bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cell cycle regulator GpsB functions as cytosolic adaptor for multiple cell wall enzymes
Authors: Cleverley Robert M. , Rutter Zoe J. , Rismondo Jeanine , Corona Federico , Tsui Ho-Ching Tiffany , Alatawi Fuad A. , Daniel Richard A. , Halbedel Sven , Massidda Orietta , Winkler Malcolm E. , Lewis Richard J. 
Published: September 2018

AbstractBacterial growth and cell division requires precise spatiotemporal regulation of the synthesis and remodelling of the peptidoglycan layer that surrounds the cytoplasmic membrane. GpsB is a cytosolic protein that affects cell wall synthesis by binding to the cytoplasmic mini-domains of peptidoglycan synthases to ensure their correct subcellular localisation. Here we have discovered critical structural features for the interaction of GpsB with peptidoglycan synthases from three different bacteria and demonstrated their importance for cell wall growth and viability. We have used these structural motifs to predict and confirm novel partners of GpsB in Bacillus subtilis, illuminating the role of this key regulator of peptidoglycan synthesis. GpsB thus functions as an adaptor, to mediate the interaction between membrane proteins, scaffolding proteins, signalling proteins and enzymes to generate larger protein complexes at specific sites in a bacterial cell cycle-dependent manner. Given the importance of GpsB in pathogenic bacteria, this study has not only revealed mechanistic details of how cell wall synthesis is co-ordinated with the bacterial cell cycle but could also represent a starting point for the design of much needed new antibiotics.
Subcutaneous Neurotrophin-3 infusion induces corticospinal neuroplasticity and improvements in dexterity and walking in elderly rats after large cortical stroke
Authors: Duricki Denise , Kakanos Sotiris , Haenzi Barbara , Wayman Christina , Bödecker Nora , Vogelgesang Antje , Cash Diana , Moon Lawrence 
Published: September 2018

AbstractThere is an urgent need for a therapy which reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. Neurotrophin-3 (NT3) is a growth factor made by muscle spindles and skin which is required for the survival, development and function of locomotor circuits involving afferents from muscle and skin that mediate proprioception and tactile sensation. Its level declines in muscle and other tissues postnatally. We show that levels of NT-3 in the bloodstream were low in humans with ischemia stroke relative to young healthy controls. Accordingly, we set out to determine whether subcutaneous delivery of NT3 improves sensorimotor recovery after stroke in elderly rats. We show that one-month-long subcutaneous infusion of NT3 protein induces sensorimotor recovery after cortical stroke in elderly rats. Specifically, in a randomised, blinded pre-clinical trial, we show improved dexterity, walking and sensory function in rats following cortical ischemic stroke when treatment with NT3 is initiated 24 hours after stroke. Importantly, NT-3 was given in a clinically feasible time frame via this straightforward route. MRI and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, anterograde tracing showed that corticospinal axons from the less-affected hemisphere sprouted in the spinal cord from cervical levels 2 to 8. Importantly, Phase I and II clinical trials by others show that repeated, subcutaneously administered high doses of recombinant NT-3 are safe and well tolerated in humans with other conditions. This paves the way for NT-3 as a therapy for stroke.
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy
Authors: Hebebrand Moritz , Hüffmeier Ulrike , Uebe Steffen , Ekici Arif B. , Kraus Cornelia , Krumbiegel Mandy , Reis André , Thiel Christian T. , Popp Bernt 
Published: September 2018

ABSTRACTBackgroundThe TUBA1A-associated tubulinopathy is clinically heterogeneous with brain malformations, microcephaly, developmental delay and epilepsy being the main clinical features. It is an autosomal dominant disorder mostly caused by de novo variants in TUBA1A.ResultsIn three individuals with developmental delay we identified heterozygous de novo missense variants in TUBA1A using exome sequencing. While the c.1307G>A, p.(Gly436Asp) variant was novel, the two variants c.518C>T, p.(Pro173Leu) and c.641G>A, p.(Arg214His) were previously described. We compared the variable phenotype observed in these individuals with a carefully conducted review of the current literature and identified 166 individuals, 146 born and 20 fetuses with a TUBA1A variant. In 107 cases with available clinical information we standardized the reported phenotypes according to the Human Phenotype Ontology. The most commonly reported features were developmental delay (98%), anomalies of the corpus callosum (96%), microcephaly (76%) and lissencephaly (70%), although reporting was incomplete in the different studies. We identified a total of 121 distinct variants, including 15 recurrent ones. Missense variants cluster in the C-terminal region around the most commonly affected amino acid position Arg402 (13.3%). In a three-dimensional protein modelling, 38.6% of all disease causing variants including those in the C-terminal region are predicted to affect binding of microtubule-associated proteins or motor proteins. Genotype-phenotype analysis for recurrent variants showed an overrepresentation of certain clinical features. However, individuals with these variants are often reported in the same publication.ConclusionsWith 166 individuals, we present the most comprehensive phenotypic and genotypic standardized synopsis for clinical interpretation of TUBA1A variants. Despite this considerable number, a detailed genotype-phenotype characterization is limited by large inter-study variability in reporting.
A FASII inhibitor prevents staphylococcal evasion of daptomycin by inhibiting phospholipid decoy production
Authors: Pee Carmen J. E. , Pader Vera , Ledger Elizabeth V. K. , Edwards Andrew M. 
Published: September 2018

AbstractDaptomycin is a treatment of last resort for serious infections caused by drug-resistant Gram-positive pathogens such as methicillin-resistantStaphylococcus aureus. We have shown recently thatS. aureuscan evade daptomycin by releasing phospholipid decoys that sequester and inactivate the antibiotic, leading to treatment failure. Since phospholipid release occurs via an active process we hypothesised that it could be inhibited, thereby increasing daptomycin efficacy. To identify opportunities for therapeutic interventions that block phospholipid release, we first determined how the host environment influenced the release of phospholipids and inactivation of daptomycin byS. aureus. The addition of certain host-associated fatty acids to the growth medium enhanced phospholipid release. However, in serum, the sequestration of fatty acids by albumin restricted their availability toS. aureussufficiently to prevent their use in the generation of released phospholipids. This finding implied that in host tissuesS. aureusis likely to be completely dependent upon endogenous phospholipid biosynthesis to generate lipids for release, providing a target for therapeutic intervention. To test this, we exposedS. aureusto AFN-1252, an inhibitor of the staphylococcal FASII fatty acid biosynthetic pathway, together with daptomycin. AFN-1252 efficiently blocked daptomycin-induced phospholipid decoy production, even in the case of isolates resistant to AFN-1252, which prevented the inactivation of daptomycin and resulted in sustained bacterial killing. In turn, daptomycin prevented the fatty acid-dependent emergence of AFN-1252-resistant isolates. In summary, AFN-1252 significantly enhances daptomycin activity againstS. aureusby blocking the production of phospholipid decoys, whilst daptomycin blocks the emergence of resistance to AFN-1252.
CRISPR-interference based modulation of mobile genetic elements in bacteria
Authors: Nyerges Ákos , Bálint Balázs , Cseklye Judit , Nagy István , Pál Csaba , Fehér Tamás 
Published: September 2018

ABSTRACTSpontaneous mutagenesis of synthetic genetic constructs by mobile genetic elements frequently results in the rapid loss of advantageous functions. Previous efforts to minimize such mutations required the exceedingly time-consuming manipulation of bacterial chromosomes and the complete removal of insertional sequences (ISes). To this aim, we developed a single plasmid-based system (pCRIS) that applies CRISPR-interference to inhibit the transposition of bacterial ISes. pCRIS expresses multiple guide RNAs to direct inactivated Cas9 (dCas9) to simultaneously silence IS1, IS3, IS5, and IS150at up to 38 chromosomal loci inEscherichia coli,in vivo. As a result, the transposition rate of all four targeted ISes dropped to negligible levels at both chromosomal and episomal targets, increasing the half-life of exogenous protein expression. Most notably, pCRIS, while requiring only a single plasmid delivery performed within a single day, provided a reduction of IS-mobility comparable to that seen in genome-scale chromosome engineering projects. Global transcriptomics analysis revealed nevertheless only minute alterations in the expression of untargeted genes. Finally, the transposition-silencing effect of pCRIS was easily transferable across multipleE. colistrains. The plasticity and robustness of our IS-silencing system make it a promising tool to stabilize bacterial genomes for synthetic biology and industrial biotechnology applications.
Study on physicochemical properties and microbial diversity of flammulina velutipes residue during rapid fermentation
Authors: Shi Guangying , Wang Yuxin , Wang Pingzhi , Gu Yizhu 
Published: September 2018

AbstractIn order to investigate the effects of different mass ratios of corn straw, super absorbent resin (SAR) and cellulose decomposing strains on fermentation of flammulina velutipes residue, the cellulose degradation rate, germination index, bacterial diversity, urease activity, cellulase activity and other indicators were evaluated comprehensively so as to determine the optimal fermentation parameters. The research results indicated that the three factors of corn straw, high water-absorbent resin (SAR), and cellulose-decomposing strains have the tendency to enhance fermentation in the process. In the orthogonal test, the treatment with the highest cellulose degradation rate was T6. By 24 days, all the treated seeds germination Indices (GIs) were higher than 80%, which indicated that they were basically harmless to crops. The cellulase activity and urease activity of each treatment showed the characteristics of first rising and then decreasing as the fermentation time prolonged. In general, the T6 (the added amount of corn straw was 10%, the amount of super absorbent resin was 0.15%, and the amount of cellulose-decomposing strains was 2%) was the suitable mass ratio of additives in the fermentation which provided a certain theoretical support for resource utilization of flammulina velutipes residue.
Food collection behavior ofApis melliferaandTetragonisca angustulabees inBrassica napusL. in response to different environmental covariates
Authors: Camargo Simone Cristina , Garcia Regina Conceição , de Oliveira Newton Tavares Escocard , de Vasconcelos Edmar Soares , Galhardo Douglas , Ströher Sandra Mara , Hartleben Alceu Maurício , Pires Bruno Garcia , Piñeros Gustavo Andrés Patiño , Díaz David Fernando Gómez , Ribeiro Renato de Jesus , Radtke Thiago Henrique , Santos Pedro da Rosa , de Toledo Vagner de Alencar Arnaut 
Published: September 2018

AbstractThe objective was to evaluate the behavior ofApis melliferaandTetragonisca angustulabees in pollination tests inBrassica napusat different times of the day, temperature and relative humidity. The experimental design was completely with eight treatments and two pollination tests, repeated in five randomized blocks during seven days of observations for two years, totaling 560 records. During the visits, the following parameters were recorded: collected resources, nectar collection site, time spent on flower, number of flowers visited in one minute, pollen load in the pollen basket and bee contact with anthers and stigma. Data were analyzed using generalized linear models. The number of Africanized andT. angustulabees collecting nectar increased with the passage of time throughout the day and with the decrease of relative humidity. The same was observed for nectar collection in both nectaries. The proportion of bees collecting pollen was higher in the morning hours, as well as when there was an increase in temperature for the two species of bees. Foraging behavior ofA. melliferainB. napuscrop favored its pollination, indifferent of which collected floral resource as they came into contact with anthers and stigma.T. angustulabees performed pollination only during pollen collection. Pollination ofB. napuswas more effective in the warmer hours of the morning, when more of both species of bees carried out pollen collection. Due to its foraging behavior,A. melliferahad greater efficiency for pollination ofB. napus; however, the association with T. angustulamay potentiate the benefits generated for the crop by cross-pollination.
Studies on effect of gold nanoparticles onMeloidogyne incognitaand tomato plants growth and development
Authors: Thakur Rajni Kant , Dhirta Babita , Shirkot Poonam 
Published: September 2018

AbstractThe plant parasitic nematodes are one of world major agricultural pest, causing in excess of 157 billion dollars in worldwide damage annually. This study has provided evidence that gold nanoparticles have great utility for management of root-knot nematodes in tomato crop. The effect of gold nanoparticles onMeloidogyne incognitaJ2 was remarkable under the direct exposure in water, after three hours of incubation of Meloidogyne incognita with GNPs showed the 100% mortality. The lesser survival rate ofMeloidogyne incognitain soil treatment showed the strong nematicidal effect of gold nanoparticles. Subsequently, the pot experiment had shown the beneficial effects of gold nanoparticles for intensively managing the root-knot nematode. The Pot experiment not only showed us that GNPs were lethal to root-knot nematodes were also induces growth of tomato plants and didn’t have any kind of negative impact on plant growth. In our study, GNPs were found to be safe and lethal to Meloidogyne incognita.
Microplastic-mediated transport of PCBs? A depuration study with Daphnia magna
Authors: Gerdes Zandra , Ogonowski Martin , Nybom Inna , Ek Caroline , Adolfsson-Erici Margaretha , Barth Andreas , Gorokhova Elena 
Published: September 2018

AbstractThe role of microplastic (MP) as a carrier of persistent organic pollutants (POPs) to aquatic organisms has been a topic of debate. However, theoretically, the reverse POP transport can occur at higher relative contaminant concentrations in the organism than in the microplastic. The effect of microplastic on the PCB removal in planktonic animals was evaluated using the cladoceran Daphnia magna with a high body burden of polychlorinated biphenyls (PCB 18, 40, 128 and 209) exposed to a mixture of microplastic and algae (with 77% MP by mass); daphnids exposed to only algae served as the control. As the endpoints, we used PCB body burden, growth, fecundity and elemental composition (%C and %N) of the daphnids. We found that PCB 209 was removed more efficiently in the daphnids fed with microplastic, while there was no difference for the ΣPCBs between the microplastic-exposed and control animals. Effects of the microplastic exposure on fecundity were of low biological significance, even though both the starting PCB body burden and the microplastic exposure concentrations were high and greatly exceeding environmentally relevant concentrations.
The functional organisation of the hippocampus along its long axis is gradual and predicts recollection
Authors: Przezdzik Izabela , Faber Myrthe , Fernández Guillén , Beckmann Christian F. , Haak Koen V. 
Published: September 2018

AbstractUnderstanding the functional organisation of the hippocampus is crucial for understanding its role in cognition and disorders in which it is implicated. Different views have been proposed of how function is distributed along its long axis: one view suggests segregation, whereas the alternative view postulates a more gradual organisation. Here, we applied a novel ‘connectopic mapping’ data-analysis approach to the resting-state fMRI data of participants of the Human Connectome Project, and demonstrate that the functional organisation of the hippocampal longitudinal axis is gradual rather than segregated into parcels. In addition, we show that inter-individual variations in this gradual organisation predicts variations in recollection memory better than a characterisation based on parcellation. These results present an important step forward in understanding the functional organisation of the human hippocampus and have important implications for translating between rodent and human research.
Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements
Authors: Deng Lin , Wu R. Alex. , Kochenova Olga V. , Pellman David , Walter Johannes C. 
Published: September 2018

SUMMARYDNA replication errors generate complex chromosomal rearrangements and thereby contribute to tumorigenesis and other human diseases. Although the events that trigger these errors are not well understood, one candidate is mitotic entry before the completion of DNA replication. To address the impact of mitosis on DNA replication, we employed Xenopus egg extracts. When mitotic CDK (Cyclin B1-CDK1) is used to drive these extracts into mitosis, the E3 ubiquitin ligase TRAIP promotes ubiquitylation of the replicative CMG (CDC45/MCM2–7/GINS) helicase at stalled forks and at forks that have completed DNA synthesis. In both cases, ubiquitylation is followed by CMG extraction from chromatin by the CDC48/p97 ATPase. At stalled forks, CMG removal results in fork breakage and complex end joining events involving deletions and template-switching. Our results identify TRAIP-dependent replisome disassembly as a novel trigger of replication fork collapse and propose it underlies complex DNA rearrangements in mitosis.HIGHLIGHTSTRAIP-dependent MCM7 ubiquitylation removes all CMGs from chromatin in mitosisCMG unloading from stalled forks causes replication fork breakageReplication fork breakage in mitosis causes complex rearrangementsNew model of replication fork collapse
Tightly-linked antagonistic-effect loci underlie polygenic demographic variation inC. elegans
Authors: Bernstein Max R. , Zdraljevic Stefan , Andersen Erik C. , Rockman Matthew V. 
Published: September 2018

AbstractRecent work has provided strong empirical support for the classic polygenic model for trait variation. Population-based findings suggest that most regions of genome harbor variation affecting most traits. This view is hard to reconcile with the experience of researchers who define gene functions using mutagenesis, comparing mutants one at a time to the wild type. Here, we use the approach of experimental genetics to show that indeed, most genomic regions carry variants with detectable effects on complex traits. We used high-throughput phenotyping to characterize demography as a multivariate trait in growing populations ofCaenorhabditis eleganssensitized by nickel stress. We show that demography under these conditions is genetically complex in a panel of recombinant inbred lines. We then focused on a 1.4-Mb region of the X chromosome. When we compared two near isogenic lines (NILs) that differ only at this region, they were phenotypically indistinguishable. When we used additional NILs to subdivide the region into fifteen intervals, each encompassing ~0.001 of the genome, we found that eleven of intervals have significant effects. These effects are often similar in magnitude to those of genome-wide significant QTLs mapped in the recombinant inbred lines but are antagonized by the effects of variants in adjacent intervals. Contrary to the expectation of small additive effects, our findings point to large-effect variants whose effects are masked by epistasis or linkage disequilibrium between alleles of opposing effect.
High-order theta harmonics account for the detection of slow gamma
Authors: Zhou Y. , Sheremet A. , Qin Y. , Kennedy J.P. , DiCola N.M. , Maurer A. P. 
Published: September 2018

ABSTRACTLocal field potential (LFP) oscillations are the superposition of excitatory/inhibitory postsynaptic potentials. In the hippocampus, the 20-55 Hz range (‘slow gamma’) is proposed to support cognition independent of other frequencies. However, this band overlaps with theta harmonics. We aimed to dissociate the generators of slow gamma versus theta harmonics with current source density and different LFP decompositions. Hippocampal theta harmonic and slow gamma generators were not dissociable. Moreover, comparison of wavelet, ensemble empirical-mode (EEMD), and Fourier decompositions produced distinct outcomes with wavelet and EEMD failing to resolve high-order theta harmonics well defined by Fourier analysis. The varying sizes of the time-frequency atoms used by wavelet distributed the higher-order harmonics over a broader range giving the impression of a low frequency burst (“slow gamma”). The absence of detectable slow gamma refutes a multiplexed model of cognition in favor of the energy cascade hypothesis in which dependency across oscillatory frequencies exists.
Interleukin-6 Receptor Signalling and Abdominal Aortic Aneurysm Growth Rates
Authors: Paige Ellie , Clément Marc , Lareyre Fabien , Sweeting Michael , Raffort Juliette , Grenier Céline , Finigan Alison , Harrison James , Peters James E. , Sun Benjamin B. , Butterworth Adam S. , Harrison Seamus C. , Bown Matthew J. , Lindholt Jes S. , Badger Stephen A. , Kullo Iftikhar J. , Powell Janet , Norman Paul E. , Scott D Julian A. , Bailey Marc A. , Rose-John Stefan , Danesh John , Freitag Daniel F. , Paul Dirk S. , Mallat Ziad 
Published: September 2018

AbstractBackgroundThe Asp358Ala variant (rs2228145; A>C) in the interleukin-6 receptor (IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth, and to assess the effect of blocking the IL-6 signalling pathway in mouse models of aneurysm rupture.MethodUsing data from 2,863 participants with AAA from nine prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/year). In a series of complementary randomised trials in mice, the effect of blocking the IL-6 signalling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter and time to aortic rupture and death.ResultsAfter adjusting for age and sex, baseline aneurysm size was 0.55mm (95% confidence interval [CI]: 0.13, 0.98mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. There was no evidence of a reduction in AAA growth rate (change in growth=-0.06mm per year [−0.18, 0.06] per copy of the minor allele). In two mouse models of AAA, selective blockage of the IL-6 trans-signalling pathway, but not combined blockage of both, the classical and trans-signalling pathways, was associated with improved survival (p<0.05).ConclusionsOur proof-of-principle data are compatible with the concept that IL-6 trans-signalling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.