bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in competitive ability for the occupancy of shelters in triatomines
Authors: ZACHARIAS C. A. , MINOLI S. A. , MANRIQUE G. 
Published: February 2017

AbstractTriatomines (Hemiptera: Reduviidae: Triatominae) are nocturnal blood‐sucking insects. During daylight hours they remain in an akinetic state inside their shelters, whereas at dusk they become active and move outside. When they are outside their shelters during the photophase, triatomines are vulnerable to diurnal predators and the period just before dawn is critical to their survival. This work analyses the existence of competitive interactions involved in the occupancy of shelters by triatomines. Behavioural assays were performed in which nymphs of different stages, nutritional status or species were released in an experimental arena containing a space‐limited artificial shelter. The proportions of individuals occupying the shelter during the photophase were quantified to estimate the competitive abilities of each stage and species. Intraspecific comparisons showed higher levels of shelter occupancy for fourth over fifth instars and fed over unfed nymphs of Triatoma infestans. Interspecific comparisons showed higher rates of shelter occupancy for Triatoma sordida in comparison with T. infestans, and for T. infestans over Rhodnius prolixus. Arrival order was also relevant to determining shelter occupancy levels: early arrival was advantageous in comparison with later arrival. The study of intra‐ and interspecific competitive interactions for shelter occupancy provides relevant information about colonization and recolonization processes in the natural environments of triatomines.
A re‐appraisal of the conventional history of antibiosis and Penicillin
Authors: Arseculeratne S. N. , Arseculeratne G. 
Published: February 2017

SummaryThe popular perception of the history of antibiosis and penicillin is that Alexander Fleming was the sole researcher on penicillin. The literature, however, has documentation of preceding persons who reported definitively on these topics, from the late 19th century. Divergent reports on “firsts” in the discovery of antimicrobial activity of Penicillium and on the use of penicillin as a therapeutic agent, are present. This review adds knowledge from diverse sources, and restores historical priorities to the conventional story of Penicillin.
Changing Landscape for Peritoneal Dialysis: Optimizing Utilization
Authors: Schreiber Martin J. 
Published: February 2017

AbstractThe future growth of peritoneal dialysis (PD) will be directly linked to the shift in US healthcare to a value‐based payment model due to PD's lower yearly cost, early survival advantage over in‐center hemodialysis, and improved quality of life for patients treating their kidney disease in the home. Under this model, nephrology practices will need an increased focus on managing the transition from chronic kidney disease to end‐stage renal disease (ESRD), providing patient education with the aim of accomplishing modality selection and access placement ahead of dialysis initiation. Physicians must expand their knowledge base in home therapies and work toward increased technique survival through implementation of specific practice initiatives that highlight PD catheter placement success, preservation of residual renal function, consideration of incremental PD, and competence in urgent start PD. Avoidance of both early and late PD technique failures is also critical to PD program growth. Large dialysis organizations must continue to measure and improve quality metrics for PD, expand their focus beyond the sole provision of PD to holistic patient care, and initiate programs to reduce PD hospitalization rates and encourage physicians to consider the benefits of PD as an initial modality for appropriate patients. New and innovative strategies are needed to address the main reasons for PD technique failure, improve the connectivity of the patient in the home, leverage home biometric data to improve overall outcomes, and develop PD cycler devices that lower patient treatment burden and reduce both treatment fatigue and treatment‐dependent complications.
Outcomes and prognostic factors of surgical treatments for brachycephalic obstructive airway syndrome in 3 breeds
Authors: Liu Nai‐Chieh , Oechtering Gerhard U. , Adams Vicki J. , Kalmar Lajos , Sargan David R. , Ladlow Jane F. 
Published: February 2017

AbstractObjectiveTo determine prognostic indicators for the surgical treatment of brachycephalic obstructive airway syndrome (BOAS) and to compare the prognosis of 2 multilevel surgical procedures.Study DesignProspective clinical study.Sample PopulationClient‐owned pugs, French bulldogs, and bulldogs (n = 50).MethodsNoninvasive whole‐body barometric plethysmography (WBBP) was used to assess respiratory function before, 1 month and 6 months after upper airway corrective surgery. Postoperatively, BOAS indices (ie, ascending severity score generated from WBBP data, 0%‐100%) that equaled to or exceeded the cut‐off values of BOAS in the diagnostic models were considered to have a “poor prognosis.” A multivariate logistic regression was used to assess predictors for prognosis.ResultsThe median BOAS indices decreased after surgery (from 76% to 63%,P < .0001), although dogs with indices in this range would still be considered clinically affected. Age (odds ratios [OR] = 0.96, 95% confidence interval [CI]: 0.93‐0.99,P < .05), body condition (OR = 0.06, 95% CI: 0.01‐0.39,P < .01), laryngeal collapse (OR = 6.1, 95% CI: 1‐37.22,P < .05), and surgical techniques (OR = 7.94, 95% CI: 1.17‐54.01,P < .05) were associated with postoperative prognosis. The multivariate model suggests modified multilevel surgery (MMS) may have a better outcome than traditional multilevel surgery (TMS) (P = .034). The positive predictive value of the logistic model was 84% (95% CI: 68‐94%) and the area under the receiver operating characteristic (ROC) curve was 89% (95% CI: 78‐99%,P<.0001).ConclusionsYounger age, normal body condition, presence of laryngeal collapse, and treatment with TMS were negative prognostic factors after surgical treatment of BOAS. MMS is recommended, particularly in dogs with a higher probability of poor prognosis.
Social Innovation: A New Paradigm Of Innovation Outcome Strategy In The Context Of Strategic Knowledge Management Processes
Authors: Jali Muhamad Nizam , Abas Zakaria , Ariffin Ahmad Shabudin 
Published: February 2017

The current knowledge-innovation led economy requires a new paradigm of innovation to address critical issues, among others, namely: poor social health, poor living conditions, poor education systems, public income inequality, massive unemployment, poor economic growth and lack of new technological advances. Thus this paper explores the concept of social innovation in the context of strategic knowledge management processes. This paper suggested that social innovation is an outstanding solution in addressing social, economic and technological issues highlighted above, because the outcome of social innovation encompasses social, economic and technological payoffs concurrently. Strategic knowledge management processes, creates superior knowledge resource that is regarded as a new and novel solution that can be embedded into products, processes and services which in turn leads to the outcome of improving the quality of people’s life, stimulate economic growth and enhance technological advances i.e. social innovation. The old paradigm of innovation that refers to technological innovation is seen inadequate and obsolete in dealing with aforesaid social, economic and technological issues because it is very much focused and centred in fulfilling private needs. Therefore, social innovation and strategic knowledge management processes must be seriously considered by the policy makers, private sectors and also public institutions given the massive contribution that it might bring forward to many nations’ core aspirations.
Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation
Authors: Harris Shelley E. , De Blasio Miles J. , Davis Melissa A. , Kelly Amy C. , Davenport Hailey M. , Wooding F. B. Peter , Blache Dominique , Meredith David , Anderson Miranda , Fowden Abigail L. , Limesand Sean W. , Forhead Alison J. 
Published: February 2017

Key points
Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown.
Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin.
In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose‐dependent manner, while high concentrations of insulin and leptin stimulated proliferation.
The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life.
The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas.
AbstractDevelopment of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long‐term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T3), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T3 in a dose‐dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T3, insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life.
Lipid Signaling via Pkh1/2 Regulates Fungal CO
2
Sensing through the Kinase Sch9
Authors: Pohlers Susann , Martin Ronny , Krüger Thomas , Hellwig Daniela , Hänel Frank , Kniemeyer Olaf , Saluz Hans Peter , Van Dijck Patrick , Ernst Joachim F. , Brakhage Axel , Mühlschlegel Fritz A. , Kurzai Oliver 
Published: February 2017

ABSTRACT

Adaptation to alternating CO
2
concentrations is crucial for all organisms. Carbonic anhydrases—metalloenzymes that have been found in all domains of life—enable fixation of scarce CO
2
by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO
2
). Expression of
NCE103
is regulated in response to CO
2
availability. In
Saccharomyces cerevisiae
,
NCE103
is activated by the transcription factor ScCst6, and in
Candida albicans
and
Candida glabrata
, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an
S. cerevisiae
kinase/phosphatase mutant library for the ability to regulate
NCE103
in a CO
2
-dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the
sch9
Δ mutant strain showed deregulated
NCE103
expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9
in vitro
confirmed Sch9 as the Cst6 kinase. We could show that CO
2
-dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species
C. albicans
and
C. glabrata
. Deletion of
SCH9
homologues of both species impaired CO
2
-dependent regulation of
NCE103
expression, which indicates a conservation of the CO
2
adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO
2
adaptation to lipid signaling via Pkh1/2 in fungi.

IMPORTANCE
All living organisms have to cope with alternating CO
2
concentrations as CO
2
levels range from very low in the atmosphere (0.04%) to high (5% and more) in other niches, including the human body. In fungi, CO
2
is sensed via two pathways. The first regulates virulence in pathogenic yeast by direct activation of adenylyl cyclase. The second pathway, although playing a fundamental role in fungal metabolism, is much less understood. Here the transcription factor Cst6/Rca1 controls carbon homeostasis by regulating carbonic anhydrase expression. Upstream signaling in this pathway remains elusive. We identify Sch9 as the kinase controlling Cst6/Rca1 activity in yeast and demonstrate that this pathway is conserved in pathogenic yeast species, which highlights identified key players as potential pharmacological targets. Furthermore, we provide a direct link between adaptation to changing CO
2
conditions and lipid/Pkh1/2 signaling in yeast, thus establishing a new signaling cascade central to metabolic adaptation.
A novel molecular assay using hybridisation probes and melt curve analysis forCALRexon 9 mutation detection in myeloproliferative neoplasms
Authors: Keaney Thomas , O'Connor Louise , Krawczyk Janusz , Abdelrahman Moutaz A , Hayat Amjad H , Murray Margaret , O'Dwyer Michael , Percy Melanie , Langabeer Stehpen , Haslam Karl , Glynn Barry , Mullen Ciara , Keady Evelyn , Lahiff Sinéad , Smith Terry J 
Published: February 2017

AimsSomatic insertions/deletions in exon 9 of the calreticulin gene have been identified in patients with essential thrombocythemia and primary myelofibrosis. Over 55 mutations have been discovered, 80% of which consist of either type 1 52-bp deletion or type 2 5-bp insertion. Other mutations (types 3–5) in conjunction with types 1 and 2 account for >87% of identified mutations. The aim of this study was development of a rapid PCR-based assay using LightCycler Hybridisation Probes for the detection of type 1–5CALRmutations.MethodA real-time PCR assay using a novel HybProbe set was developed for use on the LightCycler 480 Instrument II. The acceptor probe was labelled with LC640 and Faststart DNA Master HybProbe kit was used for PCR reactions.ResultsAssay limit of detection was determined to be seven target copies with a probability of 95%. The specificity of the assay was determined by using synthetic constructs ofCALRwild-type andCALRmutation types 1–5 with no non-specific detection observed. Samples from 21 patients with essential thrombocythemia (ET) and 12 patients with primary myelofibrosis (PMF), together with 29 control samples from patients diagnosed with various conditions, were screened using the assay. Of these, 24 were found to have mutations inCALRexon 9, with the assay detecting 8 type 1 mutations, 12 type 2 mutations, 2 type 24 mutations, 1 type 20 mutation and 1 31-bp deletion.ConclusionsThe novel assay described has potential for application as a rapid, sensitive, high-throughput screening method in the clinical diagnostics setting.
Developmental nicotine exposure alters potassium currents in hypoglossal motoneurons of neonatal rat
Authors: Cholanian Marina , Wealing Jesse , Levine Richard B. , Fregosi Ralph F. 
Published: February 2017

We previously showed that nicotine exposure in utero and after birth via breast milk [developmental nicotine exposure (DNE)] is associated with many changes in the structure and function of hypoglossal motoneurons (XIIMNs), including a reduction in the size of the dendritic arbor and an increase in cell excitability. Interestingly, the elevated excitability was associated with a reduction in the expression of glutamate receptors on the cell body. Together, these observations are consistent with a homeostatic compensation aimed at restoring cell excitability. Compensation for increased cell excitability could also occur by changing potassium conductance, which plays a critical role in regulating resting potential, spike threshold, and repetitive spiking behavior. Here we test the hypothesis that the previously observed increase in the excitability of XIIMNs from DNE animals is associated with an increase in whole cell potassium currents. Potassium currents were measured in XIIMNs in brain stem slices derived from DNE and control rat pups ranging in age from 0 to 4 days by whole cell patch-clamp electrophysiology. All currents were measured after blockade of action potential-dependent synaptic transmission with tetrodotoxin. Compared with control cells, XIIMNs from DNE animals showed significantly larger transient and sustained potassium currents, but this was observed only under conditions of increased cell and network excitability, which we evoked by raising extracellular potassium from 3 to 9 mM. These observations suggest that the larger potassium currents in nicotine-exposed neurons are an important homeostatic compensation that prevents “runaway” excitability under stressful conditions, when neurons are receiving elevated excitatory synaptic input. NEW & NOTEWORTHY Developmental nicotine exposure is associated with increased cell excitability, which is often accompanied by compensatory changes aimed at normalizing excitability. Here we show that whole cell potassium currents are also increased in hypoglossal motoneurons from nicotine-exposed neonatal rats under conditions of increased cell and network excitability. This is consistent with a compensatory response aimed at preventing instability under conditions in which excitatory synaptic input is high and is compatible with the concept of homeostatic plasticity.
Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane–Based Chemotherapy for Early-Stage Breast Cancer
Authors: Shachar Shlomit Strulov , Deal Allison M. , Weinberg Marc , Williams Grant R. , Nyrop Kirsten A. , Popuri Karteek , Choi Seul Ki , Muss Hyman B. 
Published: February 2017

Abstract
Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane–based chemotherapy.
Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).
Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23–75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (&lt;1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05).
Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537–43. ©2017 AACR.
Stabilization of Notch1 by the Hsp90 Chaperone is Crucial for T-Cell Leukemogenesis
Authors: Wang Zhaojing , Hu Yufeng , Xiao Daibiao , Wang Jingchao , Liu Chuntao , Xu Yisheng , Shi Xiaomeng , Jiang Peng , Huang Liang , Li Peng , Liu Hudan , Qing Guoliang 
Published: February 2017

Abstract
Purpose: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the current study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity.
Experimental Design: We employed immunoaffinity purification to identify ICN1-associating partner(s) and used coimmunoprecipitation to verify the endogenous protein interaction. Pharmacologic or short hairpin RNA–mediated inhibition was applied in loss-of-function assays to assess the role of tentative binding partner(s) in modulating ICN1 protein stability as well as affecting T-ALL cell expansion in vitro and in vivo. Mechanistic analysis involved protein degradation and polyubiquitination assays.
Results: We identify the Hsp90 chaperone as a direct ICN1-binding partner essential for its stabilization and transcriptional activity. T-ALL cells exhibit constitutive endogenous ICN1–Hsp90 interaction and Hsp90 depletion markedly decreases ICN1 levels. The Hsp90-associated E3 ubiquitin ligase Stub1 mediates the ensuring proteasome-dependent ICN1 degradation. Administration of 17-AAG or PU-H71, two distinct Hsp90 inhibitors, depletes ICN1, inhibits T-ALL cell proliferation, and triggers dramatic apoptotic cell death. Systemic treatment with PU-H71 reduces ICN1 expression and profoundly inhibits murine T-ALL allografts as well as human T-ALL xenografts.
Conclusions: Our findings demonstrate Hsp90 blockade leads to ICN1 destabilization, providing an alternative strategy to antagonize oncogenic Notch1 signaling with Hsp90-selective inhibitors. Clin Cancer Res; 23(14); 3834–46. ©2017 AACR.