bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved amino acid residues and gene expression patterns associated with the substrate preferences of the competing enzymes FLS and DFR
Authors: Choudhary Nancy , Pucker Boas 
Published: November 2023

AbstractBackgroundFlavonoids, an important class of specialized metabolites, are synthesized from phenylalanine and present in almost all plant species. Different branches of flavonoid biosynthesis lead to products like flavones, flavonols, anthocyanins, and proanthocyanidins. Dihydroflavonols form the branching point towards the production of non-colored flavonols via flavonol synthase (FLS) and colored anthocyanins via dihydroflavonol 4-reductase (DFR). Despite the wealth of publicly accessible data, there remains a gap in understanding the mechanisms that mitigate competition between FLS and DFR for the shared substrate, dihydroflavonols.ResultsAn angiosperm-wide comparison of FLS and DFR sequences revealed the amino acids at positions associated with the substrate specificity in both enzymes. A global analysis of the phylogenetic distribution of these amino acid residues revealed that monocots generally possess FLS with Y132 (FLSY) and DFR with N133 (DFRN). In contrast, dicots generally possess FLSHand DFRN, DFRD, and DFRA. DFRA, which restricts substrate preference to dihydrokaempferol, previously believed to be unique to strawberry species, is found to be more widespread in angiosperms and has evolved independently multiple times. Generally, angiosperm FLS appears to prefer dihydrokaempferol, whereas DFR appears to favor dihydroquercetin or dihydromyricetin. Moreover, in the FLS-DFR competition, the dominance of one over the other is observed, with typically only one gene being expressed at any given time.ConclusionThis study illustrates how almost mutually exclusive gene expression and substrate-preference determining residues could mitigate competition between FLS and DFR, delineates the evolution of these enzymes, and provides insights into mechanisms directing the metabolic flux of the flavonoid biosynthesis, with potential implications for ornamental plants and molecular breeding strategies.
Physiology of the Weight Loss Plateau after Calorie Restriction, GLP-1 Receptor Agonism, and Bariatric Surgery
Authors: Hall Kevin D. 
Published: November 2023

AbstractObjectiveTo investigate why different weight loss interventions result in varying durations of weight loss prior to approaching plateaus.MethodsA validated mathematical model of energy balance and body composition dynamics was used to simulate mean weight loss trajectories in response to intensive calorie restriction, semaglutide 2.4 mg, tirzepatide 10 mg, and Roux en-Y gastric bypass (RYGB) surgery interventions. Each intervention was simulated by varying two model parameters affecting energy intake to fit the observed mean weight loss data. One parameter represented the persistent magnitude of the intervention to shift the system from baseline equilibrium and the other parameter represented the strength of the feedback control circuit relating weight loss to increased appetite.ResultsRYGB surgery resulted in a persistent intervention magnitude more than 4-fold greater than calorie restriction and about double that of tirzepatide and semaglutide. All interventions except calorie restriction substantially weakened the appetite feedback control circuit resulting in an extended period of weight loss prior to the plateau.ConclusionsThese preliminary mathematical modeling results suggest that both GLP-1 receptor agonism and RYGB surgery interventions act to weaken the appetite feedback control circuit regulating body weight and induce greater persistent effects to shift the body weight equilibrium as compared to intensive calorie restriction.
Molecular basis for dual functions in pilus assembly modulated by the lid of a pilus-specific sortase
Authors: Chang Chungyu , Ton-That HyLam , Osipiuk Jerzy , Joachimiak Andrzej , Das Asis , Ton-That Hung 
Published: November 2023

ABSTRACTThe biphasic assembly of Gram-positive pili begins with the covalent polymerization of distinct pilins catalyzed by a pilus-specific sortase, followed by the cell wall anchoring of the resulting polymers mediated by the housekeeping sortase. InActinomyces oris, the pilus-specific sortase SrtC2 not only polymerizes FimA pilins to assemble type 2 fimbriae with CafA at the tip, but it can also act as the anchoring sortase, linking both FimA polymers and SrtC1-catalyzed FimP polymers (type 1 fimbriae) to peptidoglycan when the housekeeping sortase SrtA is inactive. To date, the structure-function determinants governing the unique substrate specificity and dual enzymatic activity of SrtC2 have not been illuminated. Here, we present the crystal structure of SrtC2 solved to 2.10-Å resolution. SrtC2 harbors a canonical sortase fold and a lid typical for class C sortases and additional features specific to SrtC2. Structural, biochemical, and mutational analyses of SrtC2 reveal that the extended lid of SrtC2 modulates its dual activity. Specifically, we demonstrate that the polymerizing activity of SrtC2 is still maintained by alanine-substitution, partial deletion, and replacement of the SrtC2 lid with the SrtC1 lid. Strikingly, pilus incorporation of CafA is significantly reduced by these mutations, leading to compromised polymicrobial interactions mediated by CafA. In asrtAmutant, the partial deletion of the SrtC2 lid reduces surface anchoring of FimP polymers, and the lid-swapping mutation enhances this process, while both mutations diminish surface anchoring of FimA pili. Evidently, the extended lid of SrtC2 enables the enzyme the cell wall-anchoring activity in a substrate-selective fashion.
Optimal Liquid-Based DNA Preservation for DNA Barcoding of Field-Collected Fungal Specimens
Authors: Lee Yu-Ja , Phang Guan Jie , Chen Che-Chih , Ou Jie-Hao , Huang Yin-Tse 
Published: November 2023

AbstractPreserving fungal tissue DNA in the field is essential for molecular ecological research, enabling the study of fungal biodiversity and community dynamics. This study systematically compares two liquid-based preservation solutions, RNAlater and DESS, for their effectiveness in maintaining macrofungi DNA integrity during field collection and storage. The research encompasses both controlled experiments and real-world field collections. In the controlled experiments, two fungal species were preserved in RNAlater and DESS at different temperatures and durations. DNA extraction success rates were high, but DNA quality and quantity metrics exhibited variations across samples. However, both preservation solutions demonstrated their viability for preserving fungal DNA, with no significant differences between them. In the field-collected macrofungi experiment, 200 fungal specimens were collected and preserved in RNAlater and DESS. The DNA extraction success rate was 98%, with a few exceptions. The statistical analysis, including paired and independent t-tests, showed no statistically significant differences in DNA quality and quantity between the two preservation methods for the field-collected fungal samples. Overall, this study provides valuable insights into the effectiveness of RNAlater and DESS for preserving macrofungi DNA in field conditions. Researchers can confidently choose between these methods based on their specific needs, without compromising the integrity of the DNA. This research contributes to the advancement of fungal molecular ecology and has broader implications for DNA preservation strategies in ecological and environmental studies.
Structural basis of RfaH-mediated transcription-translation coupling
Authors: Molodtsov Vadim , Wang Chengyuan , Kaelber Jason T. , Blaha Gregor , Ebright Richard H. 
Published: November 2023

AbstractThe NusG paralog RfaH mediates bacterial transcription-translation coupling on genes that contain a DNA sequence element, termed anopssite, required for pausing RNA polymerase (RNAP) and for loading RfaH onto the paused RNAP. Here we report cryo-EM structures of transcription-translation complexes (TTCs) containing RfaH. The results show that RfaH bridges RNAP and the ribosome, with the RfaH N-terminal domain interacting with RNAP, and with the RfaH C-terminal domain interacting with the ribosome. The results show that the distribution of translational and orientational positions of RNAP relative to the ribosome in RfaH-coupled TTCs is more restricted than in NusG-coupled TTCs, due to the more restricted flexibility of the RfaH interdomain linker. The results further show that the structural organization of RfaH-coupled TTCs in the "loading state," in which RNAP and RfaH are located at theopssite during formation of the TTC, is the same as the structural organization of RfaH-coupled TTCs in the "loaded state," in which RNAP and RfaH are located at positions downstream of theopssite during function of the TTC. The results define the structural organization of RfaH-containing TTCs and set the stage for analysis of functions of RfaH during translation initiation and transcription-translation coupling.One sentence summaryCryo-EM reveals the structural basis of transcription-translation coupling by RfaH.
Dengue virus exploits the host tRNA epitranscriptome to promote viral replication
Authors: Chan Cheryl , Sze Newman Siu Kwan , Suzuki Yuka , Ohira Takayuki , Suzuki Tsutomu , Begley Thomas J. , Dedon Peter C. 
Published: November 2023

AbstractThe 40-50 RNA modifications of the epitranscriptome regulate posttranscriptional gene expression. Here we show that flaviviruses hijack the host tRNA epitranscriptome to promote expression of pro-viral proteins, with tRNA-modifying ALKBH1 acting as a host restriction factor in dengue virus infection. Early in the infection of human Huh-7 cells, ALKBH1 and its tRNA products 5-formylcytidine (f5C) and 2’-O-methyl-5-formylcytidine (f5Cm) were reduced. ALKBH1 knockdown mimicked viral infection, but caused increased viral NS3 protein levels during infection, while ALKBH1 overexpression reduced NS3 levels and viral replication, and increased f5C and f5Cm. Viral NS5, but not host FTSJ1, increased f5Cm levels late in infection. Consistent with reports of impaired decoding of leucine UUA codon by f5Cm-modified tRNALeu(CAA), ALKBH1 knockdown induced translation of UUA-deficient transcripts, most having pro-viral functions. Our findings support a dynamic ALKBH1/f5Cm axis during dengue infection, with virally-induced remodeling of the proteome by tRNA reprogramming and codon-biased translation.
The effect of balanced energy-protein supplementation provided to lactating women on maternal and infant outcomes: study protocol for a prospectively planned individual patient data (IPD) meta-analysis
Authors: Ciulei Mihaela A. , Zhou Shouhao , Gallagher Kelly , Taneja Sunita , Bhandari Nita , Kolsteren Patrick , Muhammad Ameer , Tielsch James M , Argaw Alemayehu , Chowdhury Ranadip , Christian Parul , Dailey-Chwalibóg Trenton , de Kok Brenda , Erchick Daniel J. , Jehan Fyezah , Katz Joanne , Khatry Subarna , Lachat Carl , Lama Tsering P , Nisar Muhammad Imran , Shafiq Yasir , Upadhyay Ravi , Gernand Alison D ,   Maternal BEP Studies Harmonization Initiative
Published: November 2023

AbstractBackgroundThe high prevalence of infant stunting and maternal undernutrition in low- and middle-income countries poses a significant public health threat. The World Health Organization recommends balanced energy-protein (BEP) supplementation to pregnant women from populations with a high prevalence of underweight (prepregnancy BMI <18.5 kg/m2), leaving a notable gap in guidance for lactating women. To address this problem, we established the Maternal BEP Studies Harmonization Initiative (BEP Initiative) to investigate the impact of BEP supplementation given to pregnant and/or lactating women on maternal and infant outcomes by synthesizing data from multiple clinical trials. This is a study protocol for our prospective individual participant data (IPD) meta-analysis on BEP lactation trials.MethodsData from four randomized controlled trials that include mother-infant dyads in India (n=816), Pakistan (n=957), Burkina Faso (n=800), and Nepal (n=726) will be pooled and analyzed. Women were randomized to BEP (one trial had a third arm with maternal BEP plus infants receiving azithromycin) or control groups at baseline (during the first week) and received the intervention through six months postpartum. A one-stage IPD meta-analysis will be done using mixed-effects linear and log-binomial regression models to account for between-trial heterogeneity. The primary outcome of infant length-for-age z scores (LAZ) at six months of age and secondary outcomes of maternal and infant indicators of nutritional status at six months of age will be examined. Also, we will examine baseline characteristics as covariates and effect modifiers for the BEP to outcome relationship. Risk of bias assessments will be carried out for each of the individual trials using the Cochrane risk of bias tool.DiscussionThis prospective IPD meta-analysis uses a one-stage IPD meta-analysis, which allows for higher statistical power to examine outcomes, more flexibility in defining variables, and has the ability to examine many individual- and study-level variables as effect modifiers, allowing conclusions on which individuals or populations may benefit more from BEP given during lactation.Trial registrationThis protocol was pre-registered in Open Science Framework (https://osf.io/9nq7z)
Detecting behavioural bias in GPS location data collected by mobile applications
Authors: Gibbs Hamish , Eggo Rosalind M. , Cheshire James 
Published: November 2023

AbstractA commonly-used form of human mobility data, called in-app mobility data, is based on GPS locations collected from a panel of mobile applications. In this paper, we analysed daily travel patterns from in-app GPS data in the United Kingdom to identify characteristic modes of travel behaviour, and assessed whether certain behavioural modes were more common among users of different groups of mobile applications. We also explored the relative importance of different mobility behaviours for the topology of an aggregated travel network. Our findings point to the presence of behavioural bias in in-app mobility data driven by the interaction between mobile device users and specific mobile applications. Our study also presents a general methodology for detecting behavioural bias in in-app mobility data, allowing for greater transparency into the characteristics of in-app mobility datasets without risking individual privacy or identifying specific mobile applications underlying a given dataset. Overall, the analysis highlights the need to understand the process of data generation for in-app mobility data, and the way that this process can bias the collective dynamics reported in aggregate mobility data.
The UK Soft Drinks Industry Levy and childhood hospital admissions for asthma in England
Authors: Rogers Nina T , Cummins Steven , Jones Catrin P , Mytton Oliver T , Roberts Chrissy H , Shaheen Seif O. , Shah Syed Ahmar , Sheikh Aziz , White Martin , Adams Jean 
Published: November 2023

AbstractSugar sweetened beverage consumption has been suggested as a risk factor for asthma symptoms in children. We examined whether the UK Soft Drinks Industry Levy (SDIL), announced in March 2016 and implemented in April 2018, was associated with changes in National Health Service hospital admission rates for asthma in children.We conducted interrupted time series analyses (2012 - 2020) to measure changes in monthly incidence rates of hospital admissions for asthma. Sub-analysis was by age-group (5-9, 10-14, 15-18 years) and neighbourhood deprivation quintiles. Estimated changes were relative to counterfactual scenarios where SDIL was neither announced, nor implemented. Compared to the counterfactual scenario there was an overall relative reduction in incidence rates of hospital admissions of 20.9% (95%CI: 29.6-12.2), 22 months post-SDIL. Reductions were similar across age-groups and deprivation quintiles with relative reductions of 24.3% (95%CI: 29.6-12.2) in children aged 10-14 years, and reductions of 23.2% (95%CI 33.4-13.1) in children living in the middle deprivation quintile. These findings provide evidence that the implementation of a tax intended to reduce childhood obesity in the UK preceded a potentially significant collateral public health benefit in the form of reduced hospital admissions for childhood asthma.
A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture
Authors: Jones Peter D. , Molina-Martínez Beatriz , Niedworok Anita , Cesare Paolo 
Published: November 2023

AbstractThree-dimensional in vitro models in microfluidic systems are promising tools for studying cell biology, with complex models using multiple cell types combined with high resolution imaging. Neuronal models demand electrical readout of the activity of networks of single neurons, yet classical planar microelectrode arrays struggle to capture extracellular action potentials when neural soma are suspended distant from the microelectrodes. This study introduces sophisticated microfluidic microelectrode arrays, specifically tailored for electrophysiology of 3D neuronal cultures. Using multilayer photolithography of permanent epoxy photoresists, we developed devices having 12 independent culture modules in a convenient format. Each module has two adjacent compartments for hydrogel-based 3D cell culture, with tunnels allowing projection of neurites between compartments. Microelectrodes integrated in the tunnels record action potentials as they pass between the compartments. Mesh ceilings separate the compartments from overlying wells, allowing for simple cell seeding and later nutrient, gas and waste exchange and application of test substances. Using these devices, we have demonstrated 3D neuronal culture, including electrophysiological recording and live imaging. This microphysiological platform will enable high-throughput investigation of neuronal networks for investigation of neurological disorders, neural pharmacology and basic neuroscience. Further models could include cocultures representing multiple brain regions or innervation models of other organs.
Monocot-specificmiR528act as the post-transcriptional regulator of strigolactone signaling viaDwarf 3in rice
Authors: Balyan Sonia , Sharma Deepika , Kansal Shivani , Panwar Vaishali , Jajo Ringyao , Chithung Tonu Angaila , Raghuvanshi Saurabh 
Published: November 2023

SummarymiRNAs are a critical component of regulatory mechanisms involved in plant growth, development, and stress response including phytohormone action. The role of miRNAs in regulating the strigolactone (SL) signaling in plants is still unexplored. Here we report that miR528 impacts the SL signaling via the post-transcriptional regulation ofDwarf 3(OsD3). Comparative miRNome analysis under drought conditions in flag leaf, inflorescence, and roots uncovered the tissue-biased unique stress response of miR528 in drought-tolerant N22 (down in inflorescence and roots; up in flag leaf). Consequently, its target,OsD3which encodes for the F-BOX/LRR-REPEAT MAX2 HOMOLOG and is a critical component of the rice SL signaling pathway exhibit opposite expression to miR528 in all three tissues. Interestingly,OsD3is a rice-specific target of miR528. miR528 overexpression plants exhibited early heading, increment in the number of tillers, flag leaf length, and width, number of panicle branches, grain per panicle, effective grains per panicle, seed length, and photosynthesis rate. miR528 overexpression plants exhibited similar traits toOsd3mutants including high tiller number, root architecture under low nitrogen conditions, and moderate insensitivity to GR24 and TIS1 levels in addition to shared transcriptional regulation. Furthermore, SL (GR24) negatively impacts the miR528 transcription. The impact of the miR528:D3 module is also reflected in the D53-mediated downstream signaling involving IPA1 regulon.
BDNF controls phosphorylation and transcriptional networks governing cytoskeleton organization and axonal regeneration
Authors: Vargas J.N.S. , Brown A.L. , Sun K. , Hagemann C. , Geary B. , Villarroel-Campos D. , Bryce-Smith S. , Zanovello M. , Lombardo M. , Ryandov E. , Stepic A. , Meysman L. , Majewski S. , Tosolini A.P. , Secrier M. , Keuss M.J. , Serio A. , Sleigh J.N. , Fratta P. , Schiavo G. 
Published: November 2023

SUMMARYAxonal degeneration underlies neuromuscular disorders and neuropathies. Dysregulation of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), in the peripheral nervous system has long been established to exacerbate axonopathy. However, the molecular programs controlled by BDNF that facilitate axonal regeneration and transport are not well-understood. Here, we unravel the transcriptomic and phosphorylation landscape shaped by BDNF in human iPSC-derived motor neurons. Using SLAM-Seq, we reveal BDNF stimulation increases global transcription rate in motor neurons and governs gene regulatory networks that converge with those engaged during axonal repair/outgrowth. Phosphoproteomic analyses demonstrate that BDNF remodels the phosphorylation landscape of cytoskeletal-binding proteins, especially of structural microtubule-associated proteins. Importantly, the localized axonal-specific activation of ERK1/2 is necessary for BDNF to enhance axonal transport of neurotrophin-containing signaling endosomes and to potentiate axonal regeneration after axotomy. Collectively, this work unveils a novel molecular paradigm that positions BDNF as a core regulator of transcriptional and phosphorylation programs driving axonal regeneration and transport in human motor neurons.HIGHLIGHTSSLAM-seq reveals increased global transcriptional rate by BDNF in human motor neuronsBDNF modulates transcriptional programs that potentiate axonal outgrowth/regenerationBDNF governs the phosphorylation landscape of cytoskeletal-binding proteinsAxonal BDNF-ERK1/2 signaling controls axonal transport and axonal regeneration
Inferring protein from mRNA concentrations using convolutional neural networks
Authors: Schwehn Patrick Maximilian , Falter-Braun Pascal 
Published: November 2023

ABSTRACTTranscript abundance is a widely used but poor predictor of protein abundance. As proteins are the actual agents executing biological functions, and because signaling outcome depends in a non-linear manner on the concentration of the network components, we aimed to develop a convolutional neural network-(CNN-) based predictor forHomo sapiensand the reference plantArabidopsis thaliana. After hyperparameter optimization and initial analysis of the training data, we employed a distinct training module for value and sequence data, respectively, predicting 40% of the variance in protein levels inHomo sapiens, respectively 48% inArabidopsis thaliana. Codon counts and peptides had the greatest predictive power. Extracting the learned weight revealed generally similar trends but also some intriguing differences between human and Arabidopsis. Many learned motifs in the 5’ and 3’ UTRs correspond to previously described regulatory features demonstrating that the model can learn ab initio mechanistically relevant features.