bluuebunny/crossref_metadata_2025 huggingface dataset:
Social media influence: a new frontier in proprietary rights?
Authors: Carn Matthew
Published: January 2023

The importance of social media has rapidly increased throughout the 21st century. The metric of influence has been key to the commercialisation of social media, with accurate methods of quantification now allowing it to be used by a litany of corporate bodies to identify appropriate individuals to act as their brand ambassadors for the purpose of marketing products. Given the flexibility of equity, it is only a matter of time before such a valuable commodity is recognised under the law of trusts as a metric for identifying beneficiaries or as the subject matter of a trust itself.
Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease
Authors: Gao Ruxin , Li Yue , Xu Zhimeng , Zhang Feng , Xu Jia , Hu Yanzhou , Yin Jingya , Yang Kun , Sun Lei , Wang Qi , He Xiaoyun , Huang Kunlun
Published: January 2023

Background and Aims:

NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation.

Approach and Results:

MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1+/−) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1+/− mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization.

Conclusions:

In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism.
Analysis of the Status of Radiation-generating Medical Devices in Mainland China
Authors: Su Yinping , Cui Shiyue , Sun Quanfu , Deng Jun , Cheng Jinsheng
Published: January 2023

The purpose of this paper is to describe the status of radiation-generating medical devices in mainland China. The number of diagnostic radiology and interventional radiology devices was collected from the national medical radiation protection monitoring information system, while the number of radiation therapy and nuclear medicine devices was from the published articles. Statistical analysis of the correlation was used to assess the relationship between the number of high technology medical devices and GDP per capita. A total of 143,064 radiation-generating medical devices were identified in mainland China, and diagnostic radiology devices accounted for 94% of those. The number of CTs was 14.84 per million, an increase by a factor of 1.45 compared to 2009. But the distribution of CTs was imbalanced among different areas: the highest number of CT per million population was 27.70 in Tibet, and the lowest was 8.55 per million population in Guangxi province. Statistical analysis of the correlation showed that the number of PET scanners per million population was positively correlated with GDP per capita, and similarly for medical accelerators. The number of mammographic devices per million population was much lower than that in other countries. The investment of radiation-generating medical devices in China was far from enough, especially for mammographic devices. More efforts should be taken to bring medical resources to regions with greater population areas in the future.

Health Phys. 124(0):000-000; 2023
Sex Chromosome Rearrangement Associated With Hormonal Abnormalities and Gender Dysphoria
Authors: Cordner Zachary A. , Mu Weiyi , Schmidt Chester W. , Kraft Chris , Thomas Kate
Published: January 2023

Although disorders arising from sex chromosome and sex steroid abnormalities are well characterized from the perspectives of endocrinology, dysmorphology, and reproductive health, relatively little is known about neuropsychiatric development, gender identity, incongruence, and dysphoria in the populations with these disorders. In this report, we describe the case of a 21-year-old gender nonbinary individual identified as male at birth who presented to an academic psychiatry consultation clinic because of life-long gender dysphoria. The patient was found to have a complex sex chromosomal rearrangement and associated hormonal abnormalities that may, at least in part, explain the patient’s history. In addition to describing a novel genetic change, this case and the accompanying review of the existing literature highlight the need for an increased focus on the psychiatric perspective, and sex and gender issues in particular, among all patients with sex chromosome abnormalities and inborn errors of steroid metabolism.
When the Supervisor Needs a Supervisor: A Case-based Guide for Developing Psychotherapy Supervisors
Authors: Murray Aimee , Frank Amber , Sudak Donna , Topor David R. , Ruble Anne E.
Published: January 2023

Supervision of psychotherapy is recognized as fundamental for attaining competency in psychotherapy. However, there is a lack of training in “best practices” of supervisory skills, and some supervisors may lack contemporary knowledge to support supervisees adequately. Training program leadership challenged by limited time and resources to provide supervisors with the necessary education and support can benefit from additional resources for developing psychotherapy supervisors. The authors present 3 core elements of navigating supervisory challenges: training, open dialogue in supervision, and a formal program-level process. Common issues in psychotherapy supervision are then presented in a case-based format. Reflection questions are included to provide an opportunity to consider a personal approach to the case, while specific guidance based on the literature addresses critical aspects of the case examples. Complex supervisory conflicts can challenge programs, but they are normative to the learning process and promote growth in our supervisors.
Hunger affects cognitive performance of dairy calves
Authors: Lecorps Benjamin , Woodroffe Raphaela E. , von Keyserlingk Marina A.G. , Weary Daniel M.
Published: January 2023

Hunger remains a significant animal welfare concern as restricted feeding practices are common on farms. Studies to date have focused on negative effects on health and productivity but little research has addressed the
feeling of hunger
, mostly due to methodological difficulties in assessing animals' subjective experiences. Here, we explored the use of a cognitive approach to disentangle motivational hunger (a normal state that is of limited welfare concern) from distressful hunger (a state associated with intense negative emotions). Cognitive performance in a foraging task is expected to follow an inverted U relationship with hunger levels, providing an opportunity to make inferences about different hunger states. We assessed the effect of milk restriction on calf cognition in two experiments using a modified hole-board test. Experiment 1 showed that reducing milk allowance from 12 to 6 l d
−1
impaired all measures of cognitive performance. Experiment 2 showed that the same type of feed restriction also disrupted calves’ capacity to re-learn. We conclude that hunger associated with reduced milk allowance can disrupt cognitive performance of dairy calves, a result consistent with the experience of distressful hunger.
Green approach for tracking the photofate of ciprofloxacin and levofloxacin in different matrices adopting synchronous fluorescence spectroscopy: a kinetic study
Authors: Draz Mohammed E. , El Wasseef Dalia , El Enany Nahed , Wahba Mary E. K.
Published: January 2023

First derivative synchronous fluorescence spectroscopy (FDSFS) was applied to detect and quantify either ciprofloxacin (CIP) or levofloxacin (LEV) simultaneously with their photodegradation products, where the photolytic pathway for each analyte was found to be pH dependent. Under the guidance of early published articles, the structure of the produced photolytic products could be concluded, and further related to their resultant fluorescence spectra. The proposed method was subjected to full validation procedure which enables its application in investigating the photodegradation kinetics for both drugs. The obtained kinetic parameters were in accordance with previous reports and could be linked to predict the antibacterial activity of the resultant photodegradation products. These facts prove the suitability of the suggested FDSFS to serve as a stability-indicating assay method and to trace the photofate of CIP and LEV in the ecosystem as potential contaminants. Furthermore, the greenness of the suggested analytical methodology was evaluated via ‘Green Analytical Procedure Index’ (GAPI), which classifies it as an eco-friendly assay. Eventually, no extraction, treatment or preparation steps were needed during all analysis steps, which renders the proposed assay an appealing tool in environmental analysis.
Sensitivity analysis of large body of control parameters in machine learning control of a square-back Ahmed body
Authors: Deng G. M. , Fan D. W. , Zhang B. F. , Liu K. , Zhou Y.
Published: January 2023

Active drag reduction (DR) of a square-back Ahmed body is experimentally studied based on machine learning or artificial intelligence (AI) control. The control system consists of four independently operated arrays of pulsed microjets, 25 pressure taps and an explorative downhill simplex method controller. Two strategies, i.e. asymmetric and symmetric actuations, are investigated, with 12 and 9 control parameters, respectively. Both achieve a DR by 13%, though with distinct flow physics and control mechanisms behind. A model linking the control parameters with the cost is developed based on Taylor expansion around the K-nearest neighbours of the smallest cost obtained from the AI control, resulting in a substantially reduced deviation between measured and predicted costs, especially when involving a large number of control parameters, compared with that based on Taylor expansion around the optimum cost. Sensitivity analysis, conducted based on the model, indicates that the control efficiency, i.e. the ratio of the power saving from DR to the total power consumption, may reach 55 and 78 for the symmetric and asymmetric strategies, respectively, given a 1–2% sacrifice on DR. This efficiency greatly exceeds that (26.5) obtained by Fan
et al.
(Fan
et al.
2020
Phys. Fluids
32
, 125117. (
doi:10.1063/5.0033156
)), whose independent control parameters are only three.
Comments on effective use of numerical modelling and extended classical shell buckling theory
Authors: Croll James
Published: January 2023

This paper argues that in the understandable enthusiasm to use the now readily available high-fidelity numerical software allowing the analysis of the complexities of shell buckling, and especially the notorious case of the axially loaded cylinder, there has been insufficient consideration of classical shell buckling theory and its more recent reduced stiffness extension. If future design is to be able to effectively exploit the potential benefits of the use of advanced composite materials and/or the use of rib reinforcement, it is suggested that these numerically driven research programmes would benefit from more explicit integration within the framework of classically extended buckling theory. This suggestion is reinforced in what follows by highlighting the results from a longstanding research programme in which classically extended buckling theory has been demonstrably enhanced through its integration with reliable numerical experimentation. This enhancement has helped to resolve a number of important issues including: identification of the most critical forms of imperfection affecting the buckling loads; how the most critical knockdown factors are influenced by changes in the shells' geometric and material characteristics and how safe design might be more explicitly related to the prescribed levels of geometric tolerances. Recommendations are made as to how such integrated research programmes could in the future further enhance our ability to design materially efficient shells against buckling.
Directional fabrication and dissolution of larval and juvenile oyster shells under ocean acidification
Authors: Chandra Rajan Kanmani , Li Yang , Dang Xin , Lim Yong Kian , Suzuki Michio , Lee Seung Woo , Vengatesen Thiyagarajan
Published: January 2023

Biomineralization is one of the key biochemical processes in calcifying bivalve species such as oysters that is affected by ocean acidification (OA). Larval life stages of oysters are made of aragonite crystals whereas the adults are made of calcite and/or aragonite. Though both calcite and aragonite are crystal polymorphs of calcium carbonate, they have different mechanical properties and hence it is important to study the micro and nano structure of different life stages of oyster shells under OA to understand the mechanisms by which OA affects biomineralization ontogeny. Here, we have studied the larval and juvenile life stages of an economically and ecologically important estuarine oyster species,Crassostrea hongkongensis, under OA with focus over shell fabrication under OA (pHNBS7.4). We also look at the effect of parental exposure to OA on larvae and juvenile microstructure. The micro and nanostructure characterization reveals directional fabrication of oyster shells, with more organized structure as biomineralization progresses. Under OA, both the larval and juvenile stages show directional dissolution, i.e. the earlier formed shell layers undergo dissolution at first, owing to longer exposure time. Despite dissolution, the micro and nanostructure of the shell remains unaffected under OA, irrespective of parental exposure history.
Chimpanzees communicate to coordinate a cultural practice
Authors: Goldsborough Zoë , Schel Anne Marijke , van Leeuwen Edwin J. C.
Published: January 2023

Human culture thrives by virtue of communication, yet whether communication plays an influential role in the cultural lives of other animals remains understudied. Here, we investigated whether chimpanzees use communication to engage in a cultural practice by analysing grooming handclasp (GHC) interactions—a socio-cultural behaviour requiring interindividual coordination for successful execution. Previous accounts attributed GHC initiations to behavioural shaping, whereby the initiator physically moulds the partner's arm into the desired GHC posture. Using frame-by-frame analysis and matched-control methodology, we find that chimpanzees do not only shape their partner's posture (22%), but also use gestural communication to initiate GHC (44%), which requires an active and synchronized response from the partner. Moreover, in a third (34%) of the GHC initiations, the requisite coordination was achieved by seemingly effortless synchrony. Lastly, using a longitudinal approach, we find that for GHC initiations, communication occurs more frequently than shaping in experienced dyads and less in mother–offspring dyads. These findings are consistent with ontogenetic ritualization, thereby reflecting first documentation of chimpanzees communicating to coordinate a cultural practice. We conclude that chimpanzees show interactional flexibility in the socio-cultural domain, opening the possibility that the interplay between communication and culture is rooted in our deep evolutionary history.
Visual processing and collective motion-related decision-making in desert locusts
Authors: Bleichman Itay , Yadav Pratibha , Ayali Amir
Published: January 2023

Collectively moving groups of animals rely on the decision-making of locally interacting individuals in order to maintain swarm cohesion. However, the complex and noisy visual environment poses a major challenge to the extraction and processing of relevant information. We addressed this challenge by studying swarming-related decision-making in desert locust last-instar nymphs. Controlled visual stimuli, in the form of random dot kinematograms, were presented to tethered locust nymphs in a trackball set-up, while monitoring movement trajectory and walking parameters. In a complementary set of experiments, the neurophysiological basis of the observed behavioural responses was explored. Our results suggest that locusts use filtering and discrimination upon encountering multiple stimuli simultaneously. Specifically, we show that locusts are sensitive to differences in speed at the individual conspecific level, and to movement coherence at the group level, and may use these to filter out non-relevant stimuli. The locusts also discriminate and assign different weights to different stimuli, with an observed interactive effect of stimulus size, relative abundance and motion direction. Our findings provide insights into the cognitive abilities of locusts in the domain of decision-making and visual-based collective motion, and support locusts as a model for investigating sensory-motor integration and motion-related decision-making in the intricate swarm environment.
The price of defence: toxins, visual signals and oxidative state in an aposematic butterfly
Authors: Blount Jonathan D. , Rowland Hannah M. , Mitchell Christopher , Speed Michael P. , Ruxton Graeme D. , Endler John A. , Brower Lincoln P.
Published: January 2023

In a variety of aposematic species, the conspicuousness of an individual's warning signal and the quantity of its chemical defence are positively correlated. This apparent honest signalling is predicted by resource competition models which assume that the production and maintenance of aposematic defences compete for access to antioxidant molecules that have dual functions as pigments and in protecting against oxidative damage. To test for such trade-offs, we raised monarch butterflies (
Danaus plexippus
) on different species of their milkweed host plants (Apocynaceae) that vary in quantities of cardenolides to test whether (i) the sequestration of cardenolides as a secondary defence is associated with costs in the form of oxidative lipid damage and reduced antioxidant defences; and (ii) lower oxidative state is associated with a reduced capacity to produce aposematic displays. In male monarchs conspicuousness was explained by an interaction between oxidative damage and sequestration: males with high levels of oxidative damage became less conspicuous with increased sequestration of cardenolides, whereas those with low oxidative damage became more conspicuous with increased levels of cardenolides. There was no significant effect of oxidative damage or concentration of sequestered cardenolides on female conspicuousness. Our results demonstrate a physiological linkage between the production of coloration and oxidative state, and differential costs of sequestration and signalling in monarch butterflies.
TransAAP: an automated annotation pipeline for membrane transporter prediction in bacterial genomes
Authors: Elbourne Liam D. H. , Wilson-Mortier Brendan , Ren Qinghu , Hassan Karl A. , Tetu Sasha G. , Paulsen Ian T.
Published: January 2023

Membrane transporters are a large group of proteins that span cell membranes and contribute to critical cell processes, including delivery of essential nutrients, ejection of waste products, and assisting the cell in sensing environmental conditions. Obtaining an accurate and specific annotation of the transporter proteins encoded by a micro-organism can provide details of its likely nutritional preferences and environmental niche(s), and identify novel transporters that could be utilized in small molecule production in industrial biotechnology. The Transporter Automated Annotation Pipeline (TransAAP) (http://www.membranetransport.org/transportDB2/TransAAP_login.html) is a fully automated web service for the prediction and annotation of membrane transport proteins in an organism from its genome sequence, by using comparisons with both curated databases such as the TCDB (Transporter Classification Database) and TDB, as well as selected Pfams and TIGRFAMs of transporter families and other methodologies. TransAAP was used to annotate transporter genes in the prokaryotic genomes in the National Center for Biotechnology Information (NCBI) RefSeq; these are presented in the transporter database TransportDB (http://www.membranetransport.org) website, which has a suite of data visualization and analysis tools. Creation and maintenance of a bioinformatic database specific for transporters in all genomic datasets is essential for microbiology research groups and the general research/biotechnology community to obtain a detailed picture of membrane transporter systems in various environments, as well as comprehensive information on specific membrane transport proteins.
3-D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System (MANTIS)
Authors: Scholaert Manon , Houmadi Raissa , Martin Jeremy , Serhan Nadine , Tauber Marie , Braun Emilie , Basso Lilian , Merle Eric , Descargues Pascal , Viguier Manuelle , Lesort Cécile , Chaput Benoît , Kanitakis Jean , Jullien Denis , Livideanu Cristina Bulai , Lamant Laurence , Pagès Emeline , Gaudenzio Nicolas
Published: January 2023

Routine clinical assays, such as conventional immunohistochemistry, often fail to resolve the regional heterogeneity of complex inflammatory skin conditions. Here we introduce MANTIS (Multiplexed Annotated Tissue Imaging System), a flexible analytic pipeline compatible with routine practice, specifically-designed for spatially-resolved immune phenotyping of the skin in experimental or clinical samples. Based on phenotype attribution matrices coupled to α-shape algorithms, MANTIS projects a representative digital immune landscape, while enabling automated detection of major inflammatory clusters and concomitant single-cell data quantification of biomarkers. We observed that severe pathological lesions from systemic lupus erythematosus, Kawasaki syndrome or COVID-19-associated skin manifestations share common quantitative immune features, while displaying a non-random distribution of cells with the formation of disease-specific dermal immune structures. Given its accuracy and flexibility, MANTIS is designed to solve the spatial organization of complex immune environments to better apprehend the pathophysiology of skin manifestations.
Functional traits of young seedlings predict trade-offs in seedling performance in three neotropical forests
Authors: Metz Margaret R. , Wright S. Joseph , Zimmerman Jess K. , Hernandéz Andrés , Smith Samuel M. , Swenson Nathan G. , Umaña M. Natalia , Valencia L. Renato , Waring-Enriquez Ina , Wordell Mason , Zambrano R. Milton , Garwood Nancy C.
Published: January 2023

Understanding the mechanisms that promote the coexistence of hundreds of species over small areas in tropical forest remains a challenge. Many tropical tree species are presumed to be functionally equivalent shade tolerant species that differ in performance trade-offs between survival in shade and the ability to quickly grow in sunlight.

Variation in plant functional traits related to resource acquisition is thought to predict variation in performance among species, perhaps explaining community assembly across habitats with gradients in resource availability. Many studies have found low predictive power, however, when linking trait measurements to species demographic rates.

Seedlings face different challenges recruiting on the forest floor and may exhibit different traits and/or performance trade-offs than older individuals face in the eventual adult niche. Seed mass is the typical proxy for seedling success, but species also differ in cotyledon strategy (reserve vs photosynthetic) or other seedling traits. These can cause species with the same average seed mass to have divergent performance in the same habitat.

We combined long-term studies of seedling dynamics with functional trait data collected at a standard developmental stage in three diverse neotropical forests to ask whether variation in coordinated suites of traits predicts variation among species in demographic performance.

Across hundreds of species in Ecuador, Panama, and Puerto Rico, we found seedlings displayed correlated suites of leaf, stem, and root traits, which strongly correlated with seed mass and cotyledon strategy. Variation among species in seedling functional traits, seed mass, and cotyledon strategy were strong predictors of trade-offs in seedling growth and survival.

Our findings highlight the importance of cotyledon strategy in addition to seed mass as a key component of seed and seedling biology. These results also underscore the importance of matching the ontogenetic stage of the trait measurement to the stage of demographic dynamics.

Synthesis:With strikingly consistent patterns across three tropical forests, we find strong evidence for the promise of functional traits to provide mechanistic links between seedling form and demographic performance.
Activity-based profiling of cullin-RING ligase networks by conformation-specific probes
Authors: Henneberg Lukas T. , Singh Jaspal , Duda David M. , Baek Kheewoong , Yanishevski David , Murray Peter J. , Mann Matthias , Sidhu Sachdev S. , Schulman Brenda
Published: January 2023

The cullin-RING E3 ligase (CRL) network comprises over 300 unique complexes that switch from inactive to activated conformations upon site-specific cullin modification by the ubiquitin-like protein NEDD8. Assessing cellular repertoires of activated CRL complexes is critical for understanding eukaryotic regulation. However, probes surveying networks controlled by site-specific ubiquitin-like protein modifications are lacking. We report development of a synthetic antibody recognizing the active conformation of a NEDD8-linked cullin. We established a pipeline probing cellular networks of activated CUL1-, CUL2-, CUL3- and CUL4-containing CRLs, revealing the CRL complexes responding to stimuli. Profiling several cell types showed their baseline neddylated CRL repertoires vary, prime efficiency of targeted protein degradation, and are differentially rewired across distinct primary cell activation pathways. Thus, conformation-specific probes can permit nonenzymatic activity-based profiling across a system of numerous multiprotein complexes, which in the case of neddylated CRLs reveals widespread regulation and could facilitate development of degrader drugs.
Genomes and transcriptomes help unravel the complex life cycle of the blastoclad fungus,Coelomomyces lativittatus,an obligate parasite of mosquitoes and microcrustaceans
Authors: Ettinger Cassandra L. , Ostovar Talieh , Yacoub Mark , Ahrendt Steven , Hice Robert H. , Federici Brian A. , Stajich Jason E.
Published: January 2023

Species of the phylum Blastocladiomycota, early diverging zoosporic (flagellated) lineages of fungi, are vastly understudied. This phylum includes the genusCoelomomyceswhich consists of more than 80 fungal species that are obligate parasites of arthropods. KnownCoelomomycesspecies lack a complete asexual life cycle, instead surviving through an obligate heteroecious alternation of generations life cycle. Despite their global distribution and interesting life cycle, little is known about the genomics of anyCoelomomycesspecies. To address this, we generated three draft-level genomes and annotations forC. lativittatusrepresenting its haploid meiospore, orange gamete, and amber gamete life stages. These draft genome assemblies ranged in size from 5002 to 5799 contigs with a total length of 19.8-22.8 Mb and a mean of 7416 protein-coding genes. We then demonstrated the utility of these genomes by combining the draft annotations as a reference for analysis ofC. lativittatustranscriptomes. We analyzed transcriptomes from across host-associated life stages including infection of larva and excised mature sporangia from the mosquito,Anopheles quadrimaculatus. We identified differentially expressed genes and enriched GO terms both across and within life stages and used these to make hypotheses aboutC. lativittatusbiology. Generally, we found theC. lativittatustranscriptome to be a complex and dynamic expression landscape; GO terms related to metabolism and transport processes were enriched during infection and terms related to dispersal were enriched during sporulation. We further identified five HMG box genes inC. lativittatus, three belonging to clades with mating type (MAT) loci from other fungi,as well as four ortholog expansions inC. lativittatuscompared to other fungi. TheC. lativittatusgenomes and transcriptomes reported here are a valuable resource and may be leveraged toward furthering understanding of the biology of these and other early diverging fungal lineages.
If it’s there, could it be a bear?
Authors: Foxon Floe
Published: January 2023

It has been suggested that the American black bear (Ursus americanus) may be responsible for a significant number of purported sightings of an alleged unknown species of hominid in North America. Previous analyses have identified correlation between ‘sasquatch’ or ‘bigfoot’ sightings and black bear populations in the Pacific Northwest using ecological niche models and simple models of expected animal sightings. The present study expands the analysis to the entire US and Canada by regressing sasquatch sightings on bear populations in each state/province while adjusting for human population and forest area in a generalized linear model. Sasquatch sightings were statistically significantly associated with bear populations such that, on the average, every 1, 000 bear increase in the bear population is associated with a 4% (95% CI: 1%–7%) increase in sasquatch sightings. Thus, as black bear populations increase, sasquatch sightings are expected to increase also. On the average, across all states and provinces in 2006, after controlling for human population and forest area, there were approximately 5, 000 bears per sasquatch sighting. Based on statistical considerations, it is likely that many supposed sasquatch are really misidentified known forms. If bigfoot is there, it may be a bear.
Dysregulated mammalian estrus cycle rescued by timed activation of VIP neurons in the circadian pacemaker and late afternoon light exposure
Authors: Kahan Anat , Coughlin Gerard M. , Borsos Máté , Brunton Bingni W. , Gradinaru Viviana
Published: January 2023

Jet lag and shift work disrupt the menstrual cycle and decrease fertility. The circadian pacemaker, the suprachiasmatic nucleus (SCN), is known to modulate ovulation, but the mechanism is unclear. Here we explore this connection by tracking the dynamics of vasoactive intestinal peptide (VIP)-expressing neurons in the SCN in freely-behaving mice. We show that SCNVIPactivity is time-of-day- and sex-dependent, and estrous-state-dependent in late afternoon, gating downstream activation of GnRH neurons. Afternoon light, as well as specific activation of SCNVIPneurons, rescues estrous cycle regularity and egg release in animals in altered light conditions, emphasizing the role of SCNVIPneurons as a time-dependent light-responsive switch. Our results reveal the dynamic mechanism by which SCNVIPneurons mediate light responses to regulate estrous states and demonstrate light-induced fertility rescue.

One Sentence Summary

Modulating and recording the activity of suprachiasmatic VIP neurons in freely behaving mice reveals their regulation of fertility by mediating the response to late afternoon light.
scRNAseq_KNIME workflow: A Customizable, Locally Executable, Interactive and Automated KNIME workflow for single-cell RNA seq
Authors: Kausar Samina , Asif Muhammad , Baudot Anaïs
Published: January 2023

Single-cell RNA sequencing (scRNA-seq) is nowadays widely used to measure gene expression in individual cells, but meaningful biological interpretation of the generated scRNA-seq data remains a complicated task. Indeed, expertise in both the biological domain under study, statistics, and computer programming are prerequisite for thorough analysis of scRNA-seq data. However, biological experts may lack data science expertise, and bioinformatician’s limited understanding of the biology may lead to time-consuming iterations.

A user-friendly and automated workflow with possibility for customization is hence of a wide interest for both the biological and bioinformatics communities, and for their fruitful collaborations. Here, we propose a locally installable, user-friendly, interactive, and automated workflow that allows the users to perform the main steps of scRNA-seq data analysis. The interface is composed of graphical entities dedicated to specific and modifiable tasks. It can easily be used by biologists and can also serve as a customizable basis for bioinformaticians.

Availability and implementation

The workflow is developed in KNIME; its tasks were defined by R scripts using KNIME R nodes. The workflow is publicly available athttps://github.com/Saminakausar/scRNAseq_KNIME.

Contact:anais.baudot@univ-amu.fr;muhasif123@gmail.com
Histone acetylation insulator SET orchestrates PP2A inhibition and super-enhancer activation
Authors: Xu He , Wu Di , Xu Jin , Lei Yubin , Lei Yalan , Yu Xianjun , Shi Si
Published: January 2023

Wide-spread growth-essential genes are hyper-transcribed in the pancreatic cancer cells. Searching for the factors that reprogram this abnormal transcription, we identified the nuclear oncogene SET that supported CDK9-induced and Pol II-mediated transcription. SET disrupted PP2A-A/C interaction via its C-terminal domains. Through blocking PP2A activity, SET assisted CDK9 to maintain Pol II CTD phosphorylation and activated mRNA transcription. Meanwhile, as a histone acetylation insulator, SET mainly suppressed histone acetylation in the gene promoters but evaded enhancers. Massive super-enhancer associated genes, including the oncogeneMET, were hence permitted to be transcribed by SET over-expression. Our findings position SET as a key factor that bridges histone acetylation and PP2A related transcription in cancer cells.
Gastrodin ameliorates synaptic impairment, reestablishes mitochondrial membrane potential and reduces oxidative stress in N2a/APP cells through ERK1/2 and GSK-3β pathways
Authors: Tang Zhi , Peng Yaqian , Wang Li , Guo Min , Chen Zhuyi , Zhang Ting , Xiao Yan , Ni Ruiqing , Qi Xiaolan
Published: January 2023

Alzheimer’s disease (AD) is featured by abnormal β-amyloid (Aβ) deposition, neurofibrillary tangle formation, downstream mitochondrial dysfunction, oxidative stress, and synaptic loss. Gastrodin, a phenolic glycoside, has shown neuroprotective effect and used in the treatment of a range of brain diseases. Here we aim to assess the mechanisms and signaling pathways involved in the neuroprotective effect of gastrodin in murine neuroblastoma N2a cells expressing human Swedish mutant amyloid precursor protein (N2a/APP). The levels of pre- and postsynaptic proteins, amyloid precursor protein C-terminal fragments (APP-CTFs), levels of tau, glycogen synthase kinase-3 β (GSK-3β), extracellular regulated kinase (ERK), and c-Jun N-terminal Kinase (JNK) were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well as immunofluorescence staining for lipid peroxidation (4◻hydroxynonenal) and DNA oxidation (8◻hydroxy◻2’◻deoxyguanosine), were performed. We found that gastrodin treatment increased the levels of presynaptic SNAP25, synaptophysin, and postsynaptic PSD95, reduced phosphorylated tau protein Ser396, and APP-CTFs in N2a/APP cells. In addition, gastrodin reduced the levels of reactive oxygen species generation, lipid peroxidation, and DNA oxidation, reestablished mitochondrial membrane potential. Upregulated levels of phosphorylated-GSK-3β, reduced levels of phosphorylated-ERK, and phosphorylated-JNK were involved the protective effect of gastrodin. In conclusion, we demonstrated a neuroprotective effect of gastrodin in N2a/APP cell line.
Reliable genetic correlation estimation via multiple sample splitting and smoothing
Authors: Mai The Tien
Published: January 2023

In this paper, we aim to investigate the problem of estimating the genetic correlation between two traits. Instead of making assumptions about the distribution of effect sizes of the genetic factors, we propose the use of a high-dimensional linear model to relate a trait to genetic factors. To estimate the genetic correlation, we develop a generic strategy that combines the use of sparse penalization methods and multiple sample splitting approaches. The final estimate is determined by taking the median of the calculations, resulting in a smoothed and reliable estimate. Through simulations, we demonstrate that our proposed approach is reliable and accurate in comparison to naive plug-in methods. To further illustrate the advantages of our method, we apply it to a real-world example of a bacterial GWAS dataset, specifically to estimate the genetic correlation between antibiotic resistant traits inStreptococus pneumoniae. This application not only validates the effectiveness of our method but also highlights its potential in real-world applications.
The phospho-regulated amphiphysin/endophilin interaction is required for synaptic vesicle endocytosis
Authors: Kontaxi Christiana , Cousin Michael A.
Published: January 2023

The multidomain adaptor protein amphiphysin-1 (Amph1) is an important coordinator of clathrin-mediated endocytosis in non-neuronal cells and synaptic vesicle (SV) endocytosis at central nerve terminals. Amph1 contains a lipid-binding N-BAR (Bin/Amphiphysin/Rvs) domain, central proline-rich (PRD) and clathrin/AP2 (CLAP) domains, and a C-terminal SH3 domain. All domains interact with either lipids or SV endocytosis proteins, with all of these interactions required for SV endocytosis, apart from the Amph1 PRD. In this study, we determined this role and confirmed requirements for established Amph1 interactions in SV endocytosis at typical small central synapses. Domain-specific interactions of Amph1 were validated usingin vitroGST pull-down assays, with the role of these interactions in SV endocytosis determined in molecular replacement experiments in primary neuronal culture. Using this approach, we confirmed important roles for CLAP and SH3 domain interactions in the control of SV endocytosis. Furthermore, we identified an interaction site for the endocytosis protein endophilin A1 in the Amph1 PRD and revealed a key role for this interaction in SV endocytosis. Finally, we discovered that the phosphorylation status of Amph1-S293 within the PRD dictates the formation of the Amph1-endophilin A1 complex and is essential for efficient SV regeneration. This work therefore identifies an activity-dependent dephosphorylation-dependent interaction that is key for efficient SV endocytosis.
Cultivation ofUlvasp. offshore the Eastern Mediterranean Sea in experimental bioreactors: seasonal growth dynamics and environmental effects
Authors: Zollmann Meiron , Liberzon Alexander , Palatnik Ruslana R. , Zilberman David , Golberg Alexander
Published: January 2023

Offshore macroalgae production could provide an alternative source of biomass for food, materials and energy. However, the offshore environment in general, and specifically the Eastern Mediterranean Sea (EMS) offshore, is a high energy and low nutrients environment and thus is challenging for macroalgae farming. This study aims to understand the effects of season, depth, and fertilization duration on growth rates and chemical composition in offshoreUlvabiomass production and develop a predictive model suitable to offshore conditions. We hypothesize that offshoreUlvagrowth rates and chemical composition will follow a seasonal trend and that applying rapid onshore fertilization could refill nutrient storages and enable continuous offshore cultivation. We test this hypothesis by measuringUlvabiomass and internal nitrogen in offshore experiments in the nitrogen-poor EMS a few kilometers offshore the Israeli coast. We construct a predictive cultivation model to estimate N concentrations in the sea during experiments. This study demonstrates the feasibility of growingUlvasp. offshore the EMS with an onshore nutrient supply and develops a better understanding of seasonal growth dynamics and environmental effects (nitrogen, waves, depth, etc.). Furthermore, the study showcases the applicability of the macroalgae cultivation model in the offshore environment and its potential contribution throughout the whole lifecycle of seaweed cultivation.
Biomimetic actin cortices shape cell-sized lipid vesicles
Authors: Baldauf Lucia , Frey Felix , Perez Marcos Arribas , Mladenov Miroslav , Way Michael , Idema Timon , Koenderink Gijsje H.
Published: January 2023

Animal cells are shaped by a thin layer of actin filaments underneath the plasma membrane known as the actin cortex. This cortex stiffens the cell surface and thus opposes cellular deformation, yet also actively generates membrane protrusions by exerting polymerization forces. It is unclear how the interplay between these two opposing mechanical functions plays out to shape the cell surface. To answer this question, we reconstitute biomimetic actin cortices nucleated by the Arp2/3 complex inside cell-sized lipid vesicles. We show that thin Arp2/3-nucleated actin cortices strongly deform and rigidify the shapes of giant unilamellar vesicles and impart a shape memory on time scales that exceeds the time of actin turnover. In addition, actin cortices can produce finger-like membrane protrusions, showing that Arp2/3-mediated actin polymerization forces alone are sufficient to initiate protrusions in the absence of actin bundling or membrane curving proteins. Combining mathematical modeling and our experimental results reveals that the concentration of actin nucleating proteins, rather than actin polymerization speed, is crucial for protrusion formation. This is because locally concentrated actin polymerization forces can drive a positive feedback loop between recruitment of actin and its nucleators to drive membrane deformation. Our work paints a picture where the actin cortex can either drive or inhibit deformations depending on the local distribution of nucleators.

Significance Statement

The cells in our body must actively change shape in order to migrate, grow and divide, but they also need to maintain their shape to withstand external forces during tissue development. Cellular shape control results from an interplay between the plasma membrane and its underlying cortex, a shell composed of crosslinked actin filaments. Using cell-free reconstitution and mathematical modelling, we show that minimal biomimetic actin cortices can mechanically rigidify lipid vesicles while at the same time driving membrane protrusion formation. Our observations suggest that the spatial distribution of actin nucleation determines whether the actin cortex drives or inhibits membrane deformations.
A century of sampling at an ecological preserve reveals declining diversity of wild bees
Authors: Graham Kelsey K. , Glaum Paul , Hartert Joseph , Gibbs Jason , Tucker Erika , Isaacs Rufus , Valdovinos Fernanda S.
Published: January 2023

We analyzed the wild bee community from 1921 to 2018 at a nature preserve in southern Michigan, USA using museum records and found significant shifts in the bee community. Across the near century of records, species richness peaked in the 1970s and 1980s. There was an intensive bee survey completed by F.C. Evans in 1972 and 1973. We attempted to replicate his effort in 2017 and 2018, and again found a significant decline in species richness and evenness. There was also evidence of declining abundance in many of the more common species. We also conducted traits analyses using neural networks, revealing that oligolectic ground-nesting bees and cleptoparasitic bees were more likely to be extirpated whereas polylectic cavity-nesting bees were more likely to have persisted. Additionally, larger body size was associated with increased probability of local extirpation for polylectic cavity-nesting species. Larger phenological range was associated with increased chances of persistence for polylectic species, while it was associated with extirpation for oligolectic ground-nesting species. Species in the contemporary samples also had a more southerly overall distribution compared to the historic one.

Open Research Statement

Data used for analyses in this manuscript, including Evans’ original dataset from 1972/1973 with updated species nomenclature, will be permanently archived at theUSDA Ag Data Commonsafter the acceptance of this manuscript and will be citable and accessible here:https://data.nal.usda.gov/dataset/century-sampling-ecological-preserve-reveals-declining-diversity-wild-bees. Complete instructions on how to access all data referenced in this manuscript can be found in Appendix S1.
Exposure to high-sugar diet induces transgenerational changes in sweet sensitivity and feeding behavior via H3K27me3 reprogramming
Authors: Yang Jie , Tang Ruijun , Chen Shiye , Chen Yinan , Zhang Liudeng , Yuan Kai , Huang Rui , Wang Liming
Published: January 2023

Human health is facing a host of new threats linked to unbalanced diets, including high sugar diet (HSD), which contributes to the development of both metabolic and behavioral disorders. Studies have shown that diet-induced metabolic dysfunctions can transmit to multiple generations of offspring and exert long-lasting health burden. Meanwhile, whether and how diet-induced behavioral abnormalities can be transmitted to the offspring remain largely unclear. Here, we showed that ancestral HSD exposure suppressed sweet sensitivity and feeding behavior in the offspring inDrosophila. These behavioral deficits were transmitted through the maternal germline and companied by the enhancement of H3K27me3 modifications. PCL-PRC2 complex, a major driver of H3K27 trimethylation, was upregulated by ancestral HSD exposure, and disrupting its activity eliminated the transgenerational inheritance of sweet sensitivity and feeding behavior deficits. Elevated H3K27me3 inhibited the expression of a transcriptional factor Cad and suppressed sweet sensitivity of the sweet-sensing gustatory neurons, reshaping the sweet perception and feeding behavior of the offspring. Taken together, we uncovered a novel molecular mechanism underlying behavioral abnormalities across multiple generations of offspring upon ancestral HSD exposure, which would contribute to the further understanding of long-term health risk of unbalanced diet.