bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional networks predating cognition-associated pyramidal lineages are restructured by erythropoietin
Authors: Singh Manvendra , Zhao Ying , Gastaldi Vinicius Daguano , Wojcik Sonja M. , Curto Yasmina , Kawaguchi Riki , Merino Ricardo M. , Garcia-Agudo Laura Fernandez , Taschenberger Holger , Brose Nils , Geschwind Daniel , Nave Klaus-Armin , Ehrenreich Hannelore 
Published: February 2023

ABSTRACTRecombinant human erythropoietin (rhEPO) has potent procognitive effects, hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO have remained obscure. Here, we provide encyclopedic transcriptional hippocampal profiling of mice treated with rhEPO. Based on ∼108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build a developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ꞌtoolꞌ, we discover novel populations of newly differentiating pyramidal neurons, overpopulating to ∼200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.
Conserved use of the sodium/bile acid cotransporter (NTCP) as an entry receptor by hepatitis B virus and domestic cat hepadnavirus
Authors: Shofa Maya , Ohkawa Akiho , Kaneko Yasuyuki , Saito Akatsuki 
Published: February 2023

AbstractTheOrthohepadnavirusgenus includes hepatitis B virus (HBV) that can cause chronic hepatitis and hepatocarcinoma in humans. Recently, a novel hepadnavirus in cats, domestic cat hepadnavirus (DCH), was identified that is genetically close to HBV. DCH infection is associated with chronic hepatitis in cats, suggesting a similarity with HBV pathogenesis and the potential to use DCH as a novel animal model for HBV research. HBV is shown to use the sodium/bile acid cotransporter (NTCP) as a major cell entry receptor, but the equivalent receptor for DCH remains unknown. Here we sought to identify the entry receptor for DCH. HBV- and DCH-derived preS1 peptides efficiently bound to both human and cat NTCPs, and residue 158 of NTCP proteins determined the species-specific binding of the DCH preS1 peptide. Myrcludex B, an HBV entry inhibitor, blocked binding of the DCH preS1 peptide. Thus, DCH and HBV may share cell entry molecules, suggesting a possibility of inter-species transmission. Furthermore, our study suggests that DHC can be useful as a novel model for HBV research.
Microplastics analytics: why we should not underestimate the importance of blank controls
Authors: Noonan Michael J. , Ribeiro Nicole G. , Mills C Lauren , de A. M. M. Ferraz Marcia 
Published: February 2023

AbstractRecent years have seen considerable scientific attention devoted towards documenting the presence of microplastics (MPs) in environmental samples. Due to omnipresence of environmental microplastics, however, disentangling environmental MPs from sample contamination is a challenge. Hence, the environmental (collection site and laboratory) microplastics contamination of samples during processing is a reality that we must address, in order to generate reproducible and reliable data. Here we investigated published literature and have found that around 1/5 of studies failed to use blank controls in their experiments. Additionally, only 34% of the studies used a controlled air environment for their samples processing (laminar flow, fume hood, closed laboratory, clean room, etc.). In that regard, we have also shown that preparing samples in the fume hood, leads to more microplastics contamination than preparing it in the laboratory bench and the laminar flow. Although it did not completely prevent microplastics contamination, the processing of sample inside the laminar flow is the best option to reduce sample contamination during processing. Overall, we showed that blank controls are a must in microplastics sample preparation, but it is often overlooked by researchers.HighlightsMost of the contaminant microplastics in blank controls were particles < 20 μm.Fume hoods result in more contamination than processing the samples on the bench.Laminar flow was the best option for reducing MPs contamination of samples.1/5 of studies failed to use blank controls, and 1/3 did not correct their data.Improving the use and description of blanks is imperative for ensuring data quality.Mandatory graphical abstract
Brain-state mediated modulation of inter-laminar dependencies in visual cortex
Authors: Das Anirban , Sheffield Alec G. , Nandy Anirvan S. , Jadi Monika P. 
Published: February 2023

ABSTRACTSpatial attention is a quintessential example of adaptive information processing in the brain and is critical for recognizing behaviorally relevant objects in a cluttered environment. Object recognition is mediated by neural encoding along the ventral visual hierarchy. How the deployment of spatial attention aids these hierarchical computations is unclear. Prior studies point to two distinct mechanisms: an improvement in the efficacy of information directed from one encoding stage to another1–5, and/or a suppression of shared information within encoding stages6,7. To test these proposals, it is crucial to estimate the attentional modulation of unique information flow across and shared information within the encoding stages of the visual hierarchy. We investigated this in the multi-stage laminar network of visual area V4, an area strongly modulated by attention8–10. Using network-based dependency estimation from multivariate data, we quantified the modulation of inter-layer information flow during a change detection task and found that deployment of attention indeed strengthened unique dependencies between the input and superficial layers. Using the partial information decomposition framework11,12, we estimated the modulation of shared dependencies and found that they are reduced specifically in the putative excitatory subpopulations within a layer. Surprisingly, we found a strengthening of unique dependencies within the laminar populations, a finding not previously predicted. Crucially, these modulation patterns were also observed during successful behavioral outcomes (hits) that are thought to be mediated by endogenous brain state fluctuations13–15, and not by experimentally imposed attentive states. Finally, phases of endogenous fluctuations that were optimal for ‘hits’ were associated with reduced neural excitability. A reduction in neural excitability, potentially mediated by diminished shared inputs, suggests a novel mechanism for enhancing unique information transmission during optimal states. By decomposing the modulation of multivariate information, and combined with prior theoretical work16, our results suggest common computations of optimal sensory states that are attained by either task demands or endogenous fluctuations.
McLTP1, a lipid transfer protein isolated from noni seeds induces effective healing of superficial burns
Authors: Kurita Bianca Moreira , de Fátima Pinheiro Rangel Gisele , Rabelo Liviane Maria Alves , de Fátima Goebel de Sousa Tamiris , Macêdo Fernanda Soares , de Carvalho Leitão Renata Ferreira , de Oliveira Hermógenes David , de Alencar Nylane Maria Nunes 
Published: February 2023

AbstractBurns are health problems that overwhelm the Unified Health System (SUS) in Brazil. Despite the new therapeutic strategies, the costs of treating burns ate still quite high, and there are no effective alternatives for healing the skin. The use of plants with therapeutic potential is popularly used, due to its low cost, easy access and great Brazilian biodiversity.McLTP1, a lipid transfer protein isolated fromMorinda citrifollia(noni) seeds, has shown antinociceptive, anti-inflammatory, antibacterial and antioxidative effects. Therefore, the aim of this study was to investigate the effect of McLTP1 on the healing of superficial burns in mice. The study was approved by CEUA NPDM – UFC (protocol: 02170619-0). The burn was induced by direct contact with a square stainless-steel plate (1.5 cm2). The animals were divided into five experimental groups (n=6-7/grupo) and treated daily with 0.9% NaCl saline solution (Sham), or with topical treatment performed with dermatological creams: Silver sulfadiazine 1% (Sulfa 1%), lanette cream (Vehicle), cream lanette containing 0.25% and 0.5% ofMcLTP1. The animals were euthanized after 14 days.McLTP1 promoted total wound closure after 2 weeks of treatment, reduced histopathological scores at 3rdday, as well as induced the formation of a thicker epithelium and collagens synthesis on 14thday, modulated inflammation by reducing MPO activity, TNF-α, IL-1β and IL-6 levels and increasing IL-10 after 3 days of burn, modulated VEGF production at three times analyzed in this study, increased TGF-β and immunostaining for FGF after 7 days, reduced immunostaining for TNF-α on the 3rdday and exerted an antioxidant function by reducing MDA and nitrite and increasing GSH at day 3. In short,McLTP1 showed an important healing action in this burn model, showing additional anti-inflammatory and antioxidant effects.
Metabolic engineering ofSaccharomyces cerevisiaefor second-generation ethanol production from xylo-oligosaccharides and acetate
Authors: Procópio Dielle Pierotti , Lee Jae Won , Shin Jonghyeok , Tramontina Robson , Ávila Patrícia Felix , Brenelli Lívia Beatriz , Squina Fabio Márcio , Damasio André , Rabelo Sarita Cândida , Goldbeck Rosana , Franco Telma Teixeira , Leak David , Jin Yong-Su , Basso Thiago Olitta 
Published: February 2023

AbstractSimultaneous intracellular depolymerization of xylo-oligosaccharides (XOS) and acetate fermentation by engineeredSaccharomyces cerevisiaeoffers an advance towards more cost-effective second-generation (2G) ethanol production. As xylan is one of the most abundant polysaccharides present in lignocellulosic residues, the transport and breakdown of XOS in an intracellular environment might bring a competitive advantage for recombinant strains in competition with contaminating microbes, which are always present in fermentation tanks; furthermore, acetic acid is a ubiquitous toxic component in lignocellulosic hydrolysates, deriving from hemicellulose and lignin breakdown. In the present work, the previously engineeredS. cerevisiaestrain, SR8A6S3, expressing NADPH-linked xylose reductase (XR), NAD+-linked xylitol dehydrogenase (XDH) (for xylose assimilation), as well as NADH-linked acetylating acetaldehyde dehydrogenase (AADH) and acetyl-CoA synthetase (ACS) (for an NADH-dependent acetate reduction pathway), was used as the host for expressing of two β-xylosidases,GH43-2andGH43-7, and a xylodextrin transporter,CDT-2, fromNeurospora crassa, yielding the engineered strain SR8A6S3-CDT2-GH432/7. Both β-xylosidases and the transporter were introduced by replacing two endogenous genes,GRE3andSOR1, that encode aldose reductase and sorbitol (xylitol) dehydrogenase, respectively, which catalyse steps in xylitol production. Xylitol accumulation during xylose fermentation is a problem for 2G ethanol production since it reduces final ethanol yield. The engineered strain, SR8A6S3-CDT2-GH432/7, produced ethanol through simultaneous co-utilization of XOS, xylose, and acetate. The mutant strain produced 60% more ethanol and 12% less xylitol than the control strain when a hemicellulosic hydrolysate was used as a mono- and oligosaccharide source. Similarly, the ethanol yield was 84% higher for the engineered strain using hydrolysed xylan compared with the parental strain. The consumption of XOS, xylose, and acetate expands the capabilities ofS. cerevisiaefor utilization of all of the carbohydrate in lignocellulose, potentially increasing the efficiency of 2G biofuel production.HighlightsIntegration of XOS pathway in an acetate-xylose-consumingS. cerevisiaestrain;Intracellular fermentation of XOS, acetate and xylose improved ethanol production;Deletion of bothsor1Δ andgre3Δ reduced xylitol production.
An 8-cage imaging system for automated analyses of mouse behavior
Authors: Hernández Thaís Del Rosario , Joshi Narendra R. , Gore Sayali V. , Kreiling Jill A. , Creton Robbert 
Published: February 2023

AbstractThe analysis of mouse behavior is used in biomedical research to study brain function in health and disease. Well-established rapid assays allow for high-throughput analyses of behavior but have several drawbacks, including measurements of daytime behaviors in a nocturnal animal, effects of animal handling, and the lack of an acclimation period in the testing apparatus. We developed a novel 8-cage imaging system, with animated visual stimuli, for automated analyses of mouse behavior in 22-hour overnight recordings. Software for image analysis was developed in two open-source programs, ImageJ and DeepLabCut. The imaging system was used to measure multiple behaviors, including acclimation to the novel cage environment, day and nighttime activity, stretch-attend postures, location in various cage areas, and habituation to animated visual stimuli. These behaviors were summarized in behavioral profiles, which may be used in further studies to examine treatments for neural disorders.
Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics
Authors: Kim Minsoo , McDonald Eli Fritz , Sabusap Carleen Mae P. , Timalsina Bibek , Joshi Disha , Hong Jeong S. , Rab Andras , Sorscher Eric J. , Plate Lars 
Published: February 2023

AbstractCystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry (AP-MS) multiplexed with isobaric Tandem Mass Tags (TMT) was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knock-downs sensitize P67L to VX-445 and further enhance the correction of this variant. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize unresponsive CFTR variants to known and available correctors.
Behavioral estimates of mating success corroborate genetic evidence for pre-copulatory sexual selection in maleAnolis sagreilizards
Authors: Bhave Rachana S. , Seears Heidi A. , Reedy Aaron M. , Wittman Tyler N. , Robinson Christopher D. , Cox Robert M. 
Published: February 2023

AbstractIn promiscuous species, fitness estimates obtained from genetic parentage may often reflect both pre- and post-copulatory components of sexual selection. Directly observing copulations can help isolate the role of pre-copulatory selection, but such behavioral data are difficult to obtain in the wild and may also overlook post-copulatory factors that alter the relationship between mating success and reproductive success. To overcome these limitations, we combined genetic parentage analysis with behavioral estimates of size-specific mating in a wild population of brown anole lizards (Anolis sagrei). Males of this species are twice as large as females and multiple mating among females is common, suggesting the scope for both pre- and post-copulatory processes to shape sexual selection on male body size. Our genetic estimates of reproductive success revealed strong positive directional selection for male size, which was also strongly associated with the number of mates inferred from parentage. In contrast, a male’s size was not associated with the fecundity of his mates or his competitive fertilization success. By simultaneously tracking copulations in the wild via the transfer of colored powder to females by males from different size quartiles, we independently confirmed that large males were more likely than small males to mate. We conclude that body size is primarily under pre-copulatory sexual selection in brown anoles, and that post-copulatory processes do not substantially alter this pre-copulatory selection. Our study also illustrates the utility of combining both behavioral and genetic methods to estimate mating success to disentangle pre- and post-copulatory processes in promiscuous species.
Long lifetime and selective accumulation of the A-type lamins accounts for the tissue specificity of Hutchinson-Gilford progeria syndrome
Authors: Hasper John , Welle Kevin , Swovick Kyle , Hryhorenko Jennifer , Ghaemmaghami Sina , Buchwalter Abigail 
Published: February 2023

AbstractMutations to theLMNAgene cause laminopathies including Hutchinson-Gilford progeria syndrome (HGPS) that severely affect the cardiovascular system. The origins of tissue specificity in these diseases are unclear, as the A-type Lamins are abundant and broadly expressed proteins. We show that A-type Lamin protein and transcript levels are uncorrelated across tissues. As protein-transcript discordance can be caused by variations in protein lifetime, we applied quantitative proteomics to profile protein turnover rates in healthy and progeroid tissues. We discover that tissue context and disease mutation each influence A-type Lamin protein lifetime. Lamin A/C has a weeks-long lifetime in the aorta, heart, and fat, where progeroid pathology is apparent, but a days-long lifetime in the liver and gastrointestinal tract, which are spared from disease. The A-type Lamins are insoluble and densely bundled in cardiovascular tissues, which may present an energetic barrier to degradation and promote long protein lifetime. Progerin is even more long-lived than Lamin A/C in the cardiovascular system and accumulates there over time. Progerin accumulation interferes broadly with protein homeostasis, as hundreds of abundant proteins turn over more slowly in progeroid tissues. These findings indicate that potential gene therapy interventions for HGPS will have significant latency and limited potency in disrupting the long-lived Progerin protein. Finally, we reveal that human disease alleles are significantly over-represented in the long-lived proteome, indicating that long protein lifetime may influence disease pathology and present a significant barrier to gene therapies for numerous human diseases.Significance statementMany human diseases are caused by mutations to broadly expressed proteins, yet disease mysteriously manifests only in specific tissues. An example of this is Hutchinson-Gilford progeria syndrome (HGPS), which is caused by a mutation to the Lamin A/C protein. We show that this mutation slows the turnover of Lamin A/C proteins in disease-afflicted tissues, causing the mutant “Progerin” protein to accumulate over time and interfere with the normal turnover of hundreds of other proteins. Because Progerin is a long-lived protein, effective therapies for this disease will need to attack the protein and not just the gene that encodes it.
Endogenous Tenocyte Activation Underlies the Regenerative Capacity of Adult Zebrafish Tendon
Authors: Tsai Stephanie L. , Villasenor Steffany , Shah Rishita , Galloway Jenna L. 
Published: February 2023

AbstractTendons are essential, frequently injured connective tissues that transmit forces from muscle to bone. Their unique highly ordered, matrix-rich structure is critical for proper function. While adult mammalian tendons heal after acute injuries, endogenous tendon cells, or tenocytes, fail to respond appropriately, resulting in the formation of disorganized fibrovascular scar tissue with impaired function and increased propensity for re-injury. Here, we show that unlike mammals, adult zebrafish tenocytes activate upon injury and fully regenerate the tendon. Using a full tear injury model in the adult zebrafish craniofacial tendon, we defined the hallmark stages and cellular basis of tendon regeneration through multiphoton imaging, lineage tracing, and transmission electron microscopy approaches. Remarkably, we observe that the zebrafish tendon can regenerate and restore normal collagen matrix ultrastructure by 6 months post-injury (mpi). We show that tendon regeneration progresses in three main phases: inflammation within 24 hours post-injury (hpi), cellular proliferation and formation of a cellular bridge between the severed tendon ends at 3-5 days post-injury (dpi), and re-differentiation and matrix remodeling beginning from 5 dpi to 6 mpi. Importantly, we demonstrate that pre-existing tenocytes are the main cellular source of regeneration. Collectively, our work debuts the zebrafish tendon as one of the only reported adult tendon regenerative models and positions it as an invaluable comparative system to identify regenerative mechanisms that may inspire new tendon injury treatments in the clinic.
Effort cost of harvest affects decisions and movement vigor of marmosets during foraging
Authors: Hage Paul , Jang In Kyu , Looi Vivian , Fakharian Mohammad Amin , Orozco Simon P. , Pi Jay S. , Sedaghat-Nejad Ehsan , Shadmehr Reza 
Published: February 2023

AbstractOur decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor.Significance statementOur results suggest that as the brainstem neuromodulatory circuits that control pupil size respond to effort costs, they alter computations in the brain regions that control decisions, encouraging work and delaying gratification, and the brain regions that control movements, reducing vigor and suppressing energy expenditure. This coordinated response suggests that decisions and actions are part of a single control policy that aims to maximize a variable relevant to fitness: the capture rate.