Therapeutic Actions Fasting/Caloric Restriction

NCBI pubmed

How bacteria control the CRISPR-Cas arsenal.

How bacteria control the CRISPR-Cas arsenal. Curr Opin Microbiol. 2017 Nov 20;42:87-95 Authors: Leon LM, Mendoza SD, Bondy-Denomy J Abstract CRISPR-Cas systems are adaptive immune systems that protect their hosts from predation by bacteriophages (phages) and parasitism by other mobile genetic elements (MGEs). Given the potent nuclease activity of CRISPR effectors, these enzymes must be carefully regulated to minimize toxicity and maximize anti-phage immunity. While attention has been given to the transcriptional regulation of these systems (reviewed in [1]), less consideration has been given to the crucial post-translational processes that govern enzyme activation and inactivation. Here, we review recent findings that describe how Cas nucleases are controlled in diverse systems to provide a robust anti-viral response while limiting auto-immunity. We also draw comparisons to a distinct bacterial immune system, restriction-modification. PMID: 29169146 [PubMed - as supplied by publisher]

The role of seed size, phenology, oogenesis and host distribution in the specificity and genetic structure in seed weevils (Curculio spp.) in mixed forests.

The role of seed size, phenology, oogenesis and host distribution in the specificity and genetic structure in seed weevils (Curculio spp.) in mixed forests. Integr Zool. 2017 Nov 23;: Authors: Arias-LeClaire H, Bonal R, García-López D, Espelta JM Abstract Synchrony between seed growth and oogenesis are suggested to largely shape trophic breadth of seed-feeding insects and ultimately contribute to their co-existence by means of resource partitioning or in the time when infestation occurs. Here we investigated: i) the role of seed phenology and sexual maturation of females in the host specificity of seed-feeding weevils (Curculio spp) predating in hazel and oak mixed forests and ii) the consequences that trophic breadth and host distribution have in the genetic structure of the weevil populations. DNA analyses were used to establish unequivocally host specificity and to determine the population genetic structure. We identified four species with different specificity, namely C. nucum females matured earlier and infested a unique host (hazelnuts) while three species (C. venosus, C. glandium, C. elephas) predated upon the acorns of the two oaks (Q. ilex and Q. humilis). The high specificity of C. nucum coupled with a more discontinuous distribution of hazel trees resulted in a significant genetic structure among sites. Also, the presence of an excess of local rare haplotypes indicated that C. nucum populations went through genetic expansion after recent bottlenecks. Conversely, these effects were not observed in the more generalist C. glandium predating upon oaks. Ultimately, co-existence of weevil species in this multi-host-parasite system is influenced by both resource and time partitioning. To what extent the restriction in gene flow among C. nucum populations may have negative consequences for their persistence in a time of increasing disturbances (e.g. drought in Mediterranean areas) deserves further research. This article is protected by copyright. All rights reserved. PMID: 29168606 [PubMed - as supplied by publisher]

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia.

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia. Indian J Med Res. 2017 Jul;146(1):49-55 Authors: Pasechnik O, Dymova MA, Stasenko VL, Blokh AI, Tatarintseva MP, Kolesnikova LP, Filipenko ML Abstract BACKGROUND & OBJECTIVES: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). METHODS: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. RESULTS: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. INTERPRETATION & CONCLUSIONS: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M. tuberculosis strains. PMID: 29168460 [PubMed - in process]

Lipocalin 2 (Lcn2) interferes with iron uptake by Brucella abortus and dampens immunoregulation during infection of RAW 264.7 macrophages.

Lipocalin 2 (Lcn2) interferes with iron uptake by Brucella abortus and dampens immunoregulation during infection of RAW 264.7 macrophages. Cell Microbiol. 2017 Nov 22;: Authors: Hop HT, Arayan LT, Huy TXN, Reyes AWB, Baek EJ, Min W, Lee HJ, Rhee MH, Watanabe K, Chang HH, Kim S Abstract Lipocalin 2 (Lcn2) is an important innate immunity component against bacterial pathogens. In this study, we report that Lcn2 is induced by Brucella (B.) abortus infection and significantly contributes to the restriction of intracellular survival of Brucella in macrophages. We found that Lcn2 prevented iron uptake by B. abortus through two distinct mechanisms. First, Lcn2 is secreted to capture bacterial siderophore(s) and abrogate iron import by Brucella. Second, Lcn2 decreases the intracellular iron levels during Brucella infection, which probably deprives the invading Brucella of the iron source needed for growth. Suppression of Lcn2 signaling resulted in a marked induction of anti-inflammatory cytokine, interleukin 10 (IL-10) which was shown to play a major role in Lcn2-induced antibrucella immunity. Similarly, IL-6 was also found to be increased when Lcn2 signaling is abrogated; however, this induction was thought to be an alternative pathway that rescues the cell from infection when the effective Lnc2 pathway is repressed. Furthermore, Lcn2 deficiency also caused a marked decrease in brucellacidal effectors, such as reactive oxygen species (ROS) and nitric oxide (NO), but not the phagolysosome fusion. Taken together, our results indicate that Lcn2 is required for the efficient restriction of intracellular B. abortus growth that is through limiting iron acquisition and shifting cells to pro-inflammatory brucellacidal activity in murine macrophages. PMID: 29168343 [PubMed - as supplied by publisher]

Revision of Podocotyloides Yamaguti, 1934 (Digenea: Opecoelidae), resurrection of Pedunculacetabulum Yamaguti, 1934 and the naming of a cryptic opecoelid species.

Revision of Podocotyloides Yamaguti, 1934 (Digenea: Opecoelidae), resurrection of Pedunculacetabulum Yamaguti, 1934 and the naming of a cryptic opecoelid species. Syst Parasitol. 2017 Nov 22;: Authors: Martin SB, Cutmore SC, Cribb TH Abstract Despite morphological and ecological inconsistencies among species, all plagioporine opecoelids with a pedunculate ventral sucker are currently considered to belong in the genus Podocotyloides Yamaguti, 1934. We revise the genus based on combined morphological and phylogenetic analyses of novel material collected from haemulid fishes in Queensland waters that we interpret to represent species congeneric with the type-species, Pod. petalophallus Yamaguti, 1934, also known from a haemulid, off Japan. Our phylogenetic analysis demonstrates polyphyly of Podocotyloides; prompts us to resurrect Pedunculacetabulum Yamaguti, 1934; and suggests that Pod. brevis Andres & Overstreet, 2013, from a deep-sea congrid in the Caribbean, and Pod. parupenei (Manter, 1963) Pritchard, 1966 and Pod. stenometra Pritchard, 1966, from mullids and chaetodontids, respectively, on the Great Barrier Reef, may each represent a distinct genus awaiting recognition. Our revised concept of Podocotyloides requires a pedunculate ventral sucker, but also a uterine sphincter prior to the genital atrium, a petalloid cirrus appendage, restriction of the vitelline follicles to the hindbody, and for the excretory vesicle to reach to the level of the ventral sucker. Of about 20 nominal species, we recognise just three in Podocotyloides (sensu stricto): Pod. petalophallus, Pod. gracilis (Yamaguti, 1952) Pritchard, 1966 and Pod. magnatestes Aleshkina & Gaevskaya, 1985. We provide new records for Pod. gracilis, and propose two new species of Podocotyloides, Pod. australis n. sp. and Pod. brevivesiculatus n. sp., and one new Pedunculacetabulum species, Ped. inopinipugnus n. sp., all from haemulids. Podocotyloides australis is morphologically indistinguishable from Pod. gracilis, and exploits the same definitive host, but is genetically and biogeographically distinct. It is thus a cryptic species, the first such opecoelid to be formally named. PMID: 29168149 [PubMed - as supplied by publisher]

TP53 Gene Polymorphisms and Occupational Skin Cancer Risks for Workers of Glass Fiber Manufacture.

TP53 Gene Polymorphisms and Occupational Skin Cancer Risks for Workers of Glass Fiber Manufacture. Iran J Public Health. 2017 Nov;46(11):1495-1501 Authors: Mukhammadiyeva GF, Karimov DO, Bakirov AB, Karimova LK Abstract Background: Determining the role of genetic markers in individual sensitivity to chemical exposures raises a possibility of risk assessment of occupational diseases and their prevention. This paper focuses on the results of the identification of molecular-genetic markers associated with occupational skin cancer susceptibility. This study aimed to explore an association between polymorphisms of the TP53 tumor suppressor gene and a risk of developing occupational skin neoplasms. Methods: This case-control study was conducted on 71 workers with occupational skin neoplasms, 99 healthy workers, and 100 healthy population-based controls in Bashkortostan Republic, Russia in 2015. Genotyping of TP53 polymorphisms (rs1042522, rs1625895, and rs17878362) was performed by restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood. Odds ratios and 95% confidence intervals were calculated to measure the strength of the association. Results: Subjects carrying allele C of rs1042522 were associated with an increased risk of occupational skin neoplasms [P=0.027, odds ratio (OR)=1.97, 95% confidence intervals (CI) 1.08-3.63]. An increased risk was also associated with allele 16bp of rs17878362 (P=0.010, OR=3.32, 95 % CI=1.31-8.78) and allele A of rs1625895 (P=0.003, OR = 5.45, 95 % CI = 1.72-19.15). Conclusion: The polymorphic variants rs1042522, rs1625895 and rs17878362 of the TP53 gene are related to increased risks of occupational skin cancer. This study suggests the potential use of molecular-genetic data to assess increased individual risks of the development and prognosis of occupational skin neoplasms. PMID: 29167767 [PubMed - in process]

Improving Cardiometabolic Health with Diet, Physical Activity, and Breaking Up Sitting: What about Sleep?

Improving Cardiometabolic Health with Diet, Physical Activity, and Breaking Up Sitting: What about Sleep? Front Physiol. 2017;8:865 Authors: Vincent GE, Jay SM, Sargent C, Vandelanotte C, Ridgers ND, Ferguson SA Abstract Cardiometabolic disease poses a serious health and economic burden worldwide and its prevalence is predicted to increase. Prolonged sitting, lack of physical activity, poor diet, and short sleep duration are ubiquitous behaviors in modern society, and all are independent risk factors in the development of cardiometabolic disease. Existing evidence demonstrates that breaking up prolonged periods of sitting is beneficial for cardiometabolic health, however, studies have not controlled for prior sleep duration. This article examines how prolonged sitting and short sleep duration independently contribute to cardiometabolic risk, and how breaking up sitting and obtaining adequate sleep may reduce this risk. We suggest that as prolonged sitting and short sleep duration influence the same cardiometabolic parameters, there is potential for short sleep to attenuate the positive impact of breaking up prolonged sitting with physical activity. Likewise, breaking up prolonged sitting and obtaining adequate sleep together could improve predictors of cardiometabolic disease, i.e., the combined effect may be stronger than either alone. To explore these perspectives, we propose a research agenda to investigate the relationship between breaking up prolonged sitting with physical activity and short sleep duration. This will provide an evidence-base for informing the design of interventions to reduce the burden of cardiometabolic disease on communities worldwide. PMID: 29167645 [PubMed]

Specification of murine ground state pluripotent stem cells to regional neuronal populations.

Specification of murine ground state pluripotent stem cells to regional neuronal populations. Sci Rep. 2017 Nov 22;7(1):16001 Authors: Alsanie WF, Niclis JC, Hunt CP, De Luzy IR, Penna V, Bye CR, Pouton CW, Haynes J, Firas J, Thompson LH, Parish CL Abstract Pluripotent stem cells (PSCs) are a valuable tool for interrogating development, disease modelling, drug discovery and transplantation. Despite the burgeoned capability to fate restrict human PSCs to specific neural lineages, comparative protocols for mouse PSCs have not similarly advanced. Mouse protocols fail to recapitulate neural development, consequently yielding highly heterogeneous populations, yet mouse PSCs remain a valuable scientific tool as differentiation is rapid, cost effective and an extensive repertoire of transgenic lines provides an invaluable resource for understanding biology. Here we developed protocols for neural fate restriction of mouse PSCs, using knowledge of embryonic development and recent progress with human equivalents. These methodologies rely upon naïve ground-state PSCs temporarily transitioning through LIF-responsive stage prior to neural induction and rapid exposure to regional morphogens. Neural subtypes generated included those of the dorsal forebrain, ventral forebrain, ventral midbrain and hindbrain. This rapid specification, without feeder layers or embryoid-body formation, resulted in high proportions of correctly specified progenitors and neurons with robust reproducibility. These generated neural progenitors/neurons will provide a valuable resource to further understand development, as well disorders affecting specific neuronal subpopulations. PMID: 29167563 [PubMed - in process]

Publisher Correction: Sex-Dependent Effects of Caloric Restriction on the Ageing of an Ambush Feeding Copepod.

Publisher Correction: Sex-Dependent Effects of Caloric Restriction on the Ageing of an Ambush Feeding Copepod. Sci Rep. 2017 Nov 22;7(1):16392 Authors: Saiz E, Calbet A, Griffell K Abstract  A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper. PMID: 29167531 [PubMed - in process]

HAdV protein V core protein is targeted by the host SUMOylation machinery to limit essential viral functions.

HAdV protein V core protein is targeted by the host SUMOylation machinery to limit essential viral functions. J Virol. 2017 Nov 22;: Authors: Freudenberger N, Meyer T, Groitl P, Dobner T, Schreiner S Abstract Human Adenoviruses (HAdV) are non-enveloped containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear-pore-complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood.The core protein V is speculated to bridge core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultanously, these altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than observed during wildtype infection.Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies.ImportanceMany decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this concept needs expansion, as the functions are more diverse. We showed that capsid protein protein VI is regulating antiviral response by modulation of the transcription factor Daxx during infection. Moreover, core protein VII interacts with SPOC1 restriction factor, being beneficial for efficient viral gene expression. Here, we were able to show that also core protein V represents a novel substrate of the host SUMOylation machinery and contains several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of the protein. Unexpectedly, we observed that introducing these mutations into HAdV promotes adenoviral replication. Conclusively, we offer novel insights into adenovirus core proteins and provide evidence that SUMOylation of HAdV factors regulates replication efficiency. PMID: 29167340 [PubMed - as supplied by publisher]

Rodent Vertical Sleeve Gastrectomy Alters Maternal Immune Health and Feto-placental Development.

Rodent Vertical Sleeve Gastrectomy Alters Maternal Immune Health and Feto-placental Development. Clin Sci (Lond). 2017 Nov 22;: Authors: Spann RA, Lawson WJ, Bidwell GL, Zamarripa CA, Maranon RO, Bandyopadhyay S, Taylor ER, Reckelhoff JF, Garrett MR, Grayson BE Abstract Bariatric surgery is increasingly employed to improve fertility and reduce obesity related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy. VSG dams studied on gestational day (G) 18 had reduced circulating T cell (CD3+ and CD8+) populations compared to lean or obese controls. Further, local interleukin 1 β and interleukin 1 receptor antagonist mRNA were increased in placenta of VSG dams. Placental barrier function was also affected, with increased trans-placental permeability to small molecules, increased matrix metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we identified increased placental mTOR signaling that may contribute to preserving the body weight of the fetuses during gestation. These changes occurred in the absence of a macronutrient deficit or gestational hypertension in the VSG dams. In summary, previous VSG in dams may contribute to fetal demise by affecting maternal immune system activity and compromise placental integrity. PMID: 29167317 [PubMed - as supplied by publisher]

Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction. Am J Physiol Gastrointest Liver Physiol. 2017 Nov 22;:ajpgi.00135.2017 Authors: Araya S, Kuster E, Gluch D, Mariotta L, Lutz C, Reding TV, Graf R, Verrey F, Camargo SMR Abstract Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern the rate of Glu influx into acinar cells was approximately 6-fold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and glutamate dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln; but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. PMID: 29167114 [PubMed - as supplied by publisher]

Postural Control During Different Unipodal Positions in Professional Ballet Dancers.

Postural Control During Different Unipodal Positions in Professional Ballet Dancers. J Dance Med Sci. 2017 Dec 15;21(4):151-155 Authors: de Mello MC, de Sá Ferreira A, Ramiro Felicio L Abstract Classical ballet involves the performance of complex movements that require high-level motor skills and good postural control. This study explored postural sway in passé en demi-pointe position in dancers and compared single-leg standing sway (with and without visual restriction) between dancers and non-dancers. Fourteen professional dancers and 14 sex- and age-matched volunteers who were not ballet dancers participated in the study. Participants stood on a force plate on the dominant leg in the following positions: 1. single-leg stance with eyes open (reference task) and with eyes closed and blindfolded for 35 seconds; and 2. passé en demi-pointe position with eyes open for 20 seconds (dancers only). The center of pressure signal was used to calculate the following variables: average velocity; anteroposterior and mediolateral velocity peaks; anteroposterior and mediolateral displacement ranges; average displacement; and ellipse area. Significant interaction effects (p < 0.001, η2 = 0.419) were observed between groups and postural tasks, with higher stabilometric values for the dancer group during the single-leg stance with eyes closed and blindfolded task, as evidenced by the average displacement of 241.0 cm in dancers and 147.1 cm in non-dancers (p = 0.025), and by the ellipse area of 9.5 cm2 for dancers and 4.9 cm2 for non-dancers (p = 0.001). In regard to the positions with eyes open, an increase was noted only in the average sway velocity and mediolateral velocity in passé en demi-pointe position compared with the single-leg stance with eyes open (p < 0.001). Greater postural sway might be interpreted as the result of either inadequate postural stability or exploratory behavior to maintain postural stability in more challenging tasks. It is concluded that professional ballet dancers show greater visual dependency for balance adjustment with reduced influence of the supporting base on postural sway. PMID: 29166985 [PubMed - in process]

Analysis of pre-weaning feeding policies and other risk factors influencing growth rates in calves on 11 commercial dairy farms.

Analysis of pre-weaning feeding policies and other risk factors influencing growth rates in calves on 11 commercial dairy farms. Animal. 2017 Nov 23;:1-11 Authors: Johnson KF, Chancellor N, Burn CC, Wathes DC Abstract Growth rates in pre-weaned calves influence their health, age at first calving and lifetime productivity. Many farms restrict milk rations to encourage solid feed intake and facilitate early weaning, but this can compromise growth. This study determined the milk feeding policies and associated growth rates on 11 commercial dairy farms in South East England, each following their normal management regime. Between 26 and 54 heifers were recruited per farm, providing a final cohort of 492, of which 71% were pure Holstein. Information on calf rearing practices (feeding, weaning, housing) and health was collected via questionnaires and weekly observations. Estimates of actual milk fed (kg solids) between 1 and 63 days were calculated for individual calves. Morphometric data (weight, height, length) were taken at weeks 1, 5 and 9 and at a median age of 7.5 months and growth rates were calculated. Most calves were fed milk replacer via automated feeders (four farms), teat feeder (one) or buckets (four) whereas two farms provided drums of acidified waste milk. Farms fed between 4 and 6 l/day of milk at mixing rates of 10% to 15%, providing 400 to 900 g/day of milk solids. Both skeletal growth rates and average daily weight gain (ADG) increased in the second month of life compared with the first: height growth from 0.17±0.14 to 0.25±0.16 cm/day and ADG from 0.48±0.25 to 0.71±0.28 kg/day. Post-weaning heifers up to 7.5 months had height increases of 0.16±0.035 cm/day and ADG of 0.83±0.16 kg/day. From 1 to 63 days 70% of calves had growth rates <0.7 kg/day and of these 19.6% gained <0.5 kg/day. Mean ADG before 9 weeks varied between farms from 0.52±0.30 to 0.75±0.20 kg/day. This was related to the amount of milk fed at both a farm and individual calf level. Increasing the total milk solids fed between 1 and 63 days from 20.4 to 46.3 kg (the 10th to 90th percentile observed) was associated with an increase of 0.11 kg/day ADG. All farms had a wide variation in growth rates despite single feeding policies. Higher circulating immunoglobulin G and IGF1 concentrations were associated with better growth, whereas low temperatures in month of birth, high scores for diarrhoea, respiratory and umbilical disease and large birth size reduced growth. Many commercially grown dairy heifers therefore experienced growth restriction in the pre-weaned period, potentially reducing their health, welfare and productivity. PMID: 29166977 [PubMed - as supplied by publisher]

Multiscale positive feedbacks contribute to unidirectional gastric disease progression induced by helicobacter pylori infection.

Multiscale positive feedbacks contribute to unidirectional gastric disease progression induced by helicobacter pylori infection. BMC Syst Biol. 2017 Nov 22;11(1):111 Authors: Ballweg R, Schozer F, Elliott K, Kuhn A, Spotts L, Aihara E, Zhang T Abstract BACKGROUND: Helicobacter Pylori (HP) is the most common risk factor for gastric cancer. Nearly half the world's population is infected with HP, but only a small percentage of those develop significant pathology. The bacteria itself does not directly cause cancer; rather it promotes an environment that is conducive to tumor formation. Upon infection, HP induces transcriptional changes in the host, leading to enhanced proliferation and host immune response. In addition, HP causes direct damage to gastric epithelial cells. RESULTS: We present a multiscale mechanistic model of HP induced changes. The model includes four modules representing the host transcriptional changes in response to infection, gastric atrophy, the Hedgehog pathway response, and the restriction point that controls cell cycle. This model was able to recapture a number of literature reported observations and was used as an "in silico" representation of the biological system for further analysis. Dynamical analysis of the model revealed that HP might induce the activation of multiple interplayed positive feedbacks, which in turn might result in a "ratchet ladder" system that promotes a unidirectional progression of gastric disease. CONCLUSIONS: The current multiscale model is able to recapitulate the observed experimental features of HP host interactions and provides dynamic insights on the epidemiologically observed heterogeneity in disease progression. This model provides a solid framework that can be further expanded and validated to include additional experimental evidence, to understand the complex multi-pathway interactions characterizing HP infection, and to design novel treatment protocols for HP induced diseases. PMID: 29166909 [PubMed - in process]

Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor.

Related Articles Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor. Cell Rep. 2017 Nov 21;21(8):2251-2263 Authors: Wahlestedt M, Ladopoulos V, Hidalgo I, Sanchez Castillo M, Hannah R, Säwén P, Wan H, Dudenhöffer-Pfeifer M, Magnusson M, Norddahl GL, Göttgens B, Bryder D Abstract A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates. Reciprocally, we observed rapid lymphoid commitment upon reduced Hlf activity. The arising phenotypes resulted from Hlf binding to active enhancers of myeloid-competent cells, transcriptional induction of myeloid, and ablation of lymphoid gene programs, with Hlf induction of nuclear factor I C (Nfic) as a functionally relevant target gene. Thereby, our studies establish Hlf as a key regulator of the earliest lineage-commitment events at the transition from multipotency to lineage-restricted progeny, with implications for both normal and malignant hematopoiesis. PMID: 29166614 [PubMed - in process]

MMP-3 (-1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)-3 and correlate with severity of COPD: a study of MMP-3, MMP-7 and MMP-12 in a Tunisian population.

Related Articles MMP-3 (-1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)-3 and correlate with severity of COPD: a study of MMP-3, MMP-7 and MMP-12 in a Tunisian population. J Gene Med. 2017 Nov 22;: Authors: Bchir S, Ben Nasr H, Garrouch A, Ben Anes A, Abbassi A, Tabka Z, Chahed K Abstract OBJECTIVE: The goal of this study was to examine the role of MMP-3 (-1171 5A/6A; Lys45Glu (A/G)), MMP-7 (-181) A/G and MMP-12 (-82 A/G; Asn357Ser (A/G)) variants in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisians. METHODS: Plethysmography was performed in all participants to measure FEV1, FVC and FEV1/FVC parameters. Genotyping of MMP-3, MMP-7 and MMP-12 polymorphisms was carried out in 138 patients with COPD and 216 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum levels of MMPs and cytokines (IL-6, TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant correlations were observed between genetic variations in MMP-3, MMP-7 and MMP-12 and the risk of development of COPD. Additionally, no impact of MMP-7 (-181) A/G and MMP-12 (-82 A/G; Asn357Ser (A/G)) polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, both MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) variants were associated with respiratory function, as well as with serum levels of MMP-3 in COPD patients. A relationship was found between the (-1171) 6A and 45Glu (G) alleles of MMP-3 gene and enhanced airflow limitation among COPD patients. Additionally, carriers of the 6A6A and 45 GG genotypes present higher MMP-3 levels than non carriers. CONCLUSION: MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) polymorphisms were associated with the decline of lung function among COPD patients. These results could be linked to the upregulation of MMP-3 in serum from COPD patients carrying the -1171 6A and 45G homozygous genotypes. PMID: 29165854 [PubMed - as supplied by publisher]

Research on the correlation between the fibrinogen β and attack of pediatric pneumonia.

Related Articles Research on the correlation between the fibrinogen β and attack of pediatric pneumonia. Eur Rev Med Pharmacol Sci. 2017 Oct;21(4 Suppl):100-105 Authors: Liu G, Wu HW, Li ZG Abstract OBJECTIVE: To investigate the correlation of the gene polymorphism of β-148C/T of fibrinogen with the expression of fibrinogen and the attack of pediatric pneumonia. PATIENTS AND METHODS: We employed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect the gene polymorphism of beta-fibrinogen gene-148C/T (β-148C/T). The expression level of fibrinogen in plasma was measured using enzyme-linked immunosorbent assay (ELISA), and the expression level of fibrinogen β protein was determined using Western-blot method. RESULTS: Compared with the healthy control group, the expression level of fibrinogen β was significantly higher in patients with pneumonia. Additionally, the frequency of CC genotype, as well as the allele of C, in the pneumonia group were significantly higher than that in the control group. Meanwhile, the frequency of TT genotype and the allele of T were remarkably lower in patients with pneumonia compared to those in the control group. No significant difference was found in comparison with the CT genotype frequency between the two groups. Compared with the patients with TT genotypes, expressions of fibrinogen, IL-6 and CRP were significantly higher in the patients with the CC and CT genotypes. However, the odds ratio (OR) of pediatric pneumonia patients with TT genotype was 0.21, OR of pediatric pneumonia patients with CT genotype was 0.77 and OR of pediatric pneumonia patients with CC genotype was 12.73. The OR of patients with T allele was 1.85 and OR of patients with C allele was 5.15. CONCLUSIONS: We concluded that β-148C/T gene polymorphism of fibrinogen was correlated with the susceptibility of pediatric pneumonia, suggesting that it may be a genetic risk factor, and fibrinogen β-148C/T gene may be involved in the onset of pediatric pneumonia through affecting the concentration of fibrinogen β in plasma. PMID: 29165755 [PubMed - in process]

Being Born Too Small and Too Early May Alter Sleep in Childhood.

Related Articles Being Born Too Small and Too Early May Alter Sleep in Childhood. Sleep. 2017 Nov 20;: Authors: Yiallourou SR, Arena BC, Wallace EM, Odoi A, Hollis S, Weichard A, Horne RSC Abstract Study Objectives: Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is associated with increased risk of prematurity and neurodevelopmental impairment. FGR also alters sleep state distribution in utero and maturation in infancy. Currently, limited data on the long-term associations of FGR and childhood sleep exist. Accordingly, we assessed the associations between preterm birth and FGR and sleep in children aged 5-12 years. Methods: 17 children born preterm and FGR, 15 children born preterm but appropriately grown (AGA) and 20 term AGA children (controls) were studied using overnight polysomnography. Sleep macro-architecture was assessed using standard criteria and sleep micro-architecture was assessed using spectral analysis of the EEG (C4-M1) with Total, Delta (0.5Hz-3.9Hz), Theta (4.0Hz-7.9Hz), Alpha (8.0Hz-11.9Hz), Sigma (12.0Hz-13.9Hz) and Beta Power (14.0Hz-30Hz) calculated. Results: For sleep macro-architecture, preterm FGR children had higher N2% compared to term AGA children (p<0.05). Preterm AGA children had reduced total sleep time, NREM% and sleep efficiency compared to term AGA children (p<0.05 for all). For sleep micro-architecture, preterm FGR children had a higher amount of Total, delta and alpha power compared to both groups (p<0.05). Sigma and beta power were lowest in the preterm AGA group compared to both groups (p<0.05 for both). Conclusions: Prematurity and FGR were associated with altered sleep macro- and micro-architecture measures indicative of reduced sleep quantity and quality in childhood. As sleep disturbance can impact both behavior and neurodevelopment in children, sleep in FGR and preterm children warrants further investigation. PMID: 29165677 [PubMed - as supplied by publisher]

Oral Contraceptives and Cigarette Smoking: A Review of the Literature and Future Directions.

Related Articles Oral Contraceptives and Cigarette Smoking: A Review of the Literature and Future Directions. Nicotine Tob Res. 2017 Nov 18;: Authors: Allen AM, Weinberger AH, Wetherill RR, Howe CL, McKee SA Abstract Introduction: Evidence continues to mount indicating that endogenous sex hormones (e.g., progesterone and estradiol) play a significant role in smoking-related outcomes. Although approximately 1 out of 4 premenopausal smokers use oral contraceptives (OCs), which significantly alter progesterone and estradiol levels, relatively little is known about how OCs may influence smoking-related outcomes. Thus, the goal of this review paper is to describe the state of the literature and offer recommendations for future directions. Methods: In March 2017, we searched seven databases, with a restriction to articles written in English, using the following keywords: nicotine, smoker(s), smoking, tobacco, cigarettes, abstinence, withdrawal, and craving(s). We did not restrict on the publication date, type or study design. Results: A total of 13 studies were identified. Three studies indicated faster nicotine metabolism in OC users compared to nonusers. Five of six laboratory studies that examined physiological stress response noted heightened response in OC users compared to nonusers. Three studies examined cessation-related symptomatology (e.g., craving) with mixed results. One cross-sectional study observed greater odds of current smoking among OC users, and no studies have explored the relationship between OC use and cessation outcomes. Conclusions: Relatively few studies were identified on the role of OCs in smoking-related outcomes. Future work could explore the relationship between OC use and mood, stress, weight gain and brain function/connectivity, as well as cessation outcomes. Understanding the role of OC use in these areas may lead to the development of novel smoking cessation interventions for premenopausal women. Implications: This is the first review of the relationship between oral contraceptives (OCs) and smoking-related outcomes. The existing literature suggests that the use of OCs is related to increased nicotine metabolism and physiological stress response. However, the relationship between OC use and smoking-related symptoms (e.g., craving) is mixed. Further, no published data were available on OC use and smoking cessation outcomes. Therefore, we recommend additional research be conducted to characterize the relationship between OC use and smoking cessation outcomes, perhaps as a function of the effect of OC use on mood, stress, weight gain and brain function/connectivity. PMID: 29165663 [PubMed - as supplied by publisher]
Prev1234Next