bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a glycan library reveals a new model for enteric virus oligosaccharide binding and virion stabilization
Authors: Lu Hua , Lehrman Mark A. , Pfeiffer Julie K. 
Published: November 2019

AbstractEnteric viruses infect the gastrointestinal tract and bacteria can promote replication and transmission of several enteric viruses. Viruses can be inactivated by exposure to heat or bleach, but poliovirus, coxsackievirus B3, and reovirus can be stabilized by bacteria or bacterial polysaccharides, limiting inactivation and aiding transmission. We previously demonstrated that certain N-acetylglucosamine (GlcNAc)-containing polysaccharides can stabilize poliovirus. However, the detailed virus-glycan binding specificity and glycan chain length requirements, and thus the mechanism of virion stabilization, has been unclear. A previous limitation was our lack of defined-length glycans to probe mechanisms and consequences of virus-glycan interactions. Here, we generated a panel of polysaccharides and oligosaccharides to determine the properties required for binding and stabilization of poliovirus. Poliovirus virions are non-enveloped icosahedral 30 nm particles with 60 copies of each of four capsid proteins, VP1-4. VP1 surrounds the fivefold axis and our past work indicates that this region likely contains the glycan binding site. We found that relatively short GlcNAc oligosaccharides, such as a six unit GlcNAc oligomer, can bind poliovirus but fail to enhance virion stability. Virion stabilization required binding of long GlcNAc polymers of greater than 20 units. Our data suggest a model where GlcNAc polymers greater than 20 units bind and bridge adjacent fivefold axes, thus aiding capsid rigidity and stability. This study provides a deeper understanding of enteric virus-bacterial glycan interactions, which is important for virion environmental stability and transmission.ImportanceEnteric viruses are transmitted through the fecal-oral route, but how enteric viruses survive in the environment is unclear. Previously, we found that bacterial polysaccharides enhance poliovirus stability against heat or bleach inactivation, but the specific molecular requirements have been unknown. Here we showed that certain short chain oligosaccharides can bind to poliovirus but do not increase virion stability. Long chain polysaccharides bind and may bridge adjacent sites on the viral surface, thus increasing capsid rigidity and stability. This work defines the unique interactions of poliovirus and glycans, which provides insight into virion environmental stability and transmission.
Host fruit as a suitable bacteria growth substrate that promotes larval development of Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Akami Mazarin , Ren Xueming , Wang Yaohui , Mansour Abdelaziz , Cao Shuai , Qi Xuewei , Ngakou Albert , Niu Chang-Ying 
Published: November 2019

AbstractThe ability of a host plant to act as a substrate or media for larval development may depend on how good it is at offering suitable nutrients for bacterial growth. In this study, we hypothesized that the suitability of a fruit type for fruit fly larval development is positively correlated with the ability of that fruit to act as a substrate/media for fruit fly symbiotic bacterial growth. We allowed a single female fruit fly to lay eggs on five different host fruits, then we monitored the larval development parameters across five generations and analyzed the bacterial community structure of larvae developing in 2 of these hosts (apple and banana) at the first and fifth generations. Results indicate that the larval length and dry weight did not vary significantly across experimental generations, but were greatly affected by fruit types and larval stages. The larval development time was extended considerably in apple and tomato but shortened in banana and mango. There was a significant shift in bacterial community structure and composition across fruits and generations. The bacterial community of larvae within the same fruit (apple and banana) clustered and was similar to the parental female (with the predominance of Proteobacteria), but there was a shift at the fifth generation (dominance of Firmicutes). Banana offered a suitable better development and growth to larvae and bacteria, respectively, compared to apple in which reduced larval development and bacterial growth were recorded. Although additional experiments are needed to adequately show that the differences in microbiome seen in fruit fly larval guts are the actual driver of different developmental outcomes of larvae on the different fruits, at the very least, our study has provided intriguing data suggesting interaction between the diets and gut microbial communities on insect development.Importance and Significance of the studyTephritid fruit flies entertain complex interactions with gut bacteria. These bacteria are known to provide nutritional benefits to their hosts, by supplementing missing nutrients from the host diets and regulating energy balance. Foraging for food is a risky exercise for the insect which is exposed to ecological adversities, including predators. Therefore, making beneficial choice among available food substrates is a question of survival for the flies and bacteria as well. Our study demonstrates interactions between the host fly and its intestinal bacteria in sustaining the larval development while foraging optimally on different fruit types. These findings add a novel step into our understanding of the interactions between the gut microbial communities and B. dorsalis and provide avenues for developing control strategies to limit the devastative incidence of the fly.
SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway
Authors: Xu Ming , Zhang Xianglan , Zhang Songnan , Piao Junjie , Yang Yang , Wang Xinyue , Lin Zhenhua 
Published: November 2019

ABSTRACTSPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays bothin vitroandin vivoelucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression.IMPORTANCEThe incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients. Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts.
Multiplex genomic edition in Ashbya gossypii using CRISPR-Cpf1
Authors: Jiménez Alberto , Hoff Birgit , Revuelta José Luis 
Published: November 2019

AbstractThe CRISPR/Cas technologies constitute an essential tool for rapid genome engineering of many organisms, including fungi. The CRISPR/Cas9 system adapted for the industrial fungus Ashbya gossypii enables the efficient genome editing for the introduction of deletions, insertions and nucleotide substitutions. However, the Cas9 system is constrained to the existence of an specific 5’-NGG-3’ PAM sequence in the target site.Here we present a new CRISPR/Cas system for A. gossypii that expands the molecular toolbox available for microbial engineering of this fungus. The use of Cpf1 nuclease from Lachnospiraceae bacterium allows to employ a T-rich PAM sequence (5’-TTTN-3’) and facilitates the implementation of a multiplexing CRISPR/Cpf1 system adapted for A. gossypii. The system has been validated for the introduction of large deletions into five different auxotrophic marker genes (HIS3, ADE2, TRP1, LEU2 and URA3). The use of both crRNA and dDNA arrays in a multi-CRISPR/Cpf1 system was demonstrated to be an efficient strategy for multiplex gene deletion of up to four genes using a single multi-CRISPR/Cpf1 plasmid. Our results also suggest that the selection of the target sequence may significantly affect to the edition efficiency of the system.
Allosteric deregulation of phenylalanine biosynthesis evolved with the emergence of vascular plants
Authors: El-Azaz Jorge , Cánovas Francisco M. , Barcelona Belén , Ávila Concepción , de la Torre Fernando 
Published: November 2019

AbstractPhenylalanine (Phe) is the precursor of essential secondary products in plants. Here we show that a key, rate-limiting step in Phe biosynthesis, which is catalyzed by arogenate dehydratase (ADT), experienced allosteric de-regulation during evolution. Enzymes from microorganisms and type-I ADTs from plants are strongly feedback-inhibited by Phe, while type-II isoforms remain active at high levels of Phe. We have found that type-II ADTs are widespread across seed plants and their overproduction resulted in a dramatic accumulation of Phe in planta, up to 40-times higher than those observed following the expression of type-I enzymes. Punctual changes in the allosteric binding site of Phe and adjacent region are responsible for the observed relaxed regulation. The phylogeny of plant ADTs evidences that the emergence of type-II isoforms with relaxed regulation occurred at some point in the transition between non-vascular plants and tracheophytes enabling the massive production of Phe-derived compounds, primarily lignin, which are attributes of vascular plants.
Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila
Authors: Botero Valentina , Stahl Bethany A. , Grenci Eliza C. , Boto Tamara , Park Scarlet J. , King Lanikea B. , Murphy Keith R. , Colodner Kenneth J. , Walker James A. , Keene Alex C. , Ja William W. , Tomchik Seth M. 
Published: November 2019

ABSTRACTNeurofibromatosis type 1 (NF1) is a genetic disorder predisposing patients to a range of features, the most characteristic of which include areas of abnormal skin pigmentation and benign tumors associated with peripheral nerves, termed neurofibromas. Less common, but more serious symptoms also include malignant peripheral nerve sheath tumors, other malignancies, and learning disabilities. The NF1 gene encodes neurofibromin, a large protein that functions as a negative regulator of Ras signaling and mediates pleiotropic cellular and organismal function. Recent evidence suggests NF1 may regulate metabolism, though the mechanisms are unknown. Here we show that the Drosophila ortholog of NF1, dNf1 regulates metabolic homeostasis in fruit flies by functioning within a discrete brain circuit. Loss of dNf1 increases metabolic rate and feeding, enhances starvation susceptibility, and decreases lipid stores while increasing lipid turnover rate. The increase in metabolic rate is independent of locomotor activity (grooming), and maps to a subset of neurons in the ventral nervous system. The feeding and metabolic rate effects are due to loss of dNf1 in the same set of neurons, suggesting that increased feeding may be a compensatory effect driven by the increase in metabolic rate and lipid turnover. Finally, we show that the Ras GAP-related domain of neurofibromin is required for normal metabolism, demonstrating that Ras signaling downstream of dNf1 mediates the metabolic effects. These data demonstrate that dNf1 regulates metabolic rate via neuronal mechanisms, suggest that cellular and systemic metabolic alterations may represent a pathophysiological mechanism in NF1, and provide a platform for investigating the cellular role of neurofibromin in metabolic homeostasis.
Mechanisms Generating Cancer Genome Complexity From A Single Cell Division Error
Authors: Umbreit Neil T. , Zhang Cheng-Zhong , Lynch Luke D. , Blaine Logan J. , Cheng Anna M. , Tourdot Richard , Sun Lili , Almubarak Hannah F. , Judge Kim , Mitchell Thomas J. , Spektor Alexander , Pellman David 
Published: November 2019

ABSTRACTThe chromosome breakage-fusion-bridge (BFB) cycle is a mutational process that produces gene amplification and genome instability. Signatures of BFB cycles can be observed in cancer genomes with chromothripsis, another catastrophic mutational process. Here, we explain this association by identifying a mutational cascade downstream of chromosome bridge formation that generates increasing amounts of chromothripsis. We uncover a new role for actomyosin forces in bridge breakage and mutagenesis. Chromothripsis then accumulates starting with aberrant interphase replication of bridge DNA, followed by an unexpected burst of mitotic DNA replication, generating extensive DNA damage. Bridge formation also disrupts the centromeric epigenetic mark, leading to micronucleus formation that itself promotes chromothripsis. We show that this mutational cascade generates the continuing evolution and sub-clonal heterogeneity characteristic of many human cancers.
C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility
Authors: Fumagalli Laura , Young Florence L. , Boeynaems Steven , Decker Mathias De , Mehta Arpan R. , Swijsen Ann , Fazal Raheem , Guo Wenting , Moisse Matthieu , Beckers Jimmy , Dedeene Lieselot , Selvaraj Bhuvaneish T. , Vandoorne Tijs , Madan Vanesa , van Blitterswijk Marka , Raitcheva Denitza , McCampbell Alexander , Poesen Koen , Gitler Aaron D. , Koch Phillip , Berghe Pieter Vanden , Thal Dietmar Rudolf , Verfaillie Catherine , Chandran Siddharthan , Van Den Bosch Ludo , Bullock Simon L. , Damme Philip Van 
Published: November 2019

ABSTRACTHexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we use human induced pluripotent stem cell-derived motor neurons to show that C9orf72 repeat expansions impair microtubule-based transport of mitochondria, a process critical for maintenance of neuronal function. Cargo transport defects are recapitulated by treating healthy neurons with the arginine-rich dipeptide repeat proteins (DPRs) that are produced by the hexanucleotide repeat expansions. Single-molecule imaging shows that these DPRs perturb motility of purified kinesin-1 and cytoplasmic dynein-1 motors along microtubules in vitro. Additional in vitro and in vivo data indicate that the DPRs impair transport by interacting with both microtubules and the motor complexes. We also show that kinesin-1 is enriched in DPR inclusions in patient brains and that increasing the level of this motor strongly suppresses the toxic effects of arginine-rich DPR expression in a Drosophila model. Collectively, our study implicates an inhibitory interaction of arginine-rich DPRs with the axonal transport machinery in C9orf72-associated ALS/FTD and thereby points to novel potential therapeutic strategies.
Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation
Authors: Wille Coral K. , Sridharan Rupa 
Published: November 2019

ABSTRACTThe ability of pluripotent stem cells to be poised to differentiate into any somatic cell type is partly derived from a unique chromatin structure that is depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79 methylation. Inhibiting the H3K79 methyltransferase, Dot1L, increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) most potently at the mid-point of the process. Surprisingly, despite the enrichment of H3K79me2 on thousands of actively transcribed genes, Dot1L inhibition (Dot1Li) results in few changes in steady state mRNA levels during reprogramming. Dot1Li spuriously upregulates genes not involved in pluripotency and does not shutdown the somatic program. Depletion of the few genes that are downregulated, such as Nfix, enhances reprogramming efficiency in cooperation with Dot1Li. Contrary to the prevalent view, Dot1Li promotes iPSC generation beyond early phases of reprogramming such as the mesenchymal to epithelial transition and from already epithelial cell types including keratinocytes. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons or muscle cells. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects somatic cells from reverting to the pluripotent state.
A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export
Authors: van den Boomen Dick J.H. , Sienkiewicz Agata , Berlin Ilana , Jongsma Marlieke L.M. , van Elsland Daphne M. , Paul Luzio J. , Neefjes Jacques J.C. , Lehner Paul J. 
Published: November 2019

SummaryCholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, using an endogenous cholesterol reporter in a genome-wide CRISPR screen we identify >70 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core component of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical additional defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export.
The first- and second-order isothermal phase transitions in Fe3Ga-type compounds
Authors: Balagurov Anatoly M. , Samoylova Nataliya Yu. , Bobrikov Ivan A. , Sumnikov Sergey V. , Golovin Igor S. 
Published: November 2019

Structural features and kinetics of the transition between ordered metastable b.c.c.-derived D03 and equilibrium f.c.c.-derived L12 phases of Fe–xGa alloys (x = 27.2% and 28.0%) have been analyzed by in situ real-time neutron diffraction during isothermal annealing in the temperature range 405–470°C. It has been revealed that the transition proceeds with alternation of the first- and second-order phase transformations according to a D03 → A2 → A1 → L12 scheme, where A2 and A1 are disordered b.c.c. and f.c.c. structures. Deformations of the crystal lattice that arise due to these transitions are determined. The kinetics of the L12 phase nucleation and growth were analyzed in the frame of the Johnson–Mehl–Avrami–Kolmogorov (JMAK) model; however, only the early stage of the D03 → L12 transition is well described by the JMAK equation. The value of the Avrami exponent corresponds to the constant growth rate of the new L12 phase and decreasing nucleation rate in the Fe–27.2Ga alloy and indicates the presence of pre-existing nucleation centres of the L12 phase in the Fe–28.0Ga alloy.
Factors associated with the severity of IPV perpetrated by substance using men towards current partner
Authors: Canfield Martha , Radcliffe Polly , D’Oliveira Ana Flavia Pires Lucas , Gilchrist Gail 
Published: November 2019

Purpose
The purpose of this paper is to examine frequency and correlates of intimate partner violence (IPV) severity perpetrated by heterosexual men receiving treatment for substance use towards a current partner in the past 12 months.

Design/methodology/approach
A secondary analysis of a self-reported questionnaire (n=162) completed by men receiving treatment for substance use in England and Brazil was conducted. Types of IPV perpetration (emotional, physical and/or sexual IPV) and frequency of occurrence were assessed. A five level ordinal variable for IPV perpetration severity was created: no IPV, minor; moderate, low severe and high severe. Psychological and cultural correlates of perpetration severity were explored using ordinal logistic regression.

Findings
Approximately four in ten men reported perpetrating IPV towards their partner in the past 12 months, one in ten reported perpetrating severe IPV (including hitting with something, kicking or beating, choking or burning, threatening with/using a weapon, sexual IPV and frequent emotional IPV) during this period. A number of correlates of perpetration severity were identified: experiencing childhood physical abuse, witnessing IPV in childhood, perpetrating IPV in previous relationships, committing violence towards another man, controlling behaviours, technology-facilitated abuse, depressive symptoms, having a substance using partner, receiving treatment for illicit drug use, hazardous drinking and poly-drug use.

Research limitations/implications
Despite the small sample size, small to large positive associations were observed between reporting IPV perpetration and several factors. These factors could be targeted to improve identification and assessment of IPV among men receiving treatment for substance use.

Originality/value
A strength of this study methodology is the use of a specific 12 months time frame for the perpetration of IPV towards current partner. The categorisation of levels of IPV perpetration based on types and frequency of violence occurrence was an additional valuable contribution of this study.