bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xenograft of microencapsulated Sertoli cells restores glucose homeostasis in db/db mice with spontaneous diabetes mellitus
Authors: Luca Giovanni , Arato Iva , Mancuso Francesca , Calvitti Mario , Falabella Giulia , Murdolo Giuseppe , Basta Giuseppe , Cameron Don F. , Hansen Barbara C. , Fallarino Francesca , Baroni Tiziano , Aglietti Maria Chiara , Tortoioli Cristina , Bodo Maria , Calafiore Riccardo 
Published: September 2016

AbstractBackgroundIncreased abdominal fat and chronic inflammation in the expanded adipose tissue of obesity contribute to the development of insulin resistance and type 2 diabetes mellitus (T2D). The emerging immunoregulatory and anti‐inflammatory properties of Sertoli cells have prompted their application to experimental models of autoimmune/inflammatory disorders, including diabetes.The main goal of this work was to verify whether transplantation of microencapsulated prepubertal porcine Sertoli cells (MC‐SC) in the subcutaneous abdominal fat depot of spontaneously diabetic and obese db/db mice (homozygous for the diabetes spontaneous mutation [Leprdb]) would: (i) improve glucose homeostasis and (ii) modulate local and systemic immune response and adipokines profiles.MethodsPorcine prepubertal Sertoli cells were isolated, according to previously established methods and enveloped in Barium alginate microcapsules by a mono air‐jet device. MC‐SC were then injected in the subcutaneous abdominal fat depot of db/db mice.ResultsWe have preliminarily shown that graft of MC‐SC restored glucose homeostasis, with normalization of glycated hemoglobin values with improvement of the intraperitoneal glucose tolerance test in 60% of the treated animals. These results were associated with consistent increase, in the adipose tissue, of uncoupling protein 1 expression, regulatory B cells, anti‐inflammatory macrophages and a concomitant decrease of proinflammatory macrophages. Furthermore, the treated animals showed a reduction in inducible NOS and proinflammatory molecules and a significant increase in an anti‐inflammatory cytokine such as IL‐10 along with concomitant rise of circulating adiponectin levels. The anti‐hyperglycemic graft effects also emerged from an increased expression of GLUT‐4, in conjunction with downregulation of GLUT‐2, in skeletal muscle and liver, respectively.ConclusionsPreliminarily, xenograft of MC‐SC holds promises for an effective cell therapy approach for treatment of experimental T2D.
Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion
Authors: Tandon Shashank , Keefe Kristen A. , Taha Sharif A. 
Published: September 2016

Key points
The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.
In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.
Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.
In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.
Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption.
AbstractEthanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press‐evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham‐ and LHb‐lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol‐induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake.
CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins
Authors: Zurawel Ashley A. , Kabeche Ruth , DiGregorio Sonja E. , Deng Lin , Menon Kartikeya M. , Opalko Hannah , Duennwald Martin L. , Moseley James B. , Supattapone Surachai 
Published: September 2016

ABSTRACT

Proteins containing polyglutamine (polyQ) regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt) with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington’s disease (HD). To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt) in
Schizosaccharomyces pombe
. In stark contrast to other unicellular fungi, such as
Saccharomyces cerevisiae
,
S. pombe
is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within
S. pombe
cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in
S. pombe
cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in
S. pombe
, in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms.

IMPORTANCE
Polyglutamine (polyQ) proteins encoded by repetitive CAG DNA sequences serve a variety of normal biological functions. Yet some proteins with abnormally expanded polyQ regions cause neurodegeneration through unknown mechanisms. To study how distinct cellular environments modulate polyQ aggregation and toxicity, we expressed CAG-expanded huntingtin fragments in
Schizosaccharomyces pombe
. In stark contrast to many other eukaryotes,
S. pombe
is uniquely devoid of proteins containing long polyQ tracts. Our results show that
S. pombe
cells, despite their low content of endogenous polyQ proteins, exhibit striking and unexpected resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the emergence and expansion of polyQ domains in eukaryotic evolution.
Chlamydial Protease-Like Activity Factor and Type III Secreted Effectors Cooperate in Inhibition of p65 Nuclear Translocation
Authors: Patton Michael John , McCorrister Stuart , Grant Chris , Westmacott Garrett , Fariss Robert , Hu Pingzhao , Zhao Kaiqiong , Blake Mary , Whitmire Bill , Yang Chunfu , Caldwell Harlan D. , McClarty Grant 
Published: September 2016

ABSTRACTThe chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry. Comparative analysis of CPAF-sufficient and CPAF-deficient infections identified a limited number of CPAF host and chlamydial protein targets. Host targets were primarily interferon-stimulated gene products, whereas chlamydial targets were type III secreted proteins. We provide evidence supporting a cooperative role for CPAF and type III secreted effectors in blocking NF-κB p65 nuclear translocation, resulting in decreased beta interferon and proinflammatory cytokine synthesis. Genetic complementation of null organisms with CPAF restored p65 nuclear translocation inhibition and proteolysis of chlamydial type III secreted effector proteins (T3SEs). We propose that CPAF and T3SEs cooperate in the inhibition of host innate immunity.IMPORTANCEChlamydia trachomatisis an important human pathogen responsible for over 100 million infections each year worldwide. Its success as an intracellular pathogen revolves around its ability to evade host immunity. The chlamydial protease-like activity factor (CPAF) is a conserved serine protease secreted into the host cytosol of infected cells that is thought to play an important role in immune evasion. Currently, CPAF’s authenticin situtarget(s) and mechanism of action in immune evasion are poorly characterized. Using a CPAF-deficient strain and high-throughput proteomics, we report novel CPAF host and chlamydial targets. Host targets were primarily interferon-stimulated genes, whereas chlamydial targets were exclusively type III secreted proteins. We propose a novel mechanism for CPAF and type III secreted proteins in the evasion of host innate immune responses. These findings provide new insights into CPAF’s function as a virulence factor and a better understanding of how chlamydiae evade host immunity.
Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation
Authors: Juttukonda Lillian J. , Chazin Walter J. , Skaar Eric P. 
Published: September 2016

ABSTRACT

During infection, bacterial pathogens must adapt to a nutrient metal-limited environment that is imposed by the host. The innate immune protein calprotectin inhibits bacterial growth
in vitro
by chelating the divalent metal ions zinc (Zn
2+
, Zn) and manganese (Mn
2+
, Mn), but pathogenic bacteria are able to cause disease in the presence of this antimicrobial protein
in vivo.
One such pathogen is
Acinetobacter baumannii
, a Gram-negative bacterium that causes pneumonia and bloodstream infections that can be complicated by resistance to multiple antibiotics.
A. baumannii
inhibition by calprotectin is dependent on calprotectin Mn binding, but the mechanisms employed by
A. baumannii
to overcome Mn limitation have not been identified. This work demonstrates that
A. baumannii
coordinates transcription of an NRAMP family Mn transporter and a urea carboxylase to resist the antimicrobial activities of calprotectin. This NRAMP family transporter facilitates Mn accumulation and growth of
A. baumannii
in the presence of calprotectin.
A. baumannii
is found to utilize urea as a sole nitrogen source, and urea utilization requires the urea carboxylase encoded in an operon with the NRAMP family transporter. Moreover, urea carboxylase activity is essential for calprotectin resistance in
A. baumannii
. Finally, evidence is provided that this system combats calprotectin
in vivo
, as deletion of the transporter impairs
A. baumannii
fitness in a mouse model of pneumonia, and this fitness defect is modulated by the presence of calprotectin. These findings reveal that
A. baumannii
has evolved mechanisms to subvert host-mediated metal sequestration and they uncover a connection between metal starvation and metabolic stress.

IMPORTANCE
Acinetobacter baumannii
is a bacterium that causes bloodstream, wound, urinary tract, and pneumonia infections, with a high disease burden in intensive care units. Treatment of
A. baumannii
infection is complicated by resistance to most antibiotics in use today, and resistance to last-resort therapies has become commonplace. New treatments for
A. baumannii
infection are desperately needed, but our current understanding of the bacterial factors required to cause infection is limited. We previously found that the abundant innate immune protein calprotectin inhibits the growth of
A. baumannii
by withholding essential metals
.
Despite this,
A. baumannii
is still able to infect wild-type mice, which produce calprotectin during infection. Here, we identify factors employed by
A. baumannii
during infection to overcome calprotectin-mediated metal sequestration. Moreover, we expose a connection between metal starvation and metabolism that may be a “chink in the armor” of
A. baumannii
and lead to new treatment options.
A Bacillus anthracis Genome Sequence from the Sverdlovsk 1979 Autopsy Specimens
Authors: Sahl Jason W. , Pearson Talima , Okinaka Richard , Schupp James M. , Gillece John D. , Heaton Hannah , Birdsell Dawn , Hepp Crystal , Fofanov Viacheslav , Noseda Ramón , Fasanella Antonio , Hoffmaster Alex , Wagner David M. , Keim Paul 
Published: September 2016

ABSTRACT

Anthrax is a zoonotic disease that occurs naturally in wild and domestic animals but has been used by both state-sponsored programs and terrorists as a biological weapon. A Soviet industrial production facility in Sverdlovsk, USSR, proved deficient in 1979 when a plume of spores was accidentally released and resulted in one of the largest known human anthrax outbreaks. In order to understand this outbreak and others, we generated a
Bacillus anthracis
population genetic database based upon whole-genome analysis to identify all single-nucleotide polymorphisms (SNPs) across a reference genome. Phylogenetic analysis has defined three major clades (A, B, and C), B and C being relatively rare compared to A. The A clade has numerous subclades, including a major polytomy named the trans-Eurasian (TEA) group. The TEA radiation is a dominant evolutionary feature of
B. anthracis
, with many contemporary populations having resulted from a large spatial dispersal of spores from a single source. Two autopsy specimens from the Sverdlovsk outbreak were deep sequenced to produce draft
B. anthracis
genomes. This allowed the phylogenetic placement of the Sverdlovsk strain into a clade with two Asian live vaccine strains, including the Russian Tsiankovskii strain. The genome was examined for evidence of drug resistance manipulation or other genetic engineering, but none was found. The Soviet Sverdlovsk strain genome is consistent with a wild-type strain from Russia that had no evidence of genetic manipulation during its industrial production. This work provides insights into the world’s largest biological weapons program and provides an extensive
B. anthracis
phylogenetic reference.

IMPORTANCE
The 1979 Russian anthrax outbreak resulted from an industrial accident at the Soviet anthrax spore production facility in the city of Sverdlovsk. Deep genomic sequencing of two autopsy specimens generated a draft genome and phylogenetic placement of the Soviet Sverdlovsk anthrax strain. While it is known that Soviet scientists had genetically manipulated
Bacillus anthracis
with the potential to evade vaccine prophylaxis and antibiotic therapeutics, there was no genomic evidence of this from the Sverdlovsk production strain genome. The whole-genome SNP genotype of the Sverdlovsk strain was used to precisely identify it and its close relatives in the context of an extensive global
B. anthracis
strain collection. This genomic identity can now be used for forensic tracking of this weapons material on a global scale and for future anthrax investigations.
Actual and preferred contraceptive sources among young people: findings from the British National Survey of Sexual Attitudes and Lifestyles
Authors: Geary Rebecca S , Tomes Caroline , Jones Kyle G , Glasier Anna , Macdowall Wendy , Datta Jessica , Sonnenberg Pam , Wellings Kaye , French Rebecca S , Mercer Catherine H , Johnson Anne M 
Published: September 2016

ObjectiveTo describe actual and preferred contraceptive sources among young people in Britain and whether discordance between these is associated with markers of sexual risk behaviour or poor sexual health.DesignCross-sectional probability sample survey.SettingBritish general population.Participants3869 men and women aged 16–24 years interviewed for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) between 2010 and 2012.Main outcome measuresReported source of contraceptive method(s) and preferred source if all were available and easily accessible.ResultsOf the 75% of young people (aged 16–24) who were heterosexually active (1619 women, 1233 men), >86% reported obtaining contraceptives in the past year. Most common sources were general practice (women, 63%) and retail (men, 60%): using multiple sources was common (women 40%, men 45%). Healthcare sources were preferred by 81% of women and 57% of men. Overall, 32% of women and 39% of men had not used their preferred source. This discordance was most common among men who preferred general practice (69%) and women who preferred retail (52%). Likelihood of discordance was higher among women who usually used a less effective contraceptive method or had an abortion. It was less likely among men who usually used a less effective method of contraception and men who were not in a steady relationship.ConclusionsMost young people in Britain obtained contraception in the past year but one-third had not used their preferred source. Healthcare sources were preferred. Discordance was associated with using less effective contraception and abortion among young women. Meeting young people's preference for obtaining contraception from healthcare sources could improve uptake of effective contraception to reduce unwanted pregnancies.
Dietary diversity, socioeconomic status and maternal body mass index (BMI): quantile regression analysis of nationally representative data from Ghana, Namibia and Sao Tome and Principe
Authors: Amugsi Dickson A , Dimbuene Zacharie T , Bakibinga Pauline , Kimani-Murage Elizabeth W , Haregu Tilahun Nigatu , Mberu Blessing 
Published: September 2016

ObjectivesTo (a) assess the association between dietary diversity (DD) score, socioeconomic status (SES) and maternal body mass index (BMI), and (b) the variation of the effects of DD and SES at different points of the conditional distribution of the BMI.MethodsThe study used Demographic and Health Surveys round 5 data sets from Ghana, Namibia and Sao Tome and Principe. The outcome variable for the analysis was maternal BMI. The DD score was computed using 24-hour dietary recall data. Quantile regression (QR) was used to examine the relationship between DD and SES, and maternal BMI, adjusting for other covariates. The QR allows the covariate effects to vary across the entire distribution of maternal BMI.ResultsWomen who consumed an additional unit of DD achieved an increase of 0.245 in BMI for those in the 90th quantile in Ghana. The effect of household wealth increases for individuals across all quantiles of the BMI distribution and in all the 3 countries. A unit change in the household wealth score was associated with an increase of 0.038, 0.052 and 0.065 units increase in BMI for individuals in the 5th quantile in Ghana, Namibia and Sao Tome and Principe, respectively. Also, 0.237, 0.301 and 0.174 units increased for those in the 90th quantile in Ghana, Namibia and Sao Tome and Principe, respectively. Education had a significant positive effect on maternal BMI across all quantiles in Namibia and negative effect at the 5th, 10th and 90th quantiles in Sao Tome and Principe.ConclusionsThere is heterogeneity in the effects of DD and SES on maternal BMI. Studies focusing on the effects of diet and socioeconomic determinants on maternal BMI should examine patterns of effects at different points of the conditional distribution of the BMI and not just the average effect.
Strategies and impacts of patient and family engagement in collaborative mental healthcare: protocol for a systematic and realist review
Authors: Menear Matthew , Gervais Michel , Careau Emmanuelle , Chouinard Maud-Christine , Cloutier Guylaine , Delorme André , Dogba Maman Joyce , Dugas Michèle , Gagnon Marie-Pierre , Gilbert Michel , Harvey Diane , Houle Janie , Kates Nick , Knowles Sara , Martin Neasa , Nease Donald , Pluye Pierre , Samson Esther , Zomahoun Hervé Tchala Vignon , Légaré France 
Published: September 2016

IntroductionCollaborative mental healthcare (CMHC) has garnered worldwide interest as an effective, team-based approach to managing common mental disorders in primary care. However, questions remain about how CMHC works and why it works in some circumstances but not others. In this study, we will review the evidence on one understudied but potentially critical component of CMHC, namely the engagement of patients and families in care. Our aims are to describe the strategies used to engage people with depression or anxiety disorders and their families in CMHC and understand how these strategies work, for whom and in what circumstances.Methods and analysisWe are conducting a review with systematic and realist review components. Review part 1 seeks to identify and describe the patient and family engagement strategies featured in CMHC interventions based on systematic searches and descriptive analysis of these interventions. We will use a 2012 Cochrane review of CMHC as a starting point and perform new searches in multiple databases and trial registers to retrieve more recent CMHC intervention studies. In review part 2, we will build and refine programme theories for each of these engagement strategies. Initial theory building will proceed iteratively through content expert consultations, electronic searches for theoretical literature and review team brainstorming sessions. Cluster searches will then retrieve additional data on contexts, mechanisms and outcomes associated with engagement strategies, and pairs of review authors will analyse and synthesise the evidence and adjust initial programme theories.Ethics and disseminationOur review follows a participatory approach with multiple knowledge users and persons with lived experience of mental illness. These partners will help us develop and tailor project outputs, including publications, policy briefs, training materials and guidance on how to make CMHC more patient-centred and family-centred.PROSPERO registration numberCRD42015025522.
Energy spectra and fluence of the neutrons produced in deformed space-time conditions
Authors: Cardone F. , Rosada A. 
Published: October 2016

In this work, spectra of energy and fluence of neutrons produced in the conditions of deformed space-time (DST), due to the violation of the local Lorentz invariance (LLI) in the nuclear interactions are shown for the first time. DST-neutrons are produced by a mechanical process in which AISI 304 steel bars undergo a sonication using ultrasounds with 20 kHz and 330 W. The energy spectrum of the DST-neutrons has been investigated both at low (less than 0.4 MeV) and at high (up to 4 MeV) energy. We could conclude that the DST-neutrons have different spectra for different energy intervals. It is therefore possible to hypothesize that the DST-neutrons production presents peculiar features not only with respect to the time (asynchrony) and space (asymmetry) but also in the neutron energy spectra.