bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling alternative stable states in Caribbean coral reefs
Authors: Blackwood Julie C. , Okasaki Connie , Archer Andre , Matt Eliza W. , Sherman Elizabeth , Montovan Kathryn 
Published: January 2018

AbstractThe resilience of Caribbean coral reefs, which are an important source of biodiversity and provide essential ecosystem services, is constantly challenged by many reef stressors including ocean acidification, hurricane damage, and overharvesting of herbivorous reef fish. The presence of two alternative stable states—a desirable state with high levels of coral cover and its coral‐depleted counterpart—has been widely documented in the literature. Increasing coral resilience to prevent phase shifts to the undesirable state is a critical research priority, and mathematical models can serve as an important tool to not only better understand the underlying dynamics of observed coral communities, but also to evaluate the potential impacts of stressors and the outcome of management strategies designed to promote coral persistence. Here, we review the existing literature of mathematical models designed to understand the processes that generate alternative stable states. We focus on models that are comprised of ordinary differential equations and, at their core, capture algal–coral dynamics.Recommendations for Resource Managers
Evidence for the existence of alternative stable states and the associated presence of hysteresis implies a need for management designed to increase the resilience of coral reef ecosystems.
In addition, holistic approaches to designing management strategies are required to both increase resilience of coral reefs and maximize the benefits of the ecosystem services they provide.
Due to the intrinsic complexity and spatial variability of coral reef ecosystems, management cannot be designed using a “one size fits all” approach. Instead, local dynamics and stressors need to be carefully considered.
Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of non‐syndromic oral cleft
Authors: Wang P , Wu T , Schwender H , Wang H , Shi B , Wang ZQ , Yuan Y , Liu DJ , Wang MY , Li J , Zhou ZB , Zhu HP , Beaty TH 
Published: January 2018

ObjectiveLittle consistent evidence is available for the association between the risk of non‐syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene–gene (G×G) interaction.Subjects and methodsWe selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case–parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted.ResultsWe found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine‐homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10−12).ConclusionsOur study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.
Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial
Authors: Gao Tina Y. , Anstice Nicola , Babu Raiju J. , Black Joanna M. , Bobier William R. , Dai Shuan , Guo Cindy X. , Hess Robert F. , Jenkins Michelle , Jiang Yannan , Kearns Lisa , Kowal Lionel , Lam Carly S. Y. , Pang Peter C. K. , Parag Varsha , South Jayshree , Staffieri Sandra Elfride , Wadham Angela , Walker Natalie , Thompson Benjamin ,   the Binocular Treatment of Amblyopia Using Videogames (BRAVO) Study Team
Published: January 2018

AbstractPurposeOptical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults.MethodsWe examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30–1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e‐ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial.ResultsEighty participants (mean age 24.6 years, range 7.6–55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t‐test p < 0.0001). Twenty‐five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction.Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow‐up and four (44%) showed further VA improvements.ConclusionsImprovements from optical treatment resulted in one‐fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.
Plasma metabolome analysis of patients with major depressive disorder
Authors: Kawamura Noriyuki , Shinoda Kosaku , Sato Hajime , Sasaki Kazunori , Suzuki Makoto , Yamaki Kumi , Fujimori Tamaki , Yamamoto Hiroyuki , Osei‐Hyiaman Douglas , Ohashi Yoshiaki 
Published: January 2018

AimThis study sought to characterize the plasma metabolite profiling of patients with major depressive disorder (MDD).MethodsPsychiatric assessments were made with the Structured Clinical Interview for DSM‐IV Axis I Disorders. In the exploratory cohort, plasma metabolite profiles of 34 MDD patients and 31 mentally healthy controls were compared using capillary electrophoresis‐mass spectrometry. Among the candidate metabolites, we focused on a metabolite showing the largest difference. The absolute concentrations were measured in two cohorts from a psychiatric primary care clinic to characterize the accuracy of the metabolite biomarker.ResultsAmong 23 metabolites significantly lower in the MDD group than in healthy controls, we focused on phosphoethanolamine (PEA) as a candidate. The reduction of PEA levels in MDD was checked in independent clinical sample sets. An ion‐chromatography‐fluorescence detection method was developed to measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43 non‐MDD subjects. The area under the receiver–operator curve (AUC) was 0.92, with sensitivity/specificity greater than 88%, at a cut‐off of 1.46 μM. In the checking cohort, with 10 MDD and 13 non‐MDD subjects, AUC was 0.89, with sensitivity/specificity of 86% and 100%, respectively, at a cut‐off of 1.48 μM. Plasma PEA inversely correlated with MDD severity, depressed mood, loss of interest, and psychomotor retardation.ConclusionThese results suggest that plasma PEA level could be a candidate biomarker of MDD in the clinical setting. Further studies comparing MDD and mentally healthy controls are needed to confirm the utility of PEA as a biomarker for depression.
Understanding the roles of glutamine synthetase, glutaminase, and glutamate decarboxylase autoantibodies in imbalanced excitatory/inhibitory neurotransmission as etiological mechanisms of autism
Authors: Hamed Najat O. , Al‐Ayadhi Laila , Osman Mohamed A. , Elkhawad Abdalla O. , Qasem Hanan , Al‐Marshoud Majida , Merghani Nada M. , El‐Ansary Afaf 
Published: January 2018

AimAutism is a heterogeneous neurological disorder that is characterized by impairments in communication and social interactions, repetitive behaviors, and sensory abnormalities. The etiology of autism remains unclear. Animal, genetic, and post‐mortem studies suggest that an imbalance exists in the neuronal excitation and inhibition system in autism. The aim of this study was to determine whether alterations of the measured parameters in children with autism are significantly associated with the risk of a sensory dysfunction.MethodsThe glutamine synthetase (GS), kidney‐type glutaminase (GLS1), and glutamic acid decarboxylase autoantibody levels were analyzed in 38 autistic children and 33 age‐ and sex‐matched controls using enzyme‐linked immunosorbent assays.ResultsThe obtained data demonstrated significant alterations in glutamate and glutamine cycle enzymes, as represented by GS and GLS1, respectively. While the glutamic acid decarboxylase autoantibodies levels were remarkably increased, no significant difference was observed compared to the healthy control participants.ConclusionThe obtained data indicate that GS and GLS1 are promising indicators of a neuronal excitation and inhibition system imbalance and that combined measured parameters are good predictive biomarkers of autism.
Results of early treatment for de novo donor‐specific antibodies in pediatric kidney transplant recipients in a cross‐sectional and longitudinal cohort
Authors: Charnaya Olga , Tuchman Shamir , Moudgil Asha 
Published: January 2018

AbstractThe development of dnDSA anti‐HLA antibodies has been shown to be a significant risk factor for graft failure. In 2008, we instituted a routine protocol of standardized monitoring and treatment of dnDSA in pediatric kidney transplant recipients. Of 67 first‐time pediatric kidney transplant recipients, 26 (38%) developed dnDSA after 1.36 (IQ 1‐2.14) years. Coefficient of variance of tacrolimus, a surrogate marker of non‐adherence, was found to be the single most important risk factor for dnDSA development. Overall, there was a significant reduction in dnDSA with treatment in 19 (76%) children. No difference in graft survival and estimated glomerular filtration rate was noted between dnDSA negative and those treated for dnDSA. There was an increased risk of hospitalization in those treated for dnDSA. This study suggests that early detection and treatment of dnDSA can help to prevent graft failure and preserve graft function in the short term. Future studies and longer follow‐up are needed to fully elucidate the effect of early detection and treatment of dnDSA in pediatric kidney transplant recipients.
Mathematical Demonstration and Experimental Activity: A Wittgensteinian Philosophy of Physics
Authors: Bitbol Michel 
Published: January 2018

AbstractThis article aims at reducing the gap between mathematics and physics from a Wittgensteinian point of view. This gap is usually characterized by two discriminating features. (1) The propositions of physics assert something which might be false; they have a hypothetical character. On the contrary, since mathematical propositions are rules that condition the form of assertions, they remain immune from falsification. (2) The propositions of physics refer to facts that may confirm or refute them. On the contrary, since mathematical propositions have no meaning independently of the demonstration procedures, it cannot be said that they refer to “facts” that pre‐exist demonstrations. If we take a closer look, however, these two differences fade away. On the one hand, the propositions of physics are more resistant to experimental tests than has been said in the wake of logical positivism. On the other hand, the “factual” empirical material is defined and co‐constituted by instruments whose arrangement is determined by the theory to be tested (just as mathematical propositions are defined and co‐constituted by demonstration procedures). I conclude by discussing the possibility of a Wittgensteinian philosophy of contemporary physics.
MUN (MERISTEM UNSTRUCTURED), encoding a SPC24 homolog of NDC80 kinetochore complex, affects development through cell division in Arabidopsis thaliana
Authors: Shin Jinwoo , Jeong Goowon , Park Jong‐Yoon , Kim Hoyeun , Lee Ilha 
Published: January 2018

SummaryKinetochore, a protein super‐complex on the centromere of chromosomes, mediates chromosome segregation during cell division by providing attachment sites for spindle microtubules. The NDC80 complex, composed of four proteins, NDC80, NUF2, SPC24 and SPC25, is localized at the outer kinetochore and connects spindle fibers to the kinetochore. Although it is conserved across species, functional studies of this complex are rare in Arabidopsis. Here, we characterize a recessive mutant, meristem unstructured‐1 (mun‐1), exhibiting an abnormal phenotype with unstructured shoot apical meristem caused by ectopic expression of the WUSCHEL gene in unexpected tissues. mun‐1 is a weak allele because of the insertion of T‐DNA in the promoter region of the SPC24 homolog. The mutant exhibits stunted growth, embryo arrest, DNA aneuploidy, and defects in chromosome segregation with a low cell division rate. Null mutants of MUN from TALEN and CRISPR/Cas9‐mediated mutagenesis showed zygotic embryonic lethality similar to nuf2‐1; however, the null mutations were fully transmissible via pollen and ovules. Interactions among the components of the NDC80 complex were confirmed in a yeast two‐hybrid assay and in planta co‐immunoprecipitation. MUN is co‐localized at the centromere with HTR12/CENH3, which is a centromere‐specific histone variant, but MUN is not required to recruit HTR12/CENH3 to the kinetochore. Our results support that MUN is a functional homolog of SPC24 in Arabidopsis, which is required for proper cell division. In addition, we report the ectopic generations of stem cell niches by the malfunction of kinetochore components.
A multi‐parent advanced generation inter‐cross (MAGIC) population for genetic analysis and improvement of cowpea (Vigna unguiculata L. Walp.)
Authors: Huynh Bao‐Lam , Ehlers Jeffrey D. , Huang Bevan Emma , Muñoz‐Amatriaín María , Lonardi Stefano , Santos Jansen R. P. , Ndeve Arsenio , Batieno Benoit J. , Boukar Ousmane , Cisse Ndiaga , Drabo Issa , Fatokun Christian , Kusi Francis , Agyare Richard Y. , Guo Yi‐Ning , Herniter Ira , Lo Sassoum , Wanamaker Steve I. , Xu Shizhong , Close Timothy J. , Roberts Philip A. 
Published: January 2018

SummaryMulti‐parent advanced generation inter‐cross (MAGIC) populations are an emerging type of resource for dissecting the genetic structure of traits and improving breeding populations. We developed a MAGIC population for cowpea (Vigna unguiculata L. Walp.) from eight founder parents. These founders were genetically diverse and carried many abiotic and biotic stress resistance, seed quality and agronomic traits relevant to cowpea improvement in the United States and sub‐Saharan Africa, where cowpea is vitally important in the human diet and local economies. The eight parents were inter‐crossed using structured matings to ensure that the population would have balanced representation from each parent, followed by single‐seed descent, resulting in 305 F8 recombinant inbred lines each carrying a mosaic of genome blocks contributed by all founders. This was confirmed by single nucleotide polymorphism genotyping with the Illumina Cowpea Consortium Array. These lines were on average 99.74% homozygous but also diverse in agronomic traits across environments. Quantitative trait loci (QTLs) were identified for several parental traits. Loci with major effects on photoperiod sensitivity and seed size were also verified by biparental genetic mapping. The recombination events were concentrated in telomeric regions. Due to its broad genetic base, this cowpea MAGIC population promises breakthroughs in genetic gain, QTL and gene discovery, enhancement of breeding populations and, for some lines, direct releases as new varieties.
Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells
Authors: Peyrusson Frédéric , Tulkens Paul M. , Van Bambeke Françoise 
Published: January 2018

ABSTRACTGepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examinedin vitroits activity against intracellularStaphylococcus aureus(involved in the persistent character of skin and skin structure infections) by use of a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (the apparent bacteriostatic concentration [Cs] was reached at an extracellular concentration about 0.7× its MIC and was not affected by mechanisms of resistance to the comparators) and (ii) caused a maximal reduction of the intracellular burden (maximum effect) of about −1.6 log10CFU (which was better than that caused by linezolid, macrolides, and daptomycin and similar to that caused by moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100× their MIC, the intracellular persisting fraction was <0.1% with moxifloxacin, 0.5% with gepotidacin, and >1% with the other drugs. The accumulation and efflux of gepotidacin in phagocytes were very fast (kinandkout, ∼0.3 min−1; the plateau was reached within 15 min) but modest (intracellular concentration-to-extracellular concentration ratio, ∼1.6). In cell fractionation studies, about 40 to 60% of the drug was recovered in the soluble fraction and ∼40% was associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses.
Partially Reciprocal Replacement of FlrA and FlrC in Regulation of Shewanella oneidensis Flagellar Biosynthesis
Authors: Gao Tong , Shi Miaomiao , Gao Haichun 
Published: January 2018

ABSTRACTIn some bacteria with a polar flagellum, an established regulatory hierarchy controlling stepwise assembly of the organelle consists of four regulators: FlrA, σ54, FlrBC, and σ28. Because all of these regulators mediate the expression of multiple targets, they are essential to the assembly of a functional flagellum and therefore to motility. However, this is not the case for the gammaproteobacteriumShewanella oneidensis: cells lacking FlrB, FlrC, or both remain flagellated and motile. In this study, we unravel the underlying mechanism, showing that FlrA and FlrC are partially substitutable for each other in regulating flagellar assembly. While both regulators are bacterial enhancer binding proteins (bEBPs) for σ54, FlrA differs from FlrC in its independence of σ54for its own transcription and its inability to activate the flagellin geneflaA. These differences largely account for the distinct phenotypes resulting from the loss or overproduction of FlrA and FlrC.IMPORTANCEThe assembly of a polar flagellum in bacteria has been characterized as relying on four regulators, FlrA, σ54, FlrBC, and σ28, in a hierarchical manner. They all are essential to the process and therefore to motility, except inS. oneidensis, in which FlrB, FlrC, or both together are not essential. Here we show that FlrA and FlrC, as bEBPs, are partially reciprocal in functionality in this species. As a consequence, the presence of one allows flagellar assembly and motility in the other's absence. Despite this, there are significant differences in the physiological roles played by these two regulators: FlrA is the master regulator of flagellar assembly, whereas FlrC fine-tunes motility. These intriguing observations open up a new avenue to further exploration of the regulation of flagellar assembly.
Epstein-Barr Virus (EBV) Latent Protein EBNA3A Directly Targets and Silences the
STK39
Gene in B Cells Infected by EBV
Authors: Bazot Quentin , Paschos Kostas , Allday Martin J. 
Published: January 2018

ABSTRACT

Epstein-Barr virus (EBV) establishes latent infection in human B cells and is associated with a wide range of cancers. The EBV nuclear antigen 3 (EBNA3) family proteins are critical for B cell transformation and function as transcriptional regulators. It is well established that EBNA3A and EBNA3C cooperate in the regulation of cellular genes. Here, we demonstrate that the gene
STK39
is repressed only by EBNA3A. This is the first example of a gene regulated only by EBNA3A in EBV-transformed lymphoblastoid cell lines (LCLs) without the help of EBNA3C. This was demonstrated using a variety of LCLs carrying either knockout, revertant, or conditional EBNA3 recombinants. Investigating the kinetics of EBNA3A-mediated changes in
STK39
expression showed that
STK39
becomes derepressed quickly after EBNA3A inactivation. This derepression is reversible as EBNA3A reactivation represses
STK39
in the same cells expressing a conditional EBNA3A.
STK39
is silenced shortly after primary B cell infection by EBV, and no
STK39
-encoded protein (SPAK) is detected 3 weeks postinfection. Chromatin immunoprecipitation (ChIP) analysis indicates that EBNA3A directly binds to a regulatory region downstream of the
STK39
transcription start site. For the first time, we demonstrated that the polycomb repressive complex 2 with the deposition of the repressive mark H3K27me3 is not only important for the maintenance of an EBNA3A target gene (
STK39
) but is also essential for the initial establishment of its silencing. Finally, we showed that DNA methyltransferases are involved in the EBNA3A-mediated repression of
STK39
.

IMPORTANCE
EBV is well known for its ability to transform B lymphocytes to continuously proliferating lymphoblastoid cell lines. This is achieved in part by the reprogramming of cellular gene transcription by EBV transcription factors, including the EBNA3 proteins that play a crucial role in this process. In the present study, we found that EBNA3A epigenetically silences
STK39
. This is the first gene where EBNA3A has been found to exert its repressive role by itself, without needing its coregulators EBNA3B and EBNA3C. Furthermore, we demonstrated that the polycomb repressor complex is essential for EBNA3A-mediated repression of
STK39
. Findings in this study provide new insights into the regulation of cellular genes by the transcription factor EBNA3A.