bluuebunny/crossref_metadata_2025_split huggingface dataset:
Executive Functioning in Pediatric Solid Organ Transplant Recipients: A Meta-analytic Review
Authors: Cushman Grace K. , Stolz Mary Gray , Blount Ronald L. , Reed Bonney 
Published: September 2019

Background.
Examining executive functioning (EF) posttransplant has become increasingly prevalent, as EF deficits are associated with poor disease-related outcomes and psychosocial functioning. The purpose of the current meta-analysis was to compare overall and domain-specific EF between healthy youth and those with a kidney, heart, or liver transplant, and identify moderating variables related to EF differences between these 2 groups.

Methods.
A literature search of PsycINFO, Pubmed, and Medline was conducted for eligible articles published until January 2019. Twenty studies met eligibility criteria and were included in the present meta-analysis.

Results.
Results from the random-effects model indicated a significant standardized mean difference in overall EF skills with transplant recipients demonstrating worse EF (g = 0.40; 95% confidence interval [CI], 0.29-0.50) than healthy youth. Specifically, transplanted youth had worse working memory (g = 0.33; 95% CI, 0.01-0.66), processing speed (g = 0.41; 95% CI, 0.19-0.62), attentional control (g = 0.53; 95% CI, 0.33-0.73), and metacognitive skills (g = 0.36; 95% CI, 0.18-0.54). Assessment type and time since transplantation were not significant moderators.

Conclusions.
Pediatric solid organ transplant recipients demonstrate worse overall EF skills and deficits in working memory, processing speed, attentional control, and metacognitive skills. Many children who have undergone solid organ transplantation will require additional support in medical and academic settings because of deficits in various EF domains.
Cell-wall synthases contribute to bacterial cell-envelope integrity by actively repairing defects
Authors: Vigouroux Antoine , Cordier Baptiste , Aristov Andrey , Oldewurtel Enno , Özbaykal Gizem , Chaze Thibault , Matondo Mariette , Bikard David , van Teeffelen Sven 
Published: September 2019

AbstracCell shape and cell-envelope integrity of bacteria are determined by the peptidoglycan cell wall. In rod-shapedEscherichia coli, two conserved sets of machinery are essential for cell-wall insertion in the cylindrical part of the cell, the Rod complex and the class-A penicillin-binding proteins (aPBPs). While the Rod complex governs rod-like cell shape, aPBP function is less well understood. aPBPs were previously hypothesized to either work in concert with the Rod complex or to independently repair cell-wall defects. First, we demonstrate through modulation of enzyme levels that class-A PBPs do not contribute to rod-like cell shape but are required for mechanical stability, supporting their independent activity. By combining measurements of cell-wall stiffness, cell-wall insertion, and PBP1b motion at the single-molecule level we then demonstrate that PBP1b, the major class-A PBP, contributes to cell-wall integrity by localizing and inserting peptidoglycan in direct response to local cell-wall defects.
DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status
Authors: Kataoka Yuki , Iimori Makoto , Fujisawa Ryo , Morikawa-Ichinose Tomomi , Niimi Shinichiro , Wakasa Takeshi , Saeki Hiroshi , Oki Eiji , Miura Daisuke , Tsurimoto Toshiki , Maehara Yoshihiko , Kitao Hiroyuki 
Published: September 2019

ABSTRACTDNA replication stress is a predominant cause of genome instability, a driver of tumorigenesis and malignant progression. Nucleoside analog-type chemotherapeutic drugs introduce DNA damage and exacerbate DNA replication stress in tumor cells. However, the mechanisms underlying tumor cytotoxicity triggered by the drugs are not fully understood. Here, we show that the fluorinated thymidine analog trifluridine (FTD), an active component of the chemotherapeutic drug trifluridine/tipiracil, delayed DNA synthesis by human replicative DNA polymerases. FTD acted as an inefficient deoxyribonucleotide triphosphate source (FTD triphosphate) and as an obstacle base (trifluorothymine) in the template DNA strand. At the cellular level, FTD decreased thymidine triphosphate in the dNTP pool and induced FTD triphosphate accumulation, resulting in replication fork stalling caused by FTD incorporation into DNA. DNA lesions involving single-stranded DNA were generated as a result of replication fork stalling, and the p53-p21 pathway was activated. Although FTD suppressed tumor cell growth irrespective of p53 status, tumor cell fate diverged at the G2/M phase transition according to p53 status; tumor cells with wild-type p53 underwent cellular senescence via mitosis skip, whereas tumor cells that lost wild-type p53 underwent apoptotic cell death via aberrant late mitosis with severely impaired separation of sister chromatids. These results suggest that DNA replication stress induced by a nucleoside analog-type chemotherapeutic drug triggers tumor cytotoxicity by determining tumor cell fate according to p53 status.SignificanceThis study identified a unique type of DNA replication stress induced by trifluridine, which directs tumor cell fate either toward cellular senescence or apoptotic cell death according to p53 status.
Is the distribution of the Acorn Woodpecker (Melanerpes formicivorus flavigula) associated with oaks and granaries? A local study in an urban area in northern South America
Authors: Oikawa Hana Londoño , Pulgarín-R Paulo C. 
Published: September 2019

ABSTRACTAbiotic and biotic factors are known to be key in limiting the geographical distribution of species. However, our understanding on the influence of habitat heterogeneity on ecological interactions and behavior in tropical animals is limited. We studied groups of Acorn Woodpeckers (Melanerpes formicivorus flavigula) in urban and rural areas in northern South America to understand how habitat and resource requirements (food storage structures) influences patterns of distribution across the Aburrá Valley, in the northern area of the Central Andes of Colombia. Using focal observations of 10 different groups over nearly a two-year period, we estimated territory size, habitat use, and described the use and presence of granaries. We found that territory size, tree diversity, and the use of granaries varied among groups. Accordingly, Acorn Woodpeckers use a wide variety of tree species to make cavities, to feed and to build granaries for social interactions. Our study supports the hypothesis that Acorn Woodpeckers do not rely on the Colombian Oak (Quercus humboldtiiBonpl.) for feeding, nesting or foraging in the Aburrá Valley, and that the construction of granaries to store food is present in urban populations, despite the lack of strong seasonal changes in tropical areas. We suggest that the distribution of the Acorn Woodpecker in our study area is strongly associated with one particular species of tree,Albizia carbonariaBritton, and the behavior of granaries construction might be hardwired in this species for the maintenance and cohesion of family groups.
European maize genomes unveil pan-genomic dynamics of repeats and genes
Authors: Haberer G. , Bauer E. , Kamal N. , Gundlach H. , Fischer I. , Seidel M.A. , Spannagl M. , Marcon C. , Ruban A. , Urbany C. , Nemri A. , Hochholdinger F. , Ouzunova M. , Houben A. , Schön C.-C. , Mayer K.F.X. 
Published: September 2019

AbstractThe exceptional diversity of maize (Zea mays) is the backbone of modern heterotic patterns and hybrid breeding. Historically, US farmers exploited this variability to establish today’s highly productive Corn Belt inbred lines from blends of dent and flint germplasm pools. Here, we report high qualityde novogenome sequences of the four European flint lines EP1, F7, DK105 and PE0075 assembled to pseudomolecules with scaffold N50 ranging between 6.1 to 10.4 Mb. Comparative analyses with the two US Corn Belt genomes B73 and PH207 elucidates the pronounced differences between both germplasm groups. While overall syntenic order and consolidated gene annotations reveal only moderate pan-genomic differences, whole genome alignments delineating the core and dispensable genome, and the analysis of repeat structures, heterochromatic knobs and orthologous long terminal repeat retrotransposons (LTRs) unveil the extreme dynamics of the maize genome. Haplotypes derived from core genome SNPs demonstrate the tessellation of modern maize resulting from a complex breeding history. The high quality genome sequences of the flint pool are a crucial complement to the maize pan-genome and provide an important tool to study maize improvement at a genome scale and to enhance modern hybrid breeding.
Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR
Authors: Puig Marta , Lerga-Jaso Jon , Giner-Delgado Carla , Pacheco Sarai , Izquierdo David , Delprat Alejandra , Gayà-Vidal Magdalena , Regan Jack F. , Karlin-Neumann George , Cáceres Mario 
Published: September 2019

ABSTRACTDespite the interest in characterizing all genomic variation, the presence of large repeats at the breakpoints of many structural variants hinders their analysis. This is especially problematic in the case of inversions, since they are balanced changes without gain or loss of DNA. Here we tested novel linkage-based droplet digital PCR (ddPCR) assays on 20 inversions ranging from 3.1 to 742 kb and flanked by long inverted repeats (IRs) of up to 134 kb. Among these, we validated 13 inversions predicted by different genome-wide techniques. In addition, we have generated new experimental human population information across 95 African, European and East-Asian individuals for 16 of them, including four already known inversions for which there were no high-throughput methods to determine directly the orientation, like the well-characterized 17q21 inversion. Through comparison with previous data, independent replicates and both inversion breakpoints, we have demonstrated that the technique is highly accurate and reproducible. Most of the studied inversions are frequent and widespread across continents, showing a negative correlation with genetic length. Moreover, all except two show clear signs of being recurrent, and the new data allowed us to define more clearly the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, thanks to the generated genotypes, we have been able to check inversion functional effects in multiple tissues, validating gene expression differences reported before for two inversions and finding new candidate associations. Our work therefore provides a tool to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications.
Ciprofloxacin facilitates the transfer of XDR plasmids from commensalE. coliinto epidemic fluoroquinolone-resistantShigella sonnei
Authors: Duy Pham Thanh , Nguyen To Nguyen Thi , Thuy Duong Vu , The Hao Chung , Alcock Felicity , Boinett Christine , Thanh Ho Ngoc Dan , Tuyen Ha Thanh , Thwaites Guy E. , Rabaa Maia A , Baker Stephen 
Published: September 2019

AbstractThe global dissemination of a ciprofloxacin-resistant (cipR)S. sonneiclone outlines the mobility of this important agent of diarrheal disease, and threatens the utility of ciprofloxacin as a first-line antimicrobial for shigellosis. Here, we aimed to track the emergence of cipRS. sonneiin Vietnam to understand how novel antimicrobial resistant (AMR)Shigellaclones become established in new locations. From 2014 to 2016, we isolated and genome sequenced 79S. sonneifrom children hospitalized with dysenteric diarrhea in southern Vietnam. The novel cipRS. sonneiclone displaced the resident ciprofloxacin-susceptible lineage while acquiring resistance against third-generation cephalosporins, macrolides, and aminoglycosides. This process was not the result of a single clonal expansion, as we identified at least thirteen independent acquisitions of ESBL-encoding plasmids. The frequency and diversity of the variable AMR repertoire in an expanding clonal background ofS. sonneiis unprecedented and we speculated that it was facilitated by horizontal gene transfer from commensal organisms in the human gut. Consequently, we characterized non-ShigellaEnterobacteriaceae fromShigella-infected and healthy children by shotgun metagenomics. We identified a wide array of AMR genes and plasmids in the commensal Enterobacteriaceae, including anE. coliisolated from aShigella-infected child with an identical ESBL plasmid to that characterized in the infectingS. sonnei. We confirmed that these AMR plasmids could be exchanged between commensalE. coliandS. sonneiand found that supplementation of ciprofloxacin into the conjugation media significantly increased the conjugation frequency of IncI/blaCTX-M-15, IncB/O/blaCTX-M-27and IncF/blaCTX-M-27plasmids. In a setting with high antimicrobial use and a high prevalence of AMR commensals, cipRS. sonneimay be propelled towards pan-resistance by adherence to outdated international treatment guidelines. Our work highlights the role of the gut microbiota in transferring resistance plasmids into enteric pathogens and provides essential data to restrict the use of ciprofloxacin globally.
Dynamic production and loss of flagellar filaments during the bacterial life cycle
Authors: Zhuang Xiang-Yu , Guo Shihao , Li Zhuoran , Zhao Ziyi , Kojima Seiji , Homma Michio , Wang Pengyuan , Lo Chien-Jung , Bai Fan 
Published: September 2019

AbstractBacterial flagella are large extracellular protein organelles that drive bacteria motility and taxis in response to environmental changes. Previous research has focused mostly on describing the flagellar assembly, its rotation speed and power output. However, whether flagella are permanent cell structures and, if not, the circumstances and timing of their production and loss during the bacterial life cycle remain poorly understood. Here we used the single polar flagellum ofVibrio alginolyticusas our model and, usingin vivofluorescence imaging, revealed that the percentage of flagellated bacteria (PFB) in a population varies substantially across different bacterial growth phases. In the early-exponential phase, the PFB increases rapidly in respect to incubation time, mostly through widespread flagella production. In the mid-exponential phase, the PFB peaks at around 76% and the partitioning of flagella between the daughter cells is 1:1 and strictly at the old poles. After entering the stationary phase, the PFB starts to decline, mainly because daughter cells stop making new flagella after cell division. Interestingly, we discovered that bacteria can actively abandon flagella after prolonged stationary culturing, though cell division has long been suspended. Lack of glucose was found to be a major factor promoting flagellar disassembly. We also revealed that the active loss of flagella was initiated by breakage in the rod connecting the extracellular filament to the basal body formed by MS- and C-rings. Our results highlight the dynamic production and loss of flagellar filaments during the bacterial life cycle.
Extinction probabilities, times to extinction, basic reproduction number and growth rates for tsetse (Glossinaspp) populations as a function of temperature
Authors: Are Elisha B. , Hargrove John W. 
Published: September 2019

AbstractIncreases in temperature over recent decades have led to a significant reduction in the populations of tsetse flies (Glossinaspp) in parts of the Zambezi Valley of Zimbabwe. If this is true for other parts of Africa, populations of tsetse may actually be going extinct in some parts of the continent. Extinction probabilities for tsetse populations have not so far been estimated as a function of temperature. We develop a time-homogeneous branching process model for situations where tsetse flies live at different levels of fixed temperatures. We derive a probability distributionpk(T) for the number of female offspring an adult female tsetse is expected to produce in her lifetime, as a function of the fixed temperature at which she is living. We show thatpk(T) can be expressed as a geometric series: its generating function is therefore a fractional linear type. We obtain expressions for the extinction probability, expected number of female offspring per female tsetse, and time to extinction. No tsetse population can escape extinction if subjected, for extended periods, to temperatures outside the range 16 °C - 32°C. Extinction probability increases more rapidly as temperatures approach and exceed the upper and lower limits. If the number of females is large enough, the population can still survive even at high temperatures (28°C - 31°C). Small decreases or increases in constant temperature in the neighbourhoods of 16°C and 31°C, respectively, can drive tsetse populations to extinction. Further study is needed to estimate extinction probabilities for tsetse populations in field situations where temperatures vary continuously.Author summaryTsetse flies (Glossinaspp) are the vectors of the African sleeping sickness. We derived an expression for the extinction probability, and mean time to extinction, of closed populations of the flies experiencing different levels of fixed temperatures. Temperatures play a key role in tsetse population dynamics: no tsetse populations can escape extinction at constant temperatures < 16°C > 32°C. The effect of temperature is more severe if tsetse populations are already depleted. Increasingly high temperatures due to climate change may alter the distribution of tsetse populations in Africa. The continent may witness local extinctions of tsetse populations in some places, and appearances in places hitherto too cold for them.
Strategies to improve scFvs as crystallization chaperones suggested by analysis of a complex with the human PHD-bromodomain SP140
Authors: Fairhead Michael , Preger Charlotta , Wigren Edvard , Strain-Damerell Claire , Ossipova Elena , Ye Mingda , Makola Mpho , Burgess-Brown Nicola A. , Persson Helena , von Delft Frank , Gräslund Susanne 
Published: September 2019

AbstractAntibody fragments have great potential as crystallization chaperones for structural biology due to their ability to either stabilise targets, trap certain conformations and/or promote crystal packing. Here we present an example of using a single-chain variable fragment (scFv) to determine the previously unsolved structure of the multidomain protein SP140. This nuclear leukocyte-specific protein contains domains related to chromatin-mediated gene expression and has been implicated in various disease states. The structure of two of the domains (PHD-bromodomain) was solved by crystallizing them as a complex with a scFv generated by phage display technology. SP140 maintains a similar overall fold to previous PHD-bromodomains and the scFv CDR loops predominately interact with the PHD, while the framework regions of the scFv makes numerous interactions with the bromodomain. Analysis of our and other complex structures suggest various protein engineering strategies that might be employed to improve the usefulness of scFvs as crystallization chaperones.
Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission
Authors: Yeo Michele , Chen Yong , Jiang Changyu , Chen Gang , Wang Kaiyuan , Bortsov Andrey , Lioudyno Maria , Zeng Qian , Wang Zilong , Busciglio Jorge , Ji Ru-Rong , Liedtke Wolfgang 
Published: September 2019

AbstractInhibitory GABA-ergic neurotransmission is fundamental for the adult vertebrate central nervous system and requires low chloride ion concentration in neurons. This basic ionic-homeostatic mechanism relies on expression and function of KCC2, a neuroprotective ionic transporter that extrudes neuronal chloride. Importantly, no other transporter can rescue KCC2 deficit, and attenuated expression of KCC2 is strongly associated with circuit malfunction in chronic pain, epilepsy, neuro-degeneration, neuro-trauma, and other neuro-psychiatric illnesses. To isolate Kcc2 gene expression-enhancing compounds, we screened 1057 cell growth-regulating compounds in cultured primary cortical neurons. We identified kenpaullone (KP), which enhanced Kcc2/KCC2 expression and function in cultured rodent and human neurons by inhibiting GSK3ß. KP effectively reduced pathologic pain in preclinical mouse models of nerve constriction injury and bone cancer. In nerve-injury pain, KP restored Kcc2 expression and GABA-evoked chloride reversal potential in the spinal cord dorsal horn. Delta-catenin, a phosphorylation-target of GSK3ß in neurons, activated the Kcc2 promoter via Kaiso transcription factor. Validating this new pathway in-vivo, transient spinal over-expression of delta-catenin mimicked KP analgesia. With relevance for pathologic pain, our discoveries of a newly repurposed compound and a novel genetically-encoded mechanism that each enhance Kcc2 gene expression enable us to re-normalize disrupted inhibitory neurotransmission through genetic re-programming.
The RAF oncogenes of vertebrates are ohnologs that derive from the two rounds of whole genome duplications early in vertebrate evolution
Authors: Black Amanda Coward , Bailey Mary Clay , Ruane-Foster Marisa , Opazo Juan C. , Hoffmann Federico G. 
Published: September 2019

ABSTRACTThe Rapidly Accelerated Fibrosarcoma (RAF) kinases are part of large group of serine/threonine-specific protein kinases that play important roles in cell differentiation and organism development. Animal RAF kinases are key connectors in the signaling cascade that links the small G protein RAS and the Mitogen-activated protein kinase phosphorylation pathway. Mutations in the RAF genes have been linked to a number of cancers including melanoma, lung cancer, colorectal cancer, thyroid cancer, and ovarian cancer. Most animals possess a single RAF gene, but vertebrates have three RAF genes in their genomes, named as A-, B-, and C-RAF, the latter also known as RAF-1. The emergence of the multiple copies of vertebrate RAFs is not well resolved, on the one hand, because of sequence and functional similarities, some authors speculate that vertebrate B-Raf is most closely related to the RAF genes of the fruit fly and Caenorhabditis elegans, whereas a competing hypothesis is that the A-, B- and C-RAF paralogs emerged from the two rounds of whole genome duplications that occurred early in the evolution of vertebrates. We applied a comparative approach grounded in synteny and phylogenetic analyses to evaluate these two scenarios. Our results are consistent with the hypothesis that the RAF genes of vertebrates are paralogs generated by whole genome duplications. Thus, the functional similarities between vertebrate B-RAF and invertebrate RAF probably reflect the retention of ancestral characters. Interestingly, data from the literature indicate that B-RAF is the paralog that associated with cancer more strongly, and also yields the most severe phenotypes when knocked out.