bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of adolescent high-fat diet and psychosocial stress on neuroendocrine stress responses and binge eating behavior in adult male Lewis rats
Authors: Sierra Julio , Simon Timothy B. , Hilal Darine Abu , Torres Yaria Arroyo , Santana José M. Santiago , Figueroa Johnny D. 
Published: November 2024

ABSTRACTChildhood obesity is a multifactorial disease affecting more than 160 million adolescents worldwide. Adolescent exposure to obesogenic environments, characterized by access to high-fat diets and stress, precipitates maladaptive eating habits in adulthood such as binge eating. Evidence suggests a strong association between Western-like high-saturated-fat (WD) food consumption and dysregulated hormone fluctuations. However, few studies have explored the long-term impact of adolescent WD and psychosocial stress on brain and behavior. This longitudinal study aimed to investigate the impact of adolescent exposure to an obesogenic diet on stress resiliency and increased susceptibility for binge-like eating behaviors. Adolescent male Lewis rats were given WD (41% fat; n=40) or control diet (CD, 16% fat; n=38) for 4 weeks before undergoing a stress paradigm of predator exposure and social instability (CDE, WDE, CDU, WDU; n=16/group). Subjects were provided intermittent WD access (24 h/week) to evaluate binge eating–like behavior in adulthood. Fecal corticosterone and testosterone were measured at four timepoints throughout adolescence and adulthood. WD rats exhibited increased body weight (p = 0.0217) and elevated testosterone in mid-adolescence (p=0.0312) and blunted stress-induced corticosterone response in mid-late adolescence (CDE:WDE, p=0.028). Adolescent hormone levels were negatively correlated with bingeing and explained the variability between adult rats expressing hyperphagic and hypophagic behaviors. These results demonstrate that exposure to WD in adolescence disrupts hormone fluctuations and stress responsivity, with effects persisting into adulthood. This underscores the importance of addressing obesogenic environments early to mitigate their lasting impact on hormone regulation and stress responsiveness.
Long-Read Sequencing Reveals Increased Isoform Diversity in Key Transcription Factor Effectors of Intercellular Signalling at the Invertebrate-Vertebrate Transition
Authors: Torres-Aquila Nuria P. , Salonna Marika , Shimeld Sebastian , Hoppler Stefan , Ferrier David E.K. 
Published: November 2024

AbstractSeveral intercellular signalling pathways (namely wingless - Wnt, Hedgehog - Hh, and Bone Morphogenetic Protein - BMP) are used repeatedly in animals throughout development and evolution, and are also frequent targets for disease-associated disruptions. We have previously shown that the major transcriptional effectors of β-catenin-dependent Wnt signalling, the TCF/LEF proteins, in contrast to other pathway components, have a higher gene number and isoform diversity in vertebrates versus invertebrates, but this increased diversity has only been poorly quantified. Considering that isoform diversity correlates with organism complexity, any increase in major signalling effectors is likely to have made a significant contribution to vertebrate evolution. Usingde novolong-read transcriptomes, we compared isoform number per gene for the chordatesCiona intestinalis, Lampetra planeriandXenopus tropicalis, thus encompassing the invertebrate sister group to vertebrates, as well as a cyclostome and a gnathostome vertebrate. Our results implicate an increase in isoform diversity of the transcription factors of major intercellular signalling pathways as having a disproportionate role in the evolutionary origin and diversification of vertebrates.
Automated plasmid design for marker-free genome editing in budding yeast
Authors: Stojković Lazar , Gligorovski Vojislav , Geramimanesh Mahsa , Labagnara Marco , Rahi Sahand Jamal 
Published: November 2024

AbstractThe ease of genome editing has contributed to the popularity of budding yeast as a model organism. However, the palette of selectable markers is in principle limited as most can only be used once. Some markers such asURA3andTRP1can be recycled through counterselection. This permits seamless genome modification with pop-in/pop-out (PIPO), in which a DNA construct first integrates in the genome and, subsequently, homologous regions recombine and excise undesired sequences. Popular approaches for creating such constructs use oligonucleotides and polymerase chain reaction (PCR). The drawbacks are that long oligonucleotides are unstable, can form secondary structures that interfere with PCR, cannot be regenerated in a typical biological laboratory, and are only widely available for lengths less than about 120, which limits the homology and efficiency that can be attained. With the rapid reduction in price, synthesizing custom DNA sequences in specific plasmid backbones has become an appealing alternative. For designing plasmids for seamless PIPO gene tagging or deletion, there are a number of factors to consider. To create only the shortest DNA sequences necessary, avoid errors in manual design, specify the amount of homology desired, and customize restriction sites, we created the computational tool PIPOline. Using it, we tested the ratios of homology that improve pop-out efficiency when targeting the genesHTB2orWHI5. We supply optimal PIPO plasmid sequences for tagging or deleting almost all S288C budding yeast open reading frames (ORFs). Finally, we demonstrate how the histone variant Htb2 marked with a red fluorescent protein can be used as a cell-cycle stage marker, alternative to superfolder GFP (sfGPF), reducing light toxicity. We expect PIPOline to streamline genome editing in budding yeast.
Mechanisms driving epigenetic and transcriptional responses of microglia in a neurodegenerative lysosomal storage disorder model
Authors: Balak Christopher D. , Schlachetzki Johannes C.M. , Lana Addison J. , West Elizabeth , Hong Christine , DuGal Jordan , Zhou Yi , Li Benjamin , Saisan Payam , Spann Nathanael J. , Sarsani Vishal , Pasillas Martina P. , O’Brien Sydney , Gordts Philip , Stevens Beth , Kamme Fredrik , Glass Christopher K. 
Published: November 2024

ABSTRACTLysosomal dysfunction is causally linked to neurodegeneration in many lysosomal storage disorders (LSDs) and is associated with various age-related neurodegenerative diseases1,2, but there is limited understanding of the mechanisms by which altered lysosomal function leads to changes in gene expression that drive pathogenic cellular phenotypes. To investigate this question, we performed systematic imaging, transcriptomic, and epigenetic studies of major brain cell types inSgshnull (KO) mice, a preclinical mouse model for Sanfilippo syndrome (Mucopolysaccharidosis Type IIIA, MPS-IIIA)3,4. MPS-IIIA is a neurodegenerative LSD caused by homozygous loss-of-function (LoF) mutations inSGSHwhich results in severe early-onset developmental, behavioral, and neurocognitive impairment5–15. Electron microscopy, immunohistochemistry, and single-nucleus RNA-sequencing analysis revealed microglia as the cell type exhibiting the most dramatic phenotypic alterations inSgshKO mice. Further temporal analysis of microglia gene expression showed dysregulation of genes associated with lysosomal function and immune signaling pathways beginning early in the course of the disease.Sgshdeficiency similarly resulted in increases in open chromatin and histone acetylation at thousands of putative microglia-specific enhancers associated with upregulated genes but had much less impact on the epigenetic landscapes of neurons or oligodendrocytes. We provide evidence for dominant and context-dependent roles of members of the MITF/TFE family as major drivers of microglia-specific epigenetic and transcriptional changes resulting from lysosomal stress that are dependent on collaborative interactions with PU.1/ETS and C/EBP transcription factors. Lastly, we show that features of the transcriptomic and epigenetic alterations observed in murineSgshdeficiency are also observed in microglia derived from mouse models of age-related neurodegeneration and in human Alzheimer’s disease patients, revealing common and disease-specific transcriptional mechanisms associated with disease-associated microglia phenotypes.
Multi-stage-mixing to control the supramolecular structure of lipid nanoparticles, thereby creating a core-then-shell arrangement that improves performance by orders of magnitude
Authors: Nong Jia , Gong Xijing , Dang Quang Minh , Tiwari Sachchidanand , Patel Manthan , Wu Jichuan , Hanna Andrew , Park Wook-Jin , Atochina-Vasserman Elena N. , Huang Hui-Ting , Marcos-Contreras Oscar A. , Morris-Blanco Kahlilia C. , Miner Jonathan J. , Weissman Drew , Muzykantov Vladimir R. , Gupta Kushol , Issadore David , Myerson Jacob W. , Wang Zhicheng , Brenner Jacob S. 
Published: November 2024

ABSTRACTAs they became the dominant gene therapy platform, lipid nanoparticles (LNPs) experienced nearly all their innovation in varying the structure of individual molecules in LNPs. This ignored control of the spatial arrangement of molecules, which is suboptimal because supramolecular structure determines function in biology. To control LNPs’ supramolecular structure, we introduce multi-stage-mixing (MSM) to successively add different molecules to LNPs. We first utilize MSM to create a core-then-shell (CTS) synthesis. CTS-LNPs display a clear core-shell structure, vastly lower frequency of LNPs containing no detectable mRNA, and improved mRNA-LNP expression. With DNA-loaded LNPs, which for decades lagged behind mRNA-LNPs due to low expression, CTS improved DNA-LNPs’ protein expression by 2-3 orders of magnitude, bringing it within range of mRNA-LNPs. These results show that supramolecular arrangement is critical to LNP performance and can be controlled by mixing methodology. Further, MSM/CTS have finally made DNA-LNPs into a practical platform for long-term gene expression.
Low-frequency Cortical Activity Reflects Context-dependent Parsing of Word Sequences
Authors: Chen Honghua , Ye Tianyi , Zhang Minhui , Ding Nai 
Published: November 2024

SummaryDuring speech listening, it has been hypothesized that the brain builds representations of large linguistic structures such as sentences, which are captured by neural activity tracking the rhythm of these structures. Nevertheless, it has been concerned that the brain may only encode words, and neural activity tracking structures may be confounded by neural activity tracking the predictability or syntactic properties of individual words. Here, to disentangle the neural responses to sentences and words, we design word sequences that are parsed into different sentences in different contexts. By analyzing neural activity recorded by magnetoencephalography, we find that low-frequency neural activity strongly depends on the context – The difference between MEG responses to the same word sequence in two contexts yields a low-frequency signal, most strongly generated in the superior temporal gyrus, which precisely tracks sentences. The predictability and syntactic properties of words can partly explain the neural response in each context but cannot explain the difference between contexts. In summary, low-frequency neural activity encodes sentences and can reliably reflect how the same word sequence is parsed in different contexts.
A NovelC. elegansModel for Tau Spreading Reveals Genes Critical for Endolysosomal Integrity and Seeded Tau Aggregation
Authors: Sandhof Carl Alexander , Martin Nicole , Tittelmeier Jessica , Schlueter Annabelle , Pezzali Martina , Schoendorf David C. , Lange Timo , Reinhardt Peter , Ried Janina S. , Liang Siwen , Uzunoglu Gamze , Gasparini Laura , Jahn Thomas R. , Ehrnhoefer Dagmar E. , Nussbaum-Krammer Carmen 
Published: November 2024

AbstractThe spreading of Tau pathology is closely associated with the progression of neurodegeneration and cognitive decline in Alzheimer’s disease and other tauopathies. A key event in this process is the rupture of endolysosomal vesicles following the intercellular transfer of Tau aggregates, releasing the transferred Tau species into the cytosol where they can promote the aggregation of endogenous Tau. However, understanding of the cellular pathways involved in this process remains limited.In this study, we investigated cellular pathways that prevent endolysosomal vesicle rupture. We established a newC. elegansmodel of Tau spreading by introducing an mCherry-labelled, disease-associated aggregation-prone fragment of human Tau (F3ΔK281::mCh) into the six touch receptor neurons. F3ΔK281::mCh transgenic animals exhibited significant neurotoxicity and mechanosensory deficits due to the accumulation of this Tau fragment. In addition, its intercellular transmission compromised the endolysosomal system in receiving hypodermal cells. Using this model, we conducted an unbiased genome-wide RNAi screen and identified 59 genes critical for maintaining endolysosomal integrity. GO-term analysis revealed an enrichment of genes related to the ESCRT complex, the ubiquitin-proteasome system, mRNA splicing, and fatty acid metabolism. Silencing of selected conserved genes exacerbated seeded Tau aggregation in a human induced pluripotent stem cell (hiPSC)-derived cortical neuron model and triggered endolysosomal rupture in HEK293T cells, confirming the crucial role of endolysosomal damage in seeded Tau aggregation.Overall, this study discovered novel cellular pathways that safeguard endolysosomal integrity. These findings may guide the development of therapeutics that improve endolysosomal integrity to halt the progression of Tau pathology.
Individual brain activity patterns during task are predicted by distinct resting-state networks that may reflect local neurobiological features
Authors: Scholz Robert , Benn R. Austin , Shevchenko Victoria , Klatzmann Ulysse , Wei Wei , Alberti Francesco , Chiou Rocco , Zhang Xi-Han , Leech Robert , Smallwood Jonathan , Margulies Daniel S. 
Published: November 2024

AbstractUnderstanding how individual cortical features shape functional brain organization offers a promising framework for examining the principles of cognitive specialization in the human brain. This study explores the relationship between various cortical characteristics—i.e resting-state functional connectivity, structural connectivity, microstructure, morphology, and geometry—and the layout of task-specific functional activations. We employ linear models to predict the functional layout of the cortex at the individual level from each of these feature modalities. Our findings demonstrate that resting-state component loadings predict individual task activations, consistently across hemispheres and independent datasets. Whereas the first few components provide a common space for functional activations across tasks, predictive higher-order component loadings demonstrated task-specificity. Cortical microstructure/morphology was notably predictive of activation strength in the occipital cortex, highlighting its relevance for cortical functional specialization. By relating resting state components to a set of reference maps of cortical organization, we identify associations that suggest possible neurobiological underpinnings of specific cognitive functions. The remaining feature modalities were only predictive of group-level functional activations. These results advance our understanding of how distinct cortical features may contribute to functional specialization, guiding future inquiry into the organization of cognitive functions on the cortex.
Sex differences in auditory function of the desert locust
Authors: Tom Austin T , Christian Thomas L , Ben Warren 
Published: November 2024

AbstractAge-related auditory decline manifests across the animal kingdom, from humans and mice to zebrafish and insects. Sex differences in auditory decline are established for humans, but there is now evidence in mice and even zebrafish. Here, we found sex differences in auditory decline in an insect, the Desert Locust and investigated its biological basis. We profiled gene expression in a dedicated auditory organ, Müller’s organ to understand the genetic underpinning of sex differences and measured sound-evoked transduction currents and electrophysiological properties of auditory neurons to quantify auditory decline. We analysed gene expression in Müller’s organ of young locusts where sex differences were absent and in older, noise-exposed locusts where sex differences were maximal. The largest differences in gene expression between the sexes was between young and stressed (aged and noise-exposed) auditory organs. We found sex-specific genes and gene ontology terms for juvenile hormone (JH) and sex-specific estrogen-related steroids. We hypothesise that sex differences in auditory decline are due to differences in hormones which then affect metabolic processes in and mitochondria.HighlightsFemale Desert Locusts have less auditory decline than males.Female’s auditory organs maintain better metabolism under stressed conditions.Sex differences in gene expression are maximal during aging and noise-exposure.Sex differences are minimal between the sexes for young and stressed auditory organs.
Manipulation of Host Cholesterol by SARS-CoV-2
Authors: Doyle Aliza , Goodson Baley A. , Kolaczkowski Oralia M. , Liu Rui , Jia Jingyue , Wang Hu , Han Xianlin , Ye Chunyan , Bradfute Steven B. , Kell Alison M. , Rosas Lemus Monica , Pu Jing 
Published: November 2024

AbstractSARS-CoV-2 infection is associated with alterations in host lipid metabolism, including disruptions in cholesterol homeostasis. However, the specific mechanisms by which viral proteins influence cholesterol remain incompletely understood. Here, we report that SARS-CoV-2 infection induces cholesterol sequestration within lysosomes, with the viral protein ORF3a identified as the primary driver of this effect. Mechanistically, we found that ORF3a interacts directly with the HOPS complex subunit VPS39 through a hydrophobic interface formed by residues W193 and Y184. A W193A mutation in ORF3a significantly rescues cholesterol egress and corrects the mislocalization of the lysosomal cholesterol transporter NPC2, which is caused by defective trafficking of the trans-Golgi network (TGN) sorting receptor, the cation-independent mannose-6-phosphate receptor (CI-MPR). We further observed a marked reduction in bis(monoacylglycero)phosphate (BMP), a lipid essential for lysosomal cholesterol egress, in both SARS-CoV-2-infected cells and ORF3a-expressing cells, suggesting BMP reduction as an additional mechanism of SARS-CoV-2-caused cholesterol sequestration. Inhibition of lysosomal cholesterol egress using the compound U18666A significantly decreased SARS-CoV-2 infection, highlighting a potential viral strategy of manipulating lysosomal cholesterol to modulate host cell susceptibility. Our findings reveal that SARS-CoV-2 ORF3a disrupts cellular cholesterol transport by altering lysosomal protein trafficking and BMP levels, providing new insights into virus-host interactions that contribute to lipid dysregulation in infected cells.
Food environment components influencing consumption trends of neglected and underutilized species in northern Benin
Authors: Bankole Bissola Malikath , Amoussa Hounkpatin Waliou , Bodjrenou Sam , Bodecker Julia , Julen Lynn , Chadare Flora Josiane , Termote Celine 
Published: November 2024

AbstractMalnutrition is a global problem driven by food systems that impact climate and biodiversity. Neglected and underutilized species (NUS) could improve diets, but what drives their choices and consumption, particularly in low and middle-income countries, is poorly documented. This study investigated the influences of the personal food environment on the consumption of NUS in three communities in the department of Atacora in northern Benin. Following a purposive sampling strategy, 24 semi-structured interviews were conducted with local and 18 with professional experts. 12 group discussions with villagers from six villages in the three communes complemented and deepened the information gathered, focusing on both barriers and factors for enhancing consumption. The data collected was translated and transcribed into French and analyzed using qualitative content analysis with Atlas.ti software. Among the investigated plant parts, an upward trend was found forMoringa oleiferaleaves andVigna radiataseeds, a downward trend forAdansonia digitatapulps, and a varied trend forOcimum gratissimumleaves andAdansonia digitatakernels and leaves. Drivers for changes in consumption were found in all four dimensions of the food environment. Among the plant parts with the main increasing trend in consumption, various aspects of desirability, above all increased food and nutrition knowledge and skills, led to a positive consumption trend. The downward trend has most often been attributed to declining accessibility, but several aspects have also made these plant parts less affordable and less desirable (taboos for example). The strong variation in dimensions’ influence on plant parts with variable trends reflects their non-unanimous changes. Research and policies should address the factors influencing the consumption of these foods. Making neglected species more accessible, affordable, and desirable can enhance food security and environmental sustainability.
Dynamic cortical behavior of plant protoplasts reveals unexpected similarities between plant and animal cells
Authors: Dickmann Johanna E. M. , Martin Marjolaine , Lionnet Claire , Nemec-Venza Zoe , Hamant Olivier 
Published: November 2024

AbstractIn contrast to animal cells with their contractile cortical cytoskeleton, plant cells are encased in walls and are usually thought to behave like stiff, pressurized vessels. When digesting the cell wall, plant protoplasts form spherical shapes, further consolidating this model. Here we challenge this apparent opposition between animal and plant cells. We show that plant protoplasts can form protrusions. More precisely, using plasma membrane markers, we reveal that 27 ± 1% of the protoplasts show dot-like protrusions and 16 ± 7% of protoplasts show long (typically 1-20 μm, up to 200 μm) protrusions that we name “filopods”. We demonstrate that this behavior is independent of the plant species, the membrane marker or the osmolyte. Protrusions can host large and long structures, such as microtubule bundles, which in turn can impact the mechanical behavior of the protrusions. We find that filopods can formde novowhen increasing osmolarity, that they most likely move passively, and that they can attach to artificial surfaces. Altogether, these observations show that forming and retaining protrusions is not exclusive to animal cells. This calls for revisiting the dynamics and probing ability of the plant cell cortex in different osmotic and mechanical environments.