bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives
Authors: Fernández Matilde , Morel Bertrand , Corral‐Lugo Andrés , Krell Tino 
Published: September 2015

SummaryChemotaxis is an essential mechanism that enables bacteria to move toward favorable ecological niches. Escherichia coli, the historical model organism for studying chemotaxis, has five well‐studied chemoreceptors. However, many bacteria with different lifestyle have more chemoreceptors, most of unknown function. Using a high throughput screening approach, we identified a chemoreceptor from Pseudomonas putida KT2440, named McpH, which specifically recognizes purine and its derivatives, adenine, guanine, xanthine, hypoxanthine and uric acid. The latter five compounds form part of the purine degradation pathway, permitting their use as sole nitrogen sources. Isothermal titration calorimetry studies show that these six compounds bind McpH‐Ligand Binding Domain (LBD) with very similar affinity. In contrast, non‐metabolizable purine derivatives (caffeine, theophylline, theobromine), nucleotides, nucleosides or pyrimidines are unable to bind McpH‐LBD. Mutation of mcpH abolished chemotaxis toward the McpH ligands identified – a phenotype that is restored by complementation. This is the first report on bacterial chemotaxis to purine derivatives and McpH the first chemoreceptor described that responds exclusively to intermediates of a catabolic pathway, illustrating a clear link between metabolism and chemotaxis. The evolution of McpH may reflect a saprophytic lifestyle, which would have exposed the studied bacterium to high concentrations of purines produced by nucleic acid degradation.
Efficient disruption and replacement of an effector gene in the oomycetePhytophthora sojaeusingCRISPR/Cas9
Authors: Fang Yufeng , Tyler Brett M. 
Published: September 2015

SummaryPhytophthora sojaeis an oomycete pathogen of soybean. As a result of its economic importance,P. sojaehas become a model for the study of oomycete genetics, physiology and pathology. The lack of efficient techniques for targeted mutagenesis and gene replacement have long hampered genetic studies of pathogenicity inPhytophthoraspecies. Here, we describe aCRISPR/Cas9 system enabling rapid and efficient genome editing inP. sojae. Using theRXLReffector geneAvr4/6as a target, we observed that, in the absence of a homologous template, the repair ofCas9‐induced DNA double‐strand breaks (DSBs) inP. sojaewas mediated by non‐homologous end‐joining (NHEJ), primarily resulting in short indels. Most mutants were homozygous, presumably as a result of gene conversion triggered byCas9‐mediated cleavage of non‐mutant alleles. When donorDNAwas present, homology‐directed repair (HDR) was observed, which resulted in the replacement ofAvr4/6with theNPT IIgene. By testing the specific virulence of severalNHEJmutants andHDR‐mediated gene replacements in soybean, we have validated the contribution ofAvr4/6 to recognition by soybeanRgene loci,Rps4 andRps6, but also uncovered additional contributions to resistance by these two loci. Our results establish a powerful tool for the study of functional genomics inPhytophthora, which provides new avenues for better control of this pathogen.
Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis
Authors: Zhang L. , Liu G. , Han X. , Liu J. , Li G.‐X. , Zou D.‐W. , Li Z.‐S. 
Published: September 2015

AbstractBackgroundReflux esophagitis (RE) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen‐activated protein kinase (MAPK) in experimental chronic RE model of rats.MethodsChronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days.Key ResultsImmunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases‐3 and ‐9. Inhibition of p38 MAPK activation in RE rats reduced CD68‐positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and IL‐1β in esophagus and protein levels of TNF‐α, IL‐6, and IL‐1β in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO), 3‐nitrotyrosin, and malondialdehyde in esophagus.Conclusions & InferencesInhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO, and reactive oxygen species.
Ubiquitin‐conjugated degradation of golden 2‐like transcription factor is mediated by CUL4‐DDB1‐based E3 ligase complex in tomato
Authors: Tang Xiaofeng , Miao Min , Niu Xiangli , Zhang Danfeng , Cao Xulv , Jin Xichen , Zhu Yunye , Fan Youhong , Wang Hongtao , Liu Ying , Sui Yuan , Wang Wenjie , Wang Anquan , Xiao Fangming , Giovannoni Jim , Liu Yongsheng 
Published: September 2015

Summary

CULLIN4‐RING ubiquitin ligases (CRL4s) as well as their targets are fundamental regulators functioning in many key developmental and stress responses in eukaryotes. In tomato (Solanum lycopersicum), molecular cloning has revealed that the underlying genes of natural spontaneous mutations high pigment 1 (hp1), high pigment 2 (hp2) and uniform ripening (u) encode UV‐DAMAGED DNA BINDING PROTEIN 1 (DDB1), DE‐ETIOLATED 1 (DET1) and GOLDEN 2‐LIKE (GLK2), respectively. However, the molecular basis of the opposite actions of tomato GLK2 vs CUL4‐DDB1‐DET1 complex on regulating plastid level and fruit quality remains unknown.

Here, we provide molecular evidence showing that the tomato GLK2 protein is a substrate of the CUL4‐DDB1‐DET1 ubiquitin ligase complex for the proteasome degradation.

SlGLK2 is degraded by the ubiquitin‐proteasome system, which is mainly determined by two lysine residues (K11 and K253). SlGLK2 associates with the CUL4‐DDB1‐DET1 E3 complex in plant cells. Genetically impairing CUL4, DDB1 or DET1 results in a retardation of SlGLK2 degradation by the 26S proteasome.

These findings are relevant to the potential of nutrient accumulation in tomato fruit by mediating the plastid level and contribute to a deeper understanding of an important regulatory loop, linking protein turnover to gene regulation.
Interaction of obesity and infections
Authors: Dhurandhar N. V. , Bailey D. , Thomas D. 
Published: September 2015

SummaryThere is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The objective of this study is to review the available literature identifying infections that potentially contribute to greater body mass index (BMI) and differential responses of overweight and obese persons to infections. A systematic literature review of human studies examining associations between infections and weight gain, differential susceptibility, severity, and response to prevention and treatment of infection according to BMI status (January 1980–July 2014) was conducted. Three hundred and forty‐three studies were eligible for inclusion. Evidence indicated that viral infection by human adenovirus Ad36 and antibiotic eradication of Helicobacter pylori were followed by weight gain. People who were overweight or obese had higher susceptibility to developing post‐surgical infections, H1N1 influenza and periodontal disease. More severe infections tended to be present in people with a larger BMI. People with a higher BMI had a reduced response to vaccinations and antimicrobial drugs. Higher doses of antibiotics were more effective in obese patients. Infections may influence BMI, and BMI status may influence response to certain infections, as well as to preventive and treatment measures. These observations have potential clinical implications.
A corneal elastic dynamic model derived from Scheimpflug imaging technology
Authors: Shih Po‐Jen , Cao Huei‐Jyun , Huang Chun‐Ju , Wang I‐Jong , Shih Wen‐Pin , Yen Jia‐Yush 
Published: September 2015

AbstractPurposeTo simultaneously extract the corneal Young's modulus and the damping ratio from Scheimpflug imaging data.MethodsA spherical diaphragm model can better represent the geometry and physics of an eyeball than the popular mass‐spring‐damper model. This research derived the dynamic model of a water‐filled spherical diaphragm based on the hydrodynamics and wave propagation theories. By applying modal analysis on the model, one can decouple the cornea vibration into individual modes and reconstruct the air puff vibration from the decoupled responses. By matching this response with the Scheimpflug imaging data from the Corvis® ST, it was then possible to extract multiple physiological properties as desired.ResultsThe dynamic modal analysis was employed to extract the corneal physiological properties of 25 Taiwanese normal subjects. Specifically, the corneal Young's moduli and damping ratios were estimated. In fact the model is dependent on the physiological parameters such as cornea thickness, densities, and intraocular pressure. It is thus also possible to extract these parameters through multi‐goal minimisation processes.ConclusionsThe spherical diaphragm model was able to better describe the dynamic response of the eyeball. The model analysis also provides additional corneal physiological properties that were not available through other means.
Age and the amplitude of accommodation measured using dynamic retinoscopy
Authors: León Alejandro , Estrada Jorge M. , Rosenfield Mark 
Published: September 2015

AbstractPurposeDynamic retinoscopy (DR) is a procedure for assessing the accommodative response using a standard clinical instrument. The present study compared measurements of the amplitude of accommodation (AA) obtained using this technique with two subjective methods (modified push‐down and minus lens). Additionally, the expected ranges for AA when measured by DR were determined.MethodAA was measured in 1298 subjects between 5 and 60 years of age using the three techniques described above. Subjects were grouped into 5‐year bins, and a descriptive univariate analysis of the data performed. Goodness‐of fit plots were constructed to examine the overall model fit. Centile curves were calculated from the final model.ResultsMean values of AA obtained using DR were significantly lower than for the two subjective techniques. For the DR findings, no significant change was observed between 5 and 19 years of age (mean AA = 8.3 D) and between 45 and 60 years of age (mean AA = 0.6 D). AA values as a function of age were best fit by the polynomial regression equation: logAA = 1.93 + 0.49(age) − 0.19(age)2.ConclusionMeasurements of AA determined using DR are significantly lower than the normative subjective findings published previously. This difference is at least partly due to the depth‐of‐field of the eye. These norms markedly overestimate accommodative responsivity. DR provides a simple technique for quantifying accommodation in the clinical setting.
A Cholesterol‐Dependent Endocytic Mechanism Generates Midbody Tubules During Cytokinesis
Authors: Kettle Emma , Page Scott L. , Morgan Garry P. , Malladi Chandra S. , Wong Chin L. , Boadle Ross A. , Marsh Brad J. , Robinson Phillip J. , Chircop Megan 
Published: September 2015

Cytokinesis is the final stage of cell division and produces two independent daughter cells. Vesicles derived from internal membrane stores, such as the Golgi, lysosomes, and early and recycling endosomes accumulate at the intracellular bridge (ICB) during cytokinesis. Here, we use electron tomography to show that many ICB vesicles are not independent but connected, forming a newly described ICB vesicular structure – narrow tubules that are often branched. These ‘midbody tubules’ labelled with horseradish peroxidase (HRP) within 10 min after addition to the surrounding medium demonstrating that they are derived from endocytosis. HRP‐labelled vesicles and tubules were observed at the rim of the ICB after only 1 min, suggesting that midbody tubules are likely to be generated by local endocytosis occurring at the ICB rim. Indeed, at least one tubule was open to the extracellular space, indicative of a local origin within the ICB. Inhibition of cholesterol‐dependent endocytosis by exposure to methyl‐β‐cyclodextrin and filipin reduced formation of HRP‐labelled midbody tubules, and induced multinucleation following ICB formation. In contrast, dynamin inhibitors, which block clathrin‐mediated endocytosis, induced multinucleation but had no effect on the formation of HRP‐labelled midbody tubules. Therefore, our data reveal the existence of a cholesterol‐dependent endocytic pathway occurring locally at the ICB, which contributes to the accumulation of vesicles and tubules that contribute to the completion of cytokinesis.
Assignment of Weight-Based Antibody Units for Seven Additional Serotypes to a Human Pneumococcal Standard Reference Serum, 007sp
Authors: Goldblatt D. , Tan C. Y. , Burbidge P. , McElhiney S. , McLaughlin L. , Tucker R. , Rauh M. , Sidhu M. , Giardina P. C. 
Published: September 2015

ABSTRACT

The pneumococcal enzyme-linked immunosorbent assay (ELISA) reference standard serum, lot 89SF, has been in use since 1990 and was replaced in 2013 with a new reference standard, 007sp, that is projected to be available for the next 25 years. 007sp was generated under an FDA-approved clinical protocol; 278 adult volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice from each immunized subject within 120 days following immunization. Pooled serum was prepared from the plasma of 262 subjects, filled at 6 ml per vial, and lyophilized. Five independent laboratories participated in bridging the serotype-specific IgG assignments for 89SF to the new reference standard, 007sp, to establish equivalent reference values for 13 pneumococcal capsular serotypes (1,3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) by using the WHO reference ELISA. In a second study involving three laboratories, a similar protocol was used to assign weight-based IgG concentrations in micrograms per ml to 007sp of seven serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) also present in the 23-valent pneumococcal unconjugated polysaccharide vaccine. In addition, the IgG assignments for a 12-member WHO quality control (QC) serum panel were also extended to cover these seven serotypes. Agreement was excellent, with a concordance correlation coefficient (
r
c
) of >0.996 when each laboratory was compared to the assigned values for the 12 WHO QC serum samples. There are four remaining pneumococcal serotypes (2, 9N, 17F, and 20) found in Pneumovax II for which IgG assignments exist for 89SF and remain to be bridged.
Molecular Characterization of a Catalase-Negative Staphylococcus aureus Blood Culture Isolate
Authors: Teo Jeanette W. P. , Kum Steven , Jureen Roland , Lin Raymond T. P. 
Published: September 2015

ABSTRACT

Here we report a catalase-negative methicillin-sensitive
Staphylococcus aureus
isolate collected from a blood culture. Sequencing through the gene encoding catalase,
katA
, demonstrated a 2-bp insertion. The resulting frameshift mutation generates a protein that has lost 26 amino acids (aa) at its C-terminal domain.
Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses
Authors: Kerr Scott A. , Jackson Eleisha L. , Lungu Oana I. , Meyer Austin G. , Demogines Ann , Ellington Andrew D. , Georgiou George , Wilke Claus O. , Sawyer Sara L. 
Published: September 2015

ABSTRACT
Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the “host jumping” potential of a virus into a new host species.

IMPORTANCE
We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible to other virus species. We present an algorithm that predicts which species have cell surface receptors that make them susceptible to Machupo virus, based on computational docking of protein structures. Few molecular models exist for predicting the risk of spillover of a particular animal virus into humans or new animal populations. Our results suggest that a combination of evolutionary analysis, structural modeling, and experimental verification may provide an efficient approach for screening and assessing the potential spillover risks of viruses circulating in animal populations.
Requirement for Host RNA-Silencing Components and the Virus-Silencing Suppressor when Second-Site Mutations Compensate for Structural Defects in the 3′ Untranslated Region
Authors: Chattopadhyay Maitreyi , Stupina Vera A. , Gao Feng , Szarko Christine R. , Kuhlmann Micki M. , Yuan Xuefeng , Shi Kerong , Simon Anne E. 
Published: September 2015

ABSTRACT

Turnip crinkle virus (TCV) contains a structured 3′ region with hairpins and pseudoknots that form a complex network of noncanonical RNA:RNA interactions supporting higher-order structure critical for translation and replication. We investigated several second-site mutations in the p38 coat protein open reading frame (ORF) that arose in response to a mutation in the asymmetric loop of a critical 3′ untranslated region (UTR) hairpin that disrupts local higher-order structure. All tested second-site mutations improved accumulation of TCV in conjunction with a partial reversion of the primary mutation (TCV-rev1) but had neutral or a negative effect on wild-type (wt) TCV or TCV with the primary mutation. SHAPE (
s
elective 2′-
h
ydroxyl
a
cylation analyzed by
p
rimer
e
xtension) structure probing indicated that these second-site mutations reside in an RNA domain that includes most of p38 (domain 2), and evidence for RNA:RNA interactions between domain 2 and 3′UTR-containing domain 1 was found. However, second-site mutations were not compensatory in the absence of p38, which is also the TCV silencing suppressor, or in
dcl-2/dcl4
or
ago1/ago2
backgrounds. One second-site mutation reduced silencing suppressor activity of p38 by altering one of two GW motifs that are required for p38 binding to double-stranded RNAs (dsRNAs) and interaction with RNA-induced silencing complex (RISC)-associated AGO1/AGO2. Another second-site mutation substantially reduced accumulation of TCV-rev1 in the absence of p38 or DCL2/DCL4. We suggest that the second-site mutations in the p38 ORF exert positive effects through a similar downstream mechanism, either by enhancing accumulation of beneficial DCL-produced viral small RNAs that positively regulate the accumulation of TCV-rev1 or by affecting the susceptibility of TCV-rev1 to RISC loaded with viral small RNAs.

IMPORTANCE
Genomes of positive-strand RNA viruses fold into high-order RNA structures. Viruses with mutations in regions critical for translation and replication often acquire second-site mutations that exert a positive compensatory effect through reestablishment of canonical base pairing with the altered region. In this study, two distal second-site mutations that individually arose in response to a primary mutation in a critical 3′ UTR hairpin in the genomic RNA of turnip crinkle virus did not directly interact with the primary mutation. Although different second-site changes had different attributes, compensation was dependent on the production of the viral p38 silencing suppressor and on the presence of silencing-required DCL and AGO proteins. Our results provide an unexpected connection between a 3′ UTR primary-site mutation proposed to disrupt higher-order structure and the RNA-silencing machinery.