bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a DNA exit gate in the human cohesin ring
Authors: Huis in ’t Veld Pim J. , Herzog Franz , Ladurner Rene , Davidson Iain F. , Piric Sabina , Kreidl Emanuel , Bhaskara Venugopal , Aebersold Ruedi , Peters Jan-Michael
Published: November 2014

Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin’s proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin’s ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.
Magnetic moment and plasma environment of HD 209458b as determined from Lyα observations
Authors: Kislyakova Kristina G. , Holmström Mats , Lammer Helmut , Odert Petra , Khodachenko Maxim L.
Published: November 2014

Transit observations of HD 209458b in the stellar Lyman-α(Lyα) line revealed strong absorption in both blue and red wings of the line interpreted as hydrogen atoms escaping from the planet’s exosphere at high velocities. The following sources for the absorption were suggested: acceleration by the stellar radiation pressure, natural spectral line broadening, or charge exchange with the stellar wind. We reproduced the observation by means of modeling that includes all aforementioned processes. Our results support a stellar wind with a velocity of ≈400 kilometers per second at the time of the observation and a planetary magnetic moment of ≈1.6 × 10
26
amperes per square meter.
Tectonic control of Yarlung Tsangpo Gorge revealed by a buried canyon in Southern Tibet
Authors: Wang Ping , Scherler Dirk , Liu-Zeng Jing , Mey Jürgen , Avouac Jean-Philippe , Zhang Yunda , Shi Dingguo
Published: November 2014

The Himalayan mountains are dissected by some of the deepest and most impressive gorges on Earth. Constraining the interplay between river incision and rock uplift is important for understanding tectonic deformation in this region. We report here the discovery of a deeply incised canyon of the Yarlung Tsangpo River, at the eastern end of the Himalaya, which is now buried under more than 500 meters of sediments. By reconstructing the former valley bottom and dating sediments at the base of the valley fill, we show that steepening of the Tsangpo Gorge started at about 2 million to 2.5 million years ago as a consequence of an increase in rock uplift rates. The high erosion rates within the gorge are therefore a direct consequence of rapid rock uplift.
His brain, her brain?
Authors: Fine Cordelia
Published: November 2014

Research exploring sex differences in the human brain must overcome “neurosexist” interpretations
Saving lives without new drugs
Authors: Cohen Jon
Published: November 2014

A push for improving basic care of Ebola patients could save many lives without experimental treatments.
Temporal targets of drug action
Authors: FitzGerald Garret A.
Published: November 2014

A circadian gene expression atlas shows that time of day is relevant to the oscillation of drug targets and the effects of medications
Preterm Birth: Now the Leading Cause of Child Death Worldwide
Authors: Lawn Joy E. , Kinney Mary
Published: November 2014

Preterm birth is now the leading cause of death among young children worldwide, requiring a united effort to focus attention and investment on preventing prematurity.
Safety and Immunogenicity of Escalating Dosages of a Single Oral Administration of Peru-15 pCTB, a Candidate Live, Attenuated Vaccine against Enterotoxigenic Escherichia coli and Vibrio cholerae
Authors: Chen Wilbur H. , Garza Jose , Choquette Monique , Hawkins Jennifer , Hoeper Amy , Bernstein David I. , Cohen Mitchell B.
Published: November 2014

EnterotoxigenicEscherichia coli(ETEC) organisms are a leading cause of infectious diarrhea in developing countries. A live, attenuated cholera strain that expresses high levels of the nontoxic B subunit of cholera toxin, which might also serve as an ETEC protective antigen, was evaluated for safety, excretion, and immunogenicity in healthy volunteers. We enrolled four inpatient dose-escalation cohorts of 15 to 16 eligible subjects to randomly (3:1) receive a single oral dose of vaccine or placebo (buffer alone), evaluating 1 ×107, 1 ×108, 1 ×109, and 1 ×1010CFU of the vaccine. The vaccine was well tolerated, although some subjects experienced moderate diarrhea. The serum Inaba vibriocidal antibody response appeared to display a dose-response relationship with increasing dosages of vaccine, plateauing at the 109-CFU dosage. The serum antitoxin (cholera toxin and heat-labile enterotoxin) antibody seroconversion rate (4-fold increase over baseline) also appeared to display a dose-response relationship. The vaccine strain was excreted in stool cultures, displaying a dose-response relationship. A single oral dose of Peru-15 pCTB at dosages up to 1 ×1010CFU was safe and immunogenic in this first-in-human trial. These encouraging data support the ongoing clinical development of this candidate combined cholera and ETEC vaccine. (This study has been registered at ClinicalTrials.gov under registration no. NCT00654108.)
Successful Protection against Tularemia in C57BL/6 Mice Is Correlated with Expansion of Francisella tularensis-Specific Effector T Cells
Authors: Griffin Amanda J. , Crane Deborah D. , Wehrly Tara D. , Bosio Catharine M.
Published: November 2014

Francisella tularensisis an intracellular, Gram-negative bacterium that causes the fatal disease tularemia. Currently, there are no licensed vaccines for tularemia and the requirements for protection against infection are poorly defined. To identify correlates of vaccine-induced immunity against tularemia, we compared different strains of the live vaccine strain (LVS) for their relative levels of virulence and ability to protect C57BL/6 mice against challenge with virulentF. tularensisstrain SchuS4. Successful vaccination, as defined by survival of C57BL/6 mice, was correlated with significantly greater numbers of effector T cells in the spleen and lung. Further, lung cells and splenocytes from fully protected animals were more effective than lung cells and splenocytes from vaccinated but nonimmune animals in limiting intracellular replication of SchuS4in vitro. Together, our data provide a unique model to compare efficacious vaccines to nonefficacious vaccines, which will enable comprehensive identification of host and bacterial components required for immunization against tularemia.
First Case Report of Fatal Sepsis Due to Campylobacter upsaliensis
Authors: Nakamura Itaru , Omori Nami , Umeda Ayaka , Ohkusu Kiyofumi , Matsumoto Tetsuya
Published: November 2014

We encountered a rare case of severe fatal infection in a 70-year-old woman due to
Campylobacter upsaliensis
, identified by PCR amplification and sequencing analysis of the 16S rRNA gene using DNA extracted from the isolates. To our knowledge, fatal sepsis due to this organism has never been described to date.
Campylobacter concisus Pseudo-Outbreak Caused by Improved Culture Conditions
Authors: Casanova Carlo , Schweiger Alexander , von Steiger Niklaus , Droz Sara , Marschall Jonas
Published: November 2014

An unusual increase in the number ofCampylobacter concisusisolates found in stool cultures provoked an outbreak investigation at Bern University Hospital. No epidemiological links were found between the cases, and theCampylobacterisolates were clonally unrelated. A change in culture conditions to a hydrogen-rich atmosphere enhancing growth ofC. concisuswas deemed responsible for this pseudo-outbreak.
Microsatellite (STR
Af
) Genotyping Cannot Differentiate between Invasive and Colonizing Aspergillus fumigatus Isolates
Authors: Escribano Pilar , Peláez Teresa , Bouza Emilio , Guinea Jesús
Published: November 2014

We studied whether short tandem repeats of
Aspergillus fumigatus
(STR
Af
) can differentiate between invasive and colonizing genotypes of
A. fumigatus
. Of the 395 genotypes detected (
n
= 1,373 isolates), 50 were clusters and 24 (6% of all genotypes) involved the patients with invasive aspergillosis and those colonized with
A. fumigatus
, indicating that genotyping cannot discriminate between invasive and colonizing isolates.
Identification of RISC-Associated Adenoviral MicroRNAs, a Subset of Their Direct Targets, and Global Changes in the Targetome upon Lytic Adenovirus 5 Infection
Authors: Bellutti Florian , Kauer Maximilian , Kneidinger Doris , Lion Thomas , Klein Reinhard
Published: November 2014

Adenoviruses encode a set of highly abundant microRNAs (mivaRNAs), which are generated by Dicer-mediated cleavage of the larger noncoding virus-associated RNAs (VA RNAs) I and II. We performed deep RNA sequencing to thoroughly investigate the relative abundance of individual single strands of mivaRNA isoforms in human A549 cells lytically infected with human adenovirus 5 (Ad5) at physiologically relevant multiplicities of infection (MOIs). In addition, we investigated their relative abundance in the endogenous RNA-induced silencing complexes (RISCs). The occupation of endogenous RISCs by mivaRNAs turned out to be pronounced but not as dominant as previously inferred from experiments with AGO2-overexpressing cells infected at high MOIs. In parallel, levels of RISC-incorporated mRNAs were investigated as well. Analysis of mRNAs enriched in RISCs in Ad5-infected cells revealed that only mRNAs with complementarity to the seed sequences of mivaRNAs derived from VA RNAI but not VA RNAII were overrepresented among them, indicating that only mivaRNAs derived from VA RNAI are likely to contribute substantially to the posttranscriptional downregulation of host gene expression. Furthermore, to generate a comprehensive picture of the entire transcriptome/targetome in lytically infected cells, we determined changes in cellular miRNA levels in both total RNA and RISC RNA as well, and bioinformatical analysis of mRNAs of total RNA/RISC fractions revealed a general, genome-wide trend toward detargeting of cellular mRNAs upon infection. Lastly, we identified the direct targets of both single strands of a VA RNAI-derived mivaRNA that constituted one of the two most abundant isoforms in RISCs of lytically infected A549 cells.

IMPORTANCE
Viral and cellular miRNAs have been recognized as important players in virus-host interactions. This work provides the currently most comprehensive picture of the entire mRNA/miRNA transcriptome and of the complete RISC targetome during lytic adenovirus infection and thus represents the basis for a deeper understanding of the interplay between the virus and the cellular RNA interference machinery. Our data suggest that, at least in the model system that was employed, lytic infection by Ad5 is accompanied by a measurable global net detargeting effect on cellular mRNAs, and analysis of RISC-associated viral small RNAs revealed that the VA RNAs are the only source of virus-encoded miRNAs. Moreover, this work allows to assess the power of individual viral miRNAs to regulate cellular gene expression and provides a list of proven and putative direct targets of these miRNAs, which is of importance, given the fact that information about validated targets of adenovirus-encoded miRNAs is scarce.
A Live Attenuated Equine H3N8 Influenza Vaccine Is Highly Immunogenic and Efficacious in Mice and Ferrets
Authors: Baz Mariana , Paskel Myeisha , Matsuoka Yumiko , Zengel James , Cheng Xing , Treanor John J. , Jin Hong , Subbarao Kanta
Published: November 2014

Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81cavaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81cavaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81cavaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans.

IMPORTANCEEquine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and protected mice and ferrets against homologous and heterologous EIV.
Syntaxin 5-Dependent Retrograde Transport to the
trans
-Golgi Network Is Required for Adeno-Associated Virus Transduction
Authors: Nonnenmacher Mathieu E. , Cintrat Jean-Christophe , Gillet Daniel , Weber Thomas
Published: November 2014

Intracellular transport of recombinant adeno-associated virus (AAV) is still incompletely understood. In particular, the trafficking steps preceding the release of incoming AAV particles from the endosomal system into the cytoplasm, allowing subsequent nuclear import and the initiation of gene expression, remain to be elucidated fully. Others and we previously showed that a significant proportion of viral particles are transported to the Golgi apparatus and that Golgi apparatus disruption caused by the drug brefeldin A efficiently blocks AAV serotype 2 (AAV2) transduction. However, because brefeldin A is known to exert pleiotropic effects on the entire endosomal system, the functional relevance of transport to the Golgi apparatus for AAV transduction remains to be established definitively. Here, we show that AAV2 trafficking toward the
trans
-Golgi network (TGN) and the Golgi apparatus correlates with transduction efficiency and relies on a nonclassical retrograde transport pathway that is independent of the retromer complex, late endosomes, and recycling endosomes. AAV2 transduction is unaffected by the knockdown of syntaxins 6 and 16, which are two major effectors in the retrograde transport of both exogenous and endogenous cargo. On the other hand, inhibition of syntaxin 5 function by small interfering RNA silencing or treatment with cyclized Retro-2 strongly decreases AAV2 transduction and transport to the Golgi apparatus. This inhibition of transduction is observed with several AAV serotypes and a number of primary and immortalized cells. Together, our data strongly suggest that syntaxin 5-mediated retrograde transport to the Golgi apparatus is a broadly conserved feature of AAV trafficking that appears to be independent of the identity of the receptors used for viral attachment.

IMPORTANCE
Gene therapy constitutes a promising approach for the treatment of life-threatening conditions refractory to any other form of remedy. Adeno-associated virus (AAV) vectors are currently being evaluated for the treatment of diseases such as Duchenne muscular dystrophy, hemophilia, heart failure, Parkinson's disease, and others. Despite their promise as gene delivery vehicles, a better understanding of the biology of AAV-based vectors is necessary to improve further their efficacy. AAV vectors must reach the nucleus in order to deliver their genome, and their intracellular transport is not fully understood. Here, we dissect an important step of the intracellular journey of AAV by showing that retrograde transport of capsids to the
trans
-Golgi network is necessary for gene delivery. We show that the AAV trafficking route differs from that of known Golgi apparatus-targeted cargos, and we raise the possibility that this nonclassical pathway is shared by most AAV variants, regardless of their attachment receptors.
Identification of the Physiological Gene Targets of the Essential Lytic Replicative Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein
Authors: Verma Dinesh , Li Da-Jiang , Krueger Brian , Renne Rolf , Swaminathan Sankar
Published: November 2014

The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 gene product is essential for lytic KSHV replication and virion production. Recombinant ORF57-null mutants fail to accumulate several lytic cycle mRNAs at wild-type levels, leading to decreased production of lytic proteins necessary for efficient replication. Several mechanisms by which ORF57 may enhance expression of lytic KSHV mRNAs have been proposed, including mRNA stabilization, mRNA nuclear export, increased polyadenylation, and transcriptional activation. ORF57 activity is also gene specific, with some genes being highly dependent on ORF57, whereas others are relatively independent. Most experiments have utilized transfection models for ORF57 and have not systematically examined the gene specificity and potential mechanisms of action of ORF57 in the context of KSHV-infected cells. In this study, the KSHV genes that are most highly upregulated by ORF57 during KSHV lytic replication were identified by a combination of high-throughput deep RNA sequencing, quantitative PCR, Northern blotting, and rapid amplification of cDNA ends methods. Comparison of gene expression from a ΔORF57 KSHV recombinant, a rescued ΔORF57 KSHV recombinant, and wild-type KSHV revealed that two clusters of lytic genes are most highly dependent on ORF57 for efficient expression. Despite contiguous location in the genome and shared polyadenylation of several of the ORF57-dependent genes, ORF57 regulation was promoter and polyadenylation signal independent, suggesting that the mRNAs are stabilized by ORF57. The eight genes identified to critically require ORF57 belong to both early and late lytic temporal classes, and seven are involved in DNA replication, virion assembly, or viral infectivity, explaining the essential role of ORF57 in infectious KSHV production.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human herpesvirus involved in the causation of several human cancers. The KSHV ORF57 protein is required for KSHV to replicate and produce infectious virus. We have identified several KSHV genes whose expression is highly dependent on ORF57 and shown that ORF57 increases expression of these genes specifically. These genes code for proteins that are required for the virus to replicate its DNA and to infect other cells. Identifying the targets and mechanism of action of ORF57 provides further approaches to discover antiviral therapy.
Evolution of and Evolutionary Relationships between Extant Vaccinia Virus Strains
Authors: Qin Li , Favis Nicole , Famulski Jakub , Evans David H.
Published: November 2014

Although vaccinia virus (VACV) was once used as a vaccine to eradicate smallpox on a worldwide scale, the biological origins of VACV are uncertain, as are the historical relationships between the different strains once used as smallpox vaccines. Here, we sequenced additional VACV strains that either represent relatively pristine examples of old vaccines (e.g., Dryvax, Lister, and Tashkent) or have been subjected to additional laboratory passage (e.g., IHD-W and WR). These genome sequences were compared with those previously reported for other VACVs as well as other orthopoxviruses. These extant VACVs do not always cluster in simple phylogenetic trees that are aligned with the known historical relationships between these strains. Rather, the pattern of deletions suggests that all existing strains likely come from a complex stock of viruses that has been passaged, distributed, and randomly sampled over time, thus obscuring simple historical or geographic links. We examined surviving nonclonal vaccine stocks, like Dryvax, which continue to harbor larger and now rare variants, including one that we have designated “clone DPP25.” DPP25 encodes genes not found in most VACV strains, including an ankyrin-F-box protein, a homolog of the variola virus (Bangladesh) B18R gene which we show can be deleted without affecting virulence in mice. We propose a simple common mechanism by which recombination of a larger and hypothetical DPP25-like ancestral strain, combined with selection for retention of critically important genes near the terminal inverted repeat boundaries (vaccinia virus growth factor gene and an interferon alpha/beta receptor homolog), could produce all known VACV variants.

IMPORTANCE
Smallpox was eradicated by using a combination of intensive disease surveillance and vaccination using vaccinia virus (VACV). Interestingly, little is known about the historical relationships between different strains of VACV and how these viruses may have evolved from a common ancestral strain. To understand these relationships, additional strains were sequenced and compared to existing strains of VACV as well as other orthopoxviruses by using whole-genome sequence alignments. Extant strains of VACV did not always cluster in simple phylogenetic trees based on known historical relationships between these strains. Based on these findings, it is possible that all existing strains of VACV are derived from a single complex stock of viruses that has been passaged, distributed, and sampled over time.
Popliteal artery thrombosis following total knee arthroplasty managed successfully with percutaneous intervention
Authors: Mathew Anoop , Abraham Biju Jacob , Fischer Louie , Punnoose Eapen
Published: November 2014

Acute popliteal artery thrombosis is a rare complication following total knee arthroplasty (TKA), with sequelae including critical limb ischaemia and amputation. We report the case of a 54-year-old woman who developed acute popliteal artery thrombosis following TKA, presenting 2 weeks after the initial symptoms. While such cases have been traditionally managed with surgical thrombectomy or bypass grafting, percutaneous aspiration thrombectomy is an emerging alternative management strategy in the early postoperative period. However, in patients in whom intervention is delayed, the efficacy of percutaneous aspiration thrombectomy is not known. Our patient had complete resolution of thrombus following percutaneous thrombus aspiration, angioplasty and tirofiban administration. Prompt diagnosis and early percutaneous intervention may avert critical limb ischaemia in patients presenting with popliteal artery thrombosis following TKA.
Dystextia as a presentation of stroke
Authors: Al Hadidi Samer , Towfiq Basim , Bachuwa Ghassan
Published: November 2014

Cerebrovascular accident remains one of the major causes of morbidity and mortality worldwide. Understanding the presentation of this common disease will be of great benefit for early diagnosis and management. We report a newly recognised symptom of stroke where there is difficulty writing mobile phone texts, an entity called dystextia. This symptom was previously reported as a presentation of complex migraine and starts to be recognised in the symptomology of stroke. Our patient with this presentation was found to have ischaemic stroke secondary to carotid vascular disease which was operated and she had a complete resolution of her symptoms with returning to her baseline shortly after hospitalisation and before her vascular intervention.
Peripartum cardiomyopathy in a woman with preeclampsia with twin pregnancy
Authors: Umazume Takeshi , Yamada Takahiro , Yamada Satoshi , Minakami Hisanori
Published: November 2014

A 27-year-old nulliparous Japanese woman with twin pregnancy developed preeclampsia at gestational week (GW) 26. Cardiac function was checked regularly as women carrying twins with preeclampsia are expected to have increased risk of peripartum cardiomyopathy (PPCM). Although conventional parameters including blood pressure, proteinuria, platelet count and liver function did not indicate early delivery, gradual worsening of left ventricular ejection fraction (LVEF) to 44% and plasma brain-type natriuretic peptide level of 254 pg/mL suggested impending PPCM and a need for early delivery at GW 32. A nadir LVEF value of 35% on postpartum day (PPD) 3 followed by a value of 49% on PPD 32 was seen in this patient with PPCM. This case highlights the risk of PPCM among women with preeclampsia carrying twins and the role of pregnancy termination in the clinical course of PPCM.
A case–control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer
Authors: Keane M G , Horsfall L , Rait G , Pereira S P
Published: November 2014

Objectives

Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary.

Setting

The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK.

Participants

All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15 395 controls.

Primary and secondary outcome measures

The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis.

Results

In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11–27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC.

Conclusions

PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools.
Does a fall prevention educational programme improve knowledge and change exercise prescribing behaviour in health and exercise professionals? A study protocol for a randomised controlled trial
Authors: Tiedemann A , Sturnieks D L , Hill A-M , Lovitt L , Clemson L , Lord S R , Harvey L , Sherrington C
Published: November 2014

Introduction

Falling in older age is a serious and costly problem. At least one in three older people fall annually. Although exercise is recognised as an effective fall prevention intervention, low numbers of older people engage in suitable programmes. Health and exercise professionals play a crucial role in addressing fall risk in older adults. This trial aims to evaluate the effect of participation in a fall prevention educational programme, compared with a wait-list control group, on health and exercise professionals’ knowledge about fall prevention and the effect on fall prevention exercise prescription behaviour and confidence to prescribe the exercises to older people.

Methods and analysis

A randomised controlled trial involving 220 consenting health and exercise professionals will be conducted. Participants will be individually randomised to an intervention group (n=110) to receive an educational workshop plus access to internet-based support resources, or a wait-list control group (n=110). The two primary outcomes, measured 3 months after randomisation, are: (1) knowledge about fall prevention and (2) self-perceived change in fall prevention exercise prescription behaviour. Secondary outcomes include: (1) participants’ confidence to prescribe fall prevention exercises; (2) the proportion of people aged 60+ years seen by trial participants in the past month who were prescribed fall prevention exercise; and (3) the proportion of fall prevention exercises prescribed by participants to older people in the past month that comply with evidence-based guidelines. Outcomes will be measured with a self-report questionnaire designed specifically for the trial.

Ethics and dissemination

The trial protocol was approved by the Human Research Ethics Committee, The University of Sydney, Australia. Trial results will be disseminated via peer reviewed journals, presentations at international conferences and participants’ newsletters.

Trial registration number

Trial protocol was registered with the Australian and New Zealand Clinical Trials Registry (Number ACTRN12614000224628) on 3 March 2014.
Plant community development of Isle Royale’s moose-spruce savannas
Authors: Rotter Michael C. , Rebertus Alan J.
Published: November 2014

In Isle Royale National Park, heavy moose browsing over the past 100 years has suppressed the regeneration of many tree species, gradually resulting in a shift towards more open forests and savannas. By 1996, 16% of the forests at the southwestern end of Isle Royale had become savanna and another 20% of forests were starting to have canopy breakup. The changes in understory vegetation brought about by savanna formation have received little attention, even though the future of moose and wolf populations on Isle Royale is tied to these vegetation changes. This study examined the vegetation of savannas ranging in age (date since formation) from <10 years to 80 years to examine how the ground flora changes over time from initial forest canopy breakup, to extensive grassland, and finally to a zootic subclimax dubbed “moose-spruce savanna.” Ordination techniques were used to describe plant communities and to identify environmental variables that influence vegetation development. Nonparametric multiplicative regression was used to predict how these variables influenced individual plants and structure within the communities. Plant communities had a notable shift from forest herbs to ruderal species, especially non-native plants. This succession was influenced strongly by the underlying bedrock and hydrology-altering moisture regimes and plant communities. Picea glauca (Moench) Voss. and Poa pratensis L. competed in a dynamic inhibitory relationship. The former facilitated forest plants while the latter out-competed other plants and promoted open swards. These interactions are dramatically changing the character of Isle Royale’s upland plant communities and will have important trophic consequences for the island.
The importance of complete tissue homogenization for accurate stoichiometric measurement of myosin light chain phosphorylation in airway smooth muscle
Authors: Wang Lu , Paré Peter D. , Seow Chun Y.
Published: November 2014

The standard method for measuring the phosphorylation of the regulatory myosin light chain (MLC20) in smooth muscle is extraction of the light chain using a urea extraction buffer, urea–glycerol gel electrophoresis of the soluble portion of the extract (supernatant) and Western blot analysis. The undissolved portion of the tissue during extraction (the pellet) is usually discarded. Because the pellet contains a finite amount of MLC20, omission of the pellet could result in inaccurate measurement of MLC20 phosphorylation. In this study we compared the level of tracheal smooth muscle MLC20 phosphorylation in the supernatant alone, with that in the complete tissue homogenate (supernatant and pellet) using the standard method. The supernatant fraction showed the well-known double bands representing phosphorylated and un-phosphorylated MLC20. The dissolved pellet fraction showed varying amounts of un-phosphorylated and phosphorylated MLC20. There was a small but statistically significant overestimation of the percent MLC20 phosphorylation if the pellet was not taken into consideration. The overestimation was 7% ± 2% (mean ± SEM) (p < 0.05) in unstimulated muscle and 2% ± 1% (p < 0.05) in acetylcholine (10−6mol/L) stimulated muscle. This finding suggests that for accurate estimation of the stoichiometry of MLC20 phosphorylation it is necessary to consider the contribution from the pellet portion of the muscle tissue homogenate.
Photosynthetic pigments estimate diet quality in forage and feces of elk (Cervus elaphus)
Authors: Christianson D. , Creel S.
Published: November 2014

Understanding the nutritional dynamics of herbivores living in highly seasonal landscapes remains a central challenge in foraging ecology with few tools available for describing variation in selection for dormant versus growing vegetation. Here, we tested whether the concentrations of photosynthetic pigments (chlorophylls and carotenoids) in forage and feces of elk (Cervus elaphus L., 1785) were correlated with other commonly used indices of forage quality (digestibility, energy content, neutral detergent fiber (NDF), and nitrogen content) and diet quality (fecal nitrogen, fecal NDF, and botanical composition of the diet). Photosynthetic pigment concentrations were strongly correlated with nitrogen content, gross energy, digestibility, and NDF of elk forages, particularly in spring. Winter and spring variation in fecal pigments and fecal nitrogen was explained with nearly identical linear models estimating the effects of season, sex, and day-of-spring, although models of fecal pigments were consistently a better fit (r2adjusted = 0.379–0.904) and estimated effect sizes more precisely than models of fecal nitrogen (r2adjusted = 0.247–0.773). A positive correlation with forage digestibility, nutrient concentration, and (or) botanical composition of the diet implies fecal photosynthetic pigments may be a sensitive and informative descriptor of diet selection in free-ranging herbivores.
Giant energy harvesting potential in (100)-oriented 0.68PbMg1/3Nb2/3O3–0.32PbTiO3 with Pb(Zr0.3Ti0.7)O3/PbOx buffer layer and (001)-oriented 0.67PbMg1/3Nb2/3O3–0.33PbTiO3 thin films
Authors: Vats Gaurav , Kushwaha Himmat Singh , Vaish Rahul , Madhar Niyaz Ahamad , Shahabuddin Mohammed , Parakkandy Jafar M. , Batoo Khalid Mujasam
Published: November 2014

This work emphasis on the competence of (100)-oriented PMN–PT buffer layered (0.68 PbMg 1/3 Nb 2/3 O 3–0.32 PbTiO 3 with Pb ( Zr 0.3 Ti 0.7) O 3/ PbO x buffer layer) and (001)-oriented PMN–PT (0.67 PbMg 1/3 Nb 2/3 O 3–0.33 PbTiO 3) for low grade thermal energy harvesting using Olsen cycle. Our analysis (based on well-reported experiments in literature) reveals that these films show colossal energy harnessing possibility. Both the films are found to have maximum harnessable energy densities (PMN–PT buffer layered: 8 MJ/m3; PMN–PT: 6.5 MJ/m3) in identical ambient conditions of 30–150°C and 0–600 kV/cm. This energy harnessing plausibility is found to be nearly five times higher than the previously reported values to date.
A comparison of magnetic susceptibility measurement techniques and ferrimagnetic component analysis from recent sediments in Lake Pepin (USA)
Authors: Blumentritt Dylan J. , Lascu Ioan
Published: November 2014

Magnetic susceptibility (MS) is commonly measured on lake sediments and used as a proxy for clastic input and soil erosion, for correlating among cores in the same lake basin and aligning successive overlapping drives of the same core. There are several common techniques for measuring MS, each with its own advantages. Here we compare three such techniques measured on a sediment core from Lake Pepin: (a) loop-sensor MS logging on wet sediment of the intact core; (b) point-sensor MS logging on wet sediment of a split (lengthwise) core; and (c) discrete MS measurements of dried subsamples using a susceptibility bridge. To obtain further information about the origin of downcore MS variability, additional magnetic measurements were performed on discrete samples to model ferrimagnetic sedimentary components. Overall trends and individual features in MS curves agree reasonably well between techniques; however, the amplitude of local minima and maxima varies according to the technique used. All three MS techniques captured distinct events
c.
1900 and 1940, attributed to increases in allochthonous ferrimagnetic components. The ferrimagnetic particle flux has declined over the past half-century despite increasing sediment accumulation in Lake Pepin, suggesting a possible shift in sediment sources from fields to stream banks.
The Industrial Organization of the US Residential Mortgage Market
Authors: Stanton Richard , Walden Johan , Wallace Nancy
Published: November 2014

We show that the US residential single-family mortgage-origination market is highly concentrated once account is taken of the contractual coordination that arises from the correspondent- and warehouse-funding channels. We represent these channels as a network, using the flow of loans through three strata of the loan origination market: origination, aggregation, and securitization. We develop a network representation of the origination market and demonstrate that it is a small world, in that most nodes are close in the network. We then rank-order the interlinked aggregators and securitizers using ex post mortgage foreclosure rates as a proxy for performance. Our findings suggest that these significant interlinkages in the mortgage-origination network represent a previously underappreciated source of systemic risk. Many apparently atomistic mortgage underwriters are, in fact, coordinated to act in parallel because of their funding relationships with the large, too-big-to-fail bank holding companies.
Contingent Capital Instruments for Large Financial Institutions: A Review of the Literature
Authors: Flannery Mark J.
Published: November 2014

As the recent financial crisis unfolded, a new financial instrument—contingent convertible (coco) bonds—was widely considered as a mechanism for promptly recapitalizing overlevered financial institutions. Essentially, the conversion feature of coco bonds would replace supervisory discretion about banks’ capital adequacy with rules specifying when new equity was required. Academics and regulators conjectured that including sufficient cocos in a bank’s capital structure could substantially insulate taxpayers from private investment losses. This potential fostered a literature evaluating the effect of cocos on bank and financial sector stability, risk-taking incentives, and corporate governance. I review this literature and suggest that regulatory capital definitions should be expanded to include substantial amounts of carefully designed coco bonds as a partial substitute for common equity in regulatory capital requirements.
Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation
Authors: Chen Jinghong , Winston John H. , Fu Yu , Guptarak Jutatip , Jensen Kathryn L. , Shi Xuan-Zheng , Green Thomas A. , Sarna Sushil K.
Published: November 2014

Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depression-like behaviors. DSS rats developed anxiety- and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety- and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patch-clamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colon-projecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of Kv1.1 and Kv1.4 channels. Ulcerative colitis-like inflammation in rats induces anxiety- and depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage- and ligand-gated channels are associated with the induction of mood disorders following colon inflammation.
Role of renal sensory nerves in physiological and pathophysiological conditions
Authors: Kopp Ulla C.
Published: November 2014

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation.
Top-down modulation in human visual cortex predicts the stability of a perceptual illusion
Authors: Kloosterman Niels A. , Meindertsma Thomas , Hillebrand Arjan , van Dijk Bob W. , Lamme Victor A. F. , Donner Tobias H.
Published: November 2014

Conscious perception sometimes fluctuates strongly, even when the sensory input is constant. For example, in motion-induced blindness (MIB), a salient visual target surrounded by a moving pattern suddenly disappears from perception, only to reappear after some variable time. Whereas such changes of perception result from fluctuations of neural activity, mounting evidence suggests that the perceptual changes, in turn, may also cause modulations of activity in several brain areas, including visual cortex. In this study, we asked whether these latter modulations might affect the subsequent dynamics of perception. We used magnetoencephalography (MEG) to measure modulations in cortical population activity during MIB. We observed a transient, retinotopically widespread modulation of beta (12–30 Hz)-frequency power over visual cortex that was closely linked to the time of subjects' behavioral report of the target disappearance. This beta modulation was a top-down signal, decoupled from both the physical stimulus properties and the motor response but contingent on the behavioral relevance of the perceptual change. Critically, the modulation amplitude predicted the duration of the subsequent target disappearance. We propose that the transformation of the perceptual change into a report triggers a top-down mechanism that stabilizes the newly selected perceptual interpretation.
Serotonin differentially modulates Ca2+ transients and depolarization in a C. elegans nociceptor
Authors: Zahratka Jeffrey A. , Williams Paul D. E. , Summers Philip J. , Komuniecki Richard W. , Bamber Bruce A.
Published: November 2014

Monoamines and neuropeptides modulate neuronal excitability and synaptic strengths, shaping circuit activity to optimize behavioral output. In C. elegans, a pair of bipolar polymodal nociceptors, the ASHs, sense 1-octanol to initiate escape responses. In the present study, 1-octanol stimulated large increases in ASH Ca2+, mediated by L-type voltage-gated Ca2+ channels (VGCCs) in the cell soma and L-plus P/Q-type VGCCs in the axon, which were further amplified by Ca2+ released from intracellular stores. Importantly, 1-octanol-dependent aversive responses were not inhibited by reducing ASH L-VGCC activity genetically or pharmacologically. Serotonin, an enhancer of 1-octanol avoidance, potentiated 1-octanol-dependent ASH depolarization measured electrophysiologically, but surprisingly, decreased the ASH somal Ca2+ transients. These results suggest that ASH somal Ca2+ transient amplitudes may not always be predictive of neuronal depolarization and synaptic output. Therefore, although increases in steady-state Ca2+ can reliably indicate when neurons become active, quantitative relationships between Ca2+ transient amplitudes and neuronal activity may not be as straightforward as previously anticipated.