bluuebunny/crossref_metadata_2025 huggingface dataset:
Fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner
Authors: Wang Linqi , Tian Xiuyun , Gyawali Rachana , Lin Xiaorong
Published: June 2013

Microbes live mostly in a social community rather than in a planktonic state. Such communities have complex spatiotemporal patterns that require intercellular communication to coordinate gene expression. Here, we demonstrate that
Cryptococcus neoformans
, a model eukaryotic pathogen, responds to an extracellular signal in constructing its colony morphology. The signal that directs this community behavior is not a molecule of low molecular weight like pheromones or quorum-sensing molecules but a secreted protein. Znf2, a master regulator of morphogenesis in
Cryptococcus
, is necessary and sufficient for the production of this signal protein. Cfl1, a prominent Znf2-downstream adhesion protein (adhesin), was identified to be responsible for the paracrine communication. Consistent with its role in communication, Cfl1 is highly induced during mating colony differentiation, and some of the Cfl1 proteins undergo shedding and are released from the cell wall. The released Cfl1 is enriched in the extracellular matrix and acts as an autoinduction signal to stimulate neighboring cells to phenocopy Cfl1-expressing cells via the filamentation-signaling pathway. We further demonstrate the importance of an unannotated and yet conserved domain in Cfl1’s signaling activity. Although adhesion proteins have long been considered to be mediators of microbial pathogenicity and the structural components of biofilms, our work presented here provides the direct evidence supporting the signaling activation by microbial adhesion/matrix proteins.
Strain solitons and topological defects in bilayer graphene
Authors: Alden Jonathan S. , Tsen Adam W. , Huang Pinshane Y. , Hovden Robert , Brown Lola , Park Jiwoong , Muller David A. , McEuen Paul L.
Published: June 2013

Bilayer graphene has been a subject of intense study in recent years. The interlayer registry between the layers can have dramatic effects on the electronic properties: for example, in the presence of a perpendicular electric field, a band gap appears in the electronic spectrum of so-called Bernal-stacked graphene [Oostinga JB, et al. (2007)
Nature Materials
7:151–157]. This band gap is intimately tied to a structural spontaneous symmetry breaking in bilayer graphene, where one of the graphene layers shifts by an atomic spacing with respect to the other. This shift can happen in multiple directions, resulting in multiple stacking domains with soliton-like structural boundaries between them. Theorists have recently proposed that novel electronic states exist at these boundaries [Vaezi A, et al. (2013) arXiv:1301.1690; Zhang F, et al. (2013) arXiv:1301.4205], but very little is known about their structural properties. Here we use electron microscopy to measure with nanoscale and atomic resolution the widths, motion, and topological structure of soliton boundaries and related topological defects in bilayer graphene. We find that each soliton consists of an atomic-scale registry shift between the two graphene layers occurring over 6–11 nm. We infer the minimal energy barrier to interlayer translation and observe soliton motion during in situ heating above 1,000 °C. The abundance of these structures across a variety of samples, as well as their unusual properties, suggests that they will have substantial effects on the electronic and mechanical properties of bilayer graphene.
Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency
Authors: Tan Yuliang , Xue Yong , Song Chunying , Grunstein Michael
Published: June 2013

The presence of acetylated histone H3K56 (H3K56ac) in human ES cells (ESCs) correlates positively with the binding of Nanog, Sox2, and Oct4 (NSO) transcription factors at their target gene promoters. However, the function of H3K56ac there has been unclear. We now report that Oct4 interacts with H3K56ac in mouse ESC nuclear extracts and that perturbing H3K56 acetylation decreases Oct4–H3 binding. This interaction is likely to be direct because it can be recapitulated in vitro in an H3K56ac-dependent manner and is functionally important because H3K56ac combines with NSO factors in chromatin immunoprecipitation sequencing to mark the regions associated with pluripotency better than NSO alone. Moreover, reducing H3K56ac by short hairpin Asf1a decreases expression of pluripotency-related markers and increases expression of differentiation-related ones. Therefore, our data suggest that H3K56ac plays a central role in binding to Oct4 to promote the pluripotency of ESCs.
Shox2
is a molecular determinant of depot-specific adipocyte function
Authors: Lee Kevin Y. , Yamamoto Yuji , Boucher Jeremie , Winnay Jonathon N. , Gesta Stephane , Cobb John , Blüher Matthias , Kahn C. Ronald
Published: June 2013

Visceral and s.c. fat exhibit different intrinsic properties, including rates of lipolysis, and are associated with differential risk for the development of type 2 diabetes. These effects are in part related to cell autonomous differences in gene expression. In the present study, we show that expression of
Shox2
(Short stature homeobox 2) is higher in s.c. than visceral fat in both rodents and humans and that levels are further increased in humans with visceral obesity. Fat-specific disruption of
Shox2
in male mice results in protection from high fat diet-induced obesity, with a preferential loss of s.c. fat. The reduced adipocyte size is secondary to a twofold increase in the expression of β3 adrenergic receptor (
Adrb3
) at both the mRNA and protein level and a parallel increase in lipolytic rate. These effects are mimicked by knockdown of
Shox2
in C3H10T1/2 cells. Conversely, overexpression of
Shox2
leads to a repression of
Adrb3
expression and decrease lipolytic rate. Shox2 does not affect differentiation but directly interacts with CCAAT/enhancer binding protein alpha and attenuates its transcriptional activity of the Adrb3 promoter. Thus,
Shox2
can regulate the expression of
Adrb3
and control the rate of lipolysis and, in this way, exerts control of the phenotypic differences between visceral and s.c. adipocytes.
Permeation rates of penicillins indicate that
Escherichia coli
porins function principally as nonspecific channels
Authors: Kojima Seiji , Nikaido Hiroshi
Published: June 2013

Significance

Porin channels in the outer membrane of Gram-negative bacteria were originally thought to be nonspecific channels that discriminate among solutes only by their gross physicochemical properties, such as size, hydrophobicity, and charge. Since the discovery of the ampicillin-binding site inside one porin channel, however, such “specific” interactions are hypothesized to play significant roles especially for the permeation of drugs. We show, by the careful examination of influx and efflux of ampicillin and benzylpenicillin, that the original nonspecific model is still valid and that it is misleading to overemphasize the role of specific binding sites.
Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease
Authors: Falta Michael T. , Pinilla Clemencia , Mack Douglas G. , Tinega Alex N. , Crawford Frances , Giulianotti Marc , Santos Radleigh , Clayton Gina M. , Wang Yuxiao , Zhang Xuewu , Maier Lisa A. , Marrack Philippa , Kappler John W. , Fontenot Andrew P.
Published: June 2013

Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD.
Patterns of Nosocomial Infections, Multidrug-Resistant Microorganisms, and Mold Detection after Extensive Black-Water Flooding: A Survey from Central Thailand
Authors: Apisarnthanarak Anucha , Khawcharoenporn Thana , Mundy Linda M.
Published: June 2013

Central Thailand was severely affected by black-water flooding between September and November 2011, with resultant closure of 30 regional hospitals. Few data are available for the incidence of nosocomial infections and patterns of preflood versus postflood multidrug-resistant organisms (MDROs) and mold. We therefore conducted a survey of the hospitals in central Thailand in order to evaluate the patterns of nosocomial infections, MDROs, mold, and flood preparedness plans after these floods.

On the basis of a hospital list from the Ministry of Public Health, we identified 104 hospitals in 15 provinces of central Thailand that were affected, but not necessarily closed, by extensive floods. We designed and then conducted a survey, from July 1 through October 31, 2012, that inquired about hospital characteristics, postflood hospital preparedness plans, administrative support, institutional safely culture, incidence of nosocomial infections, and prevalence of MDROs and mold colonization or infection. All 104 secondary care (>100 beds) and tertiary care (>250 beds) hospitals in 15 central Thailand provinces were invited to participate.
The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3‐dimensional cancer cell migration
Authors: Giri Anjil , Bajpai Saumendra , Trenton Nicholaus , Jayatilaka Hasini , Longmore Gregory D. , Wirtz Denis
Published: June 2013

Arp2/3 is a protein complex that nucleates actin filament assembly in the lamellipodium in adherent cells crawling on planar 2‐dimensional (2D) substrates. However, in physiopathological situations, cell migration typically occurs within a 3‐dimensional (3D) environment, and little is known about the role of Arp2/3 and associated proteins in 3D cell migration. Using time resolved live‐cell imaging and HT1080, a fibrosarcoma cell line commonly used to study cell migration, we find that the Arp2/3 complex and associated proteins N‐WASP, WAVE1, cortactin, and Cdc42 regulate 3D cell migration. We report that this regulation is caused by formation of multigeneration dendritic protrusions, which mediate traction forces on the surrounding matrix and effective cell migration. The primary protrusions emanating directly from the cell body and prolonging the nucleus forms independent of Arp2/3 and dependent on focal adhesion proteins FAK, talin, and p130Cas. The Arp2/3 complex, N‐WASP, WAVE1, cortactin, and Cdc42 regulate the secondary protrusions branching off from the primary protrusions. In 3D matrices, fibrosarcoma cells as well as migrating breast, pancreatic, and prostate cancer cells do not display lamellipodial structures. This study characterizes the unique topology of protrusions made by cells in a 3D matrix and show that these dendritic protrusions play a critical role in 3D cell motility and matrix deformation. The relative contribution of these proteins to 3D migration is significantly different from their role in 2D migration.—Giri, A., Bajpai, S., Trenton, N., Jayatilaka, H., Longmore, G. D., Wirtz, D., The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3‐dimensional cancer cell migration. FASEBJ. 27, 4089–4099 (2013). www.fasebj.org
Percutaneous Endoscopic Gastrostomy in Children
Authors: Islek Ali , Sayar Ersin , Yilmaz Aygen , Artan Reha
Published: June 2013

Background:

Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide nutritional support for patients with normal gastrointestinal function but cannot be fed orally for a variety of reasons. Owing to safety concerns, the first feeding after PEG tube placement is generally delayed. Early feeding may be an option; however, childhood studies regarding early feeding after the PEG procedure are highly insufficient.

Methods:

A prospective randomized controlled study was conducted to compare early (4th hour) and late (12th hour) feeding after the PEG procedure. The PEG process was performed with the standard pull technique. Prophylactic antimicrobial drugs were not used. Complications such as gastric residue after feeding, vomiting, fever, systemic signs of infection, and duration of hospital stay were recorded. Tube feeding training was given to parents during their stay in the hospital in both groups. In the first and third days following PEG, the patients were visited by an experienced nurse in their homes and evaluated in terms of potential complications.

Results:

The study was completed with a total of 69 patients: 35 in the early feeding group and 34 in the late feeding group. The demographic characteristics of the groups were similar. Vomiting was rare and detected as similar in both groups (early feeding group 8.5% [3/35], late feeding group 8.8% [3/34], P = 1.00). Rarely, minor gastric residue was observed in both groups (early feeding group 11.4%, late feeding group 8.8% [P = 1.00]). The amount of gastric residue in the early feeding group was a maximum of 13.2 mL, whereas the late feeding group had a maximum of 14.3 mL. The average duration of stay in the hospital for the early and late feeding groups was calculated as 6.7 ± 0.64 and 28.3 ± 3.74 hours, respectively (P < 0.001). Leakage from gastrostomy fistulas, peritonitis, and aspiration were not observed in any patients.

Conclusions:

The feeding at the fourth hour after PEG placement was safe and well tolerated by patients and shortened the duration of the hospital stay. The use of prophylactic antibiotics seems to be unnecessary before the procedure.
Exploiting ecological principles to better understand cancer progression and treatment
Authors: Basanta David , Anderson Alexander R. A.
Published: June 2013

A small but growing number of people are finding interesting parallels between ecosystems as studied by ecologists (think of a savannah or the Amazon rainforest or a coral reef) and tumours. The idea of viewing cancer from an ecological perspective has many implications but, basically, it means that we should not see cancer just as a group of mutated cells. A more useful definition of cancer is to consider it a disruption in the complex balance of many interacting cellular and microenvironmental elements in a specific organ. This perspective means that organs undergoing carcinogenesis should be seen as sophisticated ecosystems in homoeostasis that cancer cells can disrupt. It also makes cancer seem even more complex but may ultimately provide insights that make it more treatable. Here, we discuss how ecological principles can be used to better understand cancer progression and treatment, using several mathematical and computational models to illustrate our argument.
Think globally, act locally: the role of local demographics and vaccination coverage in the dynamic response of measles infection to control
Authors: Ferrari M. J. , Grenfell B. T. , Strebel P. M.
Published: June 2013

The global reduction of the burden of morbidity and mortality owing to measles has been a major triumph of public health. However, the continued persistence of measles infection probably not only reflects local variation in progress towards vaccination target goals, but may also reflect local variation in dynamic processes of transmission, susceptible replenishment through births and stochastic local extinction. Dynamic models predict that vaccination should increase the mean age of infection and increase inter-annual variability in incidence. Through a comparative approach, we assess national-level patterns in the mean age of infection and measles persistence. We find that while the classic predictions do hold in general, the impact of vaccination on the age distribution of cases and stochastic fadeout are mediated by local birth rate. Thus, broad-scale vaccine coverage goals are unlikely to have the same impact on the interruption of measles transmission in all demographic settings. Indeed, these results suggest that the achievement of further measles reduction or elimination goals is likely to require programmatic and vaccine coverage goals that are tailored to local demographic conditions.
Vaccine refusal and the endgame: walking the last mile first
Authors: Saint-Victor Diane S. , Omer Saad B.
Published: June 2013

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, ‘the last mile is longest’. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. ‘walk the last mile first’.
Lessons from the eradication of smallpox: an interview with D. A. Henderson
Authors: Henderson D. A. , Klepac Petra
Published: June 2013

It has been more than 35 years since the last naturally occurring case of smallpox. Sufficient time has passed to allow an objective overview of what were the key factors in the success of the eradication effort and what lessons smallpox can offer to other campaigns. Professor D. A. Henderson headed the international effort to eradicate smallpox. Here, we present a summary of D. A. Henderson's perspectives on the eradication of smallpox. This text is based upon the Unither Baruch Blumberg Lecture, delivered by D. A. Henderson at the University of Oxford in November 2012 and upon conversations and correspondence with Professor Henderson.
A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival
Authors: Zheng Siyuan , Fu Jun , Vegesna Rahulsimham , Mao Yong , Heathcock Lindsey E. , Torres-Garcia Wandaliz , Ezhilarasan Ravesanker , Wang Shuzhen , McKenna Aaron , Chin Lynda , Brennan Cameron W. , Yung W.K. Alfred , Weinstein John N. , Aldape Kenneth D. , Sulman Erik P. , Chen Ken , Koul Dimpy , Verhaak Roel G.W.
Published: June 2013

With the advent of high-throughput sequencing technologies, much progress has been made in the identification of somatic structural rearrangements in cancer genomes. However, characterization of the complex alterations and their associated mechanisms remains inadequate. Here, we report a comprehensive analysis of whole-genome sequencing and DNA copy number data sets from The Cancer Genome Atlas to relate chromosomal alterations to imbalances in DNA dosage and describe the landscape of intragenic breakpoints in glioblastoma multiforme (GBM). Gene length, guanine–cytosine (GC) content, and local presence of a copy number alteration were closely associated with breakpoint susceptibility. A dense pattern of repeated focal amplifications involving the murine double minute 2 (MDM2)/cyclin-dependent kinase 4 (CDK4) oncogenes and associated with poor survival was identified in 5% of GBMs. Gene fusions and rearrangements were detected concomitant within the breakpoint-enriched region. At the gene level, we noted recurrent breakpoints in genes such as apoptosis regulator FAF1. Structural alterations of the FAF1 gene disrupted expression and led to protein depletion. Restoration of the FAF1 protein in glioma cell lines significantly increased the FAS-mediated apoptosis response. Our study uncovered a previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM.
Visualization of BRI1 and BAK1(SERK3) Membrane Receptor Heterooligomers during Brassinosteroid Signaling
Authors: Bücherl Christoph A. , van Esse G. Wilma , Kruis Alex , Luchtenberg Jeroen , Westphal Adrie H. , Aker José , van Hoek Arie , Albrecht Catherine , Borst Jan Willem , de Vries Sacco C.
Published: June 2013

The leucine-rich repeat receptor-like kinase BRASSINOSTEROID-INSENSITIVE1 (BRI1) is the main ligand-perceiving receptor for brassinosteroids (BRs) in Arabidopsis (Arabidopsis thaliana). Binding of BRs to the ectodomain of plasma membrane (PM)-located BRI1 receptors initiates an intracellular signal transduction cascade that influences various aspects of plant growth and development. Even though the major components of BR signaling have been revealed and the PM was identified as the main site of BRI1 signaling activity, the very first steps of signal transmission are still elusive. Recently, it was shown that the initiation of BR signal transduction requires the interaction of BRI1 with its SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) coreceptors. In addition, the resolved structure of the BRI1 ectodomain suggested that BRI1-ASSOCIATED KINASE1 [BAK1](SERK3) may constitute a component of the ligand-perceiving receptor complex. Therefore, we investigated the spatial correlation between BRI1 and BAK1(SERK3) in the natural habitat of both leucine-rich repeat receptor-like kinases using comparative colocalization analysis and fluorescence lifetime imaging microscopy. We show that activation of BR signaling by exogenous ligand application resulted in both elevated colocalization between BRI1 and BAK1(SERK3) and an about 50% increase of receptor heterooligomerization in the PM of live Arabidopsis root epidermal cells. However, large populations of BRI1 and BAK1(SERK3) colocalized independently of BRs. Moreover, we could visualize that approximately 7% of the BRI1 PM pool constitutively heterooligomerizes with BAK1(SERK3) in live root cells. We propose that only small populations of PM-located BRI1 and BAK1(SERK3) receptors participate in active BR signaling and that the initiation of downstream signal transduction involves preassembled BRI1-BAK1(SERK3) heterooligomers.
Mycorrhizal abundance affects the expression of plant resistance traits and herbivore performance
Authors: Vannette Rachel L. , Hunter Mark D.
Published: June 2013

The effects of mutualistic interactions on partner phenotype and fitness can vary with many factors, including the abundance of interacting partners. Partner abundance may determine the relative costs and benefits associated with the interaction. Although arbuscular mycorrhizal fungi (AMF) can strongly influence plant phenotype and community interactions, the effects of AMF abundance on plant resistance traits and multitrophic interactions are not well understood. We tested the hypothesis that increasing AMF abundance in soil will increase mycorrhizal colonization and affect plant biomass, foliar phosphorus concentration, the expression of plant resistance and herbivore performance.

We inoculated Asclepias syriaca seedlings with Glomus etunicatum, Scutellospora fulgida and a mix of the two species in 11 AMF abundance treatments. We quantified plant phosphorus (P), growth and resistance phenotype and the performance of a specialist herbivore, Danaus plexippus on plants associated with varying amounts of fungi.

Increasing abundance of S. fulgida or G. etunicatum in soil increased the proportion of plant root colonized by AMF, but root colonization by a mix of the fungi was not related to inoculum density. The abundance of S. fulgida, but not G. etunicatum, increased per cent foliar P and trichome density, but decreased latex exudation. Abundance of all AMF treatments tended to decrease specific leaf mass (SLM), and the two single‐species treatments unimodally affected the expression of total foliar cardenolides. Increasing abundance of the mix of AMF species also increased above‐ground biomass, foliar P and trichome density, but had little effect on other traits. The presence of AMF, species identity and the AMF abundance all explained significant variation in the expression of plant traits, although their relative contribution varied depending on the trait examined. Mycorrhizal abundance strongly increased caterpillar growth rate, which was associated with a decline in SLM.

Synthesis. Variation in mycorrhizal abundance can profoundly influence the expression of plant resistance and subsequent herbivore performance. AMF abundance may be a key, but overlooked factor in determining the outcome of mycorrhizal mutualisms.
Regional and remote occupational therapy: A preliminary exploration of private occupational therapy practice
Authors: Merritt Judith , Perkins David , Boreland Frances
Published: June 2013

Background/aim

Private providers of Medicare funded services are an integral part of the Australian primary health‐care system. Evidence on private occupational therapy practice in rural and remote Australian settings is sparse.

Methods

Providers of private occupational therapy services in outer regional and remote areas were surveyed regarding location and type of services provided, practice models and demographics. Descriptive statistics were used to summarise the findings.

Results

Thirty‐seven respondents completed the survey. In remote areas a number of occupational therapy services are not provided and no practices are based in very remote towns. One quarter of respondents visit at least five towns each week and one third had other paid employment. Nearly half indicated they will leave private practice within the next five years and nearly one third believed they could not sustain their practice. Medicare Chronic Disease Management was the main income source of only around half the respondents.

Conclusions

There is a potential market failure of private occupational therapy in rural and remote areas, impacting on people who need these services and on workforce replacement. Contributing factors include population imbalance between cities and regional/remote areas, financial implications where only face‐to‐face contact is paid for and low incomes and levels of health insurance in regional/remote areas. Potential strategies include addressing the lack of reimbursement for travel, enabling private providers to overcome barriers to providing student placements and recognising rural practice as a specialist field.
Relationship between the quality of children's handwriting and the Beery Buktenica developmental test of visuomotor integration after one year of writing tuition
Authors: Duiser Ivonne H. F. , van der Kamp John , Ledebt Annick , Savelsbergh Geert J. P.
Published: June 2013

Objective

We examined whether the three subtests of the Beery Buktenica developmental test of visuomotor integration predicted quality of handwriting across and within groups of boys and girls classified as proficient, at risk or non‐proficient writers according to the Concise Assessment Scale for Children's Handwriting.

Method

The Beery Buktenica developmental test of visuomotor integration and the Concise Assessment Scale for Children's Handwriting tests were administered to 240 grade 2 children.

Results

Proficient writers scored better on the visuomotor integration subtest than non‐proficient writers, while proficient and at risk writers scored better than non‐proficient writers on the motor coordination subtest. No differences were found on the visual perception subtest. Girls were more often classified as proficient writers than boys, and they scored better on the motor coordination subtest. Across groups, regression indicated that gender and both the visuomotor integration subtest and the motor coordination subtest were significant predictors for the quality of handwriting (i.e., accounted for 17% of the variance).

Conclusions

After one year of writing tuition, the visuomotor integration subtest (and to a lesser extent the motor coordination subtest) but not the visual perception subtest significant relates to quality of children's handwriting as measured with the Concise Assessment Scale for Children's Handwriting. However, the relatively little variance explained also points to other abilities and/or task constraints that underlie quality of handwriting.
Pioglitazone alleviates the mitochondrial apoptotic pathway and mito‐oxidative damage in the d‐galactose‐induced mouse model
Authors: Prakash Atish , Kumar Anil
Published: June 2013

Chronic injection of d‐galactose can cause gradual deterioration in learning and memory capacity, and activates oxidative stress, mitochondrial dysfunction and apoptotic cell death in the brain of mice. Thus, it serves as an animal model of ageing. Recent evidence has shown that mild cognitive impairment in humans might be alleviated by treatment with piogliatzone (peroxisome proliferator‐activated receptor gamma (PPARγ) agonists). To continue exploring the effects of piogliatzone in this model, we focused on behavioural alteration, oxidative damage, mitochondrial dysfunction and apoptosis in d‐galactose‐induced mice.

The ageing model was established by administration of d‐galactose (100 mg/kg) for 6 weeks. Pioglitazone (10 and 30 mg/kg) and bisphenol A diglycidyl ether (15 mg/kg) were given daily to d‐galactose‐induced senescent mice. The cognitive behaviour of mice was monitored using the Morris water maze. The anti‐oxidant status and apoptotic activity in the ageing mice was measured by determining mito‐oxidative parameters and caspase‐3 activity in brain tissue.

Systemic administration of d‐galactose significantly increased behavioural alterations, biochemical parameters, mitochondrial enzymes, and activations of caspase‐3 and acetylcholinesterase enzyme activity as compared with the control group. Piogliatzone treatment significantly improved behavioural abnormalities, biochemical, cellular alterations, and attenuated the caspase‐3 and acetylcholinesterase enzyme activity as compared with the control. Furthermore, pretreatment of BADGE (PPARγ antagonist) with pioglitazone reversed the protective effect of pioglitazone in d‐galactose‐induced mice.

The present study highlights the protective effects of pioglitzone against d‐galactose‐induced memory dysfunction, mito‐oxidative damage and apoptosis through activation of PPARγ receptors. These findings suggest that pioglitazone might be helpful for the prevention or alleviation of ageing.
Impact of yellow mite (Polyphagotarsonemus latus [Banks]) density on host's (Corchorus capsularis L.) phenology and assessment of yield loss under field conditions
Authors: Kamruzzaman A. S. M. , Alam M. Zinnatul , Miah M. Ramiz Uddin , Siddiquee Shafiquzzaman
Published: June 2013

Yellow mite, Polyphagotarsonemus latus [Banks] (Acari: Tarsonemidae) is one of the major pests of jute crops (Corchorus capsularis L.) in Bangladesh. In this study, indigenous varieties of jute were used for treatments, namely, CVL‐1, CVE‐3, BJC‐7370 and BJC‐83. The paired plot treatments (treated and untreated controls) were laid out under field conditions. The effects of yellow mite were studied at three stages of the jute plants: 60 days after sowing (DAS), 90 DAS and 120 DAS. A higher number of mite stages was observed up to 90 DAS and then declined up to 120 DAS in var. BJC‐7370 among two other varieties, Deshi and Tossa. The percentage of infestation and damage indexes (scale 0–5) were measured to relate yellow mite injuries to the number of leaves, leaf area, fresh leaf weight, dry leaf weight, soluble solids, plant height, base diameter, fiber weight, stick weight, number of flowers per plant, number of pods, pod weight per plant, seeds per pod, seed weight and 1000 seeds' weight of plants infested at three different phenological stages. The highest fiber yield loss was found in the variety BJC‐7370 (59.75%), followed by BJC‐83 (55.56%), CVE‐3 (54.30%) and CVL‐1 (50.05). The highest stick yield losses were found in the following order: BJC‐7370 (54.54%) > BJC‐83 (51.17%) > CVL‐1 (43.68%) > CVE‐3 (37.80%) and BJC‐7370 (30.33%) > CVL‐1 (27.83%) > BJC‐83 (24.16%) > CVE‐3 (22.11%) for the highest seed yield under field conditions for Corchorus capsularis. High yellow mite population in untreated checks decreased plant growth and showed significant losses in yield production for the variety BJC‐7370.
A new set of primers for COI amplification from freshwater microcrustaceans
Authors: Prosser Sean , Martínez‐Arce Arely , Elías‐Gutiérrez Manuel
Published: June 2013

Despite the contribution of DNA barcoding towards understanding the biodiversity and distribution of species, the success of COI amplification has been quite variable when it comes to freshwater zooplankton (Elías‐Gutiérrez & Valdez‐Moreno 2008; Jeffery et al. 2011). Some genera of microcrustaceans seem to be more difficult to amplify than others. For example, Macrothrix, Scapholeberis, Diaphanosoma and cyclopoids have yielded limited results. Among several possible reasons for the inability to barcode freshwater microcrustaceans is that there does not exist a specific set of primers for COI amplification. To this end, we developed a zooplankton – specific set of primers, which significantly increased average amplification success (20% increase). With these primers, we observed an overall success of over 70% for Sididae and Chydoridae, and more than 80% for Daphniidae, Moinidae, Bosminidae, Macrothricidae, Ilyocryptidae and Diaptomidae. We also demonstrate a simple alteration to a common specimen fixation method that increases the overall recovery of barcodes from freshwater zooplankton. Collectively, we believe our results will greatly aid the recovery of barcodes from these difficult groups.
HIV protease inhibitors induce senescence and alter osteoblastic potential of human bone marrow mesenchymal stem cells: beneficial effect of pravastatin
Authors: Hernandez‐Vallejo Sandra J. , Beaupere Carine , Larghero Jerome , Capeau Jacqueline , Lagathu Claire
Published: June 2013

HIV‐infected patients receiving antiretroviral therapy present an increased prevalence of age‐related comorbidities, including osteoporosis. HIV protease inhibitors (PIs) have been suspected to participate to bone loss, but the mechanisms involved are unknown. In endothelial cells, some PIs have been shown to induce the accumulation of farnesylated prelamin‐A, a biomarker of cell aging leading to cell senescence. Herein, we hypothesized that these PIs could induce premature aging of osteoblast precursors, human bone marrow mesenchymal stem cells (MSCs), and affect their capacity to differentiate into osteoblasts. Senescence was studied in proliferating human MSCs after a 30‐day exposure to atazanavir and lopinavir with or without ritonavir. When compared to untreated cells, PI‐treated MSCs had a reduced proliferative capacity that worsened with increasing passages. PI treatment led to increased oxidative stress and expression of senescence markers, including prelamin‐A. Pravastatin, which blocks prelamin‐A farnesylation, prevented PI‐induced senescence and oxidative stress, while treatment with antioxidants partly reversed these effects. Moreover, senescent MSCs presented a decreased osteoblastic potential, which was restored by pravastatin treatment. Because age‐related bone loss is associated with increased bone marrow fat, we also evaluated the capacity of PI‐treated MSCs to differentiate into adipocyte. We observed an altered adipocyte differentiation in PI‐treated MSCs that was reverted by pravastatin. We have shown that some PIs alter osteoblast formation by affecting their differentiation potential in association with altered senescence in MSCs, with a beneficial effect of statin. These data corroborate the clinical observations and allow new insight into pathophysiological mechanisms of PI‐induced bone loss in HIV‐infected patients.
Pretreatment Alcohol Drinking Goals are Associated with Treatment Outcomes
Authors: Dunn Kelly E. , Strain Eric C.
Published: June 2013

Background

A large subset of patients who enter treatment for alcohol dependence report nonabstinent drinking goals (e.g., reduction in drinking) rather than abstinence, and this pretreatment goal choice may be associated with drinking outcomes and alcohol‐related problems.

Methods

An analysis of the 16‐week Combined Pharmacotherapies and Behavioral Interventions (COMBINE) study was conducted to determine the association between self‐reported pretreatment drinking goal and drinking outcomes and alcohol‐related problems. Participants who reported a nonabstinent drinking goal (n = 340) were matched with participants who reported an abstinent drinking goal (n = 340) on 3 variables believed to contribute to treatment outcomes: COMBINE experimental group, gender, and number of prebaseline heavy drinking days.

Results

Analyses revealed no interaction between the COMBINE experimental group and drinking goal on outcome measures, so results were collapsed and examined as a function of drinking goal group. Participants who chose an abstinent drinking goal had significantly more weeks with no drinking or no heavy drinking, reported fewer heavy drinking days, reported fewer days with >1 drink, and were more likely to have a ≥50% decrease in drinks per day between baseline and week 16 of the intervention. However, both groups reported reductions over time in percent drinking days, mean drinks per day, number of heavy drinking days, and number of drinking days per week, and participants in both groups experienced significant reductions in alcohol‐related problems and improvements in psychosocial functioning.

Conclusions

Results replicate and expand upon previous studies examining the association between drinking goal and treatment outcome. These data also provide support for the standard inclusion of drinking treatment goal as a stratification variable in study interventions or as a covariate in outcome analyses and highlight several areas that warrant additional research regarding patients who enter alcohol treatment with a nonabstinent drinking goal.
Suppression and Epigenetic Regulation of MiR‐9 Contributes to Ethanol Teratology: Evidence from Zebrafish and Murine Fetal Neural Stem Cell Models
Authors: Pappalardo‐Carter Dana L. , Balaraman Sridevi , Sathyan Pratheesh , Carter Eric S. , Chen Wei‐Jung A. , Miranda Rajesh C.
Published: June 2013

Background

Fetal alcohol exposure produces multiorgan defects, making it difficult to identify underlying etiological mechanisms. However, recent evidence for ethanol (EtOH) sensitivity of the miRNA miR‐9 suggests one mechanism, whereby EtOH broadly influences development. We hypothesized that loss of miR‐9 function recapitulates aspects of EtOH teratology.

Methods

Zebrafish embryos were exposed to EtOH during gastrulation, or injected with anti‐miR‐9 or nonsense control morpholinos during the 2‐cell stage of development and collected between 24 and 72 hours postfertilization (hpf). We also assessed the expression of developmentally important, and known miR‐9 targets, FGFR‐1, FOXP2, and the nontargeted transcript, MECP2. Methylation at CpG islands of mammalian miR‐9 genes was assessed in fetal murine neural stem cells (mNSCs) by methylation‐specific PCR, and miRNA processing assessed by qRT‐PCR for pre‐miR‐9 transcripts.

Results

EtOH treatment and miR‐9 knockdown resulted in similar cranial defects including microcephaly. Additionally, EtOH transiently suppressed miR‐9, as well as FGFR‐1 and FOXP2, and alterations in miR‐9 expression were correlated with severity of EtOH‐induced teratology. In mNSCs, EtOH increased CpG dinucleotide methylation at the miR‐9‐2 locus and accumulation of pre‐miR‐9‐3.

Conclusions

EtOH exerts regulatory control at multiple levels of miR‐9 biogenesis. Moreover, early embryonic loss of miR‐9 function recapitulated the severe range of teratology associated with developmental EtOH exposure. EtOH also disrupts the relationship between miR‐9 and target gene expression, suggesting a nuanced relationship between EtOH and miRNA regulatory networks in the developing embryo. The implications of these data for the expression and function of mature miR‐9 warrant further investigation.
Binge Drinking–Induced Subtle Myocardial Injury
Authors: Waszkiewicz Napoleon , Szulc Agata , Zwierz Krzysztof
Published: June 2013

Background

Most of the clinical, histopathological, and biochemical studies consider the effect of chronic alcohol intoxication on myocardial injury. Much less attention has been paid to acute alcohol (binge drinking)–induced cardiotoxicity, even though alcohol binging is much more common than alcohol dependence.

Methods

We briefly present some of the binge drinking–induced “holiday heart” effects. The literature was searched to find effects of alcohol on heart.

Results

In binge drinking, the literature has demonstrated transient myocardial subtle changes in cardiac magnetic resonance, increased serological markers of myocardial injury and inflammation, abnormal cardiac rhythm, changes in other biochemical and ultrastructural indices of myocardial dysfunction, as well as changes in metabolism, blood pressure, heart rate, thrombosis/fibrinolysis processes, and coronary vasoconstriction.

Conclusions

Although acute low alcohol exposure has widely proven positive effect on myocardial function, heavy acute drinking frequent events are related to adverse cardiovascular effects.
Morphologic Radiographic Study of the Proximal Sesamoid Bones of the Forelimb in Thoroughbred Racehorses in Training
Authors: Beccati F. , Gialletti R. , Giontella A. , Davanzo S. , Di Meo A. , Pepe M.
Published: June 2013

The aim of this study was to identify differences in bone shape (height and width) of proximal sesamoid bones (PSB) in 2‐year‐old Thoroughbred racehorses in training. Dorsal 15° proximal‐palmarodistal oblique images of each metacarpophalangeal joint were acquired before the horses started training and at 1 year after the start of exercise and racing. There were no changes in height and width ofPSBs induced by training. There was a significant difference of height and width between medial and lateralPSBs. In both forelimbs, the medialPSBwas significantly wider and shorter than the lateralPSB. The medialPSBof the right forelimb was significantly wider than that of the left forelimb. These results might explain some limb predilection for fracture ofPSBs. The difference in strain pattern between medial and lateralPSBs in different loading conditions needs to be investigated.
Burnout in orthopaedic surgeons: a review
Authors: Arora Manit , Diwan Ashish D. , Harris Ian A.
Published: June 2013

Background

Training and practice of orthopaedic surgery are stressful endeavours, placing orthopaedic surgeons at risk of burnout. Burnout syndrome is associated with negative outcomes for patients, institutions and, especially, the surgeon. The aim of this review is to summarize available literature on burnout among orthopaedic surgeons and provide recommendations for future work in this field.

Methods

A search of MEDLINE (1946–present) and EMBASE (search terms: ‘Burnout, Professional’ AND ‘Orthopaedics’; ‘Stress, Psychological’ AND ‘Orthopaedic Surgery’; ‘Fatigue, Mental’ AND ‘Orthopaedic Surgery’) was performed. The authors focused on articles that assessed burnout among orthopaedic surgeons. All studies used the Maslach Burnout Inventory allowing for cross‐study (and cross‐country) comparisons.

Results

Burnout rates among orthopaedic surgeons are in the range of 50–60%, higher than surgeons in general (range: 30–40% for surgeons in general), with the highest rate (emotional exhaustion and depersonalization scores) among orthopaedic residents, followed by department chairs, followed by faculty members. Both objective factors (caseload, practice setting, etc.) and subjective factors (perception that career was unrewarding, perception of lack of autonomy, etc.) contribute to burnout; however, subjective factors show a stronger correlation.

Conclusion

Despite the heavy burnout rates among orthopaedic surgeons, little work has been performed in this field. Factors responsible for burnout among various orthopaedic populations should be determined, and appropriate interventions designed to reduce burnout.
Partially Linear Structure Selection in Cox Models with Varying Coefficients
Authors: Lian Heng , Lai Peng , Liang Hua
Published: June 2013

To explore the nonlinear interactions between covariates and an index variable, partially linear proportional hazards models have been proposed for censored survival data. However, specification of the partially linear structure was usually carried out in an ad‐hoc manner by first fitting a full varying‐coefficient model and visually examining the resulting fit to identify the linear part. In this article, we consider the problem of coefficient estimation and constant coefficient identification based on a double shrinkage approach. Variable selection is also considered in a coherent estimation framework, resulting in a double‐penalization procedure. Under the mild assumptions, we establish asymptotic properties for the procedure such as consistency, sparesistency, constansistency, and asymptotic normality. We evaluate the performance of the proposed method by numerical simulations and demonstrate its application using a breast cancer data set.
Suprapubic‐assisted laparoendoscopic single‐site surgery (LESS) in urology: our experience
Authors: Zou Xiaofeng , Zhang Guoxi , Xue Yijun , Yuan Yuanhu , Xiao Rihai , Wu Gengqing , Wang Xiaoning , Wu Yuting , Long Dazhi , Yang Jun , Xu Hui , Liu Folin , Zhang Xu
Published: June 2013

Objective

To report our experience with suprapubic‐assisted laparoendoscopic single‐site surgery (SA‐LESS) in urology.

Patients and Methods

In all, 236 patients underwent SA‐LESS

A 5‐ and 10‐mm (or two 5‐mm) trocars were inserted at the medial margin of the umbilicus. A 10‐ or 5‐mm trocar was inserted into the abdominal cavity below the ipsilateral pubic hairline.

The technique for the SA‐LESS is similar to that of the standard laparoscopy, with conventional instruments placed in the abdominal trocars, under direct vision achieved by a 10‐mm conventional 30 ° or 5‐mm flexible‐tip 0 ° laparoscope placed through the trocar below the pubic hairline.

Results

SA‐LESS was successfully completed in 229 patients, without the need for ancillary trocars or additional instruments. Six patients required conversion to standard laparoscopy because of intraoperative bleeding (five) and failure to progress (one). One patient underwent open conversion because of gradual bleeding during the dissection of a dense adhesive renal pedicle due to infection and fibrosis

The various SA‐LESS procedures performed included adrenalectomy (15), renal cyst excision (19), nephrectomy (78; simple 63, radical 15), nephroureterectomy (three), nephron‐sparing surgery (three), heminephroureterectomy (five), pyeloplasty (nine), pyelolithotomy (six), and ureterolithotomy (98). The median operative time was 81, 106, 92, 140, and 85 min, and the estimated blood loss was 60, 205, 115, 75, and 55 mL for adrenalectomy, simple nephrectomy, radical nephrectomy, pyeloplasty, and ureterolithotomy, respectively.

At a mean (range) follow‐up of 14.8 (2–27) months there was a hidden umbilicus scar. The scar below the pubic hairline was not detectable because of pubic hair covering.

Conclusions

SA‐LESS appears to be feasible, safe and effective.

Compared with umbilical LESS, the placement of a trocar at the umbilicus and below the pubic hairline not only decreases the difficulty of surgery but also leads to little postoperative pain and good cosmetic results.