bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rice responses to rising temperatures – challenges, perspectives and future directions
Authors: JAGADISH S. V. K. , MURTY M. V. R. , QUICK W. P. 
Published: August 2014

AbstractPhenotypic plasticity in overcoming heat stress‐induced damage across hot tropical rice‐growing regions is predominantly governed by relative humidity. Expression of transpiration cooling, an effective heat‐avoiding mechanism, will diminish with the transition from fully flooded paddies to water‐saving technologies, such as direct‐seeded and aerobic rice cultivation, thus further aggravating stress damage. This change can potentially introduce greater sensitivity to previously unaffected developmental stages such as floral meristem (panicle) initiation and spikelet differentiation, and further intensify vulnerability at the known sensitive gametogenesis and flowering stages. More than the mean temperature rise, increased variability and a more rapid increase in nighttime temperature compared with the daytime maximum present a greater challenge. This review addresses (1) the importance of vapour pressure deficit under fully flooded paddies and increased vulnerability of rice production to heat stress or intermittent occurrence of combined heat and drought stress under emerging water‐saving rice technologies; (2) the major disconnect with high night temperature response between field and controlled environments in terms of spikelet sterility; (3) highlights the most important mechanisms that affect key grain quality parameters, such as chalk formation under heat stress; and finally (4), we model and estimate heat stress‐induced spikelet sterility taking South Asia as a case study.
The ratios of urinary β2‐microglobulin and NAG to creatinine vary with age in children
Authors: Hibi Yoshiko , Uemura Osamu , Nagai Takuhito , Yamakawa Satoshi , Yamasaki Yasuhito , Yamamoto Masaki , Nakano Masaru , Kasahara Katsuaki 
Published: August 2014

AbstractBackgroundAlthough urinary biochemical markers can be assessed by their ratio to urinary creatinine (U‐Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary β‐2‐microglobulin (U‐β2MG), N‐acetyl‐β‐d‐glucosaminidase (U‐NAG), calcium (U‐Ca) and protein (U‐Pr) concentration to those of U‐Cr in children.MethodsFifty‐seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1–4, 5–9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U‐Cr values; and our standardized metric, namely 100‐fold the ratio of serum Cr to U‐Cr concentration; and the relationship of each of these to age was determined.ResultsThe ratios of U‐β2MG, U‐NAG and U‐Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U‐Pr.ConclusionsThe ratios of urinary markers of tubular function, including U‐β2MG, U‐NAG and U‐Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U‐Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.
-invisibility and a class of local similarity groups
Authors: Sauer Roman , Thumann Werner 
Published: August 2014

AbstractIn this note we show that the members of a certain class of local similarity groups are ${l}^{2}$-invisible, i.e. the (non-reduced) group homology of the regular unitary representation vanishes in all degrees. This class contains groups of type ${F}_{\infty }$, e.g. Thompson’s group $V$ and Nekrashevych–Röver groups. They yield counterexamples to a generalized zero-in-the-spectrum conjecture for groups of type ${F}_{\infty }$.
Mycobacterium tuberculosis Alters the Metalloprotease Activity of the COP9 Signalosome
Authors: Danelishvili Lia , Babrak Lmar , Rose Sasha J. , Everman Jamie , Bermudez Luiz E. 
Published: August 2014

ABSTRACTInhibition of apoptotic death of macrophages byMycobacterium tuberculosisrepresents an important mechanism of virulence that results in pathogen survival bothin vitroandin vivo. To identifyM. tuberculosisvirulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of mutants in human macrophages, and anM. tuberculosisclone with a nonfunctional Rv3354 gene was identified as incompetent to suppress apoptosis. Here, we show that the Rv3354 gene encodes a protein kinase that is secreted within mononuclear phagocytic cells and is required forM. tuberculosisvirulence. The Rv3354 effector targets the metalloprotease (JAMM) domain within subunit 5 of the COP9 signalosome (CSN5), resulting in suppression of apoptosis and in the destabilization of CSN function and regulatory cullin-RING ubiquitin E3 enzymatic activity. Our observation suggests that alteration of the metalloprotease activity of CSN by Rv3354 possibly prevents the ubiquitin-dependent proteolysis ofM. tuberculosis-secreted proteins.IMPORTANCEMacrophage protein degradation is regulated by a protein complex called a signalosome. One of the signalosomes associated with activation of ubiquitin and protein labeling for degradation was found to interact with a secreted protein fromM. tuberculosis, which binds to the complex and inactivates it. The interference with the ability to inactivate bacterial proteins secreted in the phagocyte cytosol may have crucial importance for bacterial survival within the phagocyte.
Genome-Wide Mutant Fitness Profiling Identifies Nutritional Requirements for Optimal Growth of Yersinia pestis in Deep Tissue
Authors: Palace Samantha G. , Proulx Megan K. , Lu Shan , Baker Richard E. , Goguen Jon D. 
Published: August 2014

ABSTRACT

Rapid growth in deep tissue is essential to the high virulence of
Yersinia pestis
, causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the
Y. pestis
genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent
Y. pestis
. Each mutant in the library was assayed for its ability to proliferate
in vitro
on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in
Y. pestis
virulence. We further examined the fitness defects of strains carrying mutations in two such genes—encoding a branched-chain amino acid importer (
brnQ
) and a glucose importer (
ptsG
)—both
in vivo
and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about
Y. pestis
pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes.

IMPORTANCE
Our understanding of the functions required by bacteria to grow in deep tissues is limited, in part because most growth studies of pathogenic bacteria are conducted on laboratory media that do not reflect conditions prevailing in infected animal tissues. Improving our knowledge of this aspect of bacterial biology is important as a potential pathway to the development of novel therapeutics.
Yersinia pestis
, the plague bacterium, is highly virulent due to its rapid dissemination and growth in deep tissues, making it a good model for discovering bacterial adaptations that promote rapid growth during infection. Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of
Y. pestis in vivo
that were not previously known to be important. Most of these functions are needed to acquire or synthesize nutrients. Interference with these critical nutrient acquisition pathways may be an effective strategy for designing novel antibiotics and vaccines.
Annexin A2 Mediates Mycoplasma pneumoniae Community-Acquired Respiratory Distress Syndrome Toxin Binding to Eukaryotic Cells
Authors: Somarajan Sudha R. , Al-Asadi Fadi , Ramasamy Kumaraguruparan , Pandranki Lavanya , Baseman Joel B. , Kannan T. R. 
Published: August 2014

ABSTRACT

Mycoplasma pneumoniae
synthesizes a novel human surfactant protein A (SP-A)-binding cytotoxin, designated community-acquired respiratory distress syndrome (CARDS) toxin, that exhibits ADP-ribosylating and vacuolating activities in mammalian cells and is directly linked to a range of acute and chronic airway diseases, including asthma. In our attempt to detect additional CARDS toxin-binding proteins, we subjected the membrane fraction of human A549 airway cells to affinity chromatography using recombinant CARDS toxin as bait. A 36-kDa A549 cell membrane protein bound to CARDS toxin and was identified by time of flight (TOF) mass spectroscopy as annexin A2 (AnxA2) and verified by immunoblotting with anti-AnxA2 monoclonal antibody. Dose-dependent binding of CARDS toxin to recombinant AnxA2 reinforced the specificity of the interaction, and further studies revealed that the carboxy terminus of CARDS toxin mediated binding to AnxA2. In addition, pretreatment of viable A549 cells with anti-AnxA2 monoclonal antibody or AnxA2 small interfering RNA (siRNA) reduced toxin binding and internalization. Immunofluorescence analysis of CARDS toxin-treated A549 cells demonstrated the colocalization of CARDS toxin with cell surface-associated AnxA2 upon initial binding and with intracellular AnxA2 following toxin internalization. HepG2 cells, which express low levels of AnxA2, were transfected with a plasmid expressing AnxA2 protein, resulting in enhanced binding of CARDS toxin and increased vacuolization. In addition, NCI-H441 cells, which express both AnxA2 and SP-A, upon AnxA2 siRNA transfection, showed decreased binding and subsequent vacuolization. These results indicate that CARDS toxin recognizes AnxA2 as a functional receptor, leading to CARDS toxin-induced changes in mammalian cells.

IMPORTANCE
Host cell susceptibility to bacterial toxins is usually determined by the presence and abundance of appropriate receptors, which provides a molecular basis for toxin target cell specificities. To perform its ADP-ribosylating and vacuolating activities, community-acquired respiratory distress syndrome (CARDS) toxin must bind to host cell surfaces via receptor-mediated events in order to be internalized and trafficked effectively. Earlier, we reported the binding of CARDS toxin to surfactant protein A (SP-A), and here we show how CARDS toxin uses an alternative receptor to execute its pathogenic properties. CARDS toxin binds selectively to annexin A2 (AnxA2), which exists both on the cell surface and intracellularly. Since AnxA2 regulates membrane dynamics at early stages of endocytosis and trafficking, it serves as a distinct receptor for CARDS toxin binding and internalization and enhances CARDS toxin-induced vacuolization in mammalian cells.
Efficacy and safety of linagliptin in Hispanic/Latino patients with type 2 diabetes mellitus: a pooled analysis from six randomized placebo-controlled phase 3 trials
Authors: Davidson Jaime A , Lajara Rosemarie , Aguilar Richard B , Mattheus Michaela , Woerle Hans-Juergen , von Eynatten Maximilian 
Published: August 2014

ObjectiveThe number of individuals diagnosed with type 2 diabetes mellitus is expected to rise disproportionately in Hispanic/Latino populations. We therefore aimed to assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin specifically in Hispanic/Latino patients with type 2 diabetes mellitus.Research design and methodsData from 745 patients who self-identified their ethnicity as Hispanic or Latino were pooled from six randomized, placebo-controlled phase 3 trials. Participants received linagliptin (5 mg/day) or placebo as monotherapy, or in combination with other oral antidiabetes drugs for 18 or 24 weeks.ResultsThe placebo-adjusted mean change (95% CI) in glycated hemoglobin from baseline (mean 8.2%) was –0.63% (–0.77 to –0.48; p<0.0001) at week 18, and –0.58% (–0.74 to –0.42; p<0.0001) at week 24. The placebo-adjusted mean change (95% CI) in fasting plasma glucose from baseline was −11.7 mg/dL (−19.3 to –4.0; p=0.0028) at week 18 and –14.1 mg/dL (–22.0 to –6.3; p=0.0004) at week 24. Hypoglycemia incidence was 17.4% with linagliptin and 21% with placebo. In patients not receiving concomitant sulfonylurea, the hypoglycemia incidence was 10.1% with linagliptin and 19.4% with placebo. The overall incidence of adverse events (AEs), drug-related AEs, and serious AEs with linagliptin was similar to placebo (AEs 67.6% vs 68.9%; drug-related AEs 15.1% vs 18.7%; serious AEs 3.6% vs 3.0%). The mean body weight remained unchanged in both groups.ConclusionsIn Hispanic/Latino patients with inadequately controlled type 2 diabetes mellitus, linagliptin provided clinically meaningful improvements in glycemic control without weight gain or increased risk of hypoglycemia.
Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents
Authors: Barnard Katharine D , Wysocki Tim , Allen Janet M , Elleri Daniela , Thabit Hood , Leelarathna Lalantha , Gulati Arti , Nodale Marianna , Dunger David B , Tinati Tannaze , Hovorka Roman 
Published: August 2014

ObjectiveTo explore the experiences of adolescents with type 1 diabetes mellitus (T1DM) and their parents taking part in an overnight closed loop study at home, using qualitative and quantitative research methods.Research design and methodsAdolescents aged 12–18 years on insulin pump therapy were recruited to a pilot closed loop study in the home setting. Following training on the use of a study insulin pump and continuous glucose monitoring (CGM), participants were randomized to receive either real-time CGM combined with overnight closed loop or real-time CGM alone followed by the alternative treatment for an additional 21 days with a 2–3-week washout period in between study arms. Semistructured interviews were performed to explore participants’ perceptions of the impact of the closed loop technology. At study entry and again at the end of each 21-day crossover arm of the trial, participants completed the Diabetes Technology Questionnaire (DTQ) and Hypoglycemia Fear Survey (HFS; also completed by parents).Results15 adolescents and 13 parents were interviewed. Key positive themes included reassurance/peace of mind, confidence, ‘time off’ from diabetes demands, safety, and improved diabetes control. Key negative themes included difficulties with calibration, alarms, and size of the devices. DTQ results reflected these findings. HFS scores were mixed.ConclusionsClosed loop insulin delivery represents cutting-edge technology in the treatment of T1DM. Results indicate that the psychological and physical benefits of the closed loop system outweighed the practical challenges reported. Further research from longitudinal studies is required to determine the long-term psychosocial benefit of the closed loop technology.
A community-based survey for different abnormal glucose metabolism among pregnant women in a random household study (SAUDI-DM)
Authors: Al-Rubeaan Khalid , Al-Manaa Hamad A , Khoja Tawfik A , Youssef Amira M , Al-Sharqawi Ahmad H , Siddiqui Khalid , Ahmad Najlaa A 
Published: August 2014

ObjectiveTo assess the prevalence and risk factors of gestational diabetes mellitus (GDM) in a population known to have a high prevalence of abnormal glucose metabolism.MethodsA household random population-based cross-sectional study of 13 627 women in the childbearing age, who were subjected to fasting plasma glucose if they were not known to have been diagnosed before with any type of diabetes. GDM cases were diagnosed using the International Association of Diabetes and Pregnancy Study Group (IAPSG) criteria.ResultsThe overall GDM prevalence was 36.6%, categorised into 32.4% new cases and 4.2% known cases. Another 3.6% had preconception type 1 or 2 diabetes. GDM cases were older and had a significantly higher body mass index, in addition to a higher rate of macrocosmic baby and history of GDM. Monthly income, educational level, living in urban areas and smoking were not found to be significantly different between normal and GDM cases. The most important and significant risk factors for GDM were history of GDM, macrosomic baby, obesity and age >30 years. However, hypertension, low high-density lipoprotein, family history of diabetes and increased triglycerides did not show any significant effect on GDM prevalence in this cohort.ConclusionsThis society is facing a real burden of abnormal glucose metabolism during pregnancy, where almost half of the pregnant women are subjected to maternal and neonatal complications. Early screening of pregnant women, especially those at a high risk for GDM, is mandatory to identify and manage those cases.
Xtep: Winning Young Chinese Consumers in Less Developed Cities
Authors: Luk Sherriff T. K. , Chen Ivy S. N. , Leung Chi Hong 
Published: August 2014

Most foreign brands target first tier cities in China, thinking that demand in lower tier cities is unable to support their stores. The case describes how Xtep, a Chinese sportswear brand, succeeded in building a strong position in second and third tier cities by tapping into youth's need for expression through competitive pricing and aggressive sports and entertainment marketing. By targeting customers in less developed cities, it also avoided direct competition with wellknown brands. This case also describes the sportswear industry, the development of second and third tier cities in China and the consumer behaviour of residents. The case requires analysis of some of the changes that are taking place in second and third tier cities in China and their implications for firms.
Wondering About Things
Authors: Field George B. 
Published: August 2014

Here you will find facts about and the opinions of an American astrophysicist who practiced in the second half of the twentieth century. The title explains why I did it. I invented some new ideas, I applied them to some astro objects, I computed things with pen and paper; I ended up thinking that I had succeeded in pushing the field ahead a bit. Attracted by Newtonian theory, I did some experiments too. I love hydrodynamics and magnetic fields in space. The math is beautiful, and the objects are stupendous in their brilliant displays. For some reason I meditated on gases between the stars, their pressures and motions. I left the stars to others, believing that their physics was under control. As I grew older, I had to decide whether to direct others rather than just myself and ended up at the Harvard–Smithsonian Center for Astrophysics doing both. It was thrilling because I had never had management experience and was flying by the seat of my pants, as I guess other astrodirectors do. In the process, I advised the US government on future directions in astronomy, chairing a number of committees. It is astonishing that the government is interested in astronomy, and it is exciting to interact with the people in the National Academy of Sciences (NAS), the Congress, and the Executive branch who have dedicated their lives to enable the expansion of our knowledge of astronomy. Along the way I studied more abstract concepts in physics, including magnetic helicity and its relation to the winding numbers of nonabelian particle physics. These are topological concepts that I should have learned in grad school but did not. This review has two parts. The first part is for scientists, and covers my life in chronological order. The second part is for laymen who are interested in science. It gives a flavor of my scientific work with no math and a minimum of jargon.
Novel Paracrine Modulation of Notch–DLL4 Signaling by Fibulin-3 Promotes Angiogenesis in High-Grade Gliomas
Authors: Nandhu Mohan S. , Hu Bin , Cole Susan E. , Erdreich-Epstein Anat , Rodriguez-Gil Diego J. , Viapiano Mariano S. 
Published: August 2014

Abstract
High-grade gliomas are characterized by exuberant vascularization, diffuse invasion, and significant chemoresistance, resulting in a recurrent phenotype that makes them impossible to eradicate in the long term. Targeting protumoral signals in the glioma microenvironment could have significant impact against tumor cells and the supporting niche that facilitates their growth. Fibulin-3 is a protein secreted by glioma cells, but absent in normal brain, that promotes tumor invasion and survival. We show here that fibulin-3 is a paracrine activator of Notch signaling in endothelial cells and promotes glioma angiogenesis. Fibulin-3 overexpression increased tumor VEGF levels, microvascular density, and vessel permeability, whereas fibulin-3 knockdown reduced vessel density in xenograft models of glioma. Fibulin-3 localization in human glioblastomas showed dense fiber-like condensations around tumor blood vessels, which were absent in normal brain, suggesting a remarkable association of this protein with tumor endothelium. At the cellular level, fibulin-3 enhanced endothelial cell motility and association to glioma cells, reduced endothelial cell sprouting, and increased formation of endothelial tubules in a VEGF-independent and Notch-dependent manner. Fibulin-3 increased ADAM10/17 activity in endothelial cells by inhibiting the metalloprotease inhibitor TIMP3; this resulted in increased Notch cleavage and increased expression of DLL4 independently of VEGF signaling. Inhibition of ADAM10/17 or knockdown of DLL4 reduced the proangiogenic effects of fibulin-3 in culture. Taken together, these results reveal a novel, proangiogenic role of fibulin-3 in gliomas, highlighting the relevance of this protein as an important molecular target in the tumor microenvironment. Cancer Res; 74(19); 5435–48. ©2014 AACR.
Paracrine Network: Another Step in the Complexity of Resistance to EGFR Blockade?
Authors: Salazar Ramon , Capellà Gabriel , Tabernero Josep 
Published: August 2014

Abstract
Increased secretion of EGFR ligands amphiregulin and TGFα by limited KRAS-mutant clones is suggested as a paracrine resistance mechanism to anti-EGFR antibodies in colorectal cancer models. These findings are biologically sound but need to be replicated, including in the clinical setting, to foresee whether they are clinically relevant and therapeutically exploitable. Clin Cancer Res; 20(24); 6227–9. ©2014 AACR.