bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel QTL for the number of spikelets per panicle using a cross between indica‐ and japonica‐type high‐yielding rice cultivars in Japan
Authors: Takai Toshiyuki , Nakano Hiroshi , Yoshinaga Satoshi , Kondo Motohiko 
Published: March 2018

AbstractYield is a complex trait. To improve it, the accumulation of the favourable alleles of valuable genes is required for each yield‐related trait. In this study, we used two high‐yielding rice cultivars developed in Japan, indica‐type ‘Takanari’ and japonica‐type ‘Momiroman’, for a genetic analysis of the sink capacity‐related traits. An F2 population showed transgressive segregation for the number of spikelets per panicle. Quantitative trait locus (QTL) analysis detected four QTLs for the trait. Two of the QTLs were most likely identical to previously cloned GN1a and APO1, and their Takanari alleles had positive effects. The Momiroman alleles of the other two QTLs had positive effects, and one of these QTLs was most likely identical to SPIKE/GPS. The QTL on the long arm of chromosome 3 appeared to be novel; it clustered with QTLs for grain length and days‐to‐heading. Substitution mapping revealed that the close linkage of QTLs caused the clustering. These results suggest that the combination of the favourable alleles of detected QTLs could lead to greater sink capacity than that of the parental cultivars.
Social Security and Old Age Unemployment Risk with Efficient Wage Bargaining
Authors: Reichlin Pietro 
Published: March 2018

AbstractI analyze a life‐cycle economy with old age productivity risk where wages, employment, and severance payments are set through efficient bargaining between risk averse unions and risk neutral firms. Allocations with limited union membership are second‐best inefficient as they generate too little labor supply in young age, too much consumption before retirement, too little employment of older workers (early retirement), and too little insurance against old age unemployment. Providing public transfers to early retirees (disability benefits or early pensions) might help to increase the degree of risk sharing at the cost of lower old age employment. Depending on whether absolute risk aversion is increasing or decreasing in consumption, these policies might or might not produce efficiency gains at equilibrium.
A geopolitics of trauma: Refugee administration and protracted uncertainty in Turkey
Authors: Loyd Jenna M. , Ehrkamp Patricia , Secor Anna J. 
Published: March 2018

In this paper we map out what we are calling a “geopolitics of trauma” by examining the role of trauma in transnational refugee regimes and the individualisation of geopolitical relations through mental health diagnosis and service provision. Focusing on one site of entry into the international regime of refugee administration, we present findings from fieldwork that we conducted in August, 2015 in Turkey with NGOs and IGOs involved in the protection, mental health and psychosocial service provision, and resettlement of refugees. The findings that we present demonstrate the challenges of refugee care and management on the front lines in Turkey and the significance of mental health diagnosis, treatment and documentation in the early stages of refugee administration. We suggest that practices of refugee screening and resettlement are imbued with traumatic stressors and trace how trauma intersects with the administration of refugees in different sites and at different times. We argue that the protracted situation of refugees in Turkey (many of whom will wait eight years for their Refugee Status Determination interview) and the multiple interviews and demands for documentation through which a displaced person applies for refugee status and third‐country resettlement become sites of ongoing traumatisation for the refugee subject. Further, in the practices of screening and documentation, we can trace the medicalisation of the refugee subject as not only a question of care but also a practice of legibility on which the state and international organisations base their decisions about inclusion and exclusion. The geopolitics of trauma thus emerges not only in cartographies of war, displacement and resettlement, but also in the minute details and performative demands of the refugee determination and resettlement process.
Survey of the prevalence and methodology of quality assurance for B‐mode ultrasound image quality among veterinary sonographers
Authors: Hoscheit Larry P. , Heng Hock Gan , Lim Chee Kin , Weng Hsin‐Yi 
Published: March 2018

AbstractImage quality in B‐mode ultrasound is important as it reflects the diagnostic accuracy and diagnostic information provided during clinical scanning. Quality assurance programs for B‐mode ultrasound systems/components are comprised of initial quality acceptance testing and subsequent regularly scheduled quality control testing. The importance of quality assurance programs for B‐mode ultrasound image quality using ultrasound phantoms is well documented in the human medical and medical physics literature. The purpose of this prospective, cross‐sectional, survey study was to determine the prevalence and methodology of quality acceptance testing and quality control testing of image quality for ultrasound system/components among veterinary sonographers. An online electronic survey was sent to 1497 members of veterinary imaging organizations: the American College of Veterinary Radiology, the Veterinary Ultrasound Society, and the European Association of Veterinary Diagnostic Imaging, and a total of 167 responses were received. The results showed that the percentages of veterinary sonographers performing quality acceptance testing and quality control testing are 42% (64/151; 95% confidence interval 34–52%) and 26% (40/156: 95% confidence interval 19–33%) respectively. Of the respondents who claimed to have quality acceptance testing or quality control testing of image quality in place for their ultrasound system/components, 0% have performed quality acceptance testing or quality control testing correctly (quality acceptance testing 95% confidence interval: 0–6%, quality control testing 95% confidence interval: 0–11%). Further education and guidelines are recommended for veterinary sonographers in the area of quality acceptance testing and quality control testing for B‐mode ultrasound equipment/components.
Approximation forte pour les variétés avec une action d’un groupe linéaire
Authors: Cao Yang 
Published: March 2018

Let$G$be a connected linear algebraic group over a number field$k$. Let$U{\hookrightarrow}X$be a$G$-equivariant open embedding of a$G$-homogeneous space$U$with connected stabilizers into a smooth$G$-variety$X$. We prove that$X$satisfies strong approximation with Brauer–Manin condition off a set$S$of places of$k$under either of the following hypotheses:(i)$S$is the set of archimedean places;(ii)$S$is a non-empty finite set and$\bar{k}^{\times }=\bar{k}[X]^{\times }$.The proof builds upon the case$X=U$, which has been the object of several works.
Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy
Authors: Vossen M. G. , Ehmann L. , Pferschy S. , Maier-Salamon A. , Haidinger M. , Weiser C. , Wenisch J. M. , Saria K. , Kajahn C. , Jilch S. , Lemmerer R. , Bécède M. , Zeitlinger M. , Kloft C. , Jäger W. , Thalhammer F. 
Published: March 2018

ABSTRACT

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against
Pseudomonas aeruginosa
and
Enterobacteriaceae
. Current dosing regimens recommend the administration of 0.25 to 0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for
Enterobacteriaceae
is set at 2 mg/liter. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.)
The Lysine 299 Residue Endows the Multisubunit Mrp1 Antiporter with Dominant Roles in Na
+
Resistance and pH Homeostasis in Corynebacterium glutamicum
Authors: Xu Ning , Zheng Yingying , Wang Xiaochen , Krulwich Terry A. , Ma Yanhe , Liu Jun 
Published: March 2018

ABSTRACT

Corynebacterium glutamicum
is generally regarded as a moderately salt- and alkali-tolerant industrial organism. However, relatively little is known about the molecular mechanisms underlying these specific adaptations. Here, we found that the Mrp1 antiporter played crucial roles in conferring both environmental Na
+
resistance and alkali tolerance whereas the Mrp2 antiporter was necessary in coping with high-KCl stress at alkaline pH. Furthermore, the Δ
mrp1
Δ
mrp2
double mutant showed the most-severe growth retardation and failed to grow under high-salt or alkaline conditions. Consistent with growth properties, the Na
+
/H
+
antiporters of
C. glutamicum
were differentially expressed in response to specific salt or alkaline stress, and an alkaline stimulus particularly induced transcript levels of the Mrp-type antiporters. When the major Mrp1 antiporter was overwhelmed,
C. glutamicum
might employ alternative coordinate strategies to regulate antiport activities. Site-directed mutagenesis demonstrated that several conserved residues were required for optimal Na
+
resistance, such as Mrp1A K
299
, Mrp1C I
76
, Mrp1A H
230
, and Mrp1D E
136
. Moreover, the chromosomal replacement of lysine 299 in the Mrp1A subunit resulted in a higher intracellular Na
+
level and a more alkaline intracellular pH value, thereby causing a remarkable growth attenuation. Homology modeling of the Mrp1 subcomplex suggested two possible ion translocation pathways, and lysine 299 might exert its effect by affecting the stability and flexibility of the cytoplasm-facing channel in the Mrp1A subunit. Overall, these findings will provide new clues to the understanding of salt-alkali adaptation during
C. glutamicum
stress acclimatization.

IMPORTANCE
The capacity to adapt to harsh environments is crucial for bacterial survival and product yields, including industrially useful
Corynebacterium glutamicum
. Although
C. glutamicum
exhibits a marked resistance to salt-alkaline stress, the possible mechanism for these adaptations is still unclear. Here, we present the physiological functions and expression patterns of
C. glutamicum
putative Na
+
/H
+
antiporters and conserved residues of Mrp1 subunits, which respond to different salt and alkaline stresses. We found that the Mrp-type antiporters, particularly the Mrp1 antiporter, played a predominant role in maintaining intracellular nontoxic Na
+
levels and alkaline pH homeostasis. Loss of the major Mrp1 antiporter had a profound effect on gene expression of other antiporters under salt or alkaline conditions. The lysine 299 residue may play its essential roles in conferring salt and alkaline tolerance by affecting the ion translocation channel of the Mrp1A subunit. These findings will contribute to a better understanding of Na
+
/H
+
antiporters in sodium antiport and pH regulation.
Reconstituting the History of Cronobacter Evolution Driven by Differentiated CRISPR Activity
Authors: Zeng Haiyan , Zhang Jumei , Wu Qingping , He Wenjing , Wu Haoming , Ye Yingwang , Li Chengsi , Ling Na , Chen Moutong , Wang Juan , Cai Shuzhen , Lei Tao , Ding Yu , Xue Liang 
Published: March 2018

ABSTRACT

Cronobacter
strains harboring the CRISPR-Cas system are important foodborne pathogens causing serious neonatal infections. However, the specific role of the CRISPR-Cas system in bacterial evolution remains relatively unexplored. In this study, we investigated the impact of the CRISPR-Cas system on
Cronobacter
evolution and obtained 137 new whole-genome
Cronobacter
sequences by next-generation sequencing technology. Among the strains examined (
n
= 240), 90.6% (193/213) of prevalent species
Cronobacter sakazakii
,
Cronobacter
malonaticus
, and
Cronobacter
dublinensis
strains had intact CRISPR-Cas systems. Two rare species,
Cronobacter
condimenti
(
n
= 2) and
Cronobacter
universalis
(
n
= 6), lacked and preserved the CRISPR-Cas system at a low frequency (1/6), respectively. These results suggest that the presence of one CRISPR-Cas system is important for a
Cronobacter
species to maintain genome homeostasis for survival. The
Cronobacter
ancestral strain is likely to have harbored both subtype I-E and I-F CRISPR-Cas systems; during the long evolutionary process, subtype I-E was retained while subtype I-F selectively degenerated in
Cronobacter
species and was even lost by the major
Cronobacter
pathovars. Moreover, significantly higher CRISPR activity was observed in the plant-associated species
C
.
dublinensis
than in the virulence-related species
C. sakazakii
and
C
.
malonaticus
. Similar spacers of CRISPR arrays were rarely found among species, suggesting intensive change through adaptive acquisition and loss. Differentiated CRISPR activity appears to be the product of environmental selective pressure and might contribute to the bidirectional divergence and speciation of
Cronobacter
.

IMPORTANCE
This study reports the evolutionary history of
Cronobacter
under the selective pressure of the CRISPR-Cas system. One CRISPR-Cas system in
Cronobacter
is important for maintaining genome homeostasis, whereas two types of systems may be redundant and not conducive to acquiring beneficial DNA for environmental adaptation and pathogenicity. Differentiated CRISPR activity has contributed to the bidirectional divergence and genetic diversity of
Cronobacter
. This perspective makes a significant contribution to the literature by providing new insights into CRISPR-Cas systems in general, while further expanding the roles of CRISPR beyond conferring adaptive immunity and demonstrating a link to adaptation and species divergence in a genus. Moreover, our study provides new insights into the balance between genome homeostasis and the uptake of beneficial DNA related to CRISPR-based activity in the evolution of
Cronobacter
.
Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections
Authors: Patel Mira C. , Shirey Kari Ann , Boukhvalova Marina S. , Vogel Stefanie N. , Blanco Jorge C. G. 
Published: March 2018

ABSTRACT
Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI.

IMPORTANCE
Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.
Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
Authors: Chiang Chih-Yuan , Uzoma Ijeoma , Moore Richard T. , Gilbert Merle , Duplantier Allen J. , Panchal Rekha G. 
Published: March 2018

ABSTRACT
Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strategies are critical for addressing the threat posed by multidrug-resistant bacteria. Host-directed therapies utilize small-molecule drugs and proteins to alter the host response to pathogen infection. Here, we highlight strategies for modulating the host inflammatory response to enhance bacterial clearance, small-molecule potentiation of innate immunity, and targeting of host factors that are exploited by pathogen virulence factors. Application of state-of-the-art “omic” technologies, including proteomics, transcriptomics, and image-omics (image-based high-throughput phenotypic screening), combined with powerful bioinformatics tools will enable the modeling of key signaling pathways in the host-pathogen interplay and aid in the identification of host proteins for therapeutic targeting and the discovery of host-directed small molecules that will regulate bacterial infection. We conclude with an outlook on research needed to overcome the challenges associated with transitioning host-directed therapies into a clinical setting.
UDP-Glucuronic Acid Transport Is Required for Virulence of
Cryptococcus neoformans
Authors: Li Lucy X. , Rautengarten Carsten , Heazlewood Joshua L. , Doering Tamara L. 
Published: March 2018

ABSTRACT

Glycans play diverse biological roles, ranging from structural and regulatory functions to mediating cellular interactions. For pathogens, they are also often required for virulence and survival in the host. In
Cryptococcus neoformans
, an opportunistic pathogen of humans, the acidic monosaccharide glucuronic acid (GlcA) is a critical component of multiple essential glycoconjugates. One of these glycoconjugates is the polysaccharide capsule, a major virulence factor that enables this yeast to modulate the host immune response and resist antimicrobial defenses. This allows cryptococci to colonize the lung and brain, leading to hundreds of thousands of deaths each year worldwide. Synthesis of most glycans, including capsule polysaccharides, occurs in the secretory pathway. However, the activated precursors for this process, nucleotide sugars, are made primarily in the cytosol. This topological problem is resolved by the action of nucleotide sugar transporters (NSTs). We discovered that Uut1 is the sole UDP-GlcA transporter in
C. neoformans
and is unique among NSTs for its narrow substrate range and high affinity for UDP-GlcA. Mutant cells with
UUT1
deleted lack capsule polysaccharides and are highly sensitive to environmental stress. As a result, the deletion mutant is internalized and cleared by phagocytes more readily than wild-type cells are and is completely avirulent in mice. These findings expand our understanding of the requirements for capsule synthesis and cryptococcal virulence and elucidate a critical protein family.

IMPORTANCE
Cryptococcus neoformans
causes lethal meningitis in almost two hundred thousand immunocompromised patients each year. Much of this fungal pathogen’s ability to resist host defenses and cause disease is mediated by carbohydrate structures, including a complex polysaccharide capsule around the cell. Like most eukaryotic glycoconjugates, capsule polysaccharides are made within the secretory pathway, although their precursors are generated in the cytosol. Specific transporters are therefore required to convey these raw materials to the site of synthesis. One precursor of particular interest is UDP-glucuronic acid, which donates glucuronic acid to growing capsule polysaccharides. We discovered a highly specific, high-affinity transporter for this molecule. Deletion of the gene encoding this unusual protein abolishes capsule synthesis, alters stress resistance, and eliminates fungal virulence. In this work, we have identified a novel transporter, elucidated capsule synthesis and thereby aspects of fungal pathogenesis, and opened directions for potential antifungal therapy.