bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity promotes Fumonisin B1 toxicity and induces hepatitis
Authors: Dopavogui Léonie , Régnier Marion , Polizzi Arnaud , Ponchon Quentin , Smati Sarra , Klement Wendy , Lasserre Frédéric , Lukowicz Céline , Lippi Yannick , Fougerat Anne , Bertrand-Michel Justine , Naylies Claire , Canlet Cécile , Debrauwer Laurent , Gamet-Payrastre Laurence , Dauriat Charlène , Casas Josefina , Croubels Siska , De Baere Siegrid , Burger Hester M. , Chassaing Benoit , Ellero-Simatos Sandrine , Guillou Hervé , Oswald Isabelle P. , Loiseau Nicolas 
Published: July 2022

ABSTRACTBackground and aimObesity is a major public health issue worldwide. Obesity is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin produced mainly by theFusarium verticillioides. FB1, a common contaminant of corn, is the most abundant and best characterized member of the fumonisins family. This toxin provokes severe mycotoxicosis in animals, which leads to hepatotoxicity and alterations in the immune response and intestinal barrier permeability. We investigated here whether diet-induced obesity could modulate the sensitivity to oral FB1 exposure, with emphasis on gut health and hepatotoxicity.MethodsThe metabolic effects of FB1 were assessed in obese and non-obese male C57BL/6J mice. For 15 weeks, mice received a high-fat diet (HFD) or normal chow diet (CHOW). During the last three weeks, mice were exposed or not to FB1 (10 mg/kg body weight/day) through drinking water.ResultsAs expected, HFD feeding induced significant body weight gain, glucose intolerance, and hepatic steatosis. FB1-exposed mice displayed a higher sphinganine/sphingosine ratio, a well-known FB1 biomarker of exposure, due to inhibition of ceramide synthases activity by FB1. Combined exposure to HFD and FB1 resulted in body weight loss and a decrease in fasting blood glucose level. This co-exposition also induces gut dysbiosis, an increase in plasma FB1 level, a decrease in liver weight and hepatic steatosis. Moreover, plasma transaminase levels were significantly increased and associated with liver inflammation in HFD/FB1-treated mice. Liver gene expression analysis revealed that the combined exposure to HFD and FB1 was associated with reduced expression of genes involved in lipogenesis and increased expression of immune response and cell cycle-associated genes.ConclusionThese results suggest that, in the context of obesity, FB1 exposure promotes gut dysbiosis and severe liver inflammation. To our knowledge, this study provides the first example of obesity-induced hepatitis in response to a food contaminant.
Deep self-supervised learning for biosynthetic gene cluster detection and product classification
Authors: Rios-Martinez Carolina , Bhattacharya Nicholas , Amini Ava P. , Crawford Lorin , Yang Kevin K. 
Published: July 2022

AbstractNatural products are chemical compounds that form the basis of many therapeutics used in the pharmaceutical industry. In microbes, natural products are synthesized by groups of colocalized genes called biosynthetic gene clusters (BGCs). With advances in high-throughput sequencing, there has been an increase of complete microbial isolate genomes and metagenomes, from which a vast number of BGCs are undiscovered. Here, we introduce a self-supervised learning approach designed to identify and characterize BGCs from such data. To do this, we represent BGCs as chains of functional protein domains and train a masked language model on these domains. We assess the ability of our approach to detect BGCs and characterize BGC properties in bacterial genomes. We also demonstrate that our model can learn meaningful representations of BGCs and their constituent domains, detect BGCs in microbial genomes, and predict BGC product classes. These results highlight self-supervised neural networks as a promising framework for improving BGC prediction and classification.Author summaryBiosynthetic gene clusters (BGCs) encode for natural products of diverse chemical structures and function, but they are often difficult to discover and characterize. Many bioinformatic and deep learning approaches have leveraged the abundance of genomic data to recognize BGCs in bacterial genomes. However, the characterization of BGC properties remains the main bottleneck in identifying novel BGCs and their natural products. In this paper, we present a self-supervised masked language model that learns meaningful representations of BGCs with improved downstream detection and classification.
Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ25-35-induced Alzheimer’s disease in C57BL/6 mice
Authors: Kuo Yu-Yi , Chen Wei-Ting , Lin Guan-Bo , Chen You-Ming , Liu Hsu-Hsiang , Chao Chih-Yu 
Published: July 2022

AbstractDespite continuation of some controversies, Alzheimer’s disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive β-amyloid (Aβ) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aβ have been ineffective or offer only temporary relief at best, due to blood-brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) as an alternative AD therapy and compared its effect with continuous hyperthermia (HT)in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of Aβ25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and NOR test, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal Aβ and BACE1 expressions as well as the neuroinflammation markers Iba-1 and GFAP levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of IDE and antioxidative enzyme SOD2 than HT. Besides, after establishment of neuroprotective mechanism, removal of TC-HT-induced ROS can further augment protection of neural cells against Aβ. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into clinical application with the use of focused ultrasound (FUS).
Engineering cellular communication between light-activated synthetic cells and bacteria
Authors: Smith Jefferson M. , Hartmann Denis , Booth Michael J. 
Published: July 2022

AbstractGene-expressing compartments assembled from simple, modular parts, are a versatile platform for creating minimal synthetic cells. In a manner synonymous with natural cells, these life-like assemblies utilise information encoded in DNA within the compartment’s interior to dictate which proteins are expressed and consequently the overall function of the synthetic cell. Hence, by incorporating gene regulatory motifs into the DNA templates, in situ gene expression can be controlled according to specific stimuli. In this work, cell-free protein synthesis within synthetic cells was controlled using light by encoding genes of interest on light-activated DNA templates. Light-activated DNA contained a photocleavable blockade within the T7 promoter region that tightly repressed transcription until the blocking groups were removed with UV light. In this way, synthetic cells were activated remotely, in a spatiotemporally controlled manner. By applying this strategy to the expression of an acyl homo-serine lactone synthetase, BjaI, quorum-sensing based communication between synthetic cells and bacteria was controlled with light. This work provides a framework for the remote-controlled production and delivery of small molecules from non-living matter to living matter, with applications in biology and medicine.
Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLR-/- mice
Authors: Thompson Dawn , Mahmood Shehroz , Morrice Nicola , Kamli-Salino Sarah , Dekeryte Ruta , Hoffmann Philip , Doherty Mary K. , Whitfield Philip D. , Delibegović Mirela , Mody Nimesh 
Published: July 2022

ABSTRACTFenretinide is a synthetic retinoid that can prevent obesity and improve insulin sensitivity in mice by directly altering retinol/retinoic acid homeostasis and inhibiting excess ceramide biosynthesis. We determined the effects of Fenretinide on LDLR-/- mice fed high-fat/high-cholesterol diet +/- Fenretinide, a model of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Fenretinide prevented obesity, improved insulin sensitivity and completely inhibited hepatic triglyceride accumulation, ballooning and steatosis. Moreover, Fenretinide decreased the expression of hepatic genes driving NAFLD, inflammation and fibrosis e.g. Hsd17b13, Cd68 and Col1a1. The mechanisms of Fenretinide’s beneficial effects in association with decreased adiposity were mediated by inhibition of ceramide synthesis, via hepatic DES1 protein, leading to increased dihydroceramide precursors. However, Fenretinide treatment in LDLR-/- mice enhanced circulating triglycerides and worsened aortic plaque formation. Interestingly, Fenretinide led to a 4-fold increase in hepatic sphingomyelinase Smpd3 expression, via a retinoic acid-mediated mechanism and a further increase in circulating ceramide levels, linking induction of ceramide generation via sphingomyelin hydrolysis to a novel mechanism of increased atherosclerosis. Thus, despite beneficial metabolic effects, Fenretinide treatment may under certain circumstances enhance the development of atherosclerosis. However, targeting both DES1 and Smpd3 may be a novel, more potent therapeutic approach for the treatment of metabolic syndrome.
REGENERATION VIA SOMATIC EMBRYOGENESIS FROM SEED EXPLANT OF MEDICINAL PLANT SOLANUM VIRGINIANUM (L.)
Authors: Patil Dhanashree S. , Patil Swaroopa A. 
Published: July 2022

AbstractSolanum virginianum (L.) belonging to family Solanaceae is an important medicinal plant, used in traditional ayurvedic medicines. It is one of the ten constituents of “Dashmoola”. Present work deals with the development of efficient procedure for inducing somatic embryogenesis followed by regeneration of Solanum virginianum (L.). Initially, seeds of S. virginianum were used as explant and inoculated on ½ MS basal medium. The stem explant from in vitro germinated seeds was used for callus induction. MS medium supplemented with BAP (1mg/L) was used for callus induction. Callus proliferation started when initiated callus was subcultured on different concentrations and combination of BAP, IAA, IBA, 2,4-D and NAA. Where highest embryogenesis took place in BAP (2mg/l)+IAA(5mg/l) combination. The somatic embryos were transferred onto MS basal medium for maturation. These embryos matured and were converted into complete plantlets with well developed shoot and root system.
Warning coloration, body size and the evolution of gregarious behavior in butterfly larvae
Authors: McLellan Callum F , Montgomery Stephen H , Cuthill Innes C 
Published: July 2022

AbstractMany species gain anti-predator benefits by combining gregarious behavior with warning coloration, yet there is debate over which trait evolves first, and which is the secondary adaptive enhancement. Body size can also influence how predators receive aposematic signals, and potentially constrain the evolution of gregarious behavior. To our knowledge, the causative links between the evolution of gregariousness, aposematism and larger body sizes have not been fully resolved. Here, using the most recently resolved butterfly phylogeny and an extensive new dataset of larval traits, we reveal the evolutionary interactions between important traits linked to larval gregariousness. We show that larval gregariousness has arisen many times across the butterflies, and aposematism is a likely prerequisite for gregariousness to evolve. We also find that body size may be an important factor for determining the coloration of solitary, but not gregarious larvae. Additionally, by exposing artificial ‘larvae’ to wild avian predation, we show that undefended, cryptic ‘larvae’ are heavily predated when aggregated but benefit from solitariness, whereas the reverse is true for aposematic prey. Our data reinforce the importance of aposematism for gregarious larval survival, whilst identifying new questions about the roles of body size and toxicity in the evolution of grouping behavior.
Invasion and secondary site colonization as a function of in vitro primary tumor matrix stiffness
Authors: Shah Lekha , Latif Ayşe , Williams Kaye J. , Mancuso Elena , Tirella Annalisa 
Published: July 2022

AbstractIncreased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, which shares a large burden of breast cancer deaths, has not yet been understood. To better understand the cause-effect relationship of tissue stiffness on breast cancer’s metastatic potential, we fabricated three-dimensional (3D) models to mimic breast and bone tissue in vitro. Based on our previous work, we used alginate-based hydrogels allowing precise control over stiffness and composition of extracellular breast tissue matrix; and 3D printed poly-caprolactone (PCL)-composite scaffolds to mimic the bone. The latter were further modified by promoting bone-ECM deposition using Saos-2 cells. After a decellularization step, PCL scaffolds were assembled with alginate-gelatin hydrogels and a novel breast-to-bone in vitro model was established. It was observed that increased stiffness of hydrogel resulted in higher migration and invasion capacity of MDA-MB 231 cells. Additionally, PTHrP and IL-6 expression, both of which are implicated in bone metastasis, were higher when cells from stiff hydrogels were cultured in bone/PCL scaffolds. These breast-to-bone in vitro models pose as a novel non-animal technology to pave the way for incorporating important tissue microenvironmental factors of the disease physiology (e.g. tissue stiffness) and emerge as promising future platforms for monitoring metastatic disease phenotypes and therapeutic efficacy.
Mining the human gut microbiome identifies mycobacterial d-arabinan degrading enzymes
Authors: Al-Jourani Omar , Benedict Samuel , Ross Jennifer , Layton Abigail , van der Peet Phillip , Marando Victoria M. , Bailey Nicholas P. , Heunis Tiaan , Manion Joseph , Mensitieri Francesca , Franklin Aaron , Abellon-Ruiz Javier , Oram Sophia L. , Parsons Lauren , Cartmell Alan , Wright Gareth S. A. , Baslé Arnaud , Trost Matthias , Henrissat Bernard , Munoz-Munoz Jose , Hirt Robert P. , Kiessling Laura L. , Lovering Andrew , Williams Spencer J. , Lowe Elisabeth C. , Moynihan Patrick J. 
Published: July 2022

AbstractDivision and degradation of bacterial cell walls requires coordinated action of a myriad of enzymes. This particularly applies to the elaborate cell walls of acid-fast organisms such asMycobacterium tuberculosis, which consist of a multi-layered cell wall that contains an unusual glycan called arabinogalactan. Enzymes that cleave thed-arabinan core of this structure have not previously been identified in any organism. We have interrogated the diverse carbohydrate degrading enzymes expressed by the human gut microbiota and uncovered four families of glycoside hydrolases with the capability to degrade thed-arabinan ord-galactan components of arabinogalactan. Using novel exo-d-galactofuranosidases from gut bacteria we generated enrichedd-arabinan and used it to identifyD. gadeias a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan. We have identified new members of the DUF2961 family (GH172), and a novel family of glycoside hydrolases (DUF4185) that display endo-d-arabinofuranase activity. The DUF4185 enzymes are conserved in mycobacteria and found in many microbes, suggesting that the ability to degrade mycobacterial glycans plays an important role in the biology of diverse organisms. All mycobacteria encode two conserved endo-d-arabinanases that display different preferences for thed-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.
Remodeling of Il4-Il13-Il5 locus underlies selective gene expression
Authors: Nagashima Hiroyuki , Petermann Franziska , Pękowska Aleksandra , Chaitankar Vijender , Kanno Yuka , O’Shea John J. 
Published: July 2022

AbstractThe type 2 cytokines, interleukin (IL)-4, IL-5 and IL-13 reside within a tandem multi-gene cluster in mammals. These cytokines represent the hallmark of type 2 immune responses controlling parasites, promoting tissue repair as well as causing allergic diseases. Both innate and adaptive lymphocytes secrete type 2 cytokines with discordant production spectra. We took a holistic structural and functional view of the type 2 cytokine locus before and after activation, comparing innate (ILC2) and adaptive (Th2) lymphocytes to understand mechanisms underlying their distinctive programs. Rapid induction of IL-5 dominates in ILC2, whereas IL-4 does so in Th2 cells. Using high-resolution chromatin conformation capture we found that global cellular chromatin architecture remained constant, whereas the type 2 cytokine locus rapidly remodeled. In ILC2, Il13 and Il5 loci were aligned in proximity whereas Il4 locus was insulated. In Th2 cells, Il4 and Il13 positioned in proximity while the Il5 locus remained distal. Select REs were separately deleted in mice to confirm cell-type specific and activation-dependent roles in type 2 responses in vivo. Thus, contrary to the premise that chromatin architecture plays a minimal role in steady-state gene induction, signal-dependent remodeling of 3D configuration underlies the discordant cytokine outputs in ILC2s versus Th2 cells.
Large-scale in vivo CRISPR screens identify SAGA complex members as a key regulators of HSC lineage commitment and aging
Authors: Haney Michael S. , Shankar Archana , Hsu Ian , Miyauchi Masashi , Pálovics Róbert , Khoo Hwei Minn , Igarashi Kyomi J. , Bhadury Joydeep , Munson Christy , Mack Paul K. , Tan Tze-Kai , Wyss-Coray Tony , Nakauchi Hiromitsu , Wilkinson Adam C. 
Published: July 2022

ABSTRACTThe biological mechanisms that sustain the vast blood production required for healthy life remain incompletely understood. To address this knowledge gap, we developed an in vivo hematopoietic stem cell (HSC)-based large-scale CRISPR knockout screening platform to enable the genetic interrogation of hematopoiesis and broad aspects of immune cell function in vivo. Targeting ∼7000 genes with this methodology, we discovered SAGA complex members Tada2b and Taf5l as key regulators of HSC lineage commitment. Loss of Tada2b or Taf5l inhibited hematopoiesis in vivo and was associated with upregulation of interferon response gene expression. SAGA complex member expression is significantly reduced in aged HSCs and upregulated with heterochronic parabiosis, suggesting a novel mechanism of age-associated hematopoietic decline and rejuvenation. Our study provides a rich functional genetics resource of hematopoiesis regulators accessible through a public interactive database (www.hematopoiesiscrisprscreens.com), a novel mechanism regulating age-related decline of hematopoiesis, and a new methodology with broad applications to systematically probe the development and functions of the lymphohematopoietic system.
Laboratory evolution and polyploid SCRaMbLE reveal genomic plasticity to synthetic chromosome defects and rearrangements
Authors: Williams Thomas C. , Kroukamp Heinrich , Xu Xin , Wightman Elizabeth L. I. , Llorente Briardo , Borneman Anthony R. , Carpenter Alexander C. , Van Wyk Niel , Espinosa Monica I. , Daniel Elizabeth L. , Walker Roy S. K. , Cai Yizhi , Nevalainen Helena K. M. , Curach Natalie C. , Deveson Ira W. , Mercer Timothy R. , Johnson Daniel L. , Mitchell Leslie A. , Bader Joel S. , Stracquadanio Giovanni , Boeke Jef D. , Goold Hugh D. , Pretorius Isak S. , Paulsen Ian T. 
Published: July 2022

SummaryWe have designed, constructed, and debugged a synthetic 753,096 bp version of Saccharomyces cerevisiae chromosome XIV as part of the international Sc2.0 project. We showed that certain synthetic loxPsym recombination sites can interfere with mitochondrial protein localization, that the deletion of one intron (NOG2) reduced fitness, and that a reassigned stop codon can lead to a growth defect. In parallel to these rational debugging modifications, we used Adaptive Laboratory Evolution to generate a general growth defect suppressor rearrangement in the form of increased TAR1 copy number. We also extended the utility of the Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE) system by engineering synthetic-wild-type tetraploid hybrid strains that buffer against essential gene loss. The presence of wild-type chromosomes in the hybrid tetraploids increased post-SCRaMbLE viability and heterologous DNA integration, highlighting the plasticity of the S. cerevisiae genome in the presence of rational and non-rational modifications.
FT-GO: a multiplex fluorescent tyramide signal amplification system for histochemical analysis
Authors: Yamauchi Kenta , Okamoto Shinichiro , Ishida Yoko , Konno Kohtarou , Hoshino Kisara , Furuta Takahiro , Takahashi Megumu , Koike Masato , Isa Kaoru , Watanabe Masahiko , Isa Tadashi , Hioki Hiroyuki 
Published: July 2022

AbstractTyramide signal amplification (TSA) is a highly sensitive method for histochemical analysis. Previously, we reported a TSA system, BT-GO, for bright-filed imaging. Here, we develop FT-GO (Fluorochromized Tyramide-Glucose Oxidase) as a multiplex fluorescent TSA system. FT-GO involves peroxidase-catalyzed deposition of FT with hydrogen peroxide produced in enzymatic reaction between glucose and glucose oxidase. We showed that FT-GO enhanced immunofluorescence signals while maintaining low background signals. Compared with indirect immunofluorescence detections, FT-GO demonstrated a more widespread distribution of monoaminergic projection systems in mouse and marmoset brains. For multiplex labeling with FT-GO, we quenched Ab-conjugated peroxidase using sodium azide. We applied FT-GO to multiplex fluorescent in situ hybridization, and succeeded in labeling neocortical interneuron subtypes by coupling with immunofluorescence. FT-GO immunofluorescence further increased the detectability of an adeno-associated virus tracer. Given its simplicity and a staining with a high signal-to-noise ratio, FT-GO would provide a versatile platform for histochemical analysis.
M2M-InvNet: Human Motor Cortex Mapping from Multi-Muscle Response Using TMS and Generative 3D Convolutional Network
Authors: Akbar Md Navid , Yarossi Mathew , Rampersad Sumientra , Lockwood Kyle , Masoomi Aria , Tunik Eugene , Brooks Dana , Erdoğmuş Deniz 
Published: July 2022

AbstractTranscranial magnetic stimulation (TMS) is often applied to the motor cortex to stimulate a collection of motor evoked potentials (MEPs) in groups of peripheral muscles. The causal interface between TMS and MEP is the selective activation of neurons in the motor cortex; moving around the TMS ‘spot’ over the motor cortex causes different MEP responses. A question of interest is whether a collection of MEP responses can be used to identify the stimulated locations on the cortex, which could potentially be used to then place the TMS coil to produce chosen sets of MEPs. In this work we leverage our previous report on a 3D convolutional neural network (CNN) architecture that predicted MEPs from the induced electric field, to tackle an inverse imaging task in which we start with the MEPs and estimate the stimulated regions on the motor cortex. We present and evaluate five different inverse imaging CNN architectures, both conventional and generative, in terms of several measures of reconstruction accuracy. We found that one architecture, which we propose as M2M-InvNet, consistently achieved the best performance.