bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular patterns and processes in evolving sociality: lessons from insects
Authors: Sumner Seirian , Favreau Emeline , Geist Katherine , Toth Amy L. , Rehan Sandra M. 
Published: February 2023

Social insects have provided some of the clearest insights into the origins and evolution of collective behaviour. Over 20 years ago, Maynard Smith and Szathmáry defined the most complex form of insect social behaviour—superorganismality—among the eight major transitions in evolution that explain the emergence of biological complexity. However, the mechanistic processes underlying the transition from solitary life to superorganismal living in insects remain rather elusive. An overlooked question is whether this major transition arose via incremental or step-wise modes of evolution. We suggest that examination of the molecular processes underpinning different levels of social complexity represented across the major transition from solitary to complex sociality can help address this question. We present a framework for using molecular data to assess to what extent the mechanistic processes that take place in the major transition to complex sociality and superorganismality involve nonlinear (implying step-wise evolution) or linear (implying incremental evolution) changes in the underlying molecular mechanisms. We assess the evidence for these two modes using data from social insects and discuss how this framework can be used to test the generality of molecular patterns and processes across other major transitions.
This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Intrinsic and effective severity of COVID-19 cases infected with the ancestral strain and Omicron BA.2 variant in Hong Kong
Authors: Wong Jessica Y. , Cheung Justin K. , Lin Yun , Bond Helen S. , Lau Eric H. Y. , Ip Dennis K. M. , Cowling Benjamin J. , Wu Peng 
Published: February 2023

ABSTRACTBackgroundUnderstanding severity of infections with SARS-CoV-2 and its variants is crucial to inform public health measures. Here we used COVID-19 patient data from Hong Kong to characterise the severity profile of COVID-19 and to examine factors associated with fatality of infection.MethodsTime-varying and age-specific effective severity measured by case-hospitalization risk and hospitalization risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through to 26 October 2022 over six epidemic waves, in comparison with estimates of influenza A(H1N1)pdm09 during the 2009 pandemic. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. Factors potentially associated with the fatality risk of hospitalized Omicron patients were also examined.ResultsWith 32,222 COVID-19 hospitalizations and 9,669 deaths confirmed over 6 epidemic waves in Hong Kong, the time-varying hospitalization fatality risk dramatically increased from below 10% before the largest fifth wave of Omicron BA.2, to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, the highest fatality risk was amongst unvaccinated patients aged ≥80 years and the risk was inversely associated with the number of vaccination doses received.ConclusionsOmicron has comparable intrinsic severity to the ancestral Wuhan strain although the effective severity is substantially lower in Omicron cases due to vaccination. With a moderate-to-high coverage of vaccination, hospitalized COVID-19 patients caused by Omicron subvariants appeared to have similar age-specific risks of fatality to patients hospitalized with influenza A(H1N1)pdm09.
Impacts of Virtual Reality Experiences: Enhanced Undergraduate Student Performance and Engagement with use of 360-degree video
Authors: Vola Erica , Stoltz Rebecca , Schumpert Charles A. 
Published: February 2023

AbstractVirtual reality has been used for a variety of training and gaming purposes. Recent studies have demonstrated their use in higher education enhances student engagement and positively impacts student performance. In this study, we implemented 360-degree video in an introductory biology lab and assessed student attitudes, engagement, and performance on various assessments as well as the overall course performance. Students were extremely positive about virtual reality, had minimal issues handling the technology, and indicated that engagement with the topic was better with virtual reality. Student performance increased on 2 of the 3 formative assessments analyzed, 1 of 1 summative assessment analyzed, and overall course grades in semesters with virtual reality were higher than in semesters without virtual reality. These results suggest virtual reality in higher education may enhance not only student engagement and performance, but also enhance student attitude about the topic.
Extensive profiling of histidine-containing dipeptides reveals species- and tissue-specific distribution and metabolism in mice, rats and humans
Authors: Van der Stede Thibaux , Spaas Jan , de Jager Sarah , De Brandt Jana , Hansen Camilla , Stautemas Jan , Vercammen Bjarne , De Baere Siegrid , Croubels Siska , Van Assche Charles-Henri , Pastor Berta Cillero , Vandenbosch Michiel , Van Thienen Ruud , Verboven Kenneth , Hansen Dominique , Bové Thierry , Lapauw Bruno , Van Praet Charles , Decaestecker Karel , Vanaudenaerde Bart , Eijnde Bert O , Gliemann Lasse , Hellsten Ylva , Derave Wim 
Published: February 2023

AbstractHistidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules linked to inflammatory, metabolic and neurological diseases, as well as exercise performance. Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n=26, n=25, n=19 tissues, respectively). Our data show that tissue HCD levels are uniquely regulated by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibers and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analog N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion. Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease.Significance statementBy extensively profiling the pluripotent histidine-containing dipeptides across three species, we generated many new insights into species- and tissue-specific histidine-containing dipeptide metabolism. For instance, the only stable analog that is specific for the human circulation (N-acetylcarnosine) is continuously released from muscle tissue and is positively regulated by physical exercise. The great number of analyses and experiments involving humans establishes great translational value of the findings. These new data open exciting opportunities to study histidine-containing dipeptide metabolism, including paracrine and/or endocrine signaling of these dipeptides, possibly contributing to the potent health-promoting exercise effects.
Comprehensive characterization of tumor microenvironment in colorectal cancer via histopathology-molecular analysis
Authors: Wu Xiangkun , Yan Hong , Qiu Mingxing , Qu Xiaoping , Wang Jing , Xu Shaowan , Zheng Yiran , Ge Minghui , Yan Linlin , Liang Li 
Published: February 2023

AbstractPurposeTo explain how the tumor microenvironment (TME) contributes to biological and clinical heterogeneity of colorectal cancer (CRC).MethodsUsing multi-omics analysis, single cell transcriptomic sequencing analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC).ResultsCRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathological and molecular characteristics, therapeutic efficacy, and prognosis. The C1 subtype was more sensitive to chemotherapy, the C2 and C3 subtypes were more sensitive to WNT pathway inhibitor SB216763 and Hedgehog pathway inhibitor vismodegib, and the C4 subtype was suitable for ICB treatment. Finally, we established a single-sample gene classifier for identifying the CCCRC subtypes.ConclusionsOur integrative analyses ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability might facilitate biomarker discoveries and clinical treatment decisions in the future.
Accurate label-free quantification by directLFQ to compare unlimited numbers of proteomes
Authors: Ammar Constantin , Schessner Julia Patricia , Willems Sander , Michaelis André C. , Mann Matthias 
Published: February 2023

ABSTRACTRecent advances in mass spectrometry (MS)-based proteomics enable the acquisition of increasingly large datasets within relatively short times, which exposes bottlenecks in the bioinformatics pipeline. Whereas peptide identification is already scalable, most label-free quantification (LFQ) algorithms scale quadratic or cubic with the sample numbers, which may even preclude the analysis of large-scale data. Here we introduce directLFQ, a ratiobased approach for sample normalization and the calculation of protein intensities. It estimates quantities via aligning samples and ion traces by shifting them on top of each other in logarithmic space. Importantly, directLFQ scales linearly with the number of samples, allowing analyses of large studies to finish in minutes instead of days or months. We quantify 10,000 proteomes in 10 minutes and 100,000 proteomes in less than two hours - thousand-fold faster than some implementations of the popular LFQ algorithm MaxLFQ. In-depth characterization of directLFQ reveals excellent normalization properties and benchmark results, comparing favorably to MaxLFQ for both data-dependent acquisition (DDA) and data-independent acquisition (DIA). Additionally, directLFQ provides normalized peptide intensity estimates for peptide-level comparisons. It is available as an open-source Python package and as a GUI with a one-click installer and can be used in the AlphaPept ecosystem as well as downstream of most common computational proteomics pipelines.
Rapid Molecular Mechanotyping with Microfluidic Force Spectroscopy
Authors: van Galen Martijn , Bok Annemarie , Peshkovsky Taieesa , van der Gucht Jasper , Albada Bauke , Sprakel Joris 
Published: February 2023

AbstractMolecular mechanotyping, the quantification of changes in the stability of supramolecular interactions and chemical bonds under the action of mechanical forces, is an essential tool in the field of mechanochemistry. This is conventionally done in single-molecule force-spectroscopy (smFS) assays, for example with optical tweezers or Atomic Force Microscopy. While these techniques provide detailed mechanochemical insights, they are time-consuming, technically demanding and expensive; as a result, high-throughput screening of the mechanochemical properties of molecules of interest is challenging. To resolve this, we present a rapid, simple and low-cost mechanotyping assay: microfluidic force spectroscopy (µFFS), which probes force-dependent bond stability by measuring the detachment of microparticles, bound to microfluidic channels by the interaction of interest, under hydrodynamic forcing. As this allows the simultaneous observation of hundreds of microparticles, we obtain a quantitative mechanotype in a single measurement, using readily available equipment. We validate our method by studying the stability of DNA duplexes, previously characterized through smFS. We further show that we can quantitatively describe the experimental data with simulations, which allows us to link theµFFS data to single-bond mechanochemical properties. This opens the way to use (µFFS) as a rapid molecular mechanotyping tool.
Land-cover change in Cuba may favor biodiversity: An example usingOmphalea(Angiosperma: Euphorbiaceae) andUrania boisduvalii(Lepidoptera: Uraniidae)
Authors: Nuñez-Penichet Claudia , Maita-Chamba Juan , Soberón Jorge 
Published: February 2023

ABSTRACTChanges in land cover directly affect biodiversity. Here we assessed land-cover change in Cuba in the past 35 years and analyzed how this change may affect the distribution ofOmphaleaplants andUrania boisduvaliimoths. We analyzed the vegetation cover of the Cuban archipelago between 1985 and 2020. We used Google Earth Engine to classify two satellite image compositions into seven cover types: forest and shrubs, mangrove, soil without vegetation cover, wetlands, pine forest, agriculture, and water bodies. We considered three different areas for quantifications of land-cover change: (1) protected areas, (2) areas of potential distribution ofOmphalea, and (3) areas of potential distribution of the plant within the protected areas. We found that the category of “forest and shrubs” have increased significantly in Cuba in the past 35 years and that most of the gained forest and shrub areas were agricultural land in the past. This same pattern was observed in the areas of potential distribution ofOmphalea; whereas almost all cover types were mostly stables inside the protected areas. The transformation of agricultural areas into forest and shrubs could represent an interesting opportunity for biodiversity conservation in Cuba. Other detailed studies about biodiversity composition in areas of forest and shrubs gain would greatly benefit our understanding on the value of such areas for conservation.
Genome-wide screen reveals Rab12 GTPase as a critical activator of pathogenic LRRK2 kinase
Authors: Dhekne Herschel S. , Tonelli Francesca , Yeshaw Wondwossen M. , Chiang Claire Y. , Limouse Charles , Jaimon Ebsy , Purlyte Elena , Alessi Dario R. , Pfeffer Suzanne R. 
Published: February 2023

AbstractActivating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson’s disease. LRRK2 phosphorylates a subset of Rab GTPases, particularly Rab10 and Rab8A, and we showed previously that phosphoRabs play an important role in LRRK2 membrane recruitment and activation (Vides et al., 2022). To learn more about LRRK2 pathway regulation, we carried out an unbiased, CRISPR-based genome-wide screen to identify modifiers of cellular phosphoRab10 levels. A flow cytometry assay was developed to detect changes in phosphoRab10 levels in pools of mouse NIH-3T3 cells harboring unique CRISPR guide sequences. Multiple negative and positive regulators were identified; surprisingly, knockout of the Rab12 gene was especially effective in decreasing phosphoRab10 levels in multiple cell types and knockout mouse tissues. Rab-driven increases in phosphoRab10 were specific for Rab12, LRRK2 dependent and PPM1H phosphatase reversible; they were seen with wild type and pathogenic G2019S and R1441C LRRK2. AlphaFold modeling revealed a novel Rab12 binding site in the LRRK2 Armadillo domain and we show that residues predicted to be essential for Rab12 interaction at this site influence overall phosphoRab levels in a manner distinct from Rab29 activation of LRRK2. Our data support a model in which Rab12 binding to a new site in the LRRK2 Armadillo domain activates LRRK2 kinase for Rab phosphorylation and could serve as a new therapeutic target for a novel class of LRRK2 inhibitors that do not target the kinase domain.
Marginal specificity in protein interactions constrains evolution
Authors: Ghose Dia A. , Przydzial Kaitlyn E. , Mahoney Emily M. , Keating Amy E. , Laub Michael T. 
Published: February 2023

AbstractThe evolution of novel functions in biology relies heavily on gene duplication and divergence, creating large paralogous protein families. Selective pressure to avoid detrimental cross-talk often results in paralogs that exhibit exquisite specificity for their interaction partners. But how robust or sensitive is this specificity to mutation? Here, using deep mutational scanning, we demonstrate that a paralogous family of bacterial signaling proteins exhibits marginal specificity, such that many individual substitutions give rise to substantial cross-talk between normally insulated pathways. Our results indicate that sequence space is locally crowded despite overall sparseness, and we provide evidence that this crowding has constrained the evolution of bacterial signaling proteins. These findings underscore how evolution selects for ‘good enough’ rather than optimized phenotypes, leading to restrictions on the subsequent evolvability of paralogs.Significance StatementLarge paralogous protein families are found throughout biology, the product of extensive gene duplication. To execute different functions inside cells, paralogs typically acquire different specificities, interacting with only desired, cognate partners and avoiding cross-talk with non-cognate proteins. But how robust is this interaction specificity to mutation? Can individual mutations lead to cross-talk or do paralogs diverge enough such that multiple mutations would be required, providing a mutational ‘buffer’ against cross-talk? To address these questions, we built mutant libraries that produce all possible single substitutions of a bacterial kinase and then screened for cross-talk to non-cognate proteins. Strikingly, we find that many single substitutions can produce cross-talk, meaning that these pathways typically exhibit only ‘marginal specificity’, and demonstrate that this restricts their evolvability.
Ongoing HIV replication in lymph node sanctuary sites in treated patients contributes to the total latent HIV at a very slow rate
Authors: Paryad-zanjani Sasan , Jagarapu Aditya , Piovoso Michael J. , Zurakowski Ryan 
Published: February 2023

AbstractLymph nodes (LNs) serve as a sanctuary site for HIV viruses due to the heterogeneous distribution of the antiretrovirals (ARVs) inside the LNs. There is an ongoing debate whether this represents ongoing cycles of viral replication in the LNs or merely residual virus production by latently infected cells. Previous work has claimed that the measured levels of genetic variation in proviruses sampled from the blood were inconsistent with ongoing replication. However, it is not clear what rate of variation is consistent with ongoing replication in small sanctuary sites.In this study, we used a spherically symmetric compartmental ODE model to track the HIV viral dynamics in the LN and predict the contribution of ongoing replication within the LN to the wholebody proviral pool in an ARV-suppressed patient. This model tracks the reaction-diffusion dynamics of uninfected, actively infected, and latently infected T-cells as well as free virus within the LN parenchyma and the blood, and distinguishes between latently infected cells created before ARV therapy and during ARV therapy.We simulated suppressive therapy beginning in year 5 post-infection. Each LN sanctuary site had a volume of 1 ml, and we considered cases of 1ml, 30ml, and 250ml total volume, which represent a single active sanctuary site, moderate systemic involvement, and involvement of the total lymphoid tissue. Viral load in the blood rapidly dropped and remained below the limit of detection in all cases but remained high in the LN sanctuary sites. Novel latent cells increased systemically over time but very slowly, taking between 25 and 50 years to reach 5% of the total latent pool, depending on the volume of lymphoid tissue involvement.Putative sanctuary sites in LNs are limited in volume and produce novel latent cells slowly. Assays to detect genetic drift due to such sites would require very deep sequencing if sampling only from the blood. Previous studies showing a lack of genetic drift are consistent with the expected contribution of ongoing replication in lymph node sanctuary sites.
The Regulation of Nucleic Acid Vaccine Responses by the Microbiome
Authors: Johnson Andrew M. F. , Hager Kevin , Alameh Mohamad-Gabriel , Van Phuong , Potchen Nicole , Mayer-Blackwell Koshlan , Fiore-Gartland Andrew , Minot Samuel , Lin Paulo J. C. , Tam Ying K. , Weissman Drew , Kublin James G. 
Published: February 2023

SummaryNucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine responses and which may determine their effectiveness. The microbiome is recognized as a significant regulator of immune development and response, whose role in regulating some traditional vaccine platforms has recently been discovered. Using germ-free and specific-pathogen-free mouse models in combination with different protein, DNA, and mRNA vaccine regimens, we demonstrate that the microbiome is a significant regulator of nucleic acid vaccine immunogenicity. While the presence of the microbiome enhances CD8+ T cell responses to mRNA lipid nanoparticle (LNP) immunization, the microbiome suppresses immunoglobulin and CD4+ T cell responses to DNA-prime, DNA-protein-boost immunization, indicating contrasting roles for the microbiome in the regulation of these different nucleic acid vaccine platforms. In the case of mRNA-LNP vaccination, germ-free mice display reduced dendritic cell/macrophage activation that may underlie the deficient vaccine response. Our study identifies the microbiome as a relevant determinant of nucleic acid vaccine response with implications for their continued therapeutic development and deployment.