bluuebunny/crossref_metadata_2025_split huggingface dataset:
LARP7 is a BRCA1 ubiquitinase substrate and regulates genome stability and tumorigenesis
Authors: Zhang Fang , Yan Pengyi , Yu Huijing , Le Huangying , li Zixuan , Chen Jiahuan , Liang Xiaodong , Wang Shiyan , Wei Weiting , Liu Li , Zhang Yan , Ji Xing , Xie Anyong , Chen Wantao , Han Zeguang , Pu William T. , Chen Sun , Chen Yingwei , Sun Kun , Ge Baoxie , Zhang Bing 
Published: October 2019

SummaryAttenuated DNA repair leads to genomic instability and tumorigenesis. BRCA1/BARD1 are the best known tumor suppressors that promote homology recombination (HR) and arrest cell cycle at G2/M checkpoint. As E3 ubiquitin ligases, their ubiquitinase activity has been known to involve in the HR and tumor suppression, but the mechanism remains ambiguous. Here, we demonstrated upon genotoxic stress, BRCA1 together with BARD1 catalyzed the K48 ployubiquitination on LARP7, a 7SK RNA binding protein known to control RNAPII pausing, and thereby degraded it through 26S ubiquitin-proteasome pathway. Depleting LARP7 suppressed the expression of CDK1 complex, arrested cell at G2/M DNA damage checkpoint and reduced BRCA2 phosphorylation which thereby facilitated RAD51 recruitment to damaged DNA to enhance HR. Importantly, LARP7 depletion observed in breast patients lead to the chemoradiotherapy resistance both in vitro and in vivo. Together, this study unveils a mechanism by which BRCA1/BARD1 utilizes their E3 ligase activity to control HR and cell cycle, and highlights LARP7 as a potential target for cancer prevention and therapy.HighlightsDNA damage response downregulates LARP7 through BRCA1/BARD1BRCA1/BARD1 catalyzes the K48 polyubiquitination on LARP7LARP7 promotes G2/M cell cycle transition and tumorigenesis via CDK1 complexLARP7 disputes homology-directed repair that leads to tumor therapy resistance
Development of CRSIPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
Authors: Kiga Kotaro , Tan Xin-Ee , Ibarra-Chávez Rodrigo , Watanabe Shinya , Aiba Yoshifumi , Sato’o Yusuke , Li Feng-Yu , Sasahara Teppei , Cui Bintao , Kawauchi Moriyuki , Boonsiri Tanit , Thitiananpakorn Kanate , Taki Yusuke , Azam Aa Haeruman , Suzuki Masato , Penadés José R , Cui Longzhu 
Published: October 2019

AbstractEmergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. We established a series of CRISPR-Cas13a-based antibacterial nucleocapsid, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus through promiscuous RNA cleavage after recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs were generated by packaging CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes. Contrary to Cas9-based antimicrobials that lack bacterial killing capacity when the target genes are located on a plasmid, the CapsidCas13a(s) exhibited strong bacterial killing activities upon recognizing target genes regardless of their location. The antimicrobials’ treatment efficacy was confirmed using a Galleria mellonella larvae model. Further, we demonstrated that the CapsidCas13a(s) can assist in bacterial gene detection without employing nucleic acid amplification and optical devices.
Impact of upstream landslide on perialpine lake ecosystem: an assessment using multi-temporal satellite data
Authors: Villa Paolo , Bresciani Mariano , Bolpagni Rossano , Braga Federica , Bellingeri Dario , Giardino Claudia 
Published: October 2019

AbstractMonitoring freshwater and wetland systems and their response to stressors of natural or anthropogenic origin is critical for ecosystem conservation.A multi-temporal set of 87 images acquired by Sentinel-2 satellites over three years (2016-2018) provided quantitative information for assessing the temporal evolution of key ecosystem variables in the perialpine Lake Mezzola (northern Italy), which was suffered from the impacts of a massive landslide that took place upstream of the lake basin in summer 2017.Sentinel-2 derived products revealed an increase in lake turbidity triggered by the landslide that amounted to twice the average values scored in the years preceding and following the event. Hotspots of turbidity within the lake were in particular highlighted. Moreover both submerged and riparian vegetation showed harmful impacts due to sediment deposition. A partial loss of submerged macrophyte cover was found, with delayed growth and a possible community shift in favor of species adapted to inorganic substrates. Satellite-derived seasonal dynamics showed that exceptional sediment load can overwrite climatic factors in controlling phenology of riparian reed beds, resulting in two consecutive years with shorter than normal growing season, and roughly 20% drop in productivity according to spectral proxies: compared to 2016, senescence came earlier by around 20 days on average in 2017 season, and green-up was delayed by up to 50 days (20 days, on average) in 2018, following the landslide.The approach presented could be easily implemented for continuous monitoring of similar ecosystems subject to external pressures with periods of high sediment loads.
Bread feeding is a robust and more physiological enteropathogen administration method compared to oral gavage
Authors: Derbise Anne , Echenique-Rivera Hebert , Garcia-Lopez Marta , Beau Rémi , Mattei Myriam , Dersch Petra , Pizarro-Cerdá Javier 
Published: October 2019

AbstractOral administration is a preferred model for studying infection by bacterial enteropathogens such asYersinia. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration. Using a bioluminescence-expressing strain ofYersinia pseudotuberculosis, we detected very early upon needle gavage a bioluminescent signal in the neck area together with a signal in the abdominal region, highlighting the presence of two independent sites of bacterial colonization and multiplication. Bacteria were often detected in the esophagus and trachea, as well as in the lymph nodes draining the salivary glands, suggesting that lesions made during needle introduction into the animal oral cavity lead to rapid bacterial draining to proximal lymph nodes. We then tested an alternative mode of bacterial administration using small pieces of white bread containing bacteria. Upon bread feeding infection, mice exhibited a stronger bioluminescent signal in the abdominal region as compared to needle gavage, and no signal was detected in the neck area. Moreover,Y. pseudotuberculosisincorporated in the bread is less susceptible to the acidic environment of the stomach and is therefore more efficient in causing intestinal infections. Based on our observations, bread feeding constitutes a natural and more efficient administration method which does not require specialized skills, is less traumatic for the animal, and results in diseases that more closely mimic food-borne intestinal infection.
Ageing before birth: pace and stability of prenatal growth affect telomere dynamics
Authors: Stier Antoine , Metcalfe Neil B. , Monaghan Pat 
Published: October 2019

AbstractPre-natal effects on telomere length are increasingly recognized as a potential contributor to the developmental origin of health and adult diseases. While it is becoming clear that telomere length is strongly influenced by pre-natal conditions, the factors affecting telomere dynamics during embryogenesis remain poorly understood. We manipulated both the pace and stability of prenatal growth using incubation temperature in Japanese quail and investigated the impact on telomere dynamics from embryogenesis to adulthood, along with potential drivers of telomere shortening such as oxidative damage and prenatal glucocorticoid levels. Telomere length was not affected by these manipulations for the first 75% of prenatal development, but was reduced at hatching in response to both experimentally induced fast embryo growth and growth instability. These early-life effects on telomere length persisted until adulthood. The effect of developmental instability on telomere length at hatching was potentially mediated by an increased secretion of glucocorticoid hormones during development. Both the pace and the stability of prenatal growth appear as key factors determining telomere length and dynamics up to adulthood, with fast and unstable embryo growth leading to short telomeres with the potential for adverse associated outcomes in terms of reduced longevity and greater risk of disease.
Breeding behaviour and productivity of Black-necked crane (Grus nigricolis) in Ladakh, Indian Trans-Himalaya
Authors: Chandan Pankaj , Ahmed Tanveer , Khan Afifullah 
Published: October 2019

AbstractA long-term study was conducted to understand some aspects of breeding biology of Black-necked crane (Grus nigricollis) in Changthang, Ladakh. Data on aspects such as the breeding season, courtship, mating, egg laying and incubation period, nest site fidelity, egg morphometry, breeding productivity and recruitment rate were collected between 2003 and 2012. Black-necked crane started arriving from last week of March to first half of April and showed fidelity at ten nesting sites. Courtship and mating peaked early morning (0700 hours), around noon (1100 hours) and in late evening (0600 hours) while the nest building at evening (1600 hours). The egg laying period initiated in May and extended up to July. The average incubation period was 33.88±0.3 days. Hatching success, nest survival rate and fledgling increment rate of the bird were 73.3%, 0.55 ± 0.03 and 0.41 ± 0.02 respectively with an overall breeding productivity of 0.73. The present population of Black-necked crane in Changthang, Ladakh seems to stable with an average recruitment rate of 15.7±1.4.
Genetic determinants of multi-drug resistance inAcinetobacter baumanniiat an academic hospital in Pretoria, South Africa
Authors: Nogbou Noel-David , Thabiso Phofa Dikwata , Nchabeleng Maphoshane , Musyoki Andrew Munyalo 
Published: October 2019

AbstractAntimicrobial resistance is now globally recognised as the greatest threat to human health.Acinetobacter baumanniis’(A. baumannii) clinical significance has been driven by its ability to obtain and transmit antimicrobial resistance factors. In South Africa,A. baumanniiis a leading cause of healthcare associated infections (HAI). In this study, we investigated the genetic determinants of multi-drug resistantA. baumannii(MDRAB) at a teaching hospital in Pretoria, South Africa.One hundred non repetitive isolates ofA. baumanniiwere collected for the study at Dr George Mukhari Tertiary Laboratory (DGMTL). Antimicrobial susceptibility testing was performed using the VITEK2 system (bioMerieux, France). The prevalence of common resistance associated genes and AdeABC efflux pump system associated genes were investigated using conventional PCR. Genetic relatedness of isolates was then determined using rep-PCR.Seventy (70) of 100 isolates collected were confirmed to be multi-drug resistant and wereblaOXA51positive. Phenotypically, the isolates where resistant to almost all tested antibiotics. However, one isolate showed intermediate susceptibility to tigecycline while all were susceptible to colistin. Oxacillinase encoding geneblaOXA-23was the most detected at 99% and only 1% was positive forblaOXA-40. The PCR results for metallo-betalactamase (MBL) encoding genes showed that MBLblaVIMwas the most frequently detected at 86% andblaSIM-1at 3% was the least detected. Out of 70 isolates, 56 isolates had the required gene combination for an active efflux pump. The most prevalent clone was clone A at 69% of the isolates. Regarding treatment; colistin and tigecycline are the most effective against strains encountered at DGMTL as all tested carbapenems seem to have lost their effectiveness.The major genotypic determinants for drug resistances are oxacillinases:blaOXA-51(100%) andblaOXA-23(99%). The study reports for the first time,blaOXA-40andblaSIM-1detection inA. baumanniiin South Africa.
Isolation of the Astacin-like metalloprotease coding gene (astl) and assessment of its insecticidal activity againstSpodoptera littoralisandSitophilus oryzae
Authors: Diab Mervat R. , Hussein Ibtissam H.A. , Ahmed Mahmoud M. , Mohammed Ahmed 
Published: October 2019

AbstractAstacin- like metalloprotease (astl) is a multi-domain metallopeptidase that has protease activity against a number of organisms; including fish, frogs, birds and insects. In this present investigation, the full length ofastlcDNA was cloned from spider species,Hasarius adansoni. Sequencing of the clonedastlcDNA proved that its full length including 802 bp with 714bp open reading frame encoding for 238 amino acids. The catalytic domain comprised of 489 nts was cloned and expressed by the yeast expression systemPichia pastorisand its insecticidal activity was determined against two species of agricultural insectsSpodoptera littoralis(Lepidoptera:Noctuidae) andSitophilus oryzae(Coleoptera:Curculionidae). Bioassay was performed using three concentrations (100,500 and 1000 ppm) for four days forS. littoralisand 14 days forS. oryzae.In addition, the astl was fused to the GNA snowdrop lectin in the same frame and expressed inP. pastoris. The synergistic effect of astl and GNA was examined on theS. littoralislarvae andS. oryzaeadults. The mortality percentages of the fused protein (Ha-astl/GNA) “1000 ppm” after 4 days, were 78.6%± 4.16 and 71.66% ±3.51 for first and second spodpotera larval instars, respectively. While, lower mortality of the fused protein of the same concentration was observed onS. oryzaeadults, 49.3±2.08 %.
TLR2 signaling pathway combats Streptococcus uberis infection by inducing production of mitochondrial reactive oxygen species
Authors: Li Bin , Wan Zhixin , Wang Zhenglei , Zuo Jiakun , Xu Yuanyuan , Han Xiangan , Phouthapane Vanhnaseng , Miao Jinfeng 
Published: October 2019

AbstractMastitis caused by Streptococcus uberis is a hazardous clinical disease in dairy animals. In this study, the role of Toll-like receptors (TLRs) and TLR-mediated signaling pathways in mastitis caused by S. uberis was investigated using mouse models and mammary epithelial cells (MECs). We used S. uberis to infect mammary glands of wild type, TLR2−/− and TLR4−/− mice and quantified the adaptor molecules in TLR signaling pathways, proinflammatory cytokines, tissue damage and bacterial count in mammary glands. When compared with TLR4 deficiency, TLR2 deficiency induced more severe pathological changes through myeloid differentiation primary response 88 (MyD88)-mediated signaling pathways during S. uberis infection. In MECs, TLR2 detected S. uberis infection and induced mitochondrial reactive oxygen species (mROS) to assist host control of secretion of inflammatory factors and elimination of intracellular S. uberis. Our results demonstrate that TLR2-mediated mROS have a significant effect on S. uberis-induced host defense responses in mammary glands as well as MECs.Author summaryS. uberis contributes significantly to global mastitis and remains a major obstacle for inflammation elimination due to its ability to form persistent infection in mammary tissue. The Toll-like receptor (TLR) family plays a significant role in identifying infections of intracellular bacteria and further triggering inflammatory reactions in immune cells. However, the detailed molecular mechanism by which TLR is regulated, and whether MECs, as the main cells in mammary gland, are tightly involved in these processes is poorly understood. Here, we used S. uberis to infect mammary glands of wild type, TLR2−/−, TLR4−/− mice and MECs to assess pathogenesis, proinflammatory cytokines, ROS as well as mROS levels during infection. We found that during S.uberis infection, it is TLR2 deficiency that induced more severe pathological changes through MyD88-mediated signaling pathways. In addition, our work demonstrates that mROS mediated by TLR2 has an important role in host defense response to combat S. uberis infection in mammary glands as well as MECs.
Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses
Authors: Hutchinson Luke D. , Darling Nicola J. , Nicolaou Stephanos , Gori Ilaria , Squair Daniel R. , Cohen Philip , Hill Caroline S. , Sapkota Gopal P. 
Published: October 2019

AbstractThe signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT), and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target genePAI-1. The screen revealed that small-molecular inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription ofPAI-1without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provides evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.
RecA levels modulate biofilm development inAcinetobacter baumannii
Authors: Ching Carly , Brychcy Merlin , Nguyen Brian , Muller Paul , Reverdy Alicyn , Downs Margaret , Regan Samuel , Isley Breanna , Fowle William , Chai Yunrong , Godoy Veronica G. 
Published: October 2019

AbstractInfections caused byAcinetobacter baumannii,a Gram-negative opportunistic pathogen, are difficult to eradicate due to the bacterium’s propensity to quickly gain antibiotic resistances and form biofilms, a protective bacterial multicellular community. TheA. baumanniiDNA damage response (DDR) mediates the antibiotic resistance acquisition and regulates RecA in an atypical fashion; both RecALowand RecAHighcell types are formed in response to DNA damage. The findings of this study demonstrate that the levels of RecA can influence the development, formation and dispersal, of biofilms through the global biofilm regulatorbfmR. RecA loss results in surface attachment and prominent biofilms, while elevated RecA leads to diminished attachment and dispersal. These findings suggest that the challenge to treatA. baumanniiinfections may be explained by the induction of the DDR, common during infection, as well as the delicate balance between maintaining biofilms in low RecA cells, and promoting mutagenesis and dispersal in high RecA cells. This study underscores the importance of understanding the fundamental biology of bacteria to develop more effective treatments for infections.
Inferring the structures of signaling motifs from paired dynamic traces of single cells
Authors: Haggerty R. A. , Purvis Jeremy E. 
Published: October 2019

AbstractIndividual cells show variability in their signaling dynamics that often correlates with phenotypic responses, indicating that cell-to-cell variability is not merely noise but can have functional consequences. Based on this observation, we reasoned that cell-to-cell variability under the same treatment condition could be explained by a single signaling motif that deterministically maps different upstream signals into a corresponding set of downstream responses. If this assumption holds, then repeated measurements of upstream and downstream signaling dynamics in single cells could provide information about the underlying signaling motif for a given pathway, even when no prior knowledge of that motif exists. To test these two hypotheses, we developed a computer algorithm called MISC (Motif Inference from Single Cells) that infers the underlying signaling motif from paired time-series measurements from individual cells. When applied to measurements of transcription factor and reporter gene expression in the yeast stress response, MISC predicted signaling motifs that were consistent with previous mechanistic models of transcription. The ability to detect the underlying mechanism became less certain when a cell’s upstream signal was randomly paired with another cell’s downstream response, demonstrating how averaging time-series measurements across a population obscures information about the underlying signaling mechanism. In some cases, motif predictions improved as more cells were added to the analysis. These results provide evidence that mechanistic information about cellular signaling networks can be embedded within the dynamical patterns of single cells.Author SummaryCells use molecular signaling networks to translate dynamically changing stimuli into appropriate downstream responses. Specialized network structures, or motifs, allow cells to properly decode a variety of temporal input signals. In this paper, we present an algorithm that infers signaling motifs from multiple examples of an upstream signal paired with its downstream response in the same cell. We compare the predictive power of single-cell versus averaged time-series traces and the incremental benefit of adding more single-cell traces to the algorithm. We use this approach to understand how yeast respond to environmental stresses.
Synchronized eye movements predict test scores in online video education
Authors: Madsen Jens , Julio Sara U. , Gucik Pawel J. , Steinberg Richard , Parra Lucas C. 
Published: October 2019

AbstractExperienced teachers pay close attention to their students, adjusting their teaching when students seem lost. This dynamic interaction is missing in online education. We propose to measure attention to online videos remotely by tracking eye movements, as we hypothesize that attentive students follow videos similarly with their eyes. Here we show that inter-subject correlation of eye-movements during instructional video presentation is substantially higher for attentive students, and that synchronized eye movement are predictive of individual test scores on the material presented in the video. These findings replicate for videos in a variety of production styles, learning scenarios and for recall and comprehension questions alike. We reproduce the result using standard web cameras to capture eye-movements in a classroom setting, and with over 1,000 participants at-home without the need to transmit user data. Our results suggest that online education could be made adaptive to a student’s level of attention in real-time.