bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of beta‐defensin 2 and interleukin‐4 receptor as stroke outcome biomarkers
Authors: García‐Berrocoso Teresa , Giralt Dolors , Bustamante Alejandro , Llombart Victor , Rubiera Marta , Penalba Anna , Boada Cristina , Espadaler Marc , Molina Carlos , Montaner Joan 
Published: January 2014

AbstractAcute ischemic stroke is a complex disease with huge interindividual evolution variability that makes challenging the prediction of an adverse outcome. Our aim was to study the association of bloodstream signatures to early neurological outcome after stroke, by combining a subpooling of samples strategy with protein array discovery approach. Plasma samples from 36 acute stroke patients (< 4.5 h from onset) were equally pooled within outcome groups: worsening, stability, and improvement (n = 3 pools of four patients each, for each outcome group). These nine pools were screened using a 177 antibodies library, and 35 proteins were found altered regarding outcome classification (p < 0.1). Processes of inflammation, immune response, coagulation, and apoptosis were regulated by these proteins. Ten representative candidates, mainly cytokines and chemokines, were assayed for replication in individual baseline plasma samples from 80 new stroke patients: β‐defensin2, MIP‐3b, plasminogen activator inhibitor 1 active, β‐cell‐attracting chemokine 1, Exodus‐2, interleukin‐4 receptor (IL‐4R), IL‐12p40, leukemia inhibitor factor, MIP‐1b, and tumor necrosis factor‐related weak inducer of apoptosis. Multivariate logistic regression analysis showed β‐defensin 2 (ORadj 4.87 [1.13–20.91] p = 0.033) and IL‐4R (ORadj 3.52 [1.03–12.08] p = 0.045) as independent predictors of worsening at 24 h after adjustment by clinical variables. Both biomarkers improve the prediction by 19% as compared to clinical information, suggesting a potential role for risk stratification in acute thrombolyzed stroke patients.
image
Early neurological deterioration after stroke is not easily predictable. The use of blood biomarkers might help in decision‐making processes regarding this complication. By combining a sub‐pooling of samples strategy with protein array discovery approach, we have found two new biomarkers: beta‐defensin‐2 and interleukin‐4 receptor. Both biomarkers improve the prediction of poor‐outcome over clinical variables in the acute phase of stroke.
Experimental evolution reveals habitat‐specific fitness dynamics among Wolbachia clades in Drosophila melanogaster
Authors: Versace Elisabetta , Nolte Viola , Pandey Ram Vinay , Tobler Ray , Schlötterer Christian 
Published: January 2014

AbstractThe diversity and infection dynamics of the endosymbiont Wolbachia can be influenced by many factors, such as transmission rate, cytoplasmic incompatibility, environment, selection and genetic drift. The interplay of these factors in natural populations can result in heterogeneous infection patterns with substantial differences between populations and strains. The causes of these heterogeneities are not yet understood, partly due to the complexity of natural environments. We present experimental evolution as a new approach to study Wolbachia infection dynamics in replicate populations exposed to a controlled environment. A natural Drosophila melanogaster population infected with strains of Wolbachia belonging to different clades evolved in two laboratory environments (hot and cold) for 1.5 years. In both treatments, the rate of Wolbachia infection increased until fixation. In the hot environment, the relative frequency of different Wolbachia clades remained stable over 37 generations. In the cold environment, however, we observed marked changes in the composition of the Wolbachia population: within 15 generations, one Wolbachia clade increased more than 50% in frequency, whereas the other two clades decreased in frequency, resulting in the loss of one clade. The frequency change was highly reproducible not only among replicates, but also when flies that evolved for 42 generations in the hot environment were transferred to the cold environment. These results document how environmental factors can affect the composition of Wolbachia in D. melanogaster. The high reproducibility of the pattern suggests that experimental evolution studies can efficiently determine the functional basis of habitat‐specific fitness among Wolbachia strains.
Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation
Authors: Visser Mijke , Kayser Manfred , Grosveld Frank , Palstra Robert‐Jan 
Published: January 2014

SummaryMutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pigmentation intensities. Recent studies demonstrated that the transcriptional level of OCA2 is to a large extent determined by the noncoding SNP rs12913832 located 21.5 kb upstream of the OCA2 gene promoter. In this review, we discuss current hypotheses and the available data on the mechanism of OCA2 transcriptional regulation and how this is influenced by genetic variation. Finally, we will explore how future epigenetic studies can be used to advance our insight into the functional biology that connects genetic variation to human pigmentation.
Early Pregnancy Changes in Bacterial Vaginosis‐Associated Bacteria and Preterm Delivery
Authors: Nelson Deborah B. , Hanlon Alexandra , Nachamkin Irving , Haggerty Catherine , Mastrogiannis Dimitrios S. , Liu Congzhou , Fredricks David N. 
Published: January 2014

AbstractBackgroundWe evaluated the importance of measuring early vaginal levels of eight bacterial vaginosis (BV)‐associated bacteria, at two points in pregnancy, and the risk of spontaneous preterm delivery (SPTD) among pregnant women and the subgroup of pregnant women with a history of preterm delivery (PTD).MethodsThis prospective cohort study enrolled women at five urban obstetric practices at Temple University Hospital in Philadelphia PA. Women with singleton pregnancies less than 16 weeks gestation self‐collected vaginal swabs at two points in pregnancy, prior to 16 weeks gestation and between 20–24 weeks gestation, to measure the presence and level of eight BV‐associated bacteria. Women were followed‐up for gestational age at delivery via medical records.ResultsAmong women reporting a prior PTD, women with higher levels of Leptotrichia/Sneathia species, BVAB1 and Mobiluncus spp., prior to 16 weeks gestation, were significantly more likely to experience a SPTD. In addition, pregnant women with a prior PTD and increasing levels of Leptotrichia/Sneathia species (aOR: 9.1, 95% CI 1.9, 42.9), BVAB1 (aOR: 16.4, 95% CI 4.3, 62.7) or Megasphaera phylotype 1 (aOR: 6.2, 95% CI 1.9, 20.6), through 24 weeks gestation, were significantly more likely to experience an SPTD. Among the overall group of pregnant women, the levels of BV‐associated bacteria were not related to SPTD.ConclusionAmong the group of women reporting a prior PTD, increasing levels of BVAB1, Leptotrichia/Sneathia species, and Megasphaera phylotype 1, through mid‐pregnancy were related to an increased risk of SPTD.
Restoring pistil‐side self‐incompatibility factors recapitulates an interspecific reproductive barrier between tomato species
Authors: Tovar‐Méndez Alejandro , Kumar Aruna , Kondo Katsuhiko , Ashford Amy , Baek You S. , Welch Lillian , Bedinger Patricia A. , McClure Bruce A. 
Published: January 2014

SummaryInterspecific reproductive barriers are poorly understood, but are central to the biological species concept. The pre‐zygotic barriers between red‐ and green‐fruited species in the tomato clade of the genus Solanum provide a model to better understand these barriers in plants. Compatibility usually follows the SI x SC rule: pollen from self‐compatible (SC) red‐fruited species is rejected on pistils of the predominantly self‐incompatible (SI) green‐fruited species, but the reciprocal crosses are compatible. This suggests that the interspecific reproductive barrier may be linked to the intraspecific SI mechanism. However, pollen from the SC red‐fruited species is also rejected by SC accessions of green‐fruited species that lack S‐RNase, a key protein expressed in pistils of SI Solanum species. Thus, multiple mechanisms may contribute to the barrier between red‐ and green‐fruited species. We tested whether an S‐RNase‐dependent barrier is sufficient for rejection of pollen from red‐fruited species by introducing functional S‐RNase, HT‐A and HT‐B genes from SI species into Solanum lycopersicum (cultivated tomato). We found that expressing S‐RNase in combination with either HT‐A or HT‐B in the pistil is sufficient to cause rejection of pollen from all four red‐fruited species. Thus, redundant mechanisms must operate side by side to prevent crosses between red‐ and green‐fruited species in the clade, underlining the complexity of interspecific pollination barriers. Our results also have implications for mating system transitions. We suggest that these transitions must occur in a specific sequence, and that the transition from SI to SC also affects interspecific compatibility.
Trans‐corneal reduction of anterior lens luxation in dogs with lens instability: a retrospective study of 19 dogs (2010–2013)
Authors: Montgomery Keith W. , Labelle Amber L. , Gemensky‐Metzler Anne J. 
Published: January 2014

AbstractObjectiveTo evaluate the success rate and outcome of trans‐corneal reduction of anterior lens luxation (TR‐ALL) in dogs with lens instability.Animals StudiedNineteen dogs with anterior lens luxation.ProceduresMedical records of dogs with anterior lens luxation (ALL) were reviewed: dogs were included if TR‐ALL was performed followed by medical therapy in the form of topical 0.005% latanoprost ophthalmic solution. The duration of ALL, vision status, ophthalmic examination abnormalities, reason for performing TR‐ALL and details of TR‐ALL were recorded. Success rate for TR‐ALL as well as postprocedure complications were also assessed.ResultsTwenty eyes from 19 dogs met the inclusion criteria. Median age was 6.5 years (0.3–15 years) and 47% were terriers (9/19). Successful TR‐ALL was achieved in 85% of eyes (17/20); failure was attributed to posterior synechia or vitreous expansion. Short‐term complications included corneal ulceration (2/20) and anterior uveitis (3/20); recurrence of anterior luxation occurred in only one dog. Median follow‐up for visual eyes (11) following successful TR‐ALL was 353 days (range of 1 to 1182 days). Vision was retained in 54.5% (6/11) of eyes with a median time to vision loss of 12 months as a result of glaucoma or presumed retinal detachment.ConclusionsTrans‐corneal reduction of ALL provides a non‐surgical alternative to intracapsular lens extraction (visual eyes) or enucleation (nonvisual eyes) in dogs. Long‐term visual outcome of TR‐ALL is comparable to intracapsular lens extraction for ALL.
Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli
Authors: Zhu Yao-Hong , Li Xiao-Qiong , Zhang Wei , Zhou Dong , Liu Hao-Yu , Wang Jiu-Feng 
Published: January 2014

ABSTRACT

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10
9
CFU/ml) or high (1 × 10
11
CFU/ml) doses of
Lactobacillus rhamnosus
ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic
Escherichia coli
(F4
+
ETEC) challenge. Administration of a low, but not a high, dose of
L. rhamnosus
decreased the percentage of CD3
+
CD4
+
CD8
−
T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4
+
ETEC challenge in pigs pretreated with a high dose of
L. rhamnosus
. Administration of
L. rhamnosus
increased the percentage of the small intestinal lamina propria CD3
+
CD4
+
CD8
−
cells and Peyer's patch CD3
+
CD4
−
CD8
−
and CD3
−
CD4
−
CD8
+
cells. The percentage of ileal intraepithelial CD3
+
CD4
−
CD8
+
cells increased only in the high-dose piglets. Administration of
L. rhamnosus
downregulated expression of ileal IL-17A after F4
+
ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4
+
ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by
L. rhamnosus
is associated with the generation of lamina propria CD3
+
CD4
+
CD8
−
T cells, the expansion of Peyer's patch CD3
+
CD4
−
CD8
−
and CD3
−
CD4
−
CD8
+
cells, and the attenuation of F4
+
ETEC-induced increase in CD3
+
CD4
+
CD8
+
T cells in the small intestine. However, consumption of high doses of
L. rhamnosus
may increase levels of serum IL-17A after F4
+
ETEC challenge, thus eliciting a strong proinflammatory response.
Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine
Authors: Leroux-Roels Geert , Bourguignon Patricia , Willekens Julie , Janssens Michel , Clement Frédéric , Didierlaurent Arnaud M. , Fissette Laurence , Roman François , Boutriau Dominique 
Published: January 2014

ABSTRACT

This phase II study evaluated the effect of chloroquine on the specific CD8
+
T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01
B
vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01
B
adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01
B
doses containing 10 or 30 μg of F4 (
ClinicalTrials.gov
registration number NCT00434512), were randomized (1:1) to receive the F4/AS01
B
booster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8
+
/CD4
+
T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4
+
/CD8
+
T-cell and antibody responses and no vaccine effect on CD8
+
T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01
B
booster administration.
In vitro
, chloroquine had a direct inhibitory effect on AS01
B
adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01
B
containing 10 μg of F4, CD4
+
T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01
B
booster induced strong F4-specific CD4
+
T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01
B
booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01
B
booster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4
+
T-cell responses but no significant CD8
+
T-cell responses (cytokine secretion or proliferation) in healthy adults. (This study has been registered at
ClinicalTrials.gov
under registration number NCT00972725).
Role of Phosphatidylserine in Phospholipid Flippase-Mediated Vesicle Transport in Saccharomyces cerevisiae
Authors: Takeda Miyoko , Yamagami Kanako , Tanaka Kazuma 
Published: January 2014

ABSTRACT

Phospholipid flippases translocate phospholipids from the exoplasmic to the cytoplasmic leaflet of cell membranes to generate and maintain phospholipid asymmetry. The genome of budding yeast encodes four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p), which associate with the Cdc50 family noncatalytic subunit, and one monomeric flippase Neo1p. Flippases have been implicated in the formation of transport vesicles, but the underlying mechanisms are largely unknown. We show here that overexpression of the phosphatidylserine synthase gene
CHO1
suppresses defects in the endocytic recycling pathway in flippase mutants. This suppression seems to be mediated by increased cellular phosphatidylserine. Two models can be envisioned for the suppression mechanism: (i) phosphatidylserine in the cytoplasmic leaflet recruits proteins for vesicle formation with its negative charge, and (ii) phosphatidylserine flipping to the cytoplasmic leaflet induces membrane curvature that supports vesicle formation. In a mutant depleted for flippases, a phosphatidylserine probe GFP-Lact-C2 was still localized to endosomal membranes, suggesting that the mere presence of phosphatidylserine in the cytoplasmic leaflet is not enough for vesicle formation. The
CHO1
overexpression did not suppress the growth defect in a mutant depleted or mutated for all flippases, suggesting that the suppression was dependent on flippase-mediated phospholipid flipping. Endocytic recycling was not blocked in a mutant lacking phosphatidylserine or depleted in phosphatidylethanolamine, suggesting that a specific phospholipid is not required for vesicle formation. These results suggest that flippase-dependent vesicle formation is mediated by phospholipid flipping, not by flipped phospholipids.
Assessment of Microbiological Diagnostic Procedures for Respiratory Specimens from Cystic Fibrosis Patients in German Laboratories by Use of a Questionnaire
Authors: Häfner Laura , Peters Georg , Kahl Barbara C. 
Published: January 2014

ABSTRACT
Respiratory specimens from cystic fibrosis (CF) patients challenge microbiological laboratories with their complexity of pathogens and atypical variants. We evaluated the diagnostic procedures in German laboratories by use of a questionnaire. Although most laboratories followed guidelines, some of them served only a small number of patients, while others did not use the recommended selective agars to culture the particular CF-relevant species.
Malsoor Virus, a Novel Bat Phlebovirus, Is Closely Related to Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Virus
Authors: Mourya D. T. , Yadav P. D. , Basu A. , Shete A. , Patil D. Y. , Zawar D. , Majumdar T. D. , Kokate P. , Sarkale P. , Raut C. G. , Jadhav S. M. 
Published: January 2014

ABSTRACT

During a survey in the year 2010, a novel phlebovirus was isolated from the
Rousettus leschenaultii
species of bats in western India. The virus was identified by electron microscopy from infected Vero E6 cells. Phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus.
Enterovirus 2A
pro
Targets MDA5 and MAVS in Infected Cells
Authors: Feng Qian , Langereis Martijn A. , Lork Marie , Nguyen Mai , Hato Stanleyson V. , Lanke Kjerstin , Emdad Luni , Bhoopathi Praveen , Fisher Paul B. , Lloyd Richard E. , van Kuppeveld Frank J. M. 
Published: January 2014

ABSTRACT

RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interferon production is incompletely understood. MDA5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. Additionally, MAVS is reported to be cleaved during infection with coxsackievirus B3 (CVB3) by the CVB3 proteinase 3C
pro
, whereas MAVS cleavage by enterovirus 71 has been attributed to 2A
pro
. As yet, a detailed examination of the RLR pathway as a whole during any enterovirus infection is lacking. We performed a comprehensive analysis of crucial factors of the RLR pathway, including MDA5, RIG-I, LGP2, MAVS, TBK1, and IRF3, during infection of CVB3, a human enterovirus B (HEV-B) species member. We show that CVB3 inhibits the RLR pathway upstream of TBK1 activation, as demonstrated by limited phosphorylation of TBK1 and a lack of IRF3 phosphorylation. Furthermore, we show that MDA5, MAVS, and RIG-I all undergo proteolytic degradation in CVB3-infected cells through a caspase- and proteasome-independent manner. We convincingly show that MDA5 and MAVS cleavages are both mediated by CVB3 2A
pro
, while RIG-I is cleaved by 3C
pro
. Moreover, we show that proteinases 2A
pro
and 3C
pro
of poliovirus (HEV-C) and enterovirus 71 (HEV-A) exert the same functions. This study identifies a critical role of 2A
pro
by cleaving MDA5 and MAVS and shows that enteroviruses use a common strategy to counteract the interferon response in infected cells.

IMPORTANCE
Human enteroviruses (HEVs) are important pathogens that cause a variety of diseases in humans, including poliomyelitis, hand, foot, and mouth disease, viral meningitis, cardiomyopathy, and more. Like many other viruses, enteroviruses target the host immune pathways to gain replication advantage. The MDA5/MAVS pathway is responsible for recognizing enterovirus infections in the host cell and leads to expression of type I interferons (IFN-I), crucial antiviral signaling molecules. Here we show that three species of HEVs all employ the viral proteinase 2A (2A
pro
) to proteolytically target MDA5 and MAVS, leading to an efficient blockade upstream of IFN-I transcription. These observations suggest that MDA5/MAVS antagonization is an evolutionarily conserved and beneficial mechanism of enteroviruses. Understanding the molecular mechanisms of enterovirus immune evasion strategies will help to develop countermeasures to control infections with these viruses in the future.