bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrelations between delta waves, spindles and slow oscillations in human NREM sleep and their functional role in memory
Authors: Wüst Larissa N. , Antonenko Daria , Malinowski Robert , Khakimova Liliia , Grittner Ulrike , Obermayer Klaus , Ladenbauer Julia , Flöel Agnes 
Published: September 2021

AbstractCertain neurophysiological characteristics of sleep, in particular slow oscillations (SO), sleep spindles, and their temporal coupling, have been well characterized and associated with human memory formation. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SO, have only recently been found to play a critical role in memory processing of rodents, through a competitive interplay between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta waves, their interactions with spindles and SOs as well as their functional role for memory are still lacking.Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta-spindle coupling and the interplay between delta and SO-related activity. Additionally, we determined intra-individual stability of coupling measures and their potential link to the ability to form novel memories.Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found that increased delta activity was accompanied by stronger SO-spindle coupling. Moreover, we identified the ratio between SO- and delta-nested spindles as the sleep parameter that predicted ability to form novel memories best.Our study suggests that SOs, delta waves and sleep spindles should be jointly considered when aiming to link sleep physiology and memory formation in aging.Significance statementInterrelations between delta waves, slow oscillations and sleep spindles have recently been causally linked to the balance between consolidation and forgetting in rats using optogenetics. In humans, SO-spindle coupling has been intensively investigated, but delta waves and their interaction with spindles were only studied jointly as SWA. Here we delineate the coupling of delta waves to spindles, investigate interactions of delta- and SO-related activity and investigate their role for the ability to form novel memories in healthy older individuals. Our results show differences as well as dependencies between SO- and delta-related activities including spindle coupling. Further, our results indicate that the ratio of SO- to delta-nested spindles might be the most informative sleep parameter for memory formation of older adults.
Relationship Between Inter-individual Variation in Circadian Rhythm and Sociality: A case Study Using Halictid Bees
Authors: Cartagena Sofía Meléndez , Ortiz-Alvarado Carlos A. , Ordoñez Patricia , Cordero-Martínez Claudia S. , Ambrose Alexandria F. , Roman Lizasoain Luis A , Santos Vega Milexis A , Velez Velez Andrea V , Acevedo-Gonzalez Jenny P. , Gibbs Jason , Petanidou Theodora , Tscheulin Thomas , Barthell John T. , González Victor H. , Giray Tugrul , Agosto-Rivera José L. 
Published: September 2021

AbstractThe bee family Halictidae is considered to be an optimal model for the study of social evolution due to its remarkable range of social behaviors. Past studies in circadian rhythms suggest that social species may express more diversity in circadian behaviors than solitary species. However, these previous studies did not make appropriate taxonomic comparisons. To further explore the link between circadian rhythms and sociality, we examine four halictid species with different degrees of sociality, three social species of Lasioglossum, one from Greece and two from Puerto Rico, and a solitary species of Systropha from Greece. Based on our previous observations, we hypothesized that species with greater degree of sociality will show greater inter-individual variation in circadian rhythms than solitary species. We observed distinct differences in their circadian behavior that parallel differences across sociality, where the most social species expressed the highest inter-individual variation. We predict that circadian rhythm differences will be informative of sociality across organisms.
Intronic elements associated with insomnia and restless legs syndrome exhibit cell type-specific epigenetic features contributing to MEIS1 regulation
Authors: Lam Daniel D. , Nikolic Ana Antic , Zhao Chen , Mirza-Schreiber Nazanin , Krężel Wojciech , Oexle Konrad , Winkelmann Juliane 
Published: September 2021

ABSTRACTA highly evolutionarily conserved MEIS1 intronic region is strongly associated with restless legs syndrome (RLS) and insomnia. To understand its regulatory function, we dissected the region by analyzing chromatin accessibility, enhancer-promoter contacts, DNA methylation, and eQTLs in different human neural cell types and tissues. We observed specific activity with respect to cell type and developmental maturation, indicating a prominent role for distinct highly conserved intronic elements in forebrain inhibitory neuron differentiation. Two elements were hypomethylated in neural cells with higher MEIS1 expression, suggesting a role of enhancer demethylation in gene regulation. MEIS1 eQTLs showed a striking modular chromosomal distribution, with forebrain eQTLs clustering in intron 8/9. CRISPR interference targeting of individual elements in this region attenuated MEIS1 expression, revealing a complex regulatory interplay of distinct elements. In summary, we found that MEIS1 regulation is organized in a modular pattern. Disease-associated intronic regulatory elements control MEIS1 expression with cell type and maturation stage specificity, particularly in the inhibitory neuron lineage. The precise spatiotemporal activity of these elements likely contributes to the pathogenesis of insomnia and RLS.
Integrative multi-omics identifies high risk Multiple Myeloma subgroup associated with significant DNA loss and dysregulated DNA repair and cell cycle pathways
Authors: Ortiz-Estévez María , Samur Mehmet , Towfic Fadi , Flynt Erin , Stong Nicholas , Jang In Sock , Wang Kai , Vyas Paresh , Munshi Nikhil , Avet-Loiseau Herve , Trotter Matthew W. B. , Morgan Gareth J. , Walker Brian A. , Thakurta Anjan 
Published: September 2021

AbstractDespite significant therapeutic advances in improving lives of Multiple Myeloma (MM) patients, it remains mostly incurable, with patients ultimately becoming refractory to therapies. MM is a genetically heterogeneous disease and therapeutic resistance is driven by a complex interplay of disease pathobiology and mechanisms of drug resistance. We applied a multi-omics strategy using tumor-derived gene expression, single nucleotide variant, copy number variant, and structural variant profiles to investigate molecular subgroups in 514 newly diagnosed MM (NDMM) samples and identified 12 molecularly defined MM subgroups (MDMS1-12) with distinct genomic and transcriptomic features.Our integrative approach let us identify ndMM subgroups with transversal profiles to previously described ones, based on single data types, which shows the impact of this approach for disease stratification. One key novel subgroup is our MDMS8, associated with poor clinical outcome [median overall survival, 38 months (global log-rank pval<1×10−6)], which uniquely presents a broad genomic loss (>9% of entire genome, t.test pval<1e-5) driving dysregulation of various transcriptional programs affecting DNA repair and cell cycle/mitotic processes. This subgroup was validated on multiple independent datasets, and a master regulator analyses identified transcription factors controlling MDMS8 transcriptomic profile, including CKS1B and PRKDC among others, which are regulators of the DNA repair and cell cycle pathways.Statement of SignificanceUsing multi-omics unsupervised clustering we discovered a new high-risk multiple myeloma patient segment. We linked its diverse genetic markers (previously known, and new including genomic loss) to transcriptional dysregulation (cell cycle, DNA repair and DNA damage) and identified master regulators that control these key biological pathways.
The genetics of eating behaviors: research in the age of COVID-19
Authors: Hannum Mackenzie E. , Lin Cailu , Bell Katherine , Toskala Aurora , Koch Riley , Galaniha Tharaka , Nolden Alissa , Reed Danielle R , Joseph Paule 
Published: September 2021

AbstractHow much pleasure we take in eating is more than just how much we enjoy the taste of food. Food involvement – the amount of time we spend on food beyond the immediate act of eating and tasting – is key to the human food experience. We took a biological approach to test whether food-related behaviors, together capturing food involvement, have genetic components and are partly due to inherited variation. We collected data via an internet survey from a genetically informative sample of 419 adult twins (114 monozygotic twin pairs, 31 dizygotic twin pairs, and 129 singletons). Because we conducted this research during the pandemic, we also ascertained how many participants had experienced COVID-19-associated loss of taste and smell. Since these respondents had previously participated in research in person, we measured their level of engagement to evaluate the quality of their online responses. Additive genetics explained 16-44% of the variation in some measures of food involvement, most prominently various aspects of cooking, suggesting some features of the human food experience may be inborn. Other features reflected shared (early) environment, captured by respondents’ twin status. About 6% of participants had a history of COVID-19 infection, many with transitory taste and smell loss, but all but one had recovered before the survey. Overall, these results suggest that people may have inborn as well as learned variations in their involvement with food. We also learned to adapt to research during a pandemic by considering COVID-19 status and measuring engagement in online studies of human eating behavior.
Scallop2 enables accurate assembly of multiple-end RNA-seq data
Authors: Zhang Qimin , Shi Qian , Shao Mingfu 
Published: September 2021

AbstractTranscript assembly (i.e., to reconstruct the full-length expressed transcripts from RNA-seq data) has been a critical but yet unsolved step in RNA-seq analysis. Modern RNA-seq protocols can produce paired-/multiple-end RNA-seq reads, where information is available that two or more reads originate from the same transcript. The long-range constraints implied in these paired-/multiple-end reads can be much beneficial in correctly phasing the complicated spliced isoforms. However, there often exist gaps among individual ends, which may even contain junctions, making the efficient use of such constraints algorithmically challenging. Here we introduce Scallop2, a new reference-based transcript assembler optimized for multiple-end (including paired-end) RNA-seq data. Scallop2 uses an algorithmic frame-work that first represents reads from the same molecule as the so-called multiple-end phasing paths in the context of a splice graph, then “bridges” each multiple-end phasing path into a long, single-end phasing path, and finally decomposes the splice graph into paths (i.e., transcripts) guided by the bridged phasing paths. An efficient bridging algorithm is designed to infer the true path connecting two consecutive ends following a novel formulation that is robust to sequencing errors and transcript noises. By observing that failing to bridge two ends is mainly due to incomplete splice graphs, we propose a new method to determine false starting/ending vertices of the splice graphs which has been showed efficient in reducing false positive rate. Evaluations on both (multiple-end) single-cell RNA-seq datasets from Smart-seq3 protocol and Illumina paired-end RNA-seq samples demonstrate that Scallop2 vastly outperforms recent assemblers including StringTie2, Scallop, and CLASS2 in assembly accuracy.
Protein embeddings and deep learning predict binding residues for various ligand classes
Authors: Littmann Maria , Heinzinger Michael , Dallago Christian , Weissenow Konstantin , Rost Burkhard 
Published: September 2021

AbstractOne important aspect of protein function is the binding of proteins to ligands, including small molecules, metal ions, and macromolecules such as DNA or RNA. Despite decades of experimental progress many binding sites remain obscure. Here, we proposed bindEmbed21, a method predicting whether a protein residue binds to metal ions, nucleic acids, or small molecules. The Artificial Intelligence (AI)-based method exclusively uses embeddings from the Transformer-based protein Language Model (pLM) ProtT5 as input. Using only single sequences without creating multiple sequence alignments (MSAs), bindEmbed21DL outperformed MSA-based predictions. Combination with homology-based inference increased performance to F1=48±3% (95% CI) and MCC=0.46±0.04 when merging all three ligand classes into one. All results were confirmed by three independent data sets. Focusing on very reliably predicted residues could complement experimental evidence: For the 25% most strongly predicted binding residues, at least 73% were correctly predicted even when ignoring the problem of missing experimental annotations. The new method bindEmbed21 is fast, simple, and broadly applicable - neither using structure nor MSAs. Thereby, it found binding residues in over 42% of all human proteins not otherwise implied in binding and predicted about 6% of all residues as binding to metal ions, nucleic acids, or small molecules.
Emergent intra-pair sex differences and behavioral coordination in pair bonded prairie voles
Authors: Brusman Liza E. , Protter David S. W. , Fultz Allison C. , Paulson Maya U. , Chapel Gabriel D. , Elges Isaiah O. , Cameron Ryan T. , Beery Annaliese K. , Donaldson Zoe R. 
Published: September 2021

AbstractIn pair bonding animals, coordinated behavior between partners is required for the pair to accomplish shared goals such as raising young. Despite this, experimental designs rarely assess the behavior of both partners within a bonded pair. Thus, we lack an understanding of the interdependent behavioral dynamics between partners that likely facilitate relationship success. To identify intra-pair behavioral correlates of pair bonding, we used socially monogamous prairie voles, a species in which females and males exhibit both overlapping and distinct pair bond behaviors. We tested both partners using social choice and non-choice tests at short- and long-term pairing timepoints. Females developed a preference for their partner more rapidly than males, with preference driven by different behaviors in each sex. Further, as bonds matured, intra-pair behavioral sex differences and coordinated behavior emerged – females consistently huddled more with their partner than males did, and partner huddle time became correlated between partners. When animals were allowed to freely interact with a partner or a novel in sequential free interaction tests, pairs spent more time interacting together than either animal did with a novel. Pair interaction was correlated with female, but not male, behavior. Via a social operant paradigm, we found that pair-bonded females, but not males, are more motivated to access and huddle with their partner than a novel vole. Together, our data indicate that as pair bonds mature, sex differences and coordinated behavior emerge, and that these intra-pair behavioral changes are likely organized and driven by the female animal.
The visual coupling between neighbors explains ‘flocking’ in human crowds
Authors: Dachner Gregory C. , Wirth Trenton D. , Richmond Emily , Warren William H. 
Published: September 2021

AbstractPatterns of collective motion or ‘flocking’ in birds, fish schools, and human crowds are believed to emerge from local interactions between individuals. Most models of collective motion attribute these interactions to hypothetical rules or forces, often inspired by physical systems, and described from an overhead view. We develop a visual model of human flocking from an embedded view, based on optical variables that actually govern pedestrian interactions. Specifically, people control their walking speed and direction by canceling the average optical expansion and angular velocity of their neighbors, weighted by visual occlusion. We test the model by simulating data from experiments with virtual crowds and real human ‘swarms’. The visual model outperforms our previous overhead model and explains basic properties of physics-inspired models: ‘repulsion’ forces reduce to canceling optical expansion, ‘attraction’ forces to canceling optical contraction, and ‘alignment’ to canceling the combination of expansion/contraction and angular velocity. Critically, the neighborhood of interaction follows from Euclid’s Law of perspective and the geometry of occlusion. We conclude that the local interactions underlying human flocking are a natural consequence of the laws of optics. Similar principles may apply to collective motion in other species.
The treatment of scaphoid non-unions with partial and total scaphoid in titanium custom-made 3D-printed prostheses and reconstruction of scapholunate interosseous ligament: a preliminary study
Authors: Cioffi Alessio , Rossello Mario Igor 
Published: September 2021

ABSTRACTThe treatment of sequelae of scaphoid fractures is still one of the unsolved problems of hand surgery. Between January 2019 and July 2020 in the Hand Surgery Department of San Paolo’s Hospital in Savona (Italy) 9 partial scaphoid in titanium custom-made 3D-printed prosthesis have performed in 9 patients (all men) with an average age of 27.5 years (minimum 18-maximum 37 years). The aim of the study is to evaluate over time the clinical-functional and radiographic results of the wrists treated with partial and total scaphoid titanium custom-made 3D-printed prostheses and reconstruction of SLIL.
Novel classes and evolutionary turnover of histone H2B variants in the mammalian germline
Authors: Raman Pravrutha , Rominger Callie , Young Janet M. , Molaro Antoine , Tsukiyama Toshio , Malik Harmit S. 
Published: September 2021

AbstractHistones and their post-translational modifications facilitate diverse chromatin functions in eukaryotes. Core histones (H2A, H2B, H3, and H4) package genomes after DNA replication. In contrast, variant histones promote specialized chromatin functions, including DNA repair, genome stability, and epigenetic inheritance. Previous studies have identified only a few H2B variants in animals; their roles and evolutionary origins remain largely unknown. Here, using phylogenomic analyses, we reveal the presence of five H2B variants broadly present in mammalian genomes. In addition to three previously described variants (H2B.1, subH2B, and H2B.W), we identify and describe two new variants, H2B.L and H2B.N. Four of these five H2B variants originated in mammals, whereas H2B.L arose prior to the last common ancestor of bony vertebrates. We find that though mammalian H2B variants are subject to high gene turnover, most are broadly retained in mammals, including humans. Despite an overall signature of purifying selection, H2B variants evolve more rapidly than core H2B with considerable divergence in sequence and length. All five H2B variants are expressed in the germline. H2B.L and H2B.N are predominantly expressed in oocytes, an atypical expression site for mammalian histone variants. Our findings suggest that H2B variants likely encode potentially redundant but vital functions via unusual chromatin packaging or non-chromatin functions in mammalian germline cells. Our discovery of novel histone variants highlights the advantages of comprehensive phylogenomic analyses and provides unique opportunities to study how innovations in chromatin function evolve.
Bioactive exometabolites drive maintenance competition in simple bacterial communities
Authors: Chodkowski John L. , Shade Ashley 
Published: September 2021

AbstractDuring prolonged resource limitation, bacterial cells can persist in metabolically active states of non-growth. These maintenance periods, such as those experienced in stationary phase, can include upregulation of secondary metabolism and release of exometabolites into the local environment. As resource limitation is common of many environmental microbial habitats, we hypothesized that neighboring bacterial populations employ exometabolites to compete or cooperate during maintenance, and that these exometabolite-facilitated interactions can drive community outcomes. Here, we evaluated the consequences of exometabolite interactions over stationary phase among three environmental strains:Burkholderia thailandensisE264,Chromobacterium subtsugae, andPseudomonas syringaepv.tomatoDC3000. We assembled them into synthetic communities that only permitted chemical interactions. We compared the responses (transcripts) and outputs (exometabolites) of each member with and without neighbors. We found that transcriptional dynamics were changed with different neighbors, and that some of these changes were coordinated between members. The dominant competitorB. thailandensisconsistently upregulated biosynthetic gene clusters to produce bioactive exometabolites for both exploitative and interference competition. These results demonstrate that competition strategies during maintenance can contribute to community-level outcomes. It also suggests that the traditional concept of defining competitiveness by growth outcomes may be narrow, and that maintenance competition could be an additional or alternative measure.
Coherent Gene Assemblies: Example, Yeast Cell Division Cycle, CDC
Authors: Sirovich Lawrence 
Published: September 2021

AbstractA fresh approach to the dynamics of gene assemblies is presented. Central to the exposition are the concepts of: high value genes; correlated activity; and the orderly unfolding of gene dynamics; and especially dynamic mode decomposition, DMD, a remarkable new tool for dissecting dynamics. This program is carried out, in detail, for the Orlando et al yeast database (Orlando et al. 2008).It is shown that the yeast cell division cycle, CDC, requires no more than a six dimensional space, formed by three complex temporal modal pairs, each associated with characteristic aspects of the cell cycle: (1) A mother cell cohort that follows a fast clock; (2) A daughter cell cohort that follows a slower clock; (3) inherent gene expression, unrelated to the CDC.A derived set of sixty high-value genes serves as a model for the correlated unfolding of gene activity. Confirmation of our results comes from an independent database, and other considerations. The present analysis, leads naturally, to a Fourier description, for the sparsely sampled data. From this, resolved peak times of gene expression are obtained. This in turn leads to prediction of precise times of expression in the unfolding of the CDC genes. The activation of each gene appears as uncoupled dynamics from the mother and daughter cohorts, of different durations. These deliberations lead to detailed estimates of the fraction of mother and daughter cells, specific estimates of their maturation periods, and specific estimates of the number of genes in these cells.An algorithmic framework for yeast modeling is proposed, and based on the new analyses, a range of theoretical ideas and new experiments are suggested.A Supplement contains additional material and other perspectives.