bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of ligand-binding pockets around protein-protein interfaces suggests a general mechanism for pocket formation
Authors: Gao Mu , Skolnick Jeffrey 
Published: February 2012

Protein-protein and protein-ligand interactions are ubiquitous in a biological cell. Here, we report a comprehensive study of the distribution of protein-ligand interaction sites, namely ligand-binding pockets, around protein-protein interfaces where protein-protein interactions occur. We inspected a representative set of 1,611 representative protein-protein complexes and identified pockets with a potential for binding small molecule ligands. The majority of these pockets are within a 6 Å distance from protein interfaces. Accordingly, in about half of ligand-bound protein-protein complexes, amino acids from both sides of a protein interface are involved in direct contacts with at least one ligand. Statistically, ligands are closer to a protein-protein interface than a random surface patch of the same solvent accessible surface area. Similar results are obtained in an analysis of the ligand distribution around domain-domain interfaces of 1,416 nonredundant, two-domain protein structures. Furthermore, comparable sized pockets as observed in experimental structures are present in artificially generated protein complexes, suggesting that the prominent appearance of pockets around protein interfaces is mainly a structural consequence of protein packing and thus, is an intrinsic geometric feature of protein structure. Nature may take advantage of such a structural feature by selecting and further optimizing for biological function. We propose that packing nearby protein-protein or domain-domain interfaces is a major route to the formation of ligand-binding pockets.
A two-dimensional comprehensive hydrodynamic model for femtosecond laser pulse interaction with metals
Authors: Zhao Xin , Shin Yung C 
Published: February 2012

Abstract
Femtosecond laser–metal interaction in air and the resultant early plasma evolution are investigated by a two-dimensional comprehensive hydrodynamic model in this paper. The model comprises a two-temperature model and a hydrodynamic model supplemented with a quotidian equation of state model, considering the relevant multiphysical phenomena during the laser–metal interaction. The experimental measurements for plasma expansion were carried out to validate the simulation results, using a shadowgraph technique and direct fluorescence measurement. The evolution of both the early plasma and plume plasma is investigated by the model. The early plasma is proved to be generated by electron emission and ambient gas ionization and splits into several portions during its expansion due to different mechanisms. The plume plasma comes from the target material ejection. The photoelectric emission is revealed to be the dominant electron emission mechanism at high laser intensities, while thermal emission is more important at low laser intensities. The electron emission process and early stage plasma are critical to ultrashort laser–metal interaction, especially at high laser intensities. Without considering this, the electron temperature can be overestimated by as much as 70%.
Allele-specific expression analysis methods for high-density SNP microarray data
Authors: Liu Ruijie , Maia Ana-Teresa , Russell Roslin , Caldas Carlos , Ponder Bruce A. , Ritchie Matthew E. 
Published: February 2012

Abstract
Motivation: In the past decade, a number of technologies to quantify allele-specific expression (ASE) in a genome-wide manner have become available to researchers. We investigate the application of single-nucleotide polymorphism (SNP) microarrays to this task, exploring data obtained from both cell lines and primary tissue for which both RNA and DNA profiles are available.
Results: We analyze data from two experiments that make use of high-density Illumina Infinium II genotyping arrays to measure ASE. We first preprocess each data set, which involves removal of outlier samples, careful normalization and a two-step filtering procedure to remove SNPs that show no evidence of expression in the samples being analyzed and calls that are clear genotyping errors. We then compare three different tests for detecting ASE, one of which has been previously published and two novel approaches. These tests vary at the level at which they operate (per SNP per individual or per SNP) and in the input data they require. Using SNPs from imprinted genes as true positives for ASE, we observe varying sensitivity for the different testing procedures that improves with increasing sample size. Methods that rely on RNA signal alone were found to perform best across a range of metrics. The top ranked SNPs recovered by all methods appear to be reasonable candidates for ASE.
Availability and implementation: Analysis was carried out in R (http://www.R-project.org/) using existing functions.
Contact: mritchie@wehi.edu.au.
Supplementary information: Supplementary data are available at Bioinformatics online.
Dental attendance in preschool children – a prospective study
Authors: LEROY ROOS , BOGAERTS KRIS , HOPPENBROUWERS KAREL , MARTENS LUC C. , DECLERCK DOMINIQUE 
Published: February 2012

International Journal of Paediatric Dentistry 2013; 23: 84–93
Background.  At present, our understanding of the use of dental care services is incomplete, certainly where preschool children are concerned.Objectives.  To investigate what proportion of 3‐ and 5‐year‐olds living in Flanders (Belgium) have already visited the dentist, to describe parents’ experience about their child’s dental visit, and to explore factors that may have an impact on children’s early dental visit.Design.  Data were collected from 1057 children; validated questionnaires were completed, and children were examined by trained dentist at ages 3 and 5. Logistic regression analyses were performed to explain dental attendance.Results.  At the age of 3, 62% and by 5 years, 21% had never visited the dentist. The first dental visit was considered a pleasant experience for the majority of children. Multivariable regression analyses revealed that children who were not first born, whose mothers had a higher educational level and whose parents had recently visited the dentist, had significantly higher odds for having visited the dentist at young age.Conclusions.  Parents of young children need to be informed about and motivated for an early dental visit. Promotion campaigns should focus on firstborn children, children from less educated parents, and parents who do not regularly see a dentist.
Quantitative comparison between full‐spectrum and filter‐based imaging in hyperspectral fluorescence microscopy
Authors: GAO L. , HAGEN N. , TKACZYK T.S. 
Published: February 2012

SummaryWe implement a filterless illumination scheme on a hyperspectral fluorescence microscope to achieve full‐range spectral imaging. The microscope employs polarisation filtering, spatial filtering and spectral unmixing filtering to replace the role of traditional filters. Quantitative comparisons between full‐spectrum and filter‐based microscopy are provided in the context of signal dynamic range and accuracy of measured fluorophores’ emission spectra. To show potential applications, a five‐colour cell immunofluorescence imaging experiment is theoretically simulated. Simulation results indicate that the use of proposed full‐spectrum imaging technique may result in three times improvement in signal dynamic range compared to that can be achieved in the filter‐based imaging.
Morphological Observation of a Horseshoe (fused) Kidney and its Vascular Pattern in a Horse
Authors: Shojaei B. , Kheirandish R. , Azizi S. 
Published: February 2012

SummaryThe present study describes the anatomical and microscopic features of a horseshoe kidney that was found in a 7‐year‐old male horse. The specimen consisted of two kidneys joined at their caudal poles by an isthmus composed of renal parenchyma and situated caudal to the caudal mesenteric artery. Six main renal arteries arose from the aorta and the external iliac arteries and ramified into 21 branches before entering the kidney. A hypoplastic and ectopic left testis, located in the inguinal canal, was observed as an associated anomaly.
Regulation of pancreatic exocrine secretion in goats: differential effects of short‐ and long‐term duodenal phenylalanine treatment
Authors: Yu Z. P. , Xu M. , Yao J. H. , Liu K. , Li F. , Liu Y. , Wang F. , Sun F. F. , Liu N. N. 
Published: February 2012

SummaryFour yearling goats (31.2 ± 2.5 kg), surgically fitted with common bile duct reentrant and duodenal catheter, were used in two 4 × 4 Latin square design experiments to investigate the effects of duodenal infusion of phenylalanine for different times on pancreatic exocrine secretion (PES). In experiment 1 (the long‐term experiment), goats were duodenally infused with 0, 2, 4 or 8 g/day phenylalanine for 14 day. Pancreatic juice and jugular blood samples were collected over 1‐h intervals for 6 h daily from day 11 to day 14 to encompass a 24‐h day. In experiment 2 (the short‐term experiment), goats were infused with phenylalanine for 10 h continuously at the same infusion rate as experiment 1 after feed deprivation for 24 h repeated every 10 day. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The volume and pH of pancreatic juice were measured, and a 5% subsample was composited and frozen until analysis of enzyme activities. Plasma was frozen until analysis of insulin and cholecystokinin (CCK). In experiment 1, pancreatic juice, α‐amylase secretion and plasma CCK concentration responded quadratically (p < 0.05), with the top value observed at the 2 g/day phenylalanine. Trypsin secretion had a quadratic response (p < 0.05), with secretion increasing up to 4 g/day phenylalanine and decreasing thereafter. Phenylalanine linearly decreased pancreatic protein and lipase secretion (p < 0.05). The results of correlation analysis showed significant correlations (p < 0.05) between plasma CCK concentration and secretion of α‐amylase and trypsin. However, the short‐term phenylalanine infusion did not influence (p > 0.05) pancreatic juice, protein, α‐amylase, lipase, trypsin secretion and plasma CCK concentration. These results indicate PES of ruminants is stimulated by phenylalanine and is potentially mediated by CCK in the long‐term duodenal infusion treatment, but is not influenced by phenylalanine in the short‐term duodenal infusion treatment.
Angle closure and angle‐closure glaucoma: what we are doing now and what we will be doing in the future
Authors: Friedman David S , Foster Paul J , Aung Tin , He Mingguang 
Published: February 2012

AbstractPrimary angle‐closure glaucoma (PACG) frequently leads to severe vision loss. Prevalence among older Asian populations is high and given global demographics, the number of persons with PACG will increase dramatically in the coming decades. Improvements in imaging of the anterior segment will help us to identify more of those with angle closure, and important clinical trials that are currently underway will provide important evidence to support screening and treatment approaches for PACG. In this manuscript, we intend to review the existing evidences, to introduce some important on‐going studies on PACG and to share the experience and viewpoints of the authors.
Recreational drug use in type 1 diabetes: an invisible accomplice to poor glycaemic control?
Authors: Lee P. , Greenfield J. R. , Gilbert K. , Campbell L. V. 
Published: February 2012

AbstractRecreational drug use during ‘rave’ parties is increasingly popular, but the impact of recreational drug use in type 1 diabetes (T1D) is not known. We determined the self‐reported pattern and effects of recreational/illicit drug use in Australians with T1D people by inviting people with T1D to participate in an anonymous online/paper survey of drug use, through national radio broadcast and online/hospital advertising. Of the people with T1D who responded to our survey, more than three quarters reported having used recreational/illicit drug, but few people had informed health professionals about drug use. Drug use was associated with worse glycaemic control and higher risk of diabetic ketoacidosis. Medical awareness of common, currently underreported, drug use in young people with T1D is essential. It offers the possibility of helping such patients improve related suboptimal metabolic control.
Fetal developmental change in topographical relationship between the human lateral pterygoid muscle and buccal nerve
Authors: Katori Y. , Yamamoto M. , Asakawa S. , Maki H. , Rodríguez‐Vázquez J. F. , Murakami G. , Abe S. 
Published: February 2012

AbstractIn adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower heads, between which the buccal nerve passes. Using sagittal or horizontal sections of 14 fetuses and seven embryos (five specimens at approximately 20–25 weeks; five at 14–16 weeks; four at 8 weeks; seven at 6–7 weeks), we examined the topographical relationship between the LPM and the buccal nerve. In large fetuses later than 15 weeks, the upper head of the LPM was clearly discriminated from the lower head. However, the upper head was much smaller than the lower head in the smaller fetuses. Thus, in the latter, the upper head was better described as an ‘anterior slip’ extending from the lower head or the major muscle mass to the anterior side of the buccal nerve. The postero‐anterior nerve course seemed to be determined by a branch to the temporalis muscle (i.e. the anterior deep temporal nerve). At 8 weeks, the buccal nerve passed through the roof of the small, fan‐like LPM. At 6–7 weeks, the LPM anlage was embedded between the temporobuccal nerve trunk and the inferior alveolar nerve. Therefore, parts of the LPM were likely to ‘leak’ out of slits between the origins of the mandibular nerve branches at 7–8 weeks, and seemed to grow in size during weeks 14–20 and extend anterosuperiorly along the infratemporal surface of the prominently developing greater wing of the sphenoid bone. Consequently, the topographical relationship between the LPM and the buccal nerve appeared to ‘change’ during fetal development due to delayed development of the upper head.
Kv7 (KCNQ) channel openers normalize central 2‐deoxyglucose uptake in a mouse model of mania and increase prefrontal cortical and hippocampal serine‐9 phosphorylation levels of GSK3β
Authors: Kristensen Line V. , Sandager‐Nielsen Karin , Hansen Henrik H. 
Published: February 2012

J. Neurochem. (2012) 121, 373–382.AbstractSeveral metabolic neuroimaging studies have indicated that bipolar patients with mania exhibit alterations in metabolic activity, suggesting that perturbations in corticolimbic function contribute to the functional deficits associated with the disease. Because pharmacological stimulation of Kv7 channel function has shown anti‐manic like efficacy in the D‐amphetamine and chlordiazepoxide (AMPH+CDP) induced hyperactivity mouse model of mania, we addressed whether this effect of Kv7 channels could be associated with changes in cerebral [14C]2‐deoxyglucose (2‐DG) uptake, a surrogate marker of brain metabolic activity. Acute administration of the Kv7 channel modulators, retigabine (pan Kv7.2‐Kv7.5 channel opener) and ICA‐27243 (Kv7.2/Kv7.3 channel‐preferring opener) reduced 2‐DG uptake in several mouse forebrain structures with a brain regional signature similar to the mood stabilizers, lithium and valproate. Combined administration of AMPH+CDP enhanced 2‐DG uptake in the striatum, cortex and thalamus, and both retigabine and ICA‐27243 fully prevented this stimulatory effect of AMPH+CDP. In addition, both Kv7 channel openers dose‐dependently increased phospho‐serine‐9 levels of GSK3β in the prefrontal cortex and hippocampus, a common molecular mechanism shared by anti‐manic drugs. In combination, these data emphasize the potential of Kv7 channel openers in the treatment of bipolar disorder, and suggest that heteromeric Kv7.2/Kv7.3 channels may present a novel anti‐manic therapeutic target.
No direct role for A1/A2 adenosine receptor activation to reflex cutaneous vasodilatation during whole‐body heat stress in humans
Authors: Fieger S. M. , Wong B. J. 
Published: February 2012

AbstractAimThe precise mechanisms underlying reflex cutaneous vasodilatation during hyperthermia remain unresolved. The purpose of this study was to investigate a potential contribution of adenosine A1/A2 receptor activation to reflex cutaneous vasodilatation.MethodsEight subjects were equipped with four microdialysis fibres on the left forearm, and each fibre was randomly assigned one of four treatments: (1) lactated Ringer's (control); (2) 4 mm of the non‐selective A1/A2 adenosine receptor antagonist theophylline; (3) 10 mm L‐NAME to inhibit nitric oxide (NO) synthase; and (4) combined 4 mm theophylline and 10 mm L‐NAME. Laser‐Doppler flowmetry (LDF) was used as an index of skin blood flow, and blood pressure was measured beat‐by‐beat via photoplethysmography and verified via brachial auscultation. Whole‐body heat stress to raise oral temperature 0.8 °C above baseline was induced via water‐perused suits. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal (%CVC max) via infusion of 28 mm nitroprusside and local heating to 43 °C.ResultsThere was no difference between control (65 ± 5%CVC max) and theophylline (63 ± 5%CVC max) sites. L‐NAME (44 ± 4%CVC max) and theophylline + L‐NAME (32 ± 3%CVC max) sites were significantly attenuated compared to both control and theophylline only sites (P < 0.05), and combined theophylline + L‐NAME sites were significantly reduced compared to L‐NAME only sites (P < 0.05).ConclusionThese data suggest A1/A2 adenosine receptor activation does not directly contribute to cutaneous active vasodilatation; however, a role for A1/A2 adenosine receptor activation is unmasked when NO synthase is inhibited.
Diverse Sequence Types of Klebsiella pneumoniae Contribute to the Dissemination of
bla
NDM-1
in India, Sweden, and the United Kingdom
Authors: Giske Christian G. , Fröding Inga , Hasan Chowdhury Mehedi , Turlej-Rogacka Agata , Toleman Mark , Livermore David , Woodford Neil , Walsh Timothy R. 
Published: February 2012

ABSTRACT

Clinical isolates of
Klebsiella pneumoniae
producing NDM-1 carbapenemase from India (
n
= 22), the United Kingdom (
n
= 13), and Sweden (
n
= 4) were subjected to multilocus sequence typing (MLST), automated repetitive sequence-based PCR (rep-PCR), serotyping, virulence gene screening, and plasmid replicon typing. The most frequently detected MLST sequence types (STs) were ST14 (
n
= 13; all serotype K2), ST11, ST149, ST231, and ST147. The correlation between MLST and automated rep-PCR was excellent. IncA/C was the most frequently detected plasmid replicon type (
n
= 14). ST14, ST11, and other successful clones may be important for the dissemination of
bla
NDM-1
.
CpsY Influences Streptococcus iniae Cell Wall Adaptations Important for Neutrophil Intracellular Survival
Authors: Allen Jonathan P. , Neely Melody N. 
Published: February 2012

ABSTRACT

The ability of a pathogen to evade neutrophil phagocytic killing mechanisms is critically important for dissemination and establishment of a systemic infection. Understanding how pathogens overcome these innate defenses is essential for the development of optimal therapeutic strategies for invasive infections. CpsY is a conserved transcriptional regulator previously identified as an important virulence determinant for systemic infection of
Streptococcus iniae
. While orthologs of CpsY have been associated with the regulation of methionine metabolism and uptake pathways, CpsY additionally functions in protection from neutrophil-mediated killing.
S. iniae
does not alter neutrophil phagosomal maturation but instead is able to adapt to the extreme bactericidal environment of a mature neutrophil phagosome, a property dependent upon CpsY. This CpsY-dependent adaptation appears to involve stabilization of the cell wall through peptidoglycan O-acetylation and repression of cellular autolysins. Furthermore,
S. iniae
continues to be a powerful model for investigation of bacterial adaptations during systemic streptococcal infection.
Escherichia coli Uropathogenesis
In Vitro
: Invasion, Cellular Escape, and Secondary Infection Analyzed in a Human Bladder Cell Infection Model
Authors: Andersen Thomas E. , Khandige Surabhi , Madelung Michelle , Brewer Jonathan , Kolmos Hans J. , Møller-Jensen Jakob 
Published: February 2012

ABSTRACT

Uropathogenic
Escherichia coli
(UPEC) strains are capable of invading bladder epithelial cells (BECs) on the bladder luminal surface. Based primarily on studies in mouse models, invasion is proposed to trigger an intracellular uropathogenic cascade involving intracellular bacterial proliferation followed by escape of elongated, filamentous bacteria from colonized BECs. UPEC filaments on the mouse bladder epithelium are able to revert to rod-shaped bacteria, which are believed to invade neighboring cells to initiate new rounds of intracellular colonization. So far, however, these late-stage infection events have not been replicated
in vitro
. We have established an
in vitro
model of human bladder cell infection by the use of a flow chamber (FC)-based culture system, which allows investigation of steps subsequent to initial invasion. Short-term bacterial colonization on the FC-BEC layer led to intracellular colonization. Exposing invaded BECs to a flow of urine, i.e., establishing conditions similar to those faced by UPEC reemerging on the bladder luminal surface, led to outgrowth of filamentous bacteria similar to what has been reported to occur in mice. These filaments were capable of reverting to rods that could invade other BECs. Hence, under growth conditions established to resemble those present
in vivo
, the elements of the proposed uropathogenic cascade were inducible in a human BEC model system. Here, we describe the model and show how these characteristics are reproduced
in vitro
.
Increase in Campylobacter jejuni Invasion of Intestinal Epithelial Cells under Low-Oxygen Coculture Conditions That Reflect the
In Vivo
Environment
Authors: Mills Dominic C. , Gundogdu Ozan , Elmi Abdi , Bajaj-Elliott Mona , Taylor Peter W. , Wren Brendan W. , Dorrell Nick 
Published: February 2012

ABSTRACT

Campylobacter jejuni
infection often results in bloody, inflammatory diarrhea, indicating bacterial disruption and invasion of the intestinal epithelium. While
C. jejuni
infection can be reproduced
in vitro
using intestinal epithelial cell (IEC) lines, low numbers of bacteria invading IECs do not reflect these clinical symptoms. Performing
in vitro
assays under atmospheric oxygen conditions neither is optimal for microaerophilic
C. jejuni
nor reflects the low-oxygen environment of the intestinal lumen. A vertical diffusion chamber (VDC) model system creates microaerobic conditions at the apical surface and aerobic conditions at the basolateral surface of cultured IECs, producing an
in vitro
system that closely mimics
in vivo
conditions in the human intestine. Ninefold increases in interacting and 80-fold increases in intracellular
C. jejuni
11168H wild-type strain bacteria were observed after 24-h coculture with Caco-2 IECs in VDCs under microaerobic conditions at the apical surface, compared to results under aerobic conditions. Increased bacterial interaction was matched by an enhanced and directional host innate immune response, particularly an increased basolateral secretion of the proinflammatory chemokine interleukin-8 (IL-8). Analysis of the invasive ability of a nonmotile
C. jejuni
11168H
rpoN
mutant in the VDC model system indicates that motility is an important factor in the early stages of bacterial invasion. The first report of the use of a VDC model system for studying the interactions of an invasive bacterial pathogen with IECs demonstrates the importance of performing such experiments under conditions that represent the
in vivo
situation and will allow novel insights into
C. jejuni
pathogenic mechanisms.