bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmission Mechanisms of the European Union Climate Policy to the Polish Energy Policy
Authors:   University of Economics in Katowice, Matusik Rafał
Published: July 2023

Purpose: The aim of the article is to identify and describe the relationship between climate policy of the European Union and energy policy of Poland. Design/methodology/approach: The main research problem is to understand the mechanisms of policy transmission from the European Union level to Poland and to evaluate these transmission mechanisms from the point of view of energy policy coherence. The article rests upon the results of qualitative research based mainly on official documents and the law. Findings: The article is a synthetic presentation of the policy transmission mechanisms. It points out methodological problems in the fundamental policy assumptions. Research limitations/implications: The study is limited by the potential bias of some lobbying sources, as well as the fact that energy policy development is a process. Programs are constantly being developed, which in turn means that some assumptions may be modified due to changing circumstances. Originality/value: The originality and value of the article manifests itself in a context-free diagnosis of the goals, effects and methods of implementing the tasks adopted in the climate and energy policies of the European Union and Poland.
Standing finansowy spółek groszowych notowanych na Giełdzie Papierów Wartościowych w Warszawie
Authors:   Wydział Ekonomiczno-Socjologiczny, Uniwersytet Łódzki, Lesiak Magdalena
Published: July 2023

Purpose: The main aim of the article is to assess the financial standing of penny companies listed on the Warsaw Stock Exchange. Design/methodology/approach: To determine the financial condition of the analyzed entities, the evaluation system was used in two analytical dimensions, i.e. economic and financial analysis in the area of operational efficiency, debt, financial liquidity and profitability, as well as statistical measures to assess the diversity of individual indicators. Findings: The results of the analysis showed that penny companies, to a large extent, were not characterized by a high degree of indebtedness, low financial liquidity or a lack of profits, which characterizes entities threatened with bankruptcy. Research limitations/implications: The result of the analysis carried out entitles us to conclude that penny companies are not entities that can be categorically classified as entities threatened with bankruptcy. Originality/value: The article is a study on the results of research in the area of the financial condition of penny companies listed on the Warsaw Stock Exchange.
Empresas de inserción y economía circular: el itinerario formativo como herramienta para la transición justa
Authors: Canalda Criado Sergio
Published: July 2023

En este trabajo se analiza la capacidad de la economía social para favorecer una transición ecológica socialmente justa desde el punto de vista de las personas empleadas en las entidades que forman parte de la economía social. Más concretamente, el objeto de estudio evalúa la capacidad de las empresas de inserción para garantizar el derecho a la formación de las personas sujetas a itinerarios de inserción con el fin de conseguir su plena integración en un mercado laboral en transición hacia modelos de producción más sostenibles. De esta manera, se toma como referencia la economía circular como sector específico de actuación de las empresas de inserción para contrastar la oferta formativa relacionada con la economía circular y la base formativa de los puestos de trabajo de las personas trabajadoras de las empresas de inserción.
Primate social behaviour: Benefits, challenges and diversity of relations
Authors: Amici Federica
Published: July 2023

Primates usually live in groups and interact with other group members, sometimes forming preferential long-term relationships. Sociality provides primates with benefits like support and learning opportunities that ultimately increase their fitness. Sociality also poses challenges in terms of competition and coordination, though, which primates face with the use of different behavioural and cognitive strategies. Moreover, primates show important variation in sociality, both between species, between groups, across individuals and through developmental stages. Overall, observational studies are a powerful tool to understand the richness in primate sociality, and the factors that explain the emergence and maintenance of specific forms of sociality and behavioural traits.
Rols de cacera en ximpanzés? Aspectes cognitius de l’activitat grupal en aquesta espècie
Authors: Albiach-Serrano Anna
Published: July 2023

Les observacions dels ximpanzés al seu hàbitat natural mostren que, a més de competir, aquests primats cooperen habitualment formant coalicions, patrullant els límits del seu territori i caçant en grup. Possiblement pel paper destacat que se li suposa en l’evolució de la nostra espècie, la cacera en grup ha despertat un interès considerable en la investigació. La qüestió de fons és fins a quin punt els ximpanzés cacen cooperativament de manera semblant als humans. Per respondre a aquesta pregunta, cal tenir en compte, a més del comportament, les capacitats cognitives requerides, atès que dues conductes semblants poden respondre a mecanismes psicològics diferents. La recerca de l’aspecte cognitiu de la cooperació s’ha dut a terme principalment a través d’experiments amb ximpanzés en captivitat. L’evidència disponible apunta que els ximpanzés, amb experiència, són capaços de coordinar-se, però no queda clar si també poden col·laborar, és a dir, actuar segons una estratègia compartida.
A primatological perspective on human cultural origins: When did cumulative culture evolved in our lineage
Authors: Motes-Rodrigo Alba
Published: July 2023

Humans are one of the most successful species in the planet as we inhabit almost every ecosystem on Earth. This success has been attributed to our cultural proficiency, which allows us to store in the collective minds of our populations complex knowledge that no single individual could innovate on its own. In this way, we acquire most of our behavioural repertoire from experts in our communities and, contrary to any other species, we build upon this collectively-stored information to create novel solutions to face ever-more-challenging problems. This ratcheting of behavioural complexity has led to our culture being coined cumulative. The fact that not even our closest living relatives, the great apes, possess this type of culture begs the question of when did cumulative culture evolve in our lineage. In this piece, I discuss how the field of experimental primate archaeology has contributed to this question by describing several stone-tool experiments conducted with great apes.
Introduction: Primate relatives
Authors: Albiach-Serrano Anna
Published: July 2023

The order Primates includes more than three hundred species, among which are us, human beings. Perhaps that is why we are so fascinated by their study, because of the diverse forms and behaviours of the taxon and because to understand primates better is to understand ourselves better.
Implicación y afectividad en el ejercicio profesional del Trabajo Social y la Educación Social
Authors: Navarro-Pérez José-Javier , Tarín-Cayuela Manuel , Carroll Annemaree , Capella Sergio
Published: July 2023

Cuando hablamos de implicación y afectividad también lo hacemos de características, a priori, intrínsecas al ejercicio profesional de Trabajadores Sociales y Educadores Sociales. Estas particularidades no se encuentran integradas en el proceso de verificación (VERIFICA) de los títulos universitarios, sin embargo aportan inputs a su desempeño profesional. La utilización de estas competencias invisibles que integran el currículo de los planes de estudio, son sin embargo, visibles en la realidad, ya que ayudan en la construcción de la relación educativa con personas en riesgo. El presente trabajo tiene por objetivo exponer los orígenes teóricos y metodológicos que construyen ambas estrategias y su implementación en la práctica profesional cotidiana, con infancia, adolescencia y juventud en riesgo. Los resultados profundizan en una comprensión teórica holística, que viene determinada por la relación de ayuda y la profundización en bases epistemológicas conectadas con movimientos cristianos y pedagogías comunitarias de corte preventivo participativo, educativo y comunicativo. También configura un importante impacto la metodología, ya que la existencia de acciones aisladas no alcanza los objetivos de actuación. Así pues, la conexión entre teoría y metodología constituye un abanico de propuestas y experiencias para profundizar en itinerarios, espacios donde implementar competencias y resultados de aprendizaje que guiar a través de la implicación y la afectividad.
Situated formats around the science-art-technology debate: an introduction to European Digital Arts Festivals (DAF)
Authors: Reyes-Criado José Luis
Published: July 2023

Digital Arts Festivals (DAF) are one of the most booming situated formats and performative experiences for debate, dissemination, exhibition and artistic practice around the science-art-technology intersection. From Ars Electronica or Transmediale and CTM in Berlin to the Spanish Sónar, L.E.V. or MIRA, more than 50 Digital Arts Festivals have appeared in Europe in the last few decades. Although the paradigm of the “festivalization of culture” has received a great deal of academic attention, DAFs have been minimally analysed. What are Digital Arts Festivals? How do they differ from other festivals? How can we define, categorize and analyse these festivals in depth in order to understand their role in cultural production and artistic creation today? In order to address these questions, this article presents the first results of an empirical study which began at the end of 2020 and is still ongoing and which concerns the paradigm of Digital Arts Festivals in Europe. Based on qualitative, multi-sited and wide-ranging research, and having generated a list of more than 50 DAFs in Europe and conducted a first round of semi-structured in-depth interviews with 10 festival directors, I introduce a starting definition of Digital Arts Festivals. Based on three case studies from Southern Europe – the Semibreve festival in Braga, the MIRA festival in Barcelona and the ROBOT festival in Bologna – I present a theoretical apparatus and an analytical approach in dialogue with the concept of festivalscape, that allows us to expand the study of Digital Arts Festivals, especially from the tools of cultural sociology.
Enumeration of cyclic vertices and components over the congruence $a^{11} \equiv b \pmod n$
Authors:   Department of Mathematics, Science College Kokrajhar, Thakur Sanjay Kumar , Goswami Pinkimani ,   Department of Mathematics, University of Science and Technology Meghalaya, Ray Gautam Chandra ,   Department of Mathematics, CIT Kokrajhar
Published: July 2023

For each positive integer $n$, we assign a digraph $\Gamma(n,11)$ whose set of vertices is $Z_n=\lbrace 0,1,2, \ldots, n-1\rbrace$ and there exists exactly one directed edge from the vertex $a$ to the vertex $b$ iff $a^{11}\equiv b \pmod n$. Using the ideas of modular arithmetic, cyclic vertices are presented and established for $n=3^k$ in the digraph $\Gamma(n,11)$. Also, the number of cycles and the number of components in the digraph $\Gamma(n,11)$ is presented for $n=3^k,7^k$ with the help of Carmichael’s lambda function. It is proved that for $k\geq 1$, the number of components in the digraph $\Gamma(3^k,11)$ is $(2k+1)$ and for $k>2$ the digraph $\Gamma(3^k,11)$ has $(k-1)$ non-isomorphic cycles of length greater than $1$, whereas the number of components of the digraph $\Gamma(7^k,11)$ is $(8k-3)$.
A Novel Plate for Vertical Shear Fractures of the Medial Malleolus: A Biomechanical Study
Authors: Bektas Yunus Emre , Özmanevra Ramadan , Cici Hakan , Ciklacandir Samet , Demirkiran Nihat Demirhan , Isler Yalcin , Basci Onur , Erduran Mehmet
Published: July 2023

Background: This study aimed to evaluate and compare stiffness and load to failure values of a novel medial malleolus compression plate (MP) and a 3.5-mm one-third tubular plate (TP) in the treatment of vertical shear fractures of the medial malleolus.

Methods: Fourteen identical synthetic third-generation composite polyurethane bone models of the right distal tibia were randomly separated into two groups. Fracture models were created with a custom-made osteotomy guide to provide the same fracture characteristics in every sample (AO/OTA type 44A2). Fractures were reduced, and a novel MP was applied to bone models in the MP group and a TP was applied in the TP group. All of the samples were evaluated biomechanically, and force/displacement and load to failure values were recorded.

Results: The force required to create displacement in the MP group was twice of that in the TP group. There was a significant difference between the two groups in all of the amounts of displacement (P = .006, P = .005, P = .007 and P = .015 for 0.5, 1.0, 1.5, and 2.0 mm, respectively).

Conclusions: In the treatment of vertical shear fractures of the medial malleolus, the strength of fixation with the novel MP is biomechanically higher than that with the one-third semi-TP.
Rodent ultrasonic vocal interaction resolved with millimeter precision using hybrid beamforming
Authors: Sterling Max L , Teunisse Ruben , Englitz Bernhard
Published: July 2023

Ultrasonic vocalizations (USVs) fulfill an important role in communication and navigation in many species. Because of their social and affective significance, rodent USVs are increasingly used as a behavioral measure in neurodevelopmental and neurolinguistic research. Reliably attributing USVs to their emitter during close interactions has emerged as a difficult, key challenge. If addressed, all subsequent analyses gain substantial confidence. We present a hybrid ultrasonic tracking system, Hybrid Vocalization Localizer (HyVL), that synergistically integrates a high-resolution acoustic camera with high-quality ultrasonic microphones. HyVL is the first to achieve millimeter precision (~3.4–4.8 mm, 91% assigned) in localizing USVs, ~3× better than other systems, approaching the physical limits (mouse snout ~10 mm). We analyze mouse courtship interactions and demonstrate that males and females vocalize in starkly different relative spatial positions, and that the fraction of female vocalizations has likely been overestimated previously due to imprecise localization. Further, we find that when two male mice interact with one female, one of the males takes a dominant role in the interaction both in terms of the vocalization rate and the location relative to the female. HyVL substantially improves the precision with which social communication between rodents can be studied. It is also affordable, open-source, easy to set up, can be integrated with existing setups, and reduces the required number of experiments and animals.
The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder
Authors: Weibel Catherine A , Wheeler Andrew L , James Jennifer E , Willis Sara M , McShea Hanon , Masel Joanna
Published: July 2023

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an ‘effective population size’ is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species’ effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here, we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback–Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.
A new codon adaptation metric predicts vertebrate body size and tendency to protein disorder
Authors: Weibel Catherine A. , Wheeler Andrew L. , James Jennifer E. , Willis Sara M. , Masel Joanna
Published: July 2023

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic diversity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.
The Human Mitochondrial Genome Encodes for an Interferon-Responsive Host Defense Peptide
Authors: Rice Michelle C , Imun Maria , Jung Sang Wun , Park Chan Yoon , Kim Jessica S , Lai Rochelle W , Barr Casey R , Son Jyung Mean , Tor Kathleen , Kim Emmeline , Lu Ryan J , Cohen Ilana , Benayoun Bérénice A , Lee Changhan
Published: July 2023

The mitochondrial DNA (mtDNA) can trigger immune responses and directly entrap pathogens, but it is not known to encode for active immune factors. The immune system is traditionally thought to be exclusively nuclear-encoded. Here, we report the identification of a mitochondrial-encoded host defense peptide (HDP) that presumably derives from the primordial proto-mitochondrial bacteria. We demonstrate that MOTS-c (mitochondrial open reading frame from the twelve S rRNA type-c) is a mitochondrial-encoded amphipathic and cationic peptide with direct antibacterial and immunomodulatory functions, consistent with the peptide chemistry and functions of known HDPs. MOTS-c targeted
E. coli
and methicillin-resistant
S. aureus
(MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains. In monocytes, IFNγ, LPS, and differentiation signals each induced the expression of endogenous MOTS-c. Notably, MOTS-c translocated to the nucleus to regulate gene expression during monocyte differentiation and programmed them into macrophages with unique transcriptomic signatures related to antigen presentation and IFN signaling. MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism. Our findings support MOTS-c as a first-in-class mitochondrial-encoded HDP and indicates that our immune system is not only encoded by the nuclear genome, but also by the co-evolved mitochondrial genome.
Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid
Authors: Shibl Ahmed A , Ochsenkühn Michael A , Mohamed Amin R , Isaac Ashley , Coe Lisa SY , Yun Yejie , Skrzypek Grzegorz , Raina Jean-Baptiste , Seymour Justin R , Afzal Ahmed J , Amin Shady A
Published: July 2023

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10–9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.
Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid
Authors: Shibl Ahmed A. , Ochsenkühn Michael A. , Mohamed Amin R. , Isaac Ashley , Coe Lisa S. Y. , Yun Yejie , Skrzypek Grzegorz , Raina Jean-Baptiste , Seymour Justin R. , Afzal Ahmed J. , Amin Shady A.
Published: July 2023

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism and toxicity of Aze on two microalgal-associated bacteria,
Phycobacter
and
Alteromonas
, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C
4
- TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source.
Phycobacter
took up Aze at an initial uptake rate of 3.8×10
-9
nmol cell
-1
hr
-1
and utilized it as a carbon source in concentrations ranging from 10 μM-1 mM, suggesting a broad range of acclimation to Aze availability. For inhibited bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolise Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.
Optimized path planning surpasses human efficiency in cryo-EM imaging
Authors: Li Yilai , Fan Quanfu , Xu Ziping , Lee Emma Rose , Cohn John , Demers Veronique , Lee Ja Young , Yip Lucy , Cianfrocco Michael A. , Vos Seychelle M.
Published: July 2023

Cryo-electron microscopy (cryo-EM) represents a powerful technology for determining atomic models of biological macromolecules(Kühlbrandt, 2014). Despite this promise, human-guided cryo-EM data collection practices limit the impact of cryo-EM because of a path planning problem: cryo-EM datasets typically represent 2-5% of the total sample area. Here, we address this fundamental problem by formalizing cryo-EM data collection as a path planning optimization from low signal data. Within this framework, we incorporate reinforcement learning (RL) and deep regression to design an algorithm that uses distributed surveying of cryo-EM samples at low magnification to learn optimal cryo-EM data collection policies. Our algorithm - cryoRL - solves the problem of path planning on cryo-EM grids, allowing the algorithm to maximize data quality in a limited time without human intervention. A head-to-head comparison of cryoRL versus human subjects shows that cryoRL performs in the top 10% of test subjects, surpassing the majority of users in collecting high-quality images from the same sample. CryoRL establishes a general framework that will enable human-free cryo-EM data collection to increase the impact of cryo-EM across life sciences research.
Reprogramming of the cardiac phosphoproteome in conjunction with proteome and transcriptome creates the enhanced performance and protection circuitry in response to chronic adenylyl cyclase-driven stress
Authors: Qu Jia-Hua , Chakir Khalid , Tarasov Kirill V. , Riordon Daniel R. , Perino Maria Grazia , Silvester Allwin Jennifa , Lakatta Edward G.
Published: July 2023

Our previous work demonstrated the existence of a remarkable adaptive paradigm of heart performance and protection in response to the constitutive challenge of marked cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8). However, the molecular regulatory mechanisms remain elusive. Because PKA signaling is the predominantly activated pathway in the TGAC8 left ventricle (LV) performance and protection circuitry and phosphorylation related pathways were enriched from transcriptome and proteome, we hypothesized that phosphorylation states of numerous proteins are reprogrammed in pathways where the transcriptome and proteome were activated in TGAC8 vs. WT. We conducted an unbiased phosphoproteomics analysis in order to determine the role of altered protein phosphorylation in the chronic adaptive heart performance and protection profile of adult TGAC8 LV at 3-4 months of age, and integrated the phosphoproteome with transcriptome and proteome. Based on differentially regulated phosphoproteins by genotype, numerous stress-response pathways within reprogrammed TGAC8 LV, including PKA, PI3K and AMPK signaling pathways, predicted upstream regulators, e.g., PDPK1, PAK1 and PTK2B, and downstream functions, e.g., cell viability, protein quality control, and metabolism were enriched. In addition to PKA, numerous other kinases and phosphatases were hyper-phosphorylated in TGAC8 vs. WT. Hyper-phosphorylated transcriptional factors in TGAC8 were associated with increased mRNA transcription, and immune responses and metabolic pathways. Combination of the phosphoproteome with its proteome and with the previously published TGAC8 transcriptome enabled the elucidation of which cardiac performance and adaptive protection profiles were coordinately regulated at post-translational modification (PTM) (phosphorylation), translational and transcriptional levels. Many stress-response signaling pathways, i.e., PI3K/AKT, ERK/MAPK and ubiquitin labeling, were consistently enriched and activated in the TGAC8 LV at transcriptional, translational and PTM levels. We verified some results through wet lab experiments. Thus, PTM of protein by phosphorylation, per se, contributes immensely to the heart performance and protection profile of TGAC8 LV, and is coordinately regulated with altered transcription and translation in the TGAC8 to activate critical stress-response pathways.
Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability
Authors: Duveau Fabien , Cordier Céline , Chiron Lionel , LeBec Matthias , Pouzet Sylvain , Séguin Julie , Llamosi Artémis , Sorre B. , Di Meglio Jean-Marc , Hersen Pascal
Published: July 2023

Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions. Taken together, we demonstrate that glucose availability regulates yeast responses to dynamic osmotic stress. We anticipate that our approach can be extended to other stress responsive pathways to further elucidate the key role of metabolic fluctuations in the dynamics of cellular responses to stress.
DMRT1 is a testis-determining gene in rabbits and is also essential for female fertility
Authors: Dujardin Emilie , André Marjolaine , Dewaele Aurélie , Mandon-Pépin Béatrice , Poulat Francis , Frambourg Anne , Thépot Dominique , Jouneau Luc , Jolivet Geneviève , Pailhoux Eric , Pannetier Maëlle
Published: July 2023

DMRT1 is the testis-determining factor in several species of vertebrates, but its involvement in mammalian testes differentiation, where SRY is the testis-determining gene, remains ambiguous. So far, DMRT1 loss-of-function has been described in two mammalian species and induces different phenotypes: Disorders of Sex Development (46, XY DSD) in men and male infertility in mice. We thus abolished DMRT1 expression by CRISPR/Cas9 in a third species of mammal, the rabbit. First, we observed that gonads from XY DMRT1−/− rabbit fetuses differentiated like ovaries, highlighting that DMRT1 is involved in testis determination. In addition to SRY, DMRT1 is required in the supporting cells to increase the expression of the SOX9 gene, which heads the testicular genetic cascade. Second, we highlighted another function of DMRT1 in the germline since XX and XY DMRT1−/− ovaries did not undergo meiosis and folliculogenesis. XX DMRT1−/− adult females were sterile, showing that DMRT1 is also crucial for female fertility. To conclude, these phenotypes indicate an evolutionary continuum between non-mammalian vertebrates such as birds and non-rodent mammals. Furthermore, our data support the potential involvement of DMRT1 mutations in different human pathologies, such as 46, XY DSD as well as male and female infertility.
Functional implications of the exon 9 splice insert in GluK1 kainate receptors
Authors: Dhingra Surbhi , Chopade Prachi M , Vinnakota Rajesh , Kumar Janesh
Published: July 2023

Kainate receptors are key modulators of synaptic transmission and plasticity in the central nervous system. Different kainate receptor isoforms with distinct spatiotemporal expressions have been identified in the brain. The GluK1-1 splice variant receptors, which are abundant in the adult brain, have an extra fifteen amino acids inserted in the amino-terminal domain (ATD) of the receptor resulting from alternative splicing of exon 9. However, the functional implications of this post-transcriptional modification are not yet clear. We employed a multi-pronged approach using cryogenic electron microscopy, electrophysiology, and other biophysical and biochemical tools to understand the structural and functional impact of this splice insert in the extracellular domain of GluK1 receptors. Our study reveals that the splice insert alters the key gating properties of GluK1 receptors and their modulation by the cognate auxiliary Neuropilin and tolloid-like (Neto) proteins 1 and 2. Mutational analysis identified the role of crucial splice residues that influence receptor properties and their modulation. Furthermore, the cryoEM structure of the variant shows that the presence of exon 9 in GluK1 does not affect the receptor architecture or domain arrangement in the desensitized state. Our study thus provides the first detailed structural and functional characterization of GluK1-1a receptors, highlighting the role of the splice insert in modulating receptor properties and their modulation.
Membrane contact sites regulate vacuolar fission via sphingolipid metabolism
Authors: Hanaoka Kazuki , Nishikawa Kensuke , Ikeda Atsuko , Schlarmann Philipp , Yamashita Sayumi , Nakaji Aya , Fujii Sotaro , Funato Kouichi
Published: July 2023

Membrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar fission/fusion processes are coupled with modifications in the membrane lipid composition. However, it has been still unclear whether MCS-mediated lipid metabolism controls the vacuolar morphology. Here we report that deletion of tricalbins (Tcb1, Tcb2, Tcb3), tethering proteins at endoplasmic reticulum (ER)-plasma membrane (PM) and ER-Golgi contact sites, alters fusion/fission dynamics and causes vacuolar fragmentation in the yeast
Saccharomyces cerevisiae
. In addition, we show that the sphingolipid precursor phytosphingosine accumulates in tricalbin-deleted cells, triggering the vacuolar division. Detachment of the nucleus vacuole junction (NVJ), an important contact site between the vacuole and the perinuclear ER, restored vacuolar morphology in both cells subjected to high exogenous phytosphingosine and Tcb3-deleted cells, supporting that phytosphingosine transport across the NVJ induces vacuole division. Thus, our results suggest that vacuolar morphology is maintained by MCSs through the metabolism of sphingolipids.
Dynamic allosteric networks drive adenosine A1 receptor activation and G-protein coupling
Authors: Maria-Solano Miguel A , Choi Sun
Published: July 2023

G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics of the receptor is critical for the development of therapeutics. Here, we target the adenosine A1 receptor (A1R), for which a negligible number of drugs have been approved. We combine molecular dynamics simulations, enhanced sampling techniques, network theory, and pocket detection to decipher the activation pathway of A1R, decode the allosteric networks, and identify transient pockets. The A1R activation pathway reveals hidden intermediate and pre-active states together with the inactive and fully-active states observed experimentally. The protein energy networks computed throughout these conformational states successfully unravel the extra and intracellular allosteric centers and the communication pathways that couple them. We observe that the allosteric networks are dynamic, being increased along activation and fine-tuned in the presence of the trimeric G-proteins. Overlap of transient pockets and energy networks uncovers how the allosteric coupling between pockets and distinct functional regions of the receptor is altered along activation. Through an in-depth analysis of the bridge between the activation pathway, energy networks, and transient pockets, we provide a further understanding of A1R. This information can be useful to ease the design of allosteric modulators for A1R.
Impact of Zinc and Thiourea Application on Growth and Yield of Summer Green Gram (Vigna radiata L.)
Authors: Patel D. J. , Patel N. I. , Kotadiya R. H. , Chaudhary K. H. , Birla Devilal , Dohat Manoj
Published: July 2023

Aims: To find out the Impact of zinc and thiourea application on growth and yield of summer green gram (Vigna radiata L.).

Study Design:  The experiment was laid out in Randomized Block Design (factorial concepts) with three replications.

Place and Duration of Study: A field experiment was conducted during summer season of 2020 at Agronomy Instructional Farm, SDAU, Dantiwada (Gujarat). The soil of experimental plot was loamy sand in texture.

Methodology: The experiment comprising three levels of zinc (1.5, 3.0 and 4.5 kg ha-1) and five treatments of thiourea application (control (no spray), seed soaking with thiourea @ 500 ppm, foliar spray of thiourea @ 500 ppm at 30 DAS, foliar spray of thiourea @ 500 ppm at 45 DAS and foliar spray of thiourea @ 500 ppm at 30 and 45 DAS).

Results: Almost all the growth and yield attributes as well as yield were significantly influenced due to various treatments. The plant height (47.02 cm and 46.60 cm, respectively), total number of pods plant-1 (15.92 and 19.82, respectively) and number of seeds pod-1 (7.91 and 8.26, respectively) and seed yield and stover yield were also found significantly higher in the application of either 4.5 kg Zn ha-1 or foliar sprays of thiourea @ 500 ppm at 30 and 45 DAS.

Conclusion: On the basis of experimental results, it can be concluded that to obtain higher yield of green gram crop responds positively to the application of zinc and thiourea with enhancement in the agronomical performance and productivity.
Role of Thoracic Spinal Anesthesia in Laparoscopic Cholecystectomy: A Literature Review
Authors: Mohsen Khaled Mohamed
Published: July 2023

The efficacy of thoracic spinal anesthesia (TSA) in laparoscopic cholecystectomy has been investigated through various studies focusing on patient satisfaction, pain management, and safety. In comparison to general anesthesia, Thoracic spinal anesthesia (TSA) in laparoscopic cholecystectomy was associated with shorter discharge times and greater patient satisfaction compared to general anesthesia. However, it should be noted that surgeon satisfaction was higher with general anesthesia. TSA demonstrated superior postoperative analgesia and hemodynamic stability compared to lumbar spinal anesthesia, making it a safe and effective alternative for laparoscopic cholecystectomy in healthy patients. Additionally, segmental thoracic spinal anesthesia was found to be associated with a lower incidence of postoperative pneumonia and atelectasis, making it a preferable choice for patients with respiratory comorbidities. Overall, thoracic spinal anesthesia showed promising outcomes, manageable intraoperative complications, and high patient satisfaction rates, making it a feasible regional anesthesia technique for laparoscopic cholecystectomy.
Genetic Variants Associated With Hidradenitis Suppurativa
Authors: Sun Quan , Broadaway K. Alaine , Edmiston Sharon N. , Fajgenbaum Kristen , Miller-Fleming Tyne , Westerkam Linnea Lackstrom , Melendez-Gonzalez Maria , Bui Helen , Blum Franklin R. , Levitt Brandt , Lin Lan , Hao Honglin , Harris Kathleen Mullan , Liu Zhi , Thomas Nancy E. , Cox Nancy J. , Li Yun , Mohlke Karen L. , Sayed Christopher J.
Published: July 2023

Importance

Hidradenitis suppurativa (HS) is a common and severely morbid chronic inflammatory skin disease that is reported to be highly heritable. However, the genetic understanding of HS is insufficient, and limited genome-wide association studies (GWASs) have been performed for HS, which have not identified significant risk loci.

Objective

To identify genetic variants associated with HS and to shed light on the underlying genes and genetic mechanisms.

Design, Setting, and Participants

This genetic association study recruited 753 patients with HS in the HS Program for Research and Care Excellence (HS ProCARE) at the University of North Carolina Department of Dermatology from August 2018 to July 2021. A GWAS was performed for 720 patients (after quality control) with controls from the Add Health study and then meta-analyzed with 2 large biobanks, UK Biobank (247 cases) and FinnGen (673 cases). Variants at 3 loci were tested for replication in the BioVU biobank (290 cases). Data analysis was performed from September 2021 to December 2022.

Main Outcomes and Measures

Main outcome measures are loci identified, with association of P < 1 × 10−8 considered significant.

Results

A total of 753 patients were recruited, with 720 included in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and at enrollment was 35.3 (13.52) years; 360 (50.0%) patients were Black, and 575 (79.7%) were female. In a meta-analysis of the 4 studies, 2 HS-associated loci were identified and replicated, with lead variants rs10512572 (P = 2.3 × 10−11) and rs17090189 (P = 2.1 × 10−8) near the SOX9 and KLF5 genes, respectively. Variants at these loci are located in enhancer regulatory elements detected in skin tissue.

Conclusions and Relevance

In this genetic association study, common variants associated with HS located near the SOX9 and KLF5 genes were associated with risk of HS. These or other nearby genes may be associated with genetic risk of disease and the development of clinical features, such as cysts, comedones, and inflammatory tunnels, that are unique to HS. New insights into disease pathogenesis related to these genes may help predict disease progression and novel treatment approaches in the future.
Characterization of Mass Shootings by State, 2014-2022
Authors: Barnard Leslie M. , Wright-Kelly Erin , Brooks-Russell Ashley , Betz Marian E.
Published: July 2023

This case series investigates the rates of mass shootings, along with injuries and deaths, by US state and shooting type.
Psychedelics as Therapeutics—Potential and Challenges
Authors: Volkow Nora D. , Gordon Joshua A. , Wargo Eric M.
Published: July 2023

This Viewpoint discusses the potential promise of the therapeutic use of psychedelics for mental illness and substance use disorders, acknowledging many open research questions and unique challenges with these substances.
Procyanidins Boost the Neuroprotective Effect of Minocycline for Intracerebral Haemorrhage
Authors: Yuan Taoyang , Wang Tianyou , Zhang Jianhua , Shi Shun , Gu Zhipeng , Li Yiwen , Xu Jianguo
Published: July 2023

Poor prognosis is often expected after the treatment of intracerebral haemorrhage (ICH) when the approach lacks effective neuroprotective interventions. Minocycline (Mino) is a promising clinical neuroprotective candidate for acute ICH therapy that mainly inhibits activation of microglia/macrophages. However, to address iron neurotoxicity, ferroptosis, and oxidative stress‐induced multiple neuroinjury mechanisms, the neuroprotective effect of minocycline still urgently needs to be enhanced. To address this issue, procyanidins (PACs), typical natural polyphenols, is used to improve the neuroprotective effect of Mino by constructing PACs‐Mino nanoparticles (NPs) using 3‐aminophenylboronic acid as the crosslinker. The yielding NPs possessed improved antioxidant and iron‐removing capacities in vitro. More importantly, PACs‐Mino NPs exerted excellent therapeutic effects on ICH, showing improved neuroprotective activity and resulting in neurobehavioral recovery, in an in vitro cellular model and an in vivo ICH rat model. This study can provide a general strategy that uses natural polyphenols to boost the performance of drugs for ICH treatment, and the results may be further extended to other injuries of the central nervous system, such as brain injury and spinal cord injury.
High Ionic Conductivity Motivated by Multiple Ion‐Transport Channels in 2D MOF‐Based Lithium Solid State Battery
Authors: Lian Huimin , Momen Roya , Xiao Yudong , Song Bai , Hu Xinyu , Zhu Fangjun , Liu Huaxin , Xu Laiqiang , Deng Wentao , Hou Hongshuai , Zou Guoqiang , Ji Xiaobo
Published: July 2023

Metal‐organic frameworks (MOFs) have been proposed as novel fillers for constructing polymer solid electrolytes based composite electrolytes. However, MOFs are generally used as passive fillers, in‐depth revealing the binding mode between MOFs and polyethylene oxide (PEO), the critical role of MOFs in facilitating Li+ transport in solid electrolytes is full of challenges. Herein, inspired by density functional theory (DFT) the 2D‐MOF with rich unsaturated metal coordination sites that can bind the O atom in PEO through the metal–oxygen bond,  anchor TFSI− to release Li+, resulting in a remarkable Li+ transference number of 0.58, is reported according well with the experimental results and molecular dynamics (MD) simulation. Impressively, after the introduction of the 2D‐MOF, the Li+ can rapidly hop along the benzene ring center within the 2D‐MOF plane, and the interface between the benzene ring and PEO can also serve as a fast Li+ migration pathway, delivering multiple ion‐transport channels, which present a high ion conductivity of 4.6 × 10−5 S cm−1 (25 °C). The lithium symmetric battery is stable for 1300 h at 60 °C, 0.1 mA cm−2. The assembled lithium metal solid state battery maintains high capacity of 162.8 mAh g−1 after 500 cycles at 60 °C and 0.5 C. This multiple ion‐transport channels approach brings new ideas for designing advanced solid electrolytes.
Nanoimprint Meta‐Device for Chiral Imaging
Authors: Zhang Jing Cheng , Chen Mu Ku , Liang Yao , Hong Xiao , Wang Muting , Cheng Yijun , Liu Xiaoyuan , Tsai Din Ping , Pang Stella W.
Published: July 2023

The polarization of light is a valuable information channel that has been studied extensively in optical devices. There has been limited progress in developing low‐refractive index contrast and large‐scale chiral meta‐devices that are easy to integrate and mass‐produce. In this image, a chiral imaging meta‐device with a large area and broadband chirality control is experimentally demonstrated. The centimeter‐scale Moiré meta‐device is achieved using nanoimprint technology. The Poynting vector and singularity features in the near field and chiral optical response in the far field are discussed. The proposed Moiré meta‐devices can achieve circular dichroism (CD) of more than 10%. Further chiral imaging harnessing CD mechanisms are demonstrated, which may lead to significant potential in various fields, including encryption and security, materials science, biochemistry, and medicine.