiments revealed that CEFIP overexpression further enhances calcineurin-dependent hypertrophic signal transduction, while its knockdown repressed hypertrophy and calcineurin/NFAT activity. In summary, we report on a previously uncharacterized protein CEFIP that modulates calcineurin/NFAT signaling in cardiomyocytes, a finding with possible implications for the pathogenesis of cardiomyopathy.

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Lipid oxidation inactivates the anticoagulant function of Protein Z-Dependent Protease Inhibitor (ZPI) [Lipids]

Lipid oxidation due to oxidative stress plays an important role in the pathogenesis of inflammatory and thrombotic cardiovascular diseases. Several findings suggest that lipid peroxidation can alter the function of coagulation proteins and contribute to a hypercoagulable state, but the molecular mechanisms are unclear. Here, we report that oxidized phospholipids suppress the anticoagulant function of the serpin, protein Z-dependent protease inhibitor (ZPI), a specific inhibitor of membrane-associated factor Xa (FXa) that requires protein Z (PZ), phospholipid and calcium as cofactors. We found that this suppression arises from a diminished ability of the oxidized membrane to function as a cofactor to promote ZPI inhibition of membrane-bound FXa, due fully or in part to the susceptibility of the bound ZPI-PZ complex to oxidative inactivation. Surprisingly, free ZPI was also susceptible to inactivation by oxidized membrane vesicles in the absence of calcium. Oxidized vesicles containing both phosphatidylserine and polyunsaturated fatty acids were required to promote inactivation of the ZPI-PZ complex or free ZPI, indicating that binding of the PZ-complexed or free ZPI to peroxide-modified phospholipid vesicles mediates the inactivation. Heparin protected the ZPI-PZ complex and free ZPI from inactivation, suggesting that blocking the heparin binding site on ZPI interferes with ZPI binding to lipid or to PZ. This was confirmed by direct lipid binding experiments. Native PAGE indicated that oxidization induced dissociation of the ZPI-PZ complex and increased the negative charge of ZPI. We conclude that compromised ZPI anticoagulant function could contribute to thrombus initiation and growth in oxidative stress-induced cardiovascular diseases.

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Extrinsic sialylation is dynamically regulated by systemic triggers in vivo [Glycobiology and Extracellular Matrices]

Recent reports documented that extracellular sialyltransferases can remodel both cell surface and secreted glycans by a process other than the canonical cell-autonomous glycosylation that occurs within the intracellular secretory apparatus. Despite association of the abundance of these extracellular sialyltransferases, particularly ST6Gal-1, with disease states such as cancer and a variety of inflammatory conditions, the prevalence of this extrinsic glycosylation pathway in vivo remains unknown. Here we observed no significant extrinsic sialylation in resting mice, suggesting that extrinsic sialylation is not a constitutive process. However, extrinsic sialylation in the periphery could be triggered by inflammatory challenges, such as exposure to ionizing radiation or to bacterial lipopolysaccharides. Sialic acids from circulating platelets were used in vivo to remodel target cell surfaces. Platelet activation was minimally sufficient to elicit extrinsic sialylation, as demonstrated with the FeCl3 model of mesenteric artery thrombosis. While extracellular ST6Gal-1 supports extrinsic sialylation, other sialyltransferases are present in systemic circulation. We observed in vivo extrinsic sialylation also in animals deficient in ST6Gal-1, demonstrating that extrinsic sialylation is not mediated exclusively by ST6Gal-1. Together, these observations form an emerging picture of glycans biosynthesized by the canonical cell-autonomous glycosylation pathway, but subjected to remodeling by extracellular glycan-modifying enzymes.

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Two tyrosine residues, Tyr-108 and Tyr-503, are responsible for the deprotonation of phenolic substrates in vanillyl alcohol oxidase [Enzymology]

A number of oxidoreductases from the VAO/PCMH flavoprotein family catalyze the oxidation of para-substituted phenols. One of the best-studied is vanillyl alcohol oxidase (VAO) from the fungus Penicillium simplicissimum. For oxidation of phenols by VAO to occur, they must first be bound in the enzyme′s active site in their phenolate anion form. The crystal structure of VAO reveals that two tyrosine residues, Tyr-108 and Tyr-503, are positioned so as to facilitate this deprotonation. To investigate their role in catalysis, we created three VAO variants, Y108F, Y503F, and Y108F/Y503F, and studied their biochemical properties. Steady-state kinetics indicated that the presence of at least one of the tyrosine residues is essential for efficient catalysis by VAO. Stopped-flow kinetics revealed that the reduction of VAO by chavicol or vanillyl alcohol occurs at two different rates: kobs1, which corresponds to its reaction with the deprotonated form of the substrate, and kobs2, which corresponds to its reaction with the protonated form of the substrate. In Y108F, Y503F, and Y108F/Y503F, the relative contribution of kobs2 to the reduction is larger than in wild-type VAO, suggesting deprotonation is impaired in these variants. Binding studies disclosed that the competitive inhibitor isoeugenol is predominantly in its deprotonated form when bound to wild-type VAO, but predominantly in its protonated form when bound to the variants. These results indicate that Tyr-108 and Tyr-503 are responsible for the activation of substrates in VAO, providing new insights into the catalytic mechanism of VAO and related enzymes that oxidize para-substituted phenols.

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Rising life expectancy in England has slowed since recession

The pace of improving life expectancies has halved in England since the global recession began. Austerity cuts to healthcare and social care may be to blame

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-Dimensional Duffin-Kemmer-Petiau Oscillator under a Magnetic Field in the Presence of a Minimal Length in the Noncommutative Space

Using the momentum space representation, we study the (2 + 1)-dimensional Duffin-Kemmer-Petiau oscillator for spin 0 particle under a magnetic field in the presence of a minimal length in the noncommutative space. The explicit form of energy eigenvalues is found, and the wave functions and the corresponding probability density are reported in terms of the Jacobi polynomials. Additionally, we also discuss the special cases and depict the corresponding numerical results.

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Research on the Characteristics and Mechanism of the Cumulative Release of Antimony from an Antimony Smelting Slag Stacking Area under Rainfall Leaching

We aimed to study the characteristics and the mechanism of the cumulative release of antimony at an antimony smelting slag stacking area in southern China. A series of dynamic and static leaching experiments to simulate the effects of rainfall were carried out. The results showed that the release of antimony from smelting slag increased with a decrease in the solid-liquid ratio, and the maximum accumulated release was found to be 42.13 mgSb/kg waste and 34.26 mgSb/kg waste with a solid/liquid ratio of 1 : 20; the maximum amount of antimony was released within 149–420 μm size fraction with 7.09 mg/L of the cumulative leaching. Also, the antimony release was the greatest and most rapid at pH 7.0 with the minimum release found at pH 4.0. With an increase in rainfall duration, the antimony release increased. The influence of variation in rainfall intensity on the release of antimony from smelting slag was small.

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Αναζήτηση αυτού του ιστολογίου

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