bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D-Printable Non-invasive Head Immobilization System for Non-Human Primates
Authors: Shahbazi Elia , Nguyen Drew , Swedan Tyler , Ma Timothy , Lafer-Sousa Rosa , Dinh Alvin , Azadi Reza , Ryan Amy M. , Afraz Arash 
Published: January 2024

AbstractA critical contribution to understanding the primate brain is our ability to directly record, manipulate, or image the brain in awake, behaving monkeys. A challenge with carrying out these studies is that typically the monkey’s head must be fixed in place. While non-invasive head immobilization systems (NHIS) have been demonstrated to be effective, they have not fully replaced the use of surgically applied headposts. Here, we introduce a novel NHIS, with an option for voluntary engagement, for macaques using a widely available resource: the 3D printer. We designed customized 3D-printable head-immobilization masks for monkeys and a docking system using standard CT scans and user-friendly open-source software packages (FLoRIN, Blender, Python). We examined the efficacy and stability of our mask system for collecting eye fixation data by measuring trial-by-trial gaze precision and accuracy in two mask-immobilized monkeys and three headposted monkeys, including a within-subjects comparison. Our results demonstrate that monkeys stabilized by the mask maintain gaze precision and accuracy comparable with their headposted counterparts. While the headpost outperformed the mask, the difference in precision was 0.03° of visual angle, and the difference in accuracy was less than 0.2°, well within the acceptable range for most use-cases. Our process allows for the production of 3D-printable masks based on CT or MRI scans with the flexibility to incorporate design modifications for experimental equipment and resizing, potentially serving as a promising and more easily accessible alternative to headposts and other NHISs for primate neuroscience research.
G-quadruplexes as pivotal components ofcis-regulatory elements in the human genome
Authors: Zhang Rongxin , Wang Yuqi , Wang Cheng , Sun Xiao , Mergny Jean-Louis 
Published: January 2024

AbstractCis-regulatory elements have the ability to precisely regulate gene expression in cells, and G-quadruplexes (G4s), as non-canonical secondary structures, may potentially play a role in this regulation. However, a lack of systematic studies exists to uncover the connection between these two elements. Here, we comprehensively characterized the associations between G4s and human candidatecis-regulatory elements (cCREs) inferred from the Encyclopedia of DNA Elements (ENCODE) data. Our findings demonstrate that G4s are prominently enriched in most types of cCREs, particularly in elements with promoter-like signatures (PLS). Furthermore, we observed that the co-occurrence of CTCF signals with H3K4me3 or H3K27ac signals significantly strengthens the association between cCREs and G4s. This association becomes more pronounced when examining cell type-specific cCREs and G4s. Interestingly, compared to cCREs, genetic variants occurring in G4s, especially within their G-runs, often exhibit higher regulatory potential and deleterious effects. Runs of several consecutive guanines (G-runs) in the vicinity of transcriptional start sites tend to be more constrained in mammalian evolution than cCREs’s G-runs. Besides, the presence of G4s, is often linked to a more favorable local chromatin environment for the activation and execution of regulatory functions of cCREs, potentially attributable to the formation of G4 secondary structures. Finally, we discovered that G4-associated cCREs exhibit widespread activation in a variety of cancers. Altogether, our study suggests that G4s are integral components of humancis-regulatory elements, and the G4 primary sequences are associated with the localization of the cCREs, while the G4 structures are linked to the activation of the cCREs. Therefore, we propose to define G4s as pivotal regulatory elements in the human genome.
Beyond Antibiotics: Cinnamic Acid’s role in combatting complex biofilms in the oral cavity
Authors: Al_Darwish Lama , Alajlani Muaaz , Alashkar Sharif 
Published: January 2024

AbstractTraditional antibiotic therapy has become inefficient in treating oral plaques, due to the the presence of highly adherent bacteria in complex infections of oral cavities. Our study aimed to evaluate the anti-biofilm activity of Cinnamic Acid against single and multispecies bacteria causing dental plaques. Different concentrations of cinnamic acid (1-1000 mg/L) were tested using Biofilm assays, EPS analysis, and biomass quantification. To gain insight, a drug-likeness chemoinformatics study of cinnamic acid was conducted.We found that lower concentrations (1-400mg/L) of Cinnamic Acid had a minor effect on biofilm formation inhibition. Whilst concentrations of 600mg/L and above had shown significant biofilm production, EPS production and biomass production reduced down to 80%.Cinnamic Acid has proven to contain antibacterial, antibiofilm, and drug-likeness properties and is a prominent compound in combating oral biofilm.Authors SummaryCombating oral pathogenic biofilm is an important approach in treating polymicrobial oral infections, We have tested the anti-biofilm activity of cinnamic acid at different connections (1-1000 mg/L) and against single and multispecies biofilm forming bacteria. We found that cinnamic acid had a notable reduction in biofilm formation and EPS production, and reduced total biofilm biomass. Cinnamic Also fulfills the lipinski ROFs criteria for drug-likeness.Due to its antibacterial, anti-biofilm, and drug-likeness properties, a plant-derived compound such as Cinnamic Acid can be a new prominent approach to defecting the global risk of oral pathogenic biofilms. And serve as an alternative to conventional oral care methods which have been rendered inefficient by biofilm-forming pathogens.
The role of transposon activity in shaping cis-regulatory element evolution after whole genome duplication
Authors: Monsen Øystein , Grønvold Lars , Datsomor Alex , Harvey Thomas , Kijas James , Suh Alexander , Hvidsten Torgeir R. , Sandve Simen Rød 
Published: January 2024

AbstractTwo of the most potent drivers of genome evolution in eukaryotes are whole genome duplications (WGD) and transposable element (TE) activity. These two mutational forces can also play synergistic roles; WGDs result in both cellular stress and functional redundancy, which would allow TEs to escape host-silencing mechanisms and effectively spread with reduced impact on fitness. As TEs can function as, or evolve into, TE-derived cis-regulatory elements (TE-CREs), bursts of TE-activity following WGD are likely to impact evolution of gene regulation. However, the role of TEs in genome regulatory remodelling after WGDs is unclear. Here we used the genome of Atlantic salmon, which is known to have experienced massive expansion of TEs after a WGD ∼100 Mya, as a model system to explore the synergistic roles of TEs and WGDs on genome regulatory evolution.We identified 55,080 putative TE-CREs in Atlantic salmon using chromatin accessibility data from brain and liver. Of these, 80% were tissue specific to liver (43%) or brain (37%) and TE-CREs originating from retroelements were twice as common as those originating from DNA elements. Signatures of selection shaping TE-CRE evolution were evident from depletion of TEs in open chromatin, a bias in tissue-shared TE-CREs towards older TE-insertions, as well as tissue-specific processes shaping the TE-CRE repertoire. A minority of TE-families (16%) accounted for the origin of 46% of all TE-CREs, but the transposition activity of these ‘CRE-superspreader’ families happened mostly prior to the WGD. Analyses of individual TE-CREs do however support a significantly higher rate of TE-CRE evolution from insertions happening around the time of the salmonid WGD. This pattern was particularly striking for the DTT elements, despite having generally low propensity to evolve into TE-CREs and impact transcription. Furthermore, co-expression based analyses supported the presence of TE-driven gene regulatory network evolution, including DTT elements active at the time of WGD.In conclusion, we find a strong association between TE insertions at the time of WGD and TE-CRE evolution. This association was not driven by particular TE-families with high capability to evolve into TE-CREs but likely a consequence of the concurrent surge of novel TE insertions, mostly from DTT elements, in combination with a shift in selective pressure on genome regulation following the WGD.
Ancestral Sequence Reconstruction as a tool to detect and study de novo gene emergence
Authors: Vakirlis Nikolaos , Acar Omer , Cherupally Vijay , Carvunis Anne-Ruxandra 
Published: January 2024

AbstractNew protein-coding genes can evolve from previously non-coding genomic regions through a process known as de novo gene emergence. Evidence suggests that this process has likely occurred throughout evolution and across the tree of life. Yet, confidently identifying de novo emerged genes remains challenging. Ancestral Sequence Reconstruction (ASR) is a promising approach for inferring whether a gene has emerged de novo or not, as it can enable us to inspect whether a given genomic locus ancestrally harbored protein-coding capacity. However, the use of ASR in the context of de novo emergence is still in its infancy and its capabilities, limitations, and overall potential are largely unknown. Notably, it is difficult to formally evaluate the protein-coding capacity of ancestral sequences, particularly when new gene candidates are short. How well-suited is ASR as a tool for the detection and study of de novo genes? Here, we address this question by designing an ASR workflow incorporating different tools and sets of parameters and by introducing a formal criterion that allows to estimate, within a desired level of confidence, when protein-coding capacity originated at a particular locus. Applying this workflow on ∼2,600 short, annotated budding yeast genes (<1,000 nucleotides), we found that ASR robustly predicts an ancient origin for most widely conserved genes, which constitute “easy” cases. For less robust cases, we calculated a randomization-based empirical P-value estimating whether the observed conservation between the extant and ancestral reading frame could be attributed to chance. This formal criterion allowed us to pinpoint a branch of origin for most of the less robust cases, identifying 33 genes that can unequivocally be considered de novo originated since the split of theSaccharomycesgenus, including 20S. cerevisiae-specific genes. We find that the remaining, equivocal cases, may be explained by different evolutionary scenarios including rapid evolution and multiple losses, as well as a very recent de novo origin. Overall, our findings suggest that ASR is a valuable tool to study de novo gene emergence but should be applied with caution and awareness of its limitations.
CDR Proteins ofC.elegansand Related Species: Relationship to Metaxin and FAXC Proteins
Authors: Adolph Kenneth W. 
Published: January 2024

ABSTRACTCDR (cadmium-responsive) proteins of the nematodeC. elegansand related species are shown to have structural homology to metaxin proteins and FAXC (failed axon connections) proteins of vertebrates and invertebrates. Unlike the metaxin and FAXC proteins, however, the predicted CDR proteins are only encoded in the genomes of nematodes, and not in vertebrates or other invertebrates. Metaxin-like structural features of CDR proteins are shown in this report to include: (1) GST_N_Metaxin and GST_C_Metaxin conserved protein domains, (2) metaxin-like patterns of α-helical secondary structure, and (3) a special 4-stranded β-sheet motif shared with the metaxins. FAXC proteins also possess these structural features. Phylogenetic analysis revealed that CDR proteins are related to metaxins 1, 2, and 3 and to FAXC proteins, although more closely to FAXC proteins. Nevertheless, all three types of proteins – CDR, FAXC, and metaxin – are related by evolution. Although CDR proteins have structural homology to metaxin and FAXC proteins, pairwise alignments of CDR proteins with metaxins and FAXCs demonstrated only low percentages of identical amino acids. CDR proteins can therefore be considered a separate category of proteins, distinct from metaxin and FAXC proteins. The CDR genes ofC. elegansconsist of a family of seven genes,cdr-1tocdr-7, which form a cluster of closely adjacent genes on chromosome V. Multiple genes were also found for the related speciesC. briggsaeandC. remanei. Alignment of pairs ofC. elegansCDR protein sequences encoded by differentcdrgenes demonstrated a high level of sequence homology. The neighboring genes of theC.elegans cdrgenes are different than the genes adjacent to theC.elegans faxcgenes and themtx-1andmtx-2metaxin genes.
Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy
Authors: Bar Jair , Leibowitz Raya , Reinmuth Niels , Ammendola Astrid , Jacob Eyal , Moskovitz Mor , Levy-Barda Adva , Lotem Michal , Katzenelson Rivka , Agbarya Abed , Abu-Amna Mahmoud , Gottfried Maya , Harkovsky Tatiana , Wolf Ido , Tepper Ella , Loewenthal Gil , Yellin Ben , Brody Yehuda , Dahan Nili , Yanko Maya , Lahav Coren , Harel Michal , Shoval Shani Raveh , Elon Yehonatan , Sela Itamar , Dicker Adam P. , Shaked Yuval 
Published: January 2024

ABSTRACTIntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network with CD8A serving as a central hub, suggesting T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and potential biomarkers for outcome.
Musicians’ brains at rest: Multilayer network analysis of MEG data
Authors: Mandke Kanad N , Tewarie Prejaas , Adjamian Peyman , Schürmann Martin , Meier Jil 
Published: January 2024

AbstractThe ability to proficiently play a musical instrument requires a fine-grained synchronisation between several sensorimotor and cognitive brain regions. Previous studies have demonstrated that the brain undergoes functional changes with musical training, identifiable also in resting-state data. These studies analysed fMRI or electrophysiological frequency-specific brain networks in isolation. While the analysis of such “mono-layer” networks has proven useful, it fails to capture the complexities of multiple interacting networks. To this end, we applied a multilayer network framework for analysing publicly available data (Open MEG Archive) obtained with magnetoencephalography (MEG). We investigated resting-state differences between participants with musical training (n=31) and those without (n=31). While single-layer analysis did not demonstrate any group differences, multilayer analysis revealed that musicians show a modular organisation that spans visuomotor and frontotemporal areas, known to be involved in musical performance execution, which is significantly different from non-musicians. Differences between the two groups are primarily observed in the theta (6.5-8Hz), alpha1 (8.5-10Hz) and beta1 (12.5-16Hz) frequency bands.We demonstrate that the multilayer method provides additional information that single-layer analysis cannot. Overall, the multilayer network method provides a unique opportunity to explore the pan-spectral nature of oscillatory networks, with studies of brain plasticity as a potential future application.
ABCA7-dependent Neuropeptide-Y signalling is a resilience mechanism required for synaptic integrity in Alzheimer’s disease
Authors: Tayran Hüseyin , Yilmaz Elanur , Bhattarai Prabesh , Min Yuhao , Wang Xue , Ma Yiyi , Nelson Nastasia , Kassara Nada , Cosacak Mehmet Ilyas , Dogru Ruya Merve , Reyes-Dumeyer Dolly , Reddy Joseph S , Qiao Min , Flaherty Delaney , Teich Andrew F. , Gunasekaran Tamil Iniyan , Yang Zikun , Tosto Giuseppe , Vardarajan Badri N , İş Özkan , Ertekin-Taner Nilüfer , Mayeux Richard , Kizil Caghan 
Published: January 2024

AbstractAlzheimer’s disease (AD) remains a complex challenge characterized by cognitive decline and memory loss. Genetic variations have emerged as crucial players in the etiology of AD, enabling hope for a better understanding of the disease mechanisms; yet the specific mechanism of action for those genetic variants remain uncertain. Animal models with reminiscent disease pathology could uncover previously uncharacterized roles of these genes. Using CRISPR/Cas9 gene editing, we generated a knockout model forabca7,orthologous to humanABCA7 –an established AD-risk gene. Theabca7+/-zebrafish showed reduced astroglial proliferation, synaptic density, and microglial abundance in response to amyloid beta 42 (Aβ42). Single-cell transcriptomics revealedabca7-dependent neuronal and glial cellular crosstalk through neuropeptide Y (NPY) signaling. Theabca7knockout reduced the expression ofnpy, bdnfandngfra, which are required for synaptic integrity and astroglial proliferation. With clinical data in humans, we showed reducedNPYin AD correlates with elevated Braak stage, predicted regulatory interaction betweenNPYandBDNF, identified genetic variants inNPYassociated with AD, found segregation of variants inABCA7, BDNFandNGFRin AD families, and discovered epigenetic changes in the promoter regions ofNPY, NGFRandBDNFin humans with specific single nucleotide polymorphisms inABCA7. These results suggest that ABCA7-dependent NPY signaling is required for synaptic integrity, the impairment of which generates a risk factor for AD through compromised brain resilience.Abstract FigureGraphical abstract
Dissecting the heat stress altering immune responses and skin microbiota in fish in a recirculating aquaculture system in Singapore
Authors: Ng Tze Hann , Sobana M , Chew Xian Zhe , Nair D/O Madhaven Thiviya , Chow Jing Wen , Low Adrian , Seedorf Henning , Bastos Gomes Giana 
Published: January 2024

ABSTRACTEnvironmental factors, probiotics and feed additives affect microbiota diversity in fish. Water temperature disrupts the composition and diversity of microbiota, with temperature changes triggering stress and immune responses in fish. In Singapore, water heat treatment is used to control and prevent disease outbreaks in farmed fish. Although gut microbiota responses to heat stress have been reported, little is known about the effects of heat treatment on fish immune responses and fish skin microbiota dynamics. Over a 3-mo interval, we investigated microbiota dynamics and fish immune responses associated with a heat treatment practice in a commercial fish farm with a recirculating aquaculture system (RAS). Tank water temperature was raised to 37-39 °C for 1 hour, every 2 weeks. Tank water and fish microbial communities were analysed by 16S amplicon sequencing, and host molecular expressions were determined by qPCR. We inferred that heat treatment increased stress and immune responses that protected fish from opportunistic infections. However, overreaction to temperature stress can cause dysbiosis of the skin microbiota and death. We also suggested the value of the skin microbiota Pseudomonadota: Bacteroidota (P:B) ratio as a biomarker for aquaculture fish health.IMPORTANCEAquaculture is an emerging economic activity to supply high-quality animal protein and reduce reliance on wild-caught fish products. Recently, there has been emphasis on intensive aquaculture, using a Recirculating Aquaculture System (RAS). In RAS, management of pathogens/parasites prevalence is a major challenge. Developing practical solutions for producing healthy juveniles in nursery systems will make profound contributions to sustainable aquaculture. In this study, we used an unconventional strategy, exposing juveniles to the pathobiome in the environment, followed by non-lethal heat shock treatments to enhance immunity. Short-term stress induced heat shock proteins that protected fish from opportunistic infections. We concluded that manipulating environmental-microbial-host interactions, together with enhanced functional capacity of fish immune response, has potential for disease control in aquaculture.
Offspring size resolves a latitudinal population growth rate paradox in rays and skates
Authors: Barrowclift Ellen , Bigman Jennifer S. , Digel Eric D. , Berggren Per , Dulvy Nicholas K. 
Published: January 2024

AbstractAs animal populations continue to decline, understanding global patterns of life histories will improve our predictions of species vulnerability and extinction risk to prioritise management. Sharks and rays are threatened with extinction due to overfishing, particularly in the tropics and sub-tropics. Metabolic theory suggests that warm-water species and populations will have a higher maximum intrinsic rate of population increase (rmax) and therefore will be less intrinsically sensitive to exploitation. However, recent empirical work has highlighted a paradox and shown that warm, shallow-water tropical rays have lowerrmaxthan cold, deep-water temperate skates. We test whether the different reproductive strategies of live-bearing rays and egg-laying skates explain this observed paradox by comparing variation inrmaxwith adult body mass, offspring size, temperature, and depth across 85 species of rays and skates. Our results show that the large relative offspring size of warm, shallow-water tropical rays better explains their greater intrinsic sensitivity (lowerrmax) compared to cold, deep-water temperate skates. This is consistent with life history theory that suggestsrmaxis greater in species with smaller relative offspring size. We hypothesise that the larger relative offspring size may be driven by greater predation risk in the tropics and may help explain global patterns of intrinsic sensitivity to overexploitation.