bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first report of the potentially harmful diatom Pseudo‐nitzschia caciantha from Australian coastal waters
Authors: Ajani Penelope , Kim Jin H. , Han Myung Soo , Murray Shauna A. 
Published: September 2016

SUMMARYThe diatom Pseudo‐nitzschia is a significant component of coastal waters worldwide and a producer of the potent neurotoxin, domoic acid. Sixteen species belonging to this genus have been reported from Australian waters, but the potentially toxic species
P. caciantha
has not been previously known from this region. Two clonal strains of
P. caciantha
were isolated from Coogee Beach, south‐east Australia, and the morphological, molecular and toxicological evidence for this species delineation were examined using light and transmission electron microscopy, phylogenetic analysis based on sequences of the second internal transcribed spacer and domoic acid production as measured by liquid chromatography–mass spectrometry. The results unambiguously confirmed that these isolates are the potentially toxic species
P. caciantha
, being only the second report of this species in the Southern Hemisphere. The potential for further hidden
Pseudo‐nitzschia
diversity in these waters is considerable.
Does Increasing Ethnic Representativeness Reduce Police Misconduct?
Authors: Hong Sounman 
Published: September 2016

Abstract
This article examines whether representative bureaucracy improves organizational integrity using evidence from English and Welsh police forces that implemented ambitious targets to increase the share of ethnic minority officers during 2000–2010. The evidence shows an association between an increase in police force ethnic minority representation and a subsequent reduction in police misconduct. An increase in representativeness is also shown to be associated with a decrease in the share of black complainants but not with a change in the ethnicity of those subject to complaints. This evidence suggests that diversifying a bureaucratic workforce to reflect the community it serves may effectively catalyze bureaucratic integrity. In turn, improved organizational integrity influences bureaucrats’ attitudes and behaviors toward minority citizens, resulting in greater satisfaction among minority constituents. Representative bureaucracy may be an effective internal means of controlling administrative power for the good of the citizenry.
Social Entrepreneurship, Entrepreneurship, Collectivism, and Everything in Between: Prototypes and Continuous Dimensions
Authors: Schneider Aaron 
Published: September 2016

AbstractThis article uses prototypes and continuous dimensions to place social entrepreneurship in relation to other organizational forms. This approach is more fruitful than classical attempts to stipulate essential characteristics and establish boundaries. A prototype and continuous dimension approach allows consideration of the way social entrepreneurship functions similarly to and differently from related concepts, such as traditional entrepreneurship, public social services, and collectivism. These categories can be distinguished according to the degree to which control over the way value is created, allocated, and distributed occurs socially or entrepreneurially. This approach offers the additional advantage of making the concept more precise, as subdimensions clarify the relationship to practices such as volunteerism and theories such as antidevelopment. By mapping the network of organizational forms in which social entrepreneurship can be located, we can focus on the viability and advisability of different ways of solving social problems.
Barriers to HIV Cure
Authors: Stein J. , Storcksdieck genannt Bonsmann M. , Streeck H. 
Published: September 2016

AbstractSince the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)‐related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers.
Dynamic Global Linkages of the BRICS Stock Markets with the United States and Europe Under External Crisis Shocks: Implications for Portfolio Risk Forecasting
Authors: Hammoudeh Shawkat , Kang Sang Hoon , Mensi Walid , Nguyen Duc Khuong 
Published: September 2016

AbstractCrisis shocks often lead to changes in the interdependence across stock markets and thus affect risk assessment and management. This paper investigates the extent to which the global financial crisis of 2008–09, which was triggered by the US subprime crisis in 2007, and the European debt crisis that started at the end of 2009, affects the interdependence of the leading emerging markets of the BRICS countries with those of the United States and Europe. Our empirical analysis makes use of the FIAPARCH model combined with the Dynamic Equicorrelation (DECO‐FIAPARCH), which allows for the estimation of market linkage for a large group of countries as a whole, while controlling for asymmetric volatility and long memory. The results reveal the presence of important changes in the time‐varying linkages of the BRICS stock markets with the US and European ones. In particular, the average linkages have significantly been higher between 2007 and the first half of 2012 than the remaining part of the sample, and there is also evidence of a structural change around the Lehman Brothers collapse. We also show the effects of these stylised facts on portfolio risk assessment and forecasting.
Techniques and Indications for Intraoperative Ultrasound in Horses
Authors: Stack John D. , Cousty Matthieu , Sanders Ruth , David Florent 
Published: September 2016

ObjectiveTo describe our experience using intraoperative ultrasound for various conditions in horses.Study DesignRetrospective case series.Sample PopulationHorses (n=113).MethodsMedical records including surgical reports at 2 equine hospitals (2007–2013) were reviewed to identify ultrasound‐assisted surgeries. The diagnosis, reasons for using intraoperative ultrasound, the technique employed, and the surgical procedure performed (e.g., synovial endoscopy, cut‐down, resection, dissection, curettage, and implant placement/removal) were recorded for each surgery. Intraoperative ultrasound was used to mark the optimal site for skin incision or to guide instrumentation within the tissues. The incision site was marked on the skin with staples. Depth soundings were taken on the ultrasound, using the caliper‐measuring tool to facilitate dissection. For each surgery, the primary specialist surgeon (ACVS or ECVS) retrospectively recorded whether intraoperative ultrasound was helpful, unhelpful, or harmful.ResultsIntraoperative ultrasound was rated helpful in 105/113 (93%) of surgeries, unhelpful in 7/113 (6%), and harmful in 1/113 (1%) of surgeries.ConclusionIntraoperative ultrasound can be a useful adjunct to surgical techniques for various conditions in horses.
Development of a high‐throughput method for real‐time assessment of cellular metabolism in intact long skeletal muscle fibre bundles
Authors: Li Rui , Steyn Frederik J. , Stout Michael B. , Lee Kevin , Cully Tanya R. , Calderón Juan C. , Ngo Shyuan T. 
Published: September 2016

Key points
We developed a method that allows for real‐time assessment of cellular metabolism in isolated, intact long skeletal muscle fibre bundles from adult mice.
This method can be used to study changes in mitochondrial function and fuel utilisation in live skeletal muscle fibre bundles.
Our method enables flexibility in experimental design and high‐throughput assessment of mitochondrial parameters in isolated skeletal muscle fibre bundles.
Extensor digitorum longus (EDL) fibre bundles obtained from chronic high‐fat diet fed mice had lower basal oxygen consumption under FCCP‐induced maximal respiration, when compared to control chow‐fed mice.
EDL fibre bundles obtained from chronic high‐fat diet fed mice had enhanced mitochondrial oxidation capacity under FCCP‐induced maximal respiration, when compared to control chow‐fed mice.
AbstractMetabolic dysfunction in skeletal muscle contributes to the aetiology and development of muscle diseases and metabolic diseases. As such, assessment of skeletal muscle cellular bioenergetics provides a powerful means to understand the role of skeletal muscle metabolism in disease and to identify possible therapeutic targets. Here, we developed a method that allows for the real‐time assessment of cellular respiration in intact skeletal muscle fibre bundles obtained from the extensor digitorum longus (EDL) muscle of adult mice. Using this method, we assessed the contribution of ATP turnover and proton leak to basal mitochondrial oxygen consumption rate (OCR). Our data demonstrate that the mitochondria in EDL fibres are loosely coupled. Moreover, in the presence of carbonyl cyanide‐p‐trifluoromethoxyphenylhydrazone (FCCP), we show that palmitate exposure induced comparable peak OCR and higher total OCR in EDL fibre bundles when compared to pyruvate exposure, suggesting that fatty acids might be a more sustainable fuel source for skeletal muscle when mitochondria are driven to maximal respiration. Application of this method to EDL fibre bundles obtained from chronic high‐fat diet fed mice revealed lower basal OCR and enhanced mitochondrial oxidation capacity in the presence of FCCP when compared to the chow‐diet fed control mice. By using a 96‐well microplate format, our method provides a flexible and efficient platform to investigate mitochondrial parameters of intact skeletal muscle fibres obtained from adult mice.
Obesity‐induced lymphatic dysfunction is reversible with weight loss
Authors: Nitti Matthew D. , Hespe Geoffrey E. , Kataru Raghu P. , García Nores Gabriela D. , Savetsky Ira L. , Torrisi Jeremy S. , Gardenier Jason C. , Dannenberg Andrew J. , Mehrara Babak J. 
Published: September 2016

Key points
Obesity induces lymphatic leakiness, decreases initial lymphatic vessel density, impairs collecting vessel pumping and decreases transport of macromolecules.
Obesity results in perilymphatic inducible nitric oxide synthase (iNOS) expression and accumulation of T cells and macrophages.
Deleterious effects of obesity on the lymphatic system correlate with weight gain.
Weight loss restores lymphatic function in obese animals and decreases perilymphatic iNOS and inflammatory cell accumulation.
AbstractAlthough clinical and experimental studies have shown that obesity results in lymphatic dysfunction, it remains unknown whether these changes are permanent or reversible with weight loss. In the current study, we used a mouse model of diet‐induced obesity to identify putative cellular mechanisms of obesity‐induced lymphatic dysfunction, determine whether there is a correlation between these deleterious effects and increasing weight gain, and finally examine whether lymphatic dysfunction is reversible with diet‐induced weight loss. We report that obesity is negatively correlated with cutaneous lymphatic collecting vessel pumping rate (r = –0.9812, P < 0.0005) and initial lymphatic vessel density (r = –0.9449, P < 0.005). In addition, we show a significant positive correlation between weight gain and accumulation of perilymphatic inflammatory cells (r = 0.9872, P < 0.0005) and expression of inducible nitric oxide synthase (iNOS; r = 0.9986, P < 0.0001). Weight loss resulting from conversion to a normal chow diet for 8 weeks resulted in more than a 25% decrease in body weight and normalized cutaneous lymphatic collecting vessel pumping rate, lymphatic vessel density, lymphatic leakiness, and lymphatic macromolecule clearance (all P < 0.05). In addition, weight loss markedly decreased perilymphatic inflammation and iNOS expression. Taken together, our findings show that obesity is linearly correlated with lymphatic dysfunction, perilymphatic inflammation and iNOS expression, and that weight loss via dietary modification effectively reverses these deleterious effects.
Development of a Novel Collagen Wound Model To Simulate the Activity and Distribution of Antimicrobials in Soft Tissue during Diabetic Foot Infection
Authors: Price Bianca L. , Lovering Andrew M. , Bowling Frank L. , Dobson Curtis B. 
Published: September 2016

ABSTRACTDiabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robustPseudomonas aeruginosabiofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistantStaphylococcus aureusbiofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs.
In Vitro
Activity of Solithromycin against Bordetella pertussis, an Emerging Respiratory Pathogen
Authors: Hardy Dwight J. , Vicino David , Fernandes Prabhavathi 
Published: September 2016

ABSTRACT

There has been an increase in the number of pertussis cases reported since the introduction of the acellular pertussis vaccine. While children that present with pertussis have a characteristic whooping cough, adults can simply have a persistent, nonspecific cough and remain undiagnosed. Macrolide antibiotics, such as azithromycin, are the currently recommended treatment for pertussis. Solithromycin is a new macrolide and the first fluoroketolide with broad activity against a wide spectrum of bacterial pathogens and has completed clinical development for community-acquired bacterial pneumonia. This study reports the potent
in vitro
activity of solithromycin against a collection of recent isolates of
Bordetella pertussis
.
PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally
Authors: Graci Jason D. , Jung Stephen P. , Pichardo John , Lahser Frederick , Tong Xiao , Gu Zhengxian , Colacino Joseph M. 
Published: September 2016

ABSTRACT

PTC725 is a small molecule NS4B-targeting inhibitor of hepatitis C virus (HCV) genotype (gt) 1 RNA replication that lacks activity against HCV gt2. We analyzed the Los Alamos HCV sequence database to predict susceptible/resistant HCV gt's according to the prevalence of known resistance-conferring amino acids in the NS4B protein. Our analysis predicted that HCV gt3 would be highly susceptible to the activity of PTC725. Indeed, PTC725 was shown to be active against a gt3 subgenomic replicon with a 50% effective concentration of ∼5 nM.
De novo
resistance selection identified mutations encoding amino acid substitutions mapping to the first predicted transmembrane region of NS4B, a finding consistent with results for PTC725 and other NS4B-targeting compounds against HCV gt1. This is the first report of the activity of an NS4B targeting compound against HCV gt3. In addition, we have identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region.
mgrB
Mutations Mediating Polymyxin B Resistance in Klebsiella pneumoniae Isolates from Rectal Surveillance Swabs in Brazil
Authors: Aires Caio Augusto Martins , Pereira Polyana Silva , Asensi Marise Dutra , Carvalho-Assef Ana Paula D'Alincourt 
Published: September 2016

ABSTRACT

We aimed to investigate polymyxin B (PMB) resistance and its molecular mechanisms in 126
Klebsiella pneumoniae
isolates from rectal swabs in Brazil. Ten isolates exhibited PMB resistance with interruption of
mgrB
gene by insertion sequences or missense mutations. Most of the PMB-resistant isolates harbored
bla
KPC-2
(
n
= 8) and belonged to clonal complex 258 (CC258) (
n
= 7). These results highlight the importance of monitoring the spread of polymyxin-resistant bacteria in hospitals, since few options remain to treat multidrug-resistant isolates.
Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin
Authors: Tronnet Sophie , Garcie Christophe , Rehm Nadine , Dobrindt Ulrich , Oswald Eric , Martin Patricia 
Published: September 2016

ABSTRACT

The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by iron availability, we hypothesized that iron could also modulate the production of colibactin through the transcriptional regulation of
clbA
. This study revealed an increased transcription of
clbA
under iron-limiting conditions and a decrease of
clbA
expression in iron-rich media. We demonstrate that
clbA
transcription is regulated by both the ferric uptake regulator (Fur) and the small regulatory noncoding RNA RyhB. We evidenced that the regulation of the transcription of
clbA
by Fur and RyhB leads to the regulation of colibactin production. This work highlights the complex mechanism of regulation of an important virulence factor by the two major regulators of bacterial iron homeostasis, making iron a key environmental factor contributing to bacterial virulence and carcinogenesis.
Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster
Authors: Zhang Wenlong , Zhang Naisheng , Xie Xufeng , Guo Jian , Jin Xuemin , Xue Feng , Ding Zhuang , Cao Yongguo 
Published: September 2016

ABSTRACT

Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after
Leptospira interrogans
serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.
Spontaneous Reversions of an Evolutionary Trait Loss Reveal Regulators of a Small RNA That Controls Multicellular Development in Myxobacteria
Authors: Yu Yuen-Tsu N. , Kleiner Manuel , Velicer Gregory J. 
Published: September 2016

ABSTRACT

Lost traits can reevolve, but the probability of trait reversion depends partly on a trait's genetic complexity. Myxobacterial fruiting body development is a complex trait controlled by the small RNA (sRNA) Pxr, which blocks development under conditions of nutrient abundance. In developmentally proficient strains of
Myxococcus xanthus
, starvation relaxes the inhibition by Pxr, thereby allowing development to proceed. In contrast, the lab-evolved strain OC does not develop because it fails to relay an early starvation signal that alleviates inhibition by Pxr. A descendant of OC, strain PX, previously reevolved developmental proficiency via a mutation in
pxr
that inactivates its function. A single-colony screen was used to test whether reversion of OC to developmental proficiency occurs only by mutation of
pxr
or might also occur through alternative regulatory loci. Five spontaneous mutants of OC that exhibited restored development were isolated, and all five showed defects in Pxr synthesis, structure, or processing, including one that incurred an eight-nucleotide deletion in
pxr
. Two mutations occurred in the σ
54
response regulator (RR) gene
MXAN_1078
(named
pxrR
here), immediately upstream of
pxr
. PxrR was found to positively regulate
pxr
transcription, presumably via the σ
54
promoter of
pxr
. Two other mutations were identified in a histidine kinase (HK) gene (
MXAN_1077
; named
pxrK
here) immediately upstream of
pxrR
. Evolutionarily, the rate of trait restoration documented in this study suggests that reversion of social defects in natural microbial populations may be common. Molecularly, these results suggest a mechanism by which the regulatory functions of an HK-RR two-component signaling system and an sRNA are integrated to control initiation of myxobacterial development.

IMPORTANCE
Many myxobacteria initiate a process of multicellular fruiting body development upon starvation, but key features of the regulatory network controlling the transition from growth to development remain obscure. Previous work with
Myxococcus xanthus
identified the first small RNA (sRNA) regulator (Pxr) known to serve as a gatekeeper in this life history transition, as it blocks development when nutrients are abundant. In the present study, a screen for spontaneous mutants of
M. xanthus
was developed that revealed a two-component system operon (encoding a histidine kinase and a σ
54
response regulator) associated with the production and processing of Pxr sRNA. This discovery broadens our knowledge of early developmental gene regulation and also represents an evolutionary integration of two-component signaling and sRNA gene regulation to control a bacterial social trait.