bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct SARS-CoV-2 populational immune backgrounds induce divergent RBD evolutionary preferences
Authors: Ma Wentai , Fu Haoyi , Jian Fanchong , Cao Yunlong , Li Mingkun 
Published: December 2023

AbstractImmune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct (less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of BA.5.2.48, BF.7.14, and BA.5.2.49—variants prevalent in China—with their counterparts in other countries. We found that mutations in the RBD region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher ACE2 binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them exhibited a transmission advantage. Instead, they were replaced by the imported XBB variant with stronger immune evasion since April 2023. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to the viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.
Clustering of RNA co-expression network identifies novel long non-coding RNA biomarkers in squamous cell carcinoma
Authors: Nissinen Liisa , Haalisto Josefiina , Riihilä Pilvi , Piipponen Minna , Kähäri Veli-Matti 
Published: December 2023

ABSTRACTLong non-coding RNAs (lncRNAs) have been shown to play an important role in cancer progression. Cutaneous squamous cell carcinoma is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastatic risk nor specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNA and protein-coding genes revealed six distinct clusters. One of the upregulated clusters involved genes related to cell motility. Upregulation of the expression of lncRNAs involved in cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed by qRT-PCR. Upregulation ofHOTTIPandLINC00543was also noted in SCC tumorsin vivoand was associated with worse prognosis in HNSCC and lung SCC cohorts in the TCGA data, respectively. Altogether, these results reveal a novel set of lncRNAs involved in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers or a biomarker panel and as putative therapeutic targets in locally advanced and metastatic cSCC.
Methylation Array Signals are Predictive of Chronological Age Without Bisulfite Conversion
Authors: Porter Hunter L. , Ansere Victor A. , Undi Ram Babu , Hoolehan Walker , Giles Cory B. , Brown Chase A. , Stanford David , Huycke Mark M. , Freeman Willard M. , Wren Jonathan D. 
Published: December 2023

AbstractDNA methylation data has been used to make “epigenetic clocks” which attempt to measure chronological and biological aging. These models rely on data derived from bisulfite-based measurements, which exploit a semi-selective deamination and a genomic reference to determine methylation states. Here, we demonstrate how another hallmark of aging, genomic instability, influences methylation measurements in both bisulfite sequencing and methylation arrays. We found that non-methylation factors lead to “pseudomethylation” signals that are both confounding of epigenetic clocks and uniquely age predictive. Quantifying these covariates in aging studies will be critical to building better clocks and designing appropriate studies of epigenetic aging.
Chlamydial protease-like activating factor targets SLC7A11 for degradation to induce ferroptosis and facilitate dissemination
Authors: Chen Wentao , Su Xin , Pan Yuying , Xue Yaohua , Zeng Lihong , Xu Qingqing , Yu Xueying , Yin Xiaona , Zhou Han , Feng Zhanqin , Zhang Bao , Zhao Wei , Zheng Heping 
Published: December 2023

AbstractChlamydia trachomatis, the most prevalent bacterial agent of sexually transmitted infections, possesses remarkable capacities for dissemination within the host, leading to reproductive health complications. The release of progeny through the orchestrated lysis of host cells plays a crucial role inChlamydiadissemination, but the underlying molecular mechanisms remain largely elusive. Here, we uncovered a novel mechanism by whichChlamydiainduces host cells ferroptosis to facilitate its dissemination. This process involves the degradation of host protein SLC7A11 by the chlamydial protease-like activating factor (CPAF), resulting in glutathione depletion, oxidative damage, and subsequent host cell lysis characterized by lipid peroxidation. Infection with CPAF-deficient strain fails to induce host cells ferroptosis, leading to restricted progeny release. Importantly, inhibiting ferroptosis effectively limits the release ofChlamydiaprogeny, highlighting its potential as a therapeutic strategy for controllingChlamydiadissemination. These findings provide insights into the chlamydial conserved dissemination strategy and enhance understanding of its pathogenesis.
Systematic Evaluation of Lecithin:Cholesterol Acyltransferase Binding Sites in Apolipoproteins via Peptide Based Nanodiscs: Regulatory Role of Charged Residues at Positions 4 and 7
Authors: Niemelä Akseli , Koivuniemi Artturi 
Published: December 2023

ABSTRACTLecithin:cholesterol acyltransferase (LCAT) exhibits α-activity on high-density and β-activity on low-density lipoproteins. However, the molecular determinants governing LCAT activation by different apolipoproteins remain elusive. Uncovering these determinants would offer the opportunity to design and explore advanced therapies against dyslipidemias. Here, we have conducted coarse-grained and all-atom molecular dynamics simulations of LCAT with nanodiscs made with α-helical amphiphilic peptides either derived from apolipoproteins A1 and E (apoA1 and apoE) or apoA1 mimetic peptide 22A that was optimized to activate LCAT. This study aims to explore what drives the binding of peptides to our previously identified interaction site in LCAT. We hypothesized that this approach could be used to screen for binding sites of LCAT in different apolipoproteins and would provide insights to differently localized LCAT activities. Our screening approach was able to discriminate apoA1 helixes 4, 6, and 7 as key contributors to the interaction with LCAT supporting the previous research data. The simulations provided detailed molecular determinants driving the interaction with LCAT: the formation of hydrogen bonds or salt bridges between peptides E4 or D4 and LCAT S236 or K238 residues. Additionally, salt bridging between R7 and D73 was observed, depending on the availability of R7. Expanding our investigation to diverse plasma proteins, we detected novel LCAT binding helixes in apoL1, apoB100, and serum amyloid A. Our findings suggest that the same binding determinants, involving E4 or D4 -S236 and R7-D73 interactions, influence LCAT β-activity on low-density lipoproteins, where apoE and or apoB100 are hypothesized to interact with LCAT.
Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS
Authors: Dagva Oyut , Thibessard Annabelle , Lorenzi Jean-Noël , Labat Victor , Piotrowski Emilie , Rouhier Nicolas , Myllykallio Hannu , Leblond Pierre , Bertrand Claire 
Published: December 2023

ABSTRACTThe linear chromosome ofStreptomycesexhibits a highly compartmentalized structure with a conserved central region flanked by variable arms. As double strand break (DSB) repair mechanisms play a crucial role in shaping the genome plasticity ofStreptomyces, we investigated the role of EndoMS/NucS, a recently characterized endonuclease involved in a non-canonical Mismatch Repair (MMR) mechanism in archaea and actinobacteria, that singularly corrects mismatches by creating a DSB. We showed thatStreptomycesmutants lacking NucS display a marked colonial phenotype and a drastic increase in spontaneous mutation rate.In vitrobiochemical assays revealed that NucS cooperates with the replication clamp to efficiently cleave G/T, G/G and T/T mismatched DNA by producing DSBs. These findings are consistent with the transition-shifted mutational spectrum observed in the mutant strains and reveal that NucS-dependent MMR specific task is to eliminate G/T mismatches generated by the DNA polymerase during replication. Interestingly, our data unveil a crescent-shaped distribution of the transition frequency from the replication origin towards the chromosomal ends, shedding light on a possible link between NucS-mediated DSBs andStreptomycesgenome evolution.GRAPHICAL ABSTRACT
Cell type-specific adaptation of the SARS-CoV-2 spike
Authors: Carrascosa-Sàez Marc , Marqués María-Carmen ,   The IBV-Covid19-Pipeline, Geller Ron , Elena Santiago F. , Rahmeh Amal , Dufloo Jérémy , Sanjuán Rafael 
Published: December 2023

AbstractSARS-CoV-2 can infect various human tissues and cell types, principally via interaction with its cognate receptor ACE2. However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of key entry factors. After 20 passages, cell type-specific phenotypic changes were observed. Selected spike mutations were identified and functionally characterized in terms of entry efficiency, ACE2 affinity, spike processing, TMPRSS2 usage, entry pathway and syncytia formation. We found that the effects of these mutations varied across cell types. Interestingly, two spike mutations (L48S and A372T) that emerged in cells expressing low ACE2 levels increased receptor affinity, syncytia induction, and entry efficiency under low-ACE2 conditions. Our results demonstrate specific adaptation of the SARS-CoV-2 spike to different cell types and have implications for understanding SARS-CoV-2 tissue tropism and evolution.
Seasonal variation in D2/3 dopamine receptor availability in the human brain
Authors: Sun Lihua , Malén Tuulia , Tuisku Jouni , Kaasinen Valtteri , Hietala Jarmo A. , Rinne Juha , Nuutila Pirjo , Nummenmaa Lauri 
Published: December 2023

AbstractBrain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmicin vivodopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. Here, based on historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. We found that daylength at the time of scanning was negatively correlated with availability of this type of receptors in the striatum. Likely, seasonally varying D2/3 receptor signaling also underlies the seasonality of mood, feeding, and motivational processes.Significance of the studyBrainin vivoneurotransmitter signaling demonstrates seasonal patterns. The dopamine D2/3 receptor, with both pre- and postsynaptic expressions, has been targeted by major antipsychotic and antiparkinsonian pharmaceuticals. The current study, based on a large dataset of healthy brain PET images quantifying these receptors, shows that dark seasons are associated with increased receptor availability in the striatum. Considering the previous findings of increased dopamine synthesis and lowered number of transporters, findings may suggest elevated presynaptic control of dopamine release and increased dopamine receptor sensitivity during dark seasons. The rhythmic D2/3 receptor availability may be a mechanism underlying seasonality in mood, feeding, and motivational processes.
Reduced palatability, fast flight, and tails: Decoding the defence arsenal of Eudaminae skipper butterflies in a Neotropical locality
Authors: Linke Daniel , Mejia Jacqueline Hernandez , Navarro Valery N. P. Eche , Salinas Sánchez Letty , Ribeiro Pedro de Gusmão , Elias Marianne , Matos-Maraví Pável 
Published: December 2023

AbstractPrey often relies on multiple defences to avoid predators, such as difficulty of capture, attack deflection, or unpleasant taste. Eudaminae skipper butterflies rely on behavioural (fast flight) and mechanical defences (hindwing tails), but other defences like unpalatability (consumption deterrence), and the interaction among defences, have not been assessed.We test the palatability of 12 abundant Eudaminae species from a Neotropical locality, using training and feeding experiments with domestic chicks. Further, we approximate the difficulty of capture explained by flight speed and quantified by wing loading. To test how multiple defences are associated and explained by body size and habitat preference, we perform phylogenetic Bayesian regression analyses.We found a broad range of palatability in Eudaminae, within and among species. Palatability was negatively correlated with wing loading, indicating that butterflies with higher flight speed tend to have lower palatability.The presence or absence of tails did not explain the level of butterfly palatability, showing that attack deflection and consumption deterrence are not mutually exclusive defences. Habitat preference (open or forested environments) did not explain the level of palatability in Eudaminae, but it seems that butterflies with high wing loading (fast flight) tended to occupy semi-closed (e.g., hilltops) or closed habitats (e.g., secondary forest).Finally, the level of unpalatability in Eudaminae is size dependent, larger butterflies are less palatable, perhaps due to their more likely detectability/preference by predators. Altogether, our findings shed light on the contexts favouring the prevalence of single vs. multiple defensive strategies in prey.
PD-L1 blockade immunotherapy rewires cancer emergency myelopoiesis
Authors: Boumpas Athina , Papaioannou Antonis , Bousounis Pavlos , Grigoriou Maria , Bergo Veronica , Papafragkos Iosif , Tasis Athanasios , Iskas Michael , Boon Louis , Makridakis Manousos , Vlachou Antonia , Gavriilaki Eleni , Hatzioannou Aikaterini , Mitroulis Ioannis , Trompouki Eirini , Verginis Panayotis 
Published: December 2023

AbstractImmune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit. Herein, we reveal that immunotherapy with PD-L1 blockage antibody (αPDL1) in tumour-bearing mice targets the hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (ΒΜ), mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, from both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice shifting towards an inflammatory state. Functionally, transplantation of HSPCs isolated from αPDL1-treated tumor-bearing mice exhibited resistance to cancer-associated myelopoiesis as evident by the generation of reduced frequencies of myeloid-derived suppressor cells (MDSCs) compared to cells from control-treated mice. Our findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of emergency myelopoiesis.
Comparative roles of caudate and putamen in the serial order of behavior: Effects of striatal glutamate receptor blockade on variable versus fixed spatial self-ordered sequencing in marmosets
Authors: Gould Stacey Anne , Hodgson Amy , Clarke Hannah F. , Robbins Trevor W. , Roberts Angela C. 
Published: December 2023

AbstractSelf-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. Lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intra-striatal CNQX microinfusions, we demonstrate that caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited a greater impairment. We demonstrate that continuous perseverative errors in the variable array were caused by putamen infusions, likely due to interference with the putamen’s established role in monitoring motor feedback. Caudate infusions, on the other hand caused recurrent perseveration, with deficits possibly reflecting interference with the caudate’s established role in spatial working memory and goal-directed planning. In contrast to the variable array, whilst both caudate and putamen are needed for fixed array responding, combined effects were not additive, suggesting possible competing roles. Infusions in either region led to continuous perseveration when infused individually, but not when infused simultaneously. Caudate infusions did not cause recurrent perseveration in the fixed array; instead, this was caused by putamen infusions. The results overall are consistent with a role of caudate in planning and flexible responding, but putamen in more rigid habitual or automatic responding.Significance StatementThis investigation employing local intra-striatal infusions into caudate nucleus and/or putamen of the New World marmoset reveals important roles for these regions in variable and fixed spatial self-ordered sequencing. Here, we directly implicate subcortical output regions of the lateral prefrontal cortex in self-ordered sequencing behavior. The ability to self-order sequences, as well as more broadly to plan, organize information, and respond flexibly, is impaired in many neurological diseases and psychiatric disorders. By understanding the basic neural circuitry underlying these cognitive abilities, we may better understand how to rectify them in people with deficits across a plethora of disorders.
Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling
Authors: Rangel-Sosa Martha M. , Mann Fanny , Chauvet Sophie 
Published: December 2023

ABSTRACTThe peripheral nervous system is a key regulator of cancer progression. In pancreatic ductal adenocarcinoma (PDAC), the sympathetic branch of the autonomic nervous system inhibits cancer development. This inhibition is associated with extensive sympathetic nerve sprouting in early pancreatic cancer precursor lesions. However, the underlying mechanisms behind this process remain unclear. This study aimed to investigate the roles of pancreatic Schwann cells in the structural plasticity of sympathetic neurons. We examined the changes in the number and distribution of Schwann cells in a transgenic mouse model of PDAC and in a model of metaplastic pancreatic lesions induced by chronic inflammation. Schwann cells proliferated and expanded simultaneously with new sympathetic nerve sprouts in metaplastic/neoplastic pancreatic lesions. Sparse genetic labeling showed that individual Schwann cells in these lesions had a more elongated and branched structure than those under physiological conditions. Schwann cells overexpressed proinflammatory and neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF). Sympathetic neurons upregulated the GDNF receptor and promoted cell growth in response to GDNFin vitro. Selective genetic deletion ofGdnfin Schwann cells completely blocked sympathetic nerve sprouting in metaplastic pancreatic lesionsin vivo. This study demonstrated that pancreatic Schwann cells underwent adaptive reprogramming during early cancer development, supporting a protective antitumor neuronal response. These finding could help to develop new strategies to modulate cancer associated neural plasticity.MAIN POINTSNon-myelinating pancreatic Schwann cells associate with sympathetic axon terminals supplying the pancreas.Pancreatic Schwann cells proliferate and undergo adaptive reprogramming in response to chronic inflammation and the development of pancreatic cancer.Glial cell line-derived neurotrophic factor expression in reprogrammed pancreatic Schwann cells promotes Schwann cell expansion and sympathetic axon sprouting in pancreatic cancer precursor lesions.
THE WIP6 TRANSCRIPTION FACTORTOO MANY LATERALSSPECIFIES VEIN TYPE IN C4AND C3GRASS LEAVES
Authors: Vlad Daniela , Zaidem Maricris , Perico Chiara , Sedelnikova Olga , Bhattacharya Samik , Langdale Jane A. 
Published: December 2023

ABSTRACTGrass leaves are invariantly strap shaped with an elongated distal blade and a proximal sheath that wraps around the stem. Underpinning this uniform shape is a scaffold of leaf veins, most of which extend in parallel lines along the proximo-distal leaf axis. Differences between species are apparent both in the types of veins that develop and in the spacing between them across the medio-lateral leaf axis. A prominent engineering goal is to increase vein density and the proportion of bundle sheath cells surrounding the veins in leaves of C3photosynthesizing species such as rice, in order to facilitate introduction of the more efficient C4photosynthetic pathway. Here we discover that the WIP6 zinc finger transcription factor TOO MANY LATERALS (TML) specifies vein rank in both maize (C4) and rice (C3), species with distinct venation patterns. Loss of functiontmlmutations lead to the development of large lateral veins in positions normally occupied by smaller intermediate veins. The spatial localization ofTMLtranscripts in wild-type leaves is consistent with a role in suppressing lateral vein formation in procambial cells that develop intermediate veins, specifically the class of intermediate veins that extend from the leaf blade into the leaf sheath. Attempts to manipulate TML function in rice were unsuccessful because transgene expression was silenced, suggesting that precise spatial and temporal regulation ofTMLexpression is essential during the regeneration of shoot tissue from callus. Given that transcriptome analysis demonstrated altered profiles of genes associated with cytokinin and auxin signaling in loss of function maize mutants, the necessity for tight regulation ofTMLgene expression could be an indirect consequence of hormonal inbalances as opposed to ectopic activity of a specific downstream target. Importantly, however, loss of function mutants in rice display increased vascular and bundle sheath cell occupancy in the leaf. Collectively this work provides an understanding of how vein rank is specified in grass leaves and a first step towards an anatomical chassis for C4engineering in rice.