bluuebunny/crossref_metadata_2025_split huggingface dataset:
AlcoR: alignment-free simulation, mapping, and visualization of low-complexity regions in biological data
Authors: Silva Jorge M. , Qi Weihong , Pinho Armando J. , Pratas Diogo 
Published: April 2023

AbstractLow-complexity data analysis is the area that addresses the search and quantification of regions in sequences of elements that contain low-complexity or repetitive elements. For example, these can be tandem repeats, inverted repeats, homopolymer tails, GC biased regions, similar genes, and hairpins, among many others. Identifying these regions is crucial because of their association with regulatory and structural characteristics. Moreover, their identification provides positional and quantity information where standard assembly methodologies face significant difficulties because of substantial higher depth coverage (mountains), ambiguous read mapping, or where sequencing or reconstruction defects may occur. However, the capability to distinguish low-complexity regions (LCRs) in genomic and proteomic sequences is a challenge that depends on the model’s ability to find them automatically. Low-complexity patterns can be implicit through specific or combined sources, such as algorithmic or probabilistic, and recurring to different spatial distances, namely local, medium, or distant associations.This paper addresses the challenge of automatically modeling and distinguishing LCRs, providing a new method and tool (AlcoR) for efficient and accurate segmentation and visualization of these regions in genomic and proteomic sequences. The method enables the use of models with different memories, providing the ability to distinguish local from distant low-complexity patterns. The method is reference- and alignment-free, providing additional methodologies for testing, including a highly-flexible simulation method for generating biological sequences (DNA or protein) with different complexity levels, sequence masking, and a visualization tool for automatic computation of the LCR maps into an ideogram style. We provide illustrative demonstrations using synthetic, nearly synthetic, and natural sequences showing the high efficiency and accuracy of AlcoR. As large-scale results, we use AlcoR to unprecedentedly provide a whole-chromosome low-complexity map of a recent complete human genome and the haplotype-resolved chromosome pairs of a heterozygous diploid African cassava cultivar.The AlcoR method provides the ability of fast sequence characterization through data complexity analysis, ideally for scenarios entangling the presence of new or unknown sequences. AlcoR is implemented in C language using multi-threading to increase the computational speed, is flexible for multiple applications, and does not contain external dependencies. The tool accepts any sequence in FASTA format. The source code is freely provided athttps://github.com/cobilab/alcor.
Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses
Authors: Gallimore Connor G. , Ricci David , Hamm Jordan P. 
Published: April 2023

AbstractContext modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1) -- a phenomenon known as deviance detection (DD) at the neural level, or “mismatch negativity” (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual “oddball” sequence – a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations – and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that while basic adaptation to redundant stimuli was present early (50ms) in layer 4 responses, DD emerged later (150-230ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7Hz) and high-gamma (70-80Hz) oscillations in L2/3 and decreased beta oscillations (26-36hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, while “prediction errors” engage cortical feed-forward processing streams, which emanate from L2/3.
Opportunistic evidence of the impact of bacterial infections on social integration in vampire bats
Authors: Razik Imran , Stockmaier Sebastian , Abou-Elias Michael , Carter Gerald G. 
Published: April 2023

AbstractSocial integration can affect an individual’s susceptibility to infectious disease. Conversely, infectious disease can reduce an individual’s social activity. Yet, it remains unclear to what extent short-term infections can inhibit social integration and the formation of new relationships. During a previous study on relationship formation, we captured 21 female common vampire bats (Desmodus rotundus) from different wild populations and housed them together in captivity. Upon introduction, we observed an unplanned outbreak of bacterial infections that caused cutaneous lesions. After treating infected bats with an antibiotic, 5 bats recovered, but 4 others suffered lasting injuries. Given that observations of how natural infections alter relationship formation are rare, we analyzed how allogrooming rates changed over time among familiar and new dyads consisting of the 9 infected and 12 asymptomatic bats. We found that (1) infected bats demonstrated reduced activity and social behavior, (2) more severely infected bats gave and received less allogrooming compared to asymptomatic bats, (3) the effect of infection was larger for new dyads relative to familiar dyads, and (4) this effect decreased as infected bats recovered and new dyads became more familiar. These opportunistic observations were consistent with the hypothesis that short-term infections can impact the formation of new relationships.
The Drosophila MIC10 orthologue has a propensity to polymerize into cristae-shaping filaments
Authors: Stephan Till , Stoldt Stefan , Barbot Mariam , Carney Travis D. , Lange Felix , Bates Mark , Dib Peter Bou , Shcherbata Halyna R. , Meinecke Michael , Riedel Dietmar , Dennerlein Sven , Rehling Peter , Jakobs Stefan 
Published: April 2023

AbstractMitochondria are essential eukaryotic double-membrane organelles. The convoluted mitochondrial inner membrane forms highly organized invaginations, termed cristae, which are crucial for energy metabolism. Cristae formation requires MICOS, a conserved hetero-oligomeric inner membrane complex. The MICOS core subunit MIC10 is a small transmembrane protein that oligomerizes through highly conserved glycine-rich motifs to control cristae formation. Sequence alignments show thatD. melanogasterexhibits three MIC10-like proteins with different tissue-specific expression patterns. Here, we show that the ubiquitously expressed Dmel_CG41128/MINOS1b/DmMIC10b is the major MIC10 orthologue in flies. Loss of DmMIC10b disturbs cristae architecture of mitochondria and reduces the life-span and fertility of flies. Moreover, using fluorescence nanoscopy and electron tomography, we demonstrate that despite its high similarity to the MIC10 proteins from yeast and humans, DmMIC10b exhibits the unique ability to polymerize into elongated filaments upon overexpression. DmMIC10b filaments form bundles which accumulate in the intermembrane space and alter the shape of mitochondrial cristae membranes. We show that the formation of the filaments relies on conserved glycine and cysteine residues and is suppressed by co-expression of other MICOS proteins. Thereby, our findings provide new insights into the regulation of MICOS in flies.
The neural organization of visual information in the auditory cortex of the congenitally deaf
Authors: Tal Zohar , Sayal Joana , Fang Fang , Bi Yanchao , Almeida Jorge , Fracasso Alessio 
Published: April 2023

SummaryNeuroplasticity is the ability of the human brain to reorganize and modify its activity throughout life. In congenital deafness, sensory-deprived cortex can be recruited to represent sensory information belonging to other modalities, a process known as cross-modal plasticity. Previous studies have indicated that the auditory cortex of congenitally deaf, but not of hearing individuals, is recruited during visual tasks. However, it is not clear to what extent, and how, these cross-modal responses in the deprived auditory cortex represent low-level visual spatial information or map the visual field. Here, we addressed this question directly in an fMRI case-study, aiming to map retinotopic features in the auditory cortex. Two congenitally deaf and one hearing participant went through a conventional retinotopy fMRI experiment with visual stimuli designed to map the visual system. Using population receptive field (pRF) modelling, we revealed retinotopic-related responses in the auditory cortex of the deaf, but not in the hearing. These responses, that were mostly lateralized to the right hemisphere, represented the contralateral visual field, and were characterized by large receptive fields, centred to near foveal areas. Interestingly, we found that these responses to visual stimuli predominantly reflected negative BOLD signals in the auditory cortex of the deaf, suggesting that visual information might be represented through cross-modal deactivation signals.
Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins
Authors: Domma Anthony J. , Goodrum Felicia D. , Moorman Nathaniel J. , Kamil Jeremy P. 
Published: April 2023

ABSTRACTThe phosphoinositide 3-kinase (PI3K)/AKT pathway plays crucial roles in cell viability and protein synthesis and is frequently co-opted by viruses to support their replication. Although many viruses maintain high levels of AKT activity during infection, other viruses, such as vesicular stomatitis virus and human cytomegalovirus (HCMV), cause AKT to accumulate in an inactive state. To efficiently replicate, HCMV requires FoxO transcription factors to localize to the infected cell nucleus (Zhang et. al. mBio 2022), a process directly antagonized by AKT. Therefore, we sought to investigate how HCMV inactivates AKT to achieve this. Subcellular fractionation and live cell imaging studies indicated that AKT failed to recruit to membranes upon serum-stimulation of infected cells. However, UV-inactivated virions were unable to render AKT non-responsive to serum, indicating a requirement forde novoviral gene expression. Interestingly, we were able to identify thatUL38(pUL38), a viral activator of mTORC1, is required to diminish AKT responsiveness to serum. mTORC1 contributes to insulin resistance by causing proteasomal degradation of insulin receptor substrate (IRS) proteins, such as IRS1, which are necessary for the recruitment of PI3K to growth factor receptors. In cells infected with a recombinant HCMV disrupted forUL38, AKT responsiveness to serum is retained and IRS1 is not degraded. Furthermore, ectopic expression of UL38 in uninfected cells induces IRS1 degradation, inactivating AKT. These effects of UL38 were reversed by the mTORC1 inhibitor, rapamycin. Collectively, our results demonstrate that HCMV relies upon a cell-intrinsic negative feedback loop to render AKT inactive during productive infection.
Expression and engineering of unexplored PET degrading enzymes fromMicrobispora, Nonomuraea, Micromonosporagenus
Authors: Tiong Elaine , Koo Ying Sin , Bi Jiawu , Koduru Lokanand , Koh Winston , Lim Yee Hwee , Wong Fong Tian 
Published: April 2023

ABSTRACTLow recycling rates have resulted in the alarming rate of accumulation of a widely used plastic material, polyethylene terephthalate (PET). With the build-up of plastics in our environment, there is an urgent need to source for more sustainable solutions to process them. Biological methods such as enzyme-catalyzed PET recycling or bioprocessing are seen as a potential solution to this problem. Actinobacteria, known for producing enzymes involved in the degradation of complex organic molecules, are of particular interest due to their potential to produce PET degrading enzymes. The highly thermostable enzyme, leaf-branch compost cutinase (LCC) found in Actinobacteria is one such example. This work expands on the discovery and characterization of new PET degrading enzymes fromMicrobispora, Nonomuraea, andMicromonosporagenus. Within this genus, we analyzed enzymes from the polyesterase-lipase-cutinase family, which have ∼60% similarity to LCC, where one of the enzymes was found to be capable of breaking down PET and BHET at 45-50 °C. Moreover, we were able to enhance the enzyme’s depolymerization rate through further engineering, resulting in a two-fold increase in activity.IMPORTANCEThe proliferation of PET plastic waste poses a significant threat to human and environmental health, making it an issue of increasing concern. In response to this challenge, scientists are investigating eco-friendly approaches, such as bioprocessing and microbial factories, to sustainably manage the growing quantity of plastic waste in our ecosystem. Despite the existence of enzymes capable of degrading PET, their scarcity in nature limits their applicability. The objective of this study is to enhance our understanding of this group of enzymes by identifying and characterizing novel ones that can facilitate the breakdown of PET waste. This data will expand the enzymatic repertoire and provide valuable insights into the prerequisites for successful PET degradation.
MCU gain-and loss-of-function models define the duality of mitochondrial calcium uptake in heart failure
Authors: Garbincius Joanne F. , Luongo Timothy S. , Lambert Jonathan P. , Mangold Adam S. , Murray Emma K. , Hildebrand Alycia N. , Jadiya Pooja , Elrod John W. 
Published: April 2023

ABSTRACTBackgroundMitochondrial calcium (mCa2+) uptake through the mitochondrial calcium uniporter channel (mtCU) stimulates metabolism to meet acute increases in cardiac energy demand. However, excessivemCa2+uptake during stress, as in ischemia-reperfusion, initiates permeability transition and cell death. Despite these often-reported acute physiological and pathological effects, a major unresolved controversy is whether mtCU-dependentmCa2+uptake and long-term elevation of cardiomyocytemCa2+contributes to the heart’s adaptation during sustained increases in workload.ObjectiveWe tested the hypothesis that mtCU-dependentmCa2+uptake contributes to cardiac adaptation and ventricular remodeling during sustained catecholaminergic stress.MethodsMice with tamoxifen-inducible, cardiomyocyte-specific gain (αMHC-MCM x flox-stop-MCU; MCU-Tg) or loss (αMHC-MCM xMcufl/fl;Mcu-cKO) of mtCU function received 2-wk catecholamine infusion.ResultsCardiac contractility increased after 2d of isoproterenol in control, but notMcu-cKO mice. Contractility declined and cardiac hypertrophy increased after 1-2-wk of isoproterenol in MCU-Tg mice. MCU-Tg cardiomyocytes displayed increased sensitivity to Ca2+- and isoproterenol-induced necrosis. However, loss of the mitochondrial permeability transition pore (mPTP) regulator cyclophilin D failed to attenuate contractile dysfunction and hypertrophic remodeling, and increased isoproterenol-induced cardiomyocyte death in MCU-Tg mice.ConclusionsmtCUmCa2+uptake is required for early contractile responses to adrenergic signaling, even those occurring over several days. Under sustained adrenergic load excessive MCU-dependentmCa2+uptake drives cardiomyocyte dropout, perhaps independent of classical mitochondrial permeability transition pore opening, and compromises contractile function. These findings suggest divergent consequences for acute versus sustainedmCa2+loading, and support distinct functional roles for the mPTP in settings of acutemCa2+overload versus persistentmCa2+stress.
Phase partitioning rules Rab domain formation, growth and identity
Authors: Jimenez Ana Joaquina , Divoux Séverine , Goud Bruno , Perez Franck 
Published: April 2023

AbstractDiverse cellular processes are regulated by the formation of specific membrane domains displaying specific lipid and protein compositions. Liquid-liquid phase separation (LLPS) recently emerged as one possible mechanism for their biogenesis, but the examples remain scarce and the impact of LLPS properties on this process is not well established. Rab GTPases are present on all intracellular membranes and play a crucial role in membrane identity, trafficking and compartmentalization. Domain formation is thought to play a central role in Rab functions. Here we show that several Rab partners with common structural characteristics present LLPS properties, some being able to co-condensate or on the contrary presenting immiscible properties. These properties limit the recruitment of Rabs to the membrane sub-domains defined by the condensates of their specific partners. We further show that those LLPS properties control the recruitment of Rab5 to Rabaptin5 condensates ensuring Rab5 functions in regulating endocytic vesicle tethering and fusion. We propose a universal mechanism for Rab domain formation, delimitation, growth and docking based on LLPS properties of Rab partners.
Adenovirus protein VII binds the A-box of HMGB1 to repress interferon responses
Authors: Arnold Edward A. , Kaai Robin J. , Leung Katie , Brinkley Mia R. , Kelnhofer-Millevolte Laurel E , Guo Monica S. , Avgousti Daphne C. 
Published: April 2023

ABSTRACTViruses hijack host proteins to promote infection and dampen host defenses. Adenovirus encodes the multifunctional protein VII that serves both to compact viral genomes inside the virion and disrupt host chromatin. Protein VII binds the abundant nuclear protein high mobility group box 1 (HMGB1) and sequesters HMGB1 in chromatin. HMGB1 is an abundant host nuclear protein that can also be released from infected cells as an alarmin to amplify inflammatory responses. By sequestering HMGB1, protein VII prevents its release, thus inhibiting downstream inflammatory signaling. However, the consequences of this chromatin sequestration on host transcription are unknown. Here, we employ bacterial two-hybrid interaction assays and human cell biological systems to interrogate the mechanism of the protein VII-HMGB1 interaction. HMGB1 contains two DNA binding domains, the A- and B-boxes, that bend DNA to promote transcription factor binding while the C-terminal tail regulates this interaction. We demonstrate that protein VII interacts directly with the A-box of HMGB1, an interaction that is inhibited by the HMGB1 C-terminal tail. By cellular fractionation, we show that protein VII renders A-box containing constructs insoluble, thereby acting to prevent their release from cells. This sequestration is not dependent on HMGB1’s ability to bind DNA but does require post-translational modifications on protein VII. Importantly, we demonstrate that protein VII inhibits expression of interferon β, in an HMGB1- dependent manner, but does not affect transcription of downstream interferon- stimulated genes. Together, our results demonstrate that protein VII specifically harnesses HMGB1 through its A-box domain to depress the innate immune response and promote infection.
Metformin Impairs Intestinal Fructose Metabolism
Authors: Tong Wenxin , Hannou Sarah A. , Sargsyan Ashot , Zhang Guo-Fang , Grimsrud Paul A. , Astapova Inna , Herman Mark A. 
Published: April 2023

AbstractObjectiveTo investigate the effects of metformin on intestinal carbohydrate metabolismin vivo.Method: Male mice preconditioned with a high-fat, high-sucrose diet were treated orally with metformin or a control solution for two weeks. Fructose metabolism, glucose production from fructose, and production of other fructose-derived metabolites were assessed using stably labeled fructose as a tracer.ResultsMetformin treatment decreased intestinal glucose levels and reduced incorporation of fructose-derived metabolites into glucose. This was associated with decreased intestinal fructose metabolism as indicated by decreased enterocyte F1P levels and diminished labeling of fructose-derived metabolites. Metformin also reduced fructose delivery to the liver. Proteomic analysis revealed that metformin coordinately down-regulated proteins involved carbohydrate metabolism including those involved in fructolysis and glucose production within intestinal tissue.ConclusionMetformin reduces intestinal fructose metabolism, and this is associated with broad-based changes in intestinal enzyme and protein levels involved in sugar metabolism indicating that metformin’s effects on sugar metabolism are pleiotropic.HighlightsMetformin decreases intestinal fructose absorption, metabolism, and fructose delivery to the liver.Metformin reduces intestinal glucose production from fructose-derived metabolites.Metformin reduces protein levels of multiple metabolic enzymes involved in fructose and glucose metabolism in intestinal tissue.
Engineering genetic circuits in receiver cells for diffusion-based molecular data communications
Authors: Durmaz Merve Gorkem , Tulluk Neval , Aksoy Recep Deniz , Yilmaz H. Birkan , Yang Bill , Wipat Anil , Pusane Ali Emre , Mısırlı Göksel , Tugcu Tuna 
Published: April 2023

AbstractDevelopments in bioengineering and nanotechnology have ignited the research on biological and molecular communication systems. Despite potential benefits, engineering communication systems to carry data signals using biological messenger molecules is challenging. Diffusing molecules may fall behind their schedule to arrive at a receiver, interfering with symbols of subsequent time slots and distorting the signal. Theoretical molecular communication models often focus solely on the characteristics of the communication channel and fail to provide an end-to-end system response, since they assume a simple thresholding process for a receiver cell and overlook how the receiver can detect the incoming distorted molecular signal. There is a need to develop viable end-to-end communication models. In this paper, we present a model-based framework for designing diffusion-based molecular communication systems coupled with synthetic genetic circuits. We describe a novel approach to encode information as a sequence of bits, each transmitted from a sender as a burst of specific number of molecules, control cellular behavior, and minimize cellular signal interference by employing equalization techniques from communication theory. This approach allows the encoding and de-coding of data bits efficiently using two different types of molecules that act as the data carrier and the antagonist to cancel out the heavy tail of the former. We also present Period Finder, as a tool to optimize communication parameters, including the number of molecules and symbol duration. This tool facilitates automating the choice of communication parameters and identifying the best communication scenarios that can produce efficient cellular signals.