bluuebunny/crossref_metadata_2025_split huggingface dataset:
A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis
Authors: Lesch Bluma J. , Dokshin Gregoriy A. , Young Richard A. , McCarrey John R. , Page David C. 
Published: September 2013

Significance
Germ cells, meaning the mature sperm and egg and their developmental precursors, carry the DNA that is passed from one generation to the next. Although the sperm and egg are highly specialized, differentiated cells, they meet at fertilization to produce a totipotent zygote, a cell that can generate any other cell type. We report the finding that a set of developmentally important genes is kept in a “poised” state in the germ cells: although these genes are never expressed in the germ cells themselves, they maintain a chromatin state usually associated with the potential for rapid gene activation. We propose that maintenance of this poised state in the germ cells contributes to the generation of totipotency in the fertilized zygote.
SUMOylation is essential for sex-specific assembly and function of the
Caenorhabditis elegans
dosage compensation complex on X chromosomes
Authors: Pferdehirt Rebecca R. , Meyer Barbara J. 
Published: September 2013

Significance
Dosage compensation equalizes X-chromosome transcription between nematode males (1X) and hermaphrodites (2X) via a dosage compensation complex (DCC) that binds hermaphrodite X chromosomes to repress transcription by half. We show that several DCC subunits are modified by the small ubiquitin-like modifier SUMO in response to the signal that triggers DCC assembly onto X. DCC assembly and function require SUMOylation. DCC subunit DUMPY-28 also acts in condensin complexes essential for chromosome segregation, but its SUMOylation is DCC-specific. We propose that specific signals trigger DCC protein SUMOylation, stimulating robust complex formation. SUMOylation facilitates distinct activities of proteins that function in multiple complexes.
Perception and reality – Portuguese adults' awareness of active lifestyle
Authors: Marques Adilson , Martins João , Ramos Madalena , Yazigi Flávia , Carreiro da Costa Francisco 
Published: September 2013

AbstractThis study aims to assess awareness of physical activity levels among adults and to investigate the variables associated with different types of awareness. The participants were 1042 men and 1316 women aged 31–60 years old (43.3 ± 6.1). Data were collected on physical activity behaviour, physical activity awareness, perceptions and psychological factors. Awareness was assessed by comparing self‐rated physical activity with achieving physical activity guidelines. Chi‐square and logistic regression analyses were applied to the results. About 32.4% were considered active. Moreover, 61% accurately reported their physical activity (38.3% realistic inactive and 22.7% realistic active), 29.2% overestimated their physical activity (overestimators) and 9.7% incorrectly described themselves as inactive (underestimators). Perception of an excellent health status (odds ratio, OR = 4.07, 95% confidence interval, CI: 2.07–8.00, p < 0.001) was the strongest positive association with being realistic active, followed by having a high socio‐economic status (SES) (OR = 1.53, 95% CI: 1.10–2.12, p < 0.05). Overestimator participants were more likely to have an excellent perception of health (OR = 2.58, 95% CI: 1.47–4.52, p < 0.01) and had a good experience in physical education (OR = 1.46, 95% CI:1.03–2.08, p < 0.05). Almost half of these participants erroneously perceived themselves as physically active. Gender, body mass index (BMI) and the quality of physical education at school were associated with those who misperceived their physical activity.
Cetacean–fishery interactions in Galicia (NW Spain): results and management implications of a face-to-face interview survey of local fishers
Authors: Goetz Sabine , Read Fiona L. , Santos M. Begoña , Pita C. , Pierce Graham J. 
Published: September 2013

Abstract
Galicia (NW Spain) is an important fishing region with a high potential for cetacean–fishery interactions. Cetacean depredation on catch and damage to fishing gear can potentially lead to substantial economic loss for fishers, while cetacean bycatch raises conservation concerns. With the aim of gathering information on the types and scale of interactions and of suggesting possible management strategies, we conducted face-to-face interviews with fishers in local fishing harbours, in particular to identify specific problematic interactions and to quantify the level of economic loss and bycatch rates associated with these interactions. We found that cetacean–fishery interactions are frequent, although damage to catch and fishing gear by cetaceans was mostly reported as small. Nevertheless, substantial economic loss can result from common bottlenose dolphins (Tursiops truncatus) damaging coastal gillnets and from short-beaked common dolphins (Delphinus delphis) scattering fish in purse-seine fisheries. Cetacean bycatch mortality was reported to be highest for trawls and set gillnets, and probably exceeds sustainable levels for local common and bottlenose dolphin populations. Although interview data may be biased due to the perceptions of interviewees, and therefore should be interpreted with care, the methodology allowed us to cover multiple sites and fisheries within a reasonable time frame. Minimizing cetacean–fishery interactions requires the implementation of case-specific management strategies with the active participation of fishers. For set gillnet and purse-seine fisheries, the use of acoustic deterrent devices (pingers) may prevent cetaceans from approaching and getting trapped in the nets. For trawl fisheries, where bycatch appears to be particularly high at night in water depths of 100–300 m, possible solutions include the implementation of time/area closures and the relocation of some fishing effort to deeper waters.
Migratory connectivity of two Baltic Sea salmon populations: retrospective analysis using stable isotopes of scales
Authors: Torniainen Jyrki , Vuorinen Pekka J. , Jones Roger I. , Keinänen Marja , Palm Stefan , Vuori Kristiina A. M. , Kiljunen Mikko 
Published: September 2013

Abstract
Torniainen, J., Vuorinen, P. J., Jones, R. I., Keinänen, M., Palm, S., Vuori, K. A. M., and Kiljunen, M. 2014. Migratory connectivity of two Baltic Sea salmon populations: retrospective analysis using stable isotopes of scales. – ICES Journal of Marine Science, 71: 336–344.
Migratory connectivity refers to the extent to which individuals of a migratory population behave in unison, and has significant consequences for the ecology, evolution and conservation of migratory animals. We made a retrospective assessment of the migratory connectivity of River Simojoki and River Kymijoki populations of Atlantic salmon Salmo salar L. by using stable isotope analysis of archived scales to identify the final feeding areas used before ascending rivers for spawning. We also tested differences in migratory connectivity between wild and hatchery-reared salmon and compared Carlin-tag recoveries with salmon scale stable isotope analysis as methods for studying salmon migrations. Stable isotope (δ13C, δ15N) values from the last growth region of scales from salmon caught ascending their natal rivers were compared via discriminant analysis with those from scales of salmon caught in different Baltic Sea areas during 1989–2011. Most River Simojoki salmon had likely fed in the Baltic Proper (mean ± SD for ascending fish probability 0.59 ± 0.32) with secondary likely feeding areas in the Bothnian Sea (0.21 ± 0.26) and the Gulf of Finland (0.20 ± 0.27). Most River Kymijoki salmon had likely fed in the Gulf of Finland (0.71 ± 0.42) with the Baltic Proper (0.29 ± 0.41) a secondary feeding area. The results did not indicate the Bothnian Sea to be an important feeding area. The two salmon populations showed weak migratory connectivity and rather fixed areal preference throughout the record irrespective of wild or stocked origin. Although the results from the scale stable isotope analyses were broadly consistent with previously reported Carlin-tag recoveries, we argue that the stable isotope approach offers several important advantages in the study of salmon migratory behaviour.
A Novel Nonsense Mutation in the EpCAM Gene in a Patient With Congenital Tufting Enteropathy
Authors: Thoeni Cornelia , Amir Achiya , Guo Conghui , Zhang S. , Avitzur Yaron , Heng Y.M. , Cutz Ernest , Muise Aleixo M. 
Published: September 2013

ABSTRACTObjectives:Tufting enteropathy (TE) is a classical congenital disorder of the intestinal mucosa causing protracted diarrhea in infancy as a result of a dysfunctional epithelial cell barrier, which is mainly caused by mutations in the EpCAM gene and expression of a nonfunctional epithelial cell adhesion molecule in the intestine. We report here a novel nonsense mutation in a patient suspected of having TE, resulting in a complete absence of EpCAM in duodenal enterocytes.Methods:A patient presenting with congenital diarrhea and suspected of having TE was screened for EpCAM mutations, and duodenal biopsies were stained for EpCAM using immunohistochemistry analysis.Results:We identified a novel homozygous nonsense mutation in the EpCAM gene in a patient suspected of having TE, causing a complete loss of EpCAM expression in duodenal enterocytes.Conclusions:With screening analysis for EpCAM mutations and immunohistochemistry for EpCAM expression in duodenal enterocytes, we found a novel homozygous mutation in a patient with classical protracted diarrhea in infancy finally diagnosed as TE, which results in a complete absence of EpCAM and in dysfunctional barrier formation in duodenal enterocytes.
Bitterness of Glucose/Galactose
Authors: Pode‐Shakked Ben , Reish Orit , Aktuglu‐Zeybek Cigdem , Kesselman Dafna , Dekel Benjamin , Bujanover Yoram , Anikster Yair 
Published: September 2013

ABSTRACTGlucose galactose malabsorption (GGM) is a rare autosomal recessive disorder characterized by life‐threatening osmotic diarrhea at infancy. When the intake of the offending sugars (namely, glucose, galactose and lactose) is ceased, the diarrhea promptly stops. Mutations in the SLC5A1 gene, encoding the sodium‐glucose co‐transporter located in the brush border of enterocytes, have been shown to cause the disease. More than 300 subjects of diverse origin have been reported worldwide, most of whom are a result of a consanguineous union. We examined 6 patients from 4 families presenting with complaints consistent with GGM and responsive to the appropriate fructose‐based diet. Genomic DNA of the patients was polymerase chain reaction amplified for each of the 15 exons of the SLC5A1 gene and analyzed by nucleotide sequencing. The analysis lead to the identification of 2 novel mutations: a 1915 del C mutation, a frameshift mutation leading to a premature stop at codon 645; and a substitution missense mutation of T to C on nucleotide 947 (exon 9) causing a L316P substitution. In addition, G426R and C255W mutations previously described were identified; in both cases, the patients were shown to be homozygous and their parents heterozygous for the mutation. Of note, additional patients who underwent a similar evaluation at our center for suspected GGM did not show mutations in the SLC5A1 gene. Because the latter did not previously undergo a diagnostic algorithm in full, for instance, one that may consist of a glucose breath hydrogen test and an empiric attempt of a dietary switch to galactomin, we suggest that molecular genotyping of such patients should only follow such appropriate clinical evaluation.
ERCP Can Be Safely and Effectively Performed by a Pediatric Gastroenterologist for Choledocholithiasis in a Pediatric Facility
Authors: Troendle David M. , Barth Bradley A. 
Published: September 2013

ABSTRACTObjective:The aim of this study was to demonstrate that an appropriately trained pediatric gastroenterologist can perform endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis both safely and effectively.Methods:Retrospective analysis of ERCP experience from November 2006 to May 2012. Only ERCPs performed by a pediatric gastroenterologist on pediatric patients for the indication of suspected choledocholithiasis were included for formal chart review. Patient characteristics, procedural success, and adverse events were recorded, and subsequently compared with quality standards as defined by the American Society for Gastrointestinal Endoscopy Quality Task Force.Results:A total of 154 ERCPs were performed, of which 65 (42%) were performed on unique patients for the indication of suspected choledocholithiasis. The median age was 15.2 years (range 1 month–18.4 years). The median weight was 65 kg (range 4—127 kg). Biliary cannulation was achieved in 65 (100%). All 65 patients underwent sphincterotomy. Ductal clearance was achieved in 64 (98%) patients during the initial ERCP session. Adverse events included 3 (5%) episodes of mild pancreatitis, 1 episode of moderate bleeding, and 1 episode of sphincterotomy clot causing obstruction and need for repeat ERCP within 1 week. Overall, 5 (8%) unique patients experienced a complication.Conclusions:Therapeutic ERCP for the indication of choledocholithiasis can be performed by an appropriately trained pediatric gastroenterologist at a pediatric facility with acceptable cannulation rates, stone extraction rates, and adverse event rates as defined by the American Society for Gastrointestinal Endoscopy Quality Task Force.
Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate
Authors: Protti D. A. , Di Marco S. , Huang J. Y. , Vonhoff C. R. , Nguyen V. , Solomon S. G. 
Published: September 2013

Key points
The receptive field of most retinal ganglion cells consists of an excitatory centre and an inhibitory surround.
In retinal ganglion cells of non‐primates the receptive field surround is provided by lateral inhibition in both the outer and the inner retinal synaptic layers.
We use whole cell recording methods to establish the spatial organisation of excitatory and inhibitory synaptic inputs onto ganglion cells in primate retina.
We confirm centre–surround organisation in the excitatory inputs to ganglion cells, and show further that inhibitory inputs can also show centre–surround organisation.
We show that lateral inhibition in the inner retina shapes the spatial profile of both excitatory and inhibitory synaptic inputs onto ganglion cells.
Dynamic clamp experiments provide evidence that reduction of inner retinal inhibition reduces spatial tuning in ganglion cell output.
These results show that lateral inhibition in the inner retina of primate shapes the analysis of spatial form and contrast.
Abstract  The centre–surround organisation of receptive fields is a feature of most retinal ganglion cells (RGCs) and is critical for spatial discrimination and contrast detection. Although lateral inhibitory processes are known to be important in generating the receptive field surround, the contribution of each of the two synaptic layers in the primate retina remains unclear. Here we studied the spatial organisation of excitatory and inhibitory synaptic inputs onto ON and OFF ganglion cells in the primate retina. All RGCs showed an increase in excitation in response to stimulus of preferred polarity. Inhibition onto RGCs comprised two types of responses to preferred polarity: some RGCs showed an increase in inhibition whilst others showed removal of tonic inhibition. Excitatory inputs were strongly spatially tuned but inhibitory inputs showed more variable organisation: in some neurons they were as strongly tuned as excitation, and in others inhibitory inputs showed no spatial tuning. We targeted one source of inner retinal inhibition by functionally ablating spiking amacrine cells with bath application of tetrodotoxin (TTX). TTX significantly reduced the spatial tuning of excitatory inputs. In addition, TTX reduced inhibition onto those RGCs where a stimulus of preferred polarity increased inhibition. Reconstruction of the spatial tuning properties by somatic injection of excitatory and inhibitory synaptic conductances verified that TTX‐mediated inhibition onto bipolar cells increases the strength of the surround in RGC spiking output. These results indicate that in the primate retina inhibitory mechanisms in the inner plexiform layer sharpen the spatial tuning of ganglion cells.
Characterization of Potential Drug Targets Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase in Schistosoma mansoni
Authors: Ziniel Peter D. , Desai Janish , Cass Cynthia L. , Gatto Craig , Oldfield Eric , Williams David L. 
Published: September 2013

ABSTRACT

Schistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here that
Schistosoma mansoni
farnesyl diphosphate synthase (
Sm
FPPS) and geranylgeranyl diphosphate synthase (
Sm
GGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinant
Sm
FPPS and
Sm
GGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. Recombinant
Sm
FPPS was found to be a soluble 44.2-kDa protein, while
Sm
GGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. Against
Sm
FPPS, several bisphosphonates had 50% inhibitory concentrations (IC
50
s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity against
Sm
GGPPS. Several lipophilic bisphosphonates were active against
ex vivo
adult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.
An FtsZ-Targeting Prodrug with Oral Antistaphylococcal Efficacy
In Vivo
Authors: Kaul Malvika , Mark Lilly , Zhang Yongzheng , Parhi Ajit K. , LaVoie Edmond J. , Pilch Daniel S. 
Published: September 2013

ABSTRACT

The bacterial cell division protein FtsZ represents a novel antibiotic target that has yet to be exploited clinically. The benzamide PC190723 was among the first FtsZ-targeting compounds to exhibit
in vivo
efficacy in a murine infection model system. Despite its initial promise, the poor formulation properties of the compound have limited its potential for clinical development. We describe here the development of an
N
-Mannich base derivative of PC190723 with enhanced drug-like properties and oral
in vivo
efficacy. The
N
-Mannich base derivative (TXY436) is ∼100-fold more soluble than PC190723 in an acidic aqueous vehicle (10 mM citrate, pH 2.6) suitable for oral
in vivo
administration. At physiological pH (7.4), TXY436 acts as a prodrug, converting to PC190723 with a conversion half-life of 18.2 ± 1.6 min. Pharmacokinetic analysis following intravenous administration of TXY436 into mice yielded elimination half-lives of 0.26 and 0.96 h for the TXY436 prodrug and its PC190723 product, respectively. In addition, TXY436 was found to be orally bioavailable and associated with significant extravascular distribution. Using a mouse model of systemic infection with methicillin-sensitive
Staphylococcus aureus
or methicillin-resistant
S. aureus
, we show that TXY436 is efficacious
in vivo
upon oral administration. In contrast, the oral administration of PC190723 was not efficacious. Mammalian cytotoxicity studies of TXY436 using Vero cells revealed an absence of toxicity up to compound concentrations at least 64 times greater than those associated with antistaphylococcal activity. These collective properties make TXY436 a worthy candidate for further investigation as a clinically useful agent for the treatment of staphylococcal infections.
Optimizing Empiric Antibiotic Therapy in Patients with Severe β-Lactam Allergy
Authors: Koliscak Lindsey P. , Johnson James W. , Beardsley James R. , Miller David P. , Williamson John C. , Luther Vera P. , Ohl Christopher A. 
Published: September 2013

ABSTRACT
Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe β-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of β-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.
Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin
Authors: Carapau Daniel , Mitchell Robert , Nacer Adéla , Shaw Alan , Othoro Caroline , Frevert Ute , Nardin Elizabeth 
Published: September 2013

ABSTRACTImmunization withPlasmodiumsporozoites can elicit high levels of sterile immunity, and neutralizing antibodies from protected hosts are known to target the repeat region of the circumsporozoite (CS) protein on the parasite surface. CS-based subunit vaccines have been hampered by suboptimal immunogenicity and the requirement for strong adjuvants to elicit effective humoral immunity. Pathogen-associated molecular patterns (PAMPs) that signal through Toll-like receptors (TLRs) can function as potent adjuvants for innate and adaptive immunity. We examined the immunogenicity of recombinant proteins containing a TLR5 agonist, flagellin, and either full-length or selected epitopes of thePlasmodium falciparumCS protein. Mice immunized with either of the flagellin-modified CS constructs, administered intranasally (i.n.) or subcutaneously (s.c.), developed similar levels of malaria-specific IgG1 antibody and interleukin-5 (IL-5)-producing T cells. Importantly, immunization via the i.n. but not the s.c. route elicited sporozoite neutralizing antibodies capable of inhibiting >90% of sporozoite invasionin vitroandin vivo, as measured using a transgenic rodent parasite expressingP. falciparumCS repeats. These findings demonstrate that functional sporozoite neutralizing antibody can be elicited by i.n. immunization with a flagellin-modifiedP. falciparumCS protein and raise the potential of a scalable, safe, needle-free vaccine for the 40% of the world's population at risk of malaria.