bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat
Authors: Barretto-de-Souza Lucas , Joseph Shemar A. , Lynch Francesca M. , Ng Alexandra J. , Chrsitianson John P.
Published: March 2023

Rationale

In a social context, individuals are able to detect external information from others and coordinate behavioral responses according to the situation, a phenomenon called social decision-making. Social decision-making is multifaceted, influenced by emotional and motivational factors like stress, sickness and hunger. However, the neurobiological basis for motivational state competition and interaction are not well known.

Objective

We investigated possible neural mechanisms through which internal states could shape social behavior in a social affective preference (SAP) test. In the SAP test, experimental rats given a choice to interact with naïve or stressed conspecifics exhibit an age-dependent preference to interact with stressed juvenile conspecifics, but avoid stressed adult conspecifics. First, we assessed the effect of hunger on SAP behavior. Behavior in the SAP test requires the insular cortex, which receives input from the hunger-related peptides melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus (LH). This study aimed to evaluate the role of LH and insular MCH and orexin in SAP test.

Methods

SAP tests were conducted in rats that were sated, food deprived or allowed 1 h of access to food after 14 h of deprivation (relieved condition). Separate cohorts of sated rats received cannula implants for microinjection of drugs to inhibit the LH or to block or stimulate MCH or orexin receptors in the insula prior to SAP tests or social interaction tests.

Results

Food and water deprivation prior to SAP tests with juvenile rats caused a shift in preference away from the stressed rat toward the naïve juveniles. Pharmacological inhibition of LH with muscimol (100 ng/side) abolished the preference for the juvenile stressed conspecific, as well as the preference for the adult naïve conspecific. The blockade of MCHr1 or orexin receptors in the insular cortex with SNAP94847 (50µM) or TCS1102 (1µM), respectively, also abolished the preference for the stressed juvenile conspecific, but only the antagonism of orexin receptors was able to abolish the preference for the adult naïve conspecific. Microinjection of increasing doses (50 or 500 nM) of MCH or orexin-A in the insular cortex increased the interaction time in the one-on-one social interactions test with juvenile conspecifics, however only the microinjection of orexin-A increased the interaction time with adult naïve conspecifics.

Conclusions

Taken together, these results suggest that lateral hypothalamus peptides shape the direction of social approach or avoidance via actions MCH and orexin neurotransmission in the insular cortex.
A rapid and sensitive multiplex, whole mount RNA fluorescencein situhybridization and immunohistochemistry protocol
Authors: Huang Tian , Guillotin Bruno , Rahni Ramin , Birnbaum Ken , Wagner Doris
Published: March 2023

In the past few years, there has been an explosion in single-cell transcriptomics datasets, yetin vivoconfirmation of these datasets is hampered in plants due to lack of robust validation methods. Likewise, modeling of plant development is hampered by paucity of spatial gene expression data. RNA fluorescencein situhybridization (FISH) enables investigation of gene expression in the context of tissue type. Despite development of FISH methods for plants, easy and reliable whole mount FISH protocols have not yet been reported. We adapt a 3-day whole mount RNA-FISH method for plant species based on a combination of prior protocols that employs hybridization chain reaction (HCR), which amplifies the probe signal in an antibody-free manner. Our whole mount HCR RNA-FISH method shows expected spatial signals with low background for gene transcripts with known spatial expression patterns in Arabidopsis inflorescences and monocot roots. It allows simultaneous detection of three transcripts in 3D. We also show that HCR RNA-FISH can be combined with endogenous fluorescent protein detection and with our improved immunohistochemistry (IHC) protocol. The whole mount HCR RNA-FISH and IHC methods allow easy investigation of 3D spatial gene expression patterns in entire plant tissues.
From GWAS to signal validation: An approach for estimating genetic effects while preserving genomic context
Authors: Wolf Scott , Abhyankar Varada , Melo Diogo , Ayroles Julien F. , Pallares Luisa F.
Published: March 2023

Validating associations between genotypic and phenotypic variation remains a challenge, despite advancements in association studies. Common approaches for signal validation rely on gene-level perturbations, such as loss-of-function mutations or RNAi, which test the effect of genetic modifications usually not observed in nature. CRISPR-based methods can validate associations at the SNP level, but have significant drawbacks, including resulting off-target effects and being both time-consuming and expensive. Both approaches usually modify the genome of a single genetic background, limiting the generalizability of experiments. To address these challenges, we present a simple, low-cost experimental scheme for validating genetic associations at the SNP level in outbred populations. The approach involves genotyping live outbred individuals at a focal SNP, crossing homozygous individuals with the same genotype at that locus, and contrasting phenotypes across resulting synthetic outbred populations. We tested this method inDrosophila melanogaster, measuring the longevity effects of a polymorphism at a naturally-segregating cis-eQTL for themidwaygene. Our results demonstrate the utility of this method in SNP-level validation of naturally occurring genetic variation regulating complex traits. This method provides a bridge between the statistical discovery of genotype-phenotype associations and their validation in the natural context of heterogeneous genomic contexts.
Structural basis for differential p19 targeting by IL-23 biologics
Authors: Daniele Stefano G. , Eldirany Sherif A. , Ho Minh , Bunick Christopher G.
Published: March 2023

Background

IL-23 is central to the pathogenesis of psoriasis, and is structurally comprised of p19 and p40 subunits. “Targeted” IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab differ mechanistically from ustekinumab because they bind p19, whereas ustekinumab binds p40; however, a knowledge gap exists regarding the structural composition of their epitopes and how these molecular properties relate to their clinical efficacy.

Objectives

To characterize and differentiate the structural epitopes of the IL-23 inhibitors risankizumab, guselkumab, tildrakinumab, and ustekinumab, and correlate their molecular characteristics with clinical response in plaque psoriasis therapy.

Methods

We utilized epitope data derived from hydrogen-deuterium exchange studies for risankizumab, tildrakizumab, and guselkumab, and crystallographic data for ustekinumab to map drug epitope locations, hydrophobicity, and surface charge onto the IL-23 molecular surface (Protein Data Bank ID Code 3D87) using UCSF Chimera. PDBePISA was used to calculate solvent accessible surface area (SASA). Epitope composition was determined by classifying residues as acidic, basic, polar, or hydrophobic and calculating their contribution to epitope SASA. Linear regression and analysis of variance was performed.

Results

All the p19-specific inhibitor epitopes differ in location and size, with risankizumab and guselkumab having large epitope surface areas (SA), and tildrakizumab and ustekinumab having smaller SA. The tildrakizumab epitope was mostly hydrophobic (56%), while guselkumab, risankizumab, and ustekinumab epitopes displayed >50% non-hydrophobic residues. Risankizumab and ustekinumab exhibited acidic surface charges, while tildrakizumab and guselkumab were net neutral. Each inhibitor binds an epitope with a unique size and composition, and with mostly distinct locations except for a 10-residue overlap region that lies outside of the IL-23 receptor epitope. We observed a strong correlation between epitope SA and PASI-90 rates (R2= 0.9969,p= 0.0016), as well as between epitope SA and KD(R2= 0.9772,p= 0.0115). In contrast, we found that total epitope hydrophobicity, polarity, and charge content do not correlate with clinical efficacy.

Conclusions

Structural analysis of IL-23 inhibitor epitopes reveals strong association between epitope SA and early drug efficacy in plaque psoriasis therapy, exemplifying how molecular data can explain clinical observations, inform future innovation, and help clinicians in specific drug selection for patients.
Analysis of human GPER expression in normal tissues and select cancers using immunohistochemistry
Authors: Natale Christopher A. , Seykora John T. , Ridky Todd W
Published: March 2023

GPER (G protein-coupled estrogen receptor) has been reported to play roles in several areas of physiology including cancer, metabolic disorders, and cardiovascular disease. However, the understanding of where this receptor is expressed in human tissue is limited due to limited available tools and methodologies that can reliably detect GPER protein. Recently, a highly specific monoclonal antibody against GPER (20H15L21) was developed and is suitable for immunohistochemistry. Using this antibody, we show that GPER protein expression varies markedly between normal human tissue, and also among cancer tissue. As GPER is an emerging therapeutic target for cancer and other diseases, this new understanding of GPER distribution will likely be helpful in design and interpretation of ongoing and future GPER research.
Evolutionary history of MEK1 illuminates the nature of cancer and RASopathy mutations
Authors: Andrianova Ekaterina P. , Marmion Robert A. , Shvartsman Stanislav Y. , Zhulin Igor B.
Published: March 2023

Mutations in signal transduction pathways lead to various diseases including cancers. MEK1 kinase, encoded by the humanMAP2K1gene, is one of the central components of the MAPK pathway and more than a hundred somatic mutations inMAP2K1gene were identified in various tumors. Germline mutations deregulating MEK1 also lead to congenital abnormalities, such as the Cardiofaciocutaneous Syndrome and Arteriovenous Malformation. Evaluating variants associated with a disease is a challenge and computational genomic approaches aid in this process. Establishing evolutionary history of a gene improves computational prediction of disease-causing mutations; however, the evolutionary history of MEK1 is not well understood. Here, by revealing a precise evolutionary history of MEK1 we construct a well-defined dataset of MEK1 metazoan orthologs, which provides sufficient depth to distinguish between conserved and variable amino acid positions. We used this dataset to match known and predicted disease-causing and benign mutations to evolutionary changes observed in corresponding amino acid positions. We found that all known and the vast majority of suspected disease-causing mutations are evolutionarily intolerable. We selected several MEK1 mutations that cannot be unambiguously assessed by automated variant prediction tools, but that are confidently identified as evolutionary intolerant and thus “damaging” by our approach, for experimental validation inDrosophila. In all cases, evolutionary intolerant variants caused increased mortality and severe defects in fruit fly embryos confirming their damaging nature predicted by out computational strategy. We anticipate that our analysis will serve as a blueprint to help evaluate known and novel missense variants in MEK1 and that our approach will contribute to improving automated tools for disease-associated variant interpretation.

Significance Statement

High-throughput genome sequencing has significantly improved diagnosis, management, and treatment of genetic diseases and cancers. However, in addition to its indisputable utility, genome sequencing produces many variants that cannot be easily interpreted – so called variants of uncertain significance (VUS). Various automated bioinformatics tools can help predicting functional consequences of VUS, but their accuracy is relatively low. Here, by tracing precise evolutionary history of each amino acid position in MEK1 kinase, mutations in which cause neurodegenerative diseases and cancer in humans, we can establish whether VUS seen in humans are evolutionarily tolerant. Using published data and newly performed experiments in an animal model, we show that evolutionarily tolerable variants in MEK1 are benign, whereas intolerable substitutions are damaging. Our approach will help in diagnostics of MEK1-associated diseases, it is generalizable to many other disease-associated genes, and it can help improving automated predictors.
Impaired potency of neutralizing antibodies against cell-cell fusion mediated by SARS-CoV-2
Authors: Wang Qian , Yeh Andre Yanchen , Guo Yicheng , Mohri Hiroshi , Yu Jian , Ho David D. , Liu Lihong
Published: March 2023

The SARS-CoV-2 Omicron subvariants have dominated the pandemic due to their high transmissibility and immune evasion conferred by the spike mutations. The Omicron subvariants can spread by cell-free virus infection and cell-cell fusion, the latter of which is more effective but has not been extensively investigated. In this study, we developed a simple and high-throughput assay that provides a rapid readout to quantify cell-cell fusion mediated by the SARS-CoV-2 spike proteins without using live or pseudotyped virus. This assay can be used to identify variants of concern and to screen for prophylactic and therapeutic agents. We further evaluated a panel of monoclonal antibodies (mAbs) and vaccinee sera against D614G and Omicron subvariants, finding that cell-cell fusion is substantially more resistant to mAb and serum inhibition than cell-free virus infection. Such results have important implications for the development of vaccines and antiviral antibody drugs against cell-cell fusion induced by SARS-CoV-2 spikes.
SARS-CoV-2 protein structure and sequence mutations: evolutionary analysis and effects on virus variants
Authors: Lomoio Ugo , Puccio Barbara , Tradigo Giuseppe , Guzzi Pietro Hiram , Veltri Pierangelo
Published: March 2023

Proteins sequence, structure, and function are related, so that any changes in the protein sequence may cause modifications in its structure and function. Thanks to the exponential growth of data availability, many studies have addressed different questions such as: (i) how structure evolves based on the sequence changes, (ii) how structure and function change over time. Computational experiments have contributed to the study of viral protein structures. For instance the Spike (S) protein has been investigated for its role in binding receptors and infection activity in COVID-19, hence the interest of scientific researchers in studying the effects of virus mutations due to sequence, structure and vaccination effects. Protein Contact Networks (PCNs) can be used for investigating protein structures to detect biological properties thorough network topology. We apply topological studies based on graph theory of the PCNs to compare the structural changes with sequence changes, and find that both node centrality and community extraction analysis play a relevant role in changes in protein stability and functionality caused by mutations. We compare the structural evolution to sequence changes and study mutations from a temporal perspective focusing on virus variants. We finally highlight a timeline correlation between Omicron variant identification and the vaccination campaign.
Subjective and objective indicators of neighbourhood safety and physical activity among UK adolescents
Authors: Fernandez Charlotte Constable , Patalay Praveetha , Vaughan Laura , Church David , Hamer Mark , Maddock Jane
Published: March 2023

The health benefits of regular physical activity in adolescence are well-documented. Many health-related behaviours and lifestyle choices are established in adolescence. The neighbourhood environment is a key setting for physical activity in adolescence and feeling unsafe in their neighbourhood may be a potential barrier to physical activity. This study aimed to examine associations between neighbourhood safety and physical activity using objective and subjective measures for both. Participants (n=10,913) came from the Millennium Cohort Study, a nationally representative UK longitudinal birth cohort. Results indicate that feeling unsafe in the neighbourhood, IMD crime and violent crime are barriers to physical activity participation in adolescents.
Identifying metabolic features of colorectal cancer liability using Mendelian randomization
Authors: Bull Caroline J. , Hazelwood Emma , Bell Joshua A. , Tan Vanessa Y. , Constantinescu Andrei-Emil , Borges Maria Carolina , Legge Danny N. , Burrows Kimberly , Huyghe Jeroen R. , Brenner Hermann , Castellví-Bel Sergi , Chan Andrew T , Kweon Sun-Seog , Marchand Loic Le , Li Li , Cheng Iona , Pai Rish K. , Figueiredo Jane C. , Murphy Neil , Gunter Marc J. , Timpson Nicholas J. , Vincent Emma E.
Published: March 2023

Background

Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival.

Methods

To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years.

Results

The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk.

Conclusions

These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development.

Funding

This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol -http://www.bristol.ac.uk/acrc/.
Approaches to improving mental health care for autistic people: a systematic review
Authors: Loizou Sofia , Pemovska Tamara , Stefanidou Theodora , Foye Una , Cooper Ruth , Kular Ariana , Greenburgh Anna , Baldwin Helen , Griffiths Jessica , Saunders Katherine R. K. , Barnett Phoebe , Minchin Matilda , Brady Gráinne , Ahmed Nafiso , Parker Jennie , Chipp Beverley , Olive Rachel Rowan , Jackson Robin , Timmerman Amanda , Sapiets Suzi , Driskell Eva , Parsons Bethany , Spain Debbie , Totsika Vaso , Mandy Will , Pender Richard , Clery Philippa , Trevillion Kylee , Lloyd-Evans Brynmor , Simpson Alan , Johnson Sonia
Published: March 2023

Background

Autistic people have a high likelihood of developing mental health difficulties but a low chance of receiving effective mental health care. Therefore, there is a need to identify and examine strategies to improve mental health care for autistic people.

Aims

To identify strategies that have been implemented to improve access, experiences of care and mental health outcomes for autistic adults and examine evidence on their acceptability, feasibility and effectiveness.

Method

A co-produced systematic review was conducted. MEDLINE, PsycINFO, CINHAL, medRxiv and PsyArXiv were searched. We included all study designs reporting acceptability or feasibility outcomes and empirical quantitative study designs reporting effectiveness outcomes. Data were synthesised using a narrative approach.

Results

A total of 29 articles were identified. These included 16 studies of adapted mental health interventions, seven studies of service improvements and six studies of bespoke mental health interventions developed for autistic people. There was no conclusive evidence on effectiveness. However, most bespoke and adapted approaches appeared to be feasible and acceptable. Identified adaptations appeared to be acceptable and feasible, including increasing knowledge and detection of autism, providing environmental adjustments and communication accommodations, accommodating individual differences, and modifying the structure and content of interventions.

Conclusion

Many identified strategies are feasible and acceptable and can be readily implemented in services with the potential to make mental health care more suitable for autistic people, but important research gaps remain. Future research should address these and investigate a co-produced package of service improvement measures.
Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction
Authors: Sabogal-Guaqueta Angelica Maria , Marmolejo-Garza Alejandro , Lima Marina Trombetta , Oun Asmaa , Hunneman Jasmijn , Chen Tingting , Koistinaho Jari , Lehtonen Sarka , Kortholt Arjan , Bakker Barbara M. , Eggen Bart J.L. , Boddeke Erik , Dolga Amalia
Published: March 2023

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis, or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells and little is known about the metabolic reprogramming of human microglia. In this study, we investigated the transcriptomic and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We found that both species displayed a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming was characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides the first direct comparison of energy metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.
Off-axis representation of hyperbolic mirror shapes for X-ray beamlines
Authors: Goldberg Kenneth A. , Sanchez del Rio Manuel
Published: March 2023

Mirror-centered, closed-form expressions for hyperbolic surfaces used in X-ray beamlines have been derived. Hyperbolic mirrors create a virtual focus or source point and can be used to lengthen or shorten the effective focal distance of a compound optical system. The derivations here express off-axis segments of a hyperbolic surface in terms of the real and virtual focal distances and the incident glancing angle at the center of the mirror. Conventional mathematical expressions of hyperbolic shapes describe the surfaces in Cartesian or polar coordinates centered on an axis of symmetry, necessitating cumbersome rotation and translation to mirror-centered coordinates. The representation presented here, with zero slope and the origin at the central point, is most convenient for modeling, metrology, aberration correction, and general surface analysis of off-axis configurations. The direct derivation avoids the need for nested coordinate transforms. A series expansion provides a helpful approximation; the coefficients of the implicit equation are also provided.
Effects of electron-donating ability of binding sites on coordination number: the interactions of a cyclic Schiff base with copper ions
Authors: Ranaweera Samantha A. , Donnadieu Bruno , Henry William P. , White Mark G.
Published: March 2023

The stepwise addition of Cu2+ ions to the nonplanar cyclic Schiff base 5,9,14,18-tetramethyl-1,4,10,13-tetraazacyclooctadeca-5,8,14,17-tetraene-7,16-dione (H4daaden, C18H28N4O2), yields a one-end-open dinuclear copper chelate. The pyridine adduct of the dinuclear copper chelate, namely, [μ-6,11-dimethyl-7,10-diazahexadeca-5,11-diene-2,4,13,15-tetraolato(4−)](pyridine)dicopper(II), [Cu2(C16H20N2O4)(C5H5N)], was characterized by single-crystal X-ray crystallography. The two CuII atoms of the copper chelate display different coordination modes, i.e. inner-N2O2 and outer-O2O2. The Cu atom which is bonded in the outer-O2O2 mode is axially bonded to a pyridine molecule, which suggests that the electron-donating ability of the O2O2 site to the Cu atom is poor. As a result, the O2O2-bonded Cu atom has a coordination number of five, showing square-bipyramidal geometry around the Cu atom. The N2O2-coordinated site provides sufficient electron density to the other Cu atom to be stabilized with a coordination number of four, showing square-planar geometry around the Cu atom. The electron-donating ability of the ligand coordination sites plays a key role in determining the coordination number of the Cu atoms of the dicopper chelate.
Crystal structure, Hirshfeld surface analysis and DFT study of (5E,5′E,6Z,6′Z)-6,6′-[ethane-1,2-diylbis(azanylylidene)]bis{5-[2-(4-fluorophenyl)hydrazono]-3,3-dimethylcyclohexanone} 2.5-hydrate
Authors: Kurbanova Malahat Musrat , Faizi Md. Serajul Haque , Cinar Emine Berrin , Jamal Asif , Çemberci Mustafa , Sadigova Arzu , Askerov Rizvan , Dege Necmi , Nabi Tahera
Published: March 2023

The title compound, C30H34F2N6O2·2.5H2O, was obtained by condensation of 2-[2-(4-fluorophenyl)hydrazono]-5,5-dimethylcyclohexan-1,3-dione with ethylenediamine in ethanol and crystallized as a 1:2.5 hydrate in space group C2/c. The two independent molecules, with approximate crystallographic C
2 symmetries, have different conformations and packing environments, are stabilized by intramolecular N—H...N hydrogen bonds and linked by O—H...O hydrogen bonds involving the water molecules. A Hirshfeld surface analysis showed that H...H contacts make by far the largest (48–50%) contribution to the crystal packing. From DFT calculations, the LUMO–HOMO energy gap of the molecule is 0.827 eV.
Crystal structure and Hirshfeld surface analysis of 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one hemihydrate
Authors: Ismail Ahmad Zaidi , Gunasekharan Mohanapriya , Karunakaran Thiruventhan , Mohd Faudzi Siti Munirah
Published: March 2023

High-quality single crystals of the title compound, 2C13H11NO2·H2O, were grown and a structural analysis was performed. The asymmetric unit comprises one molecule of 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP), which was recently discovered to be a promising anti-MRSA candidate, and a half-molecule of water. The compound crystallizes in the monoclinic space group P2/c. The crystal structure features intermolecular pyrrole-N—H...O (water), carbonyl/keto-C—O...H—O-phenol and phenol-C—O...H (water) hydrogen bonds, which help to consolidate the crystal packing. A Hirshfeld surface analysis for the components in the asymmetric unit showed that H...H (40.9%) and H...C/C...H (32.4%) contacts make the largest contributions to the intermolecular interactions of 3HPPP. Considering the presence of water, in its vicinity H...O/O...H and H...C/C...H are the most significant contacts, contributing 48.7 and 29.8%, respectively.
Syntheses, crystal structures and thermal properties ofcatena-poly[cadmium(II)-di-μ-bromido-μ-pyridazine-κ2N1:N2] andcatena-poly[cadmium(II)-di-μ-iodido-μ-pyridazine-κ2N1:N2]
Authors: Näther Christian , Jess Inke
Published: March 2023

The reactions of cadmium bromide and cadmium iodide with pyridazine (C4H4N2) in ethanol under solvothermal conditions led to the formation of crystals of [CdBr2(pyridazine)]n(1) and [CdI2(pyridazine)]n(2), which were characterized by single-crystal X-ray diffraction. The asymmetric units of both compounds consist of a cadmium cation located on the intersection point of a twofold screw axis and a mirror plane (2/m), a halide anion that is located on a mirror plane and a pyridazine ligand, with all atoms occupying Wyckoff position 4e(mm2). These compounds are isotypic and consist of cadmium cations that are octahedrally coordinated by four halide anions and two pyridazine ligands and are linked into [100] chains by pairs of μ-1,1-bridging halide anions and bridging pyridazine ligands. In the crystals, the pyridazine ligands of neighboring chains are stacked onto each other, indicating π–π interactions. Larger amounts of pure samples can also be obtained by stirring at room-temperature, as proven by powder X-ray diffraction. Measurements using thermogravimetry and differential thermoanalysis (TG-DTA) reveal that upon heating all the pyridiazine ligands are removed in one step, which leads to the formation of CdBr2or CdI2.
Consistent zincophosphite 4-ring `ladder' chain structural motif with isomeric ligands
Authors: Wark Stephen , Lyons Megan J. , Slawin Alexandra M. Z. , Harrison William T. A.
Published: March 2023

The syntheses and crystal structures of four hydrothermally prepared organo–zinc phosphites, viz. poly[[(2-amino-3-methylpyridine)-μ3-phosphonato-zinc] hemihydrate], {[Zn(HPO3)(C6H8N2)]·0.5H2O}
n
, (I), poly[(2-amino-4-methylpyridine)-μ3-phosphonato-zinc], [Zn(HPO3)(C6H8N2)]
n
, (II), poly[(2-amino-5-methylpyridine)-μ3-phosphonato-zinc], [Zn(HPO3)(C6H8N2)]
n
, (III), and poly[bis(2-amino-4-methylpyridinium) [tetra-μ3-phosphonato-trizinc] monohydrate], {(C6H9N2)2[Zn3(HPO3)4]·H2O}
n
, (IV), are described. Compounds (I)–(III) are constructed from vertex-sharing ZnO3N tetrahedra (the organic molecule acting as a ligand) and HPO3 pseudo pyramids in a 1:1 ratio to generate the same motif of infinite 4-ring `ladder' chains propagating in the [010], [101] and [100] directions, respectively, whereas (IV) consists of (010) layers of vertex-sharing ZnO4 and HPO3 units in a 3:4 ratio with the protonated organic molecule acting as a template. When an excess of HCl is used in the synthesis, the simple hydrated molecular salt, bis(2-amino-3-methylpyridinium) tetrachlorozincate monohydrate, (C6H8N2)2[ZnCl4]·H2O, (V), arises. Compounds (I)–(V) feature extensive networks of hydrogen bonds, both classical (N—H...O, N—H...Cl, O—H...O) and non-classical (C—H...O, C—H...Cl) in nature, which help to consolidate the extended structures.
Synthesis and structure of 4-hydroxy-N-isopropyltryptamine (4-HO-NiPT) and its precursors
Authors: Laban Uroš , Naeem Marilyn , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: March 2023

The title compound, 4-hydroxy-N-isopropyltryptamine (4) or 4-HO-NiPT (systematic name: 3-{2-[(propan-2-yl)amino]ethyl}-1H-indol-4-ol), C13H18N2O, was synthesized in three steps from 4-benzyloxyindole (1) (systematic name: 4-phenoxy-1H-indole), C15H13NO. (1) was treated with oxalyl chloride and isopropylamine to produce N-isopropyl-4-benzyloxy-3-indoleglyoxylamide (2) {systematic name: 2-[4-(benzyloxy)-1H-indol-3-yl]-2-oxo-N-(propan-2-yl)acetamide}, C20H20N2O3. (2) was reduced to generate 4-benzyloxy-N-isopropyltryptamine (3) or 4-HO-NiPT, which was characterized as its chloride salt 4-benzyloxy-N-isopropyltryptammonium chloride (3a) (systematic name: {2-[4-(benzyloxy)-1H-indol-3-yl]ethyl}(propan-2-yl)azanium chloride), C20H25N2O·Cl. Finally the benzyl group of (3) was removed via hydrogenation to generate 4-HO-NiPT. The crystal structures of the title compound and all three synthetic precursors are presented.
Meloxicam hydrochloride
Authors: Flores Manuel Fermin , Sosa Rivadeneyra Martha , Bernès Sylvain
Published: March 2023

The title salt, C14H14N3O4S2
+·Cl− [systematic name: 2-(4-hydroxy-2-methyl-1,1-dioxo-1,2-benzothiazine-3-amido)-5-methyl-1,3-thiazol-3-ium chloride] is the hydrochloride derivative of meloxicam, a drug used to treat pain and inflammation in rheumatic disorders and osteoarthritis. Although its molecular structure is similar to that previously reported for the hydrobromide analogue, both salts are not isomorphous. Different crystal structures originate from a conformational modification, arising from a degree of rotational freedom for the thiazolium ring in the cations. By taking as a reference the conformation of meloxicam, the thiazolium ring is twisted by 10.96 and −16.70° in the hydrochloride and hydrobromide salts, while the 1,2-benzothiazine core is a rigid scaffold. This behaviour could explain why meloxicam is a polymorphous compound.
Intrinsic motivations affecting millennial mobile impulsive shopping in emerging markets during the COVID-19 pandemic
Authors: Lavuri Rambabu , Kaur Jaspreet , Thaichon Park
Published: March 2023

Purpose

This study examines intrinsic motivations and antecedents that affect millennial mobile impulsive shopping in markets with the technology acceptance model (TAM) during the COVID-19 pandemic.

Design/methodology/approach

The study has been conducted by collecting data from 367 regular mobile shopping millennials, which was analyzed by structural equation modeling.

Findings

The findings reported that the perceived ease of use correlates positively with perceived usefulness. Similarly, perceived ease of use, usefulness, perceived utilitarian value and hedonic value significantly impacts shoppers' trust and attitude toward impulsive mobile shopping. Perceived trust was found to exhibit a positive association with mobile shopping. Finally, perceived usefulness, ease of use, utilitarian value, hedonic value, trust and attitude significantly positively impacted millennials' impulsive mobile shopping.

Practical implications

This study's results will help e-retailers establish novel techniques and efforts to enhance market volume and build solid connections with mobile customers by ensuring secure purchase habits. The results would also help companies develop customer satisfaction-focused business strategies.

Originality/value

This study contributes to the body of literature by finding a significant impact of attitude, trust and shopping values on impulsive mobile shopping. These constructs have not been explored as factors impacting mobile impulsive shopping, especially when it comes to a pandemic.
Leadership development programmes: part of the solution or part of the problem of women’s under-representation in leadership?
Authors: Loumpourdi Maria
Published: March 2023

Purpose

This paper aims to critically reflect on current leadership development programmes (LDPs) and their potential in addressing the issue of women’s under-representation in leadership positions. To this end, this paper queries the current processes through which employees are selected to participate in LDPs as well as how these programmes are designed.

Design/methodology/approach

Drawing on Martha Nussbaum’s capabilities approach, this conceptual paper draws attention to the pitfalls of current organisational practices aimed at women’s leadership development.

Findings

The introduction of gender quotas and the implementation of women-only LDPs are unlikely to address the persistent gender leadership gap. Instead, these practices are likely to intensify the negative effects of second-generation gender bias and perpetuate the issue of gender inequality and inequity in the workplace.

Originality/value

This paper critiques contemporary organisational practices aimed at women’s leadership development and suggests alternative practices which are more likely to respond to the issue of women’s under-representation in leadership positions.
How to handle gerontocracy
Authors: Canoy Marcel , Krabbe Yvonne , Koolman Xander
Published: March 2023

Purpose

The article demonstrates the dangers of gerontocracy and offers solutions.

Design/methodology/approach

The article combines desk research, literature review and economic analytical reasoning.

Findings

Gerontocracy in developed countries is a threat to financial, labour market and political sustainability of care for older people. Without actions today, the problem will become bigger every year, not least because of increased electoral weight of older people. This article proposes to handle gerontocracy in two ways. First is by using the potential of healthy retired people as volunteers, thereby mitigating the intergenerational solidarity challenges. Second is by taxing part of the windfall profits on the housing market, where older generation profited disproportionally.

Originality/value

The added value of the article is twofold. First, it signals a serious problem in affluent societies that is largely ignored, both in the academic world and in politics. Second, it offers original solutions that mitigate the problem.
Why did people avoid information during the COVID-19 pandemic? Understanding information sources' dynamics among Pakistani Z generation
Authors: Soroya Saira Hanif , Faiola Anthony
Published: March 2023

Purpose

Grounded in the stressor-strain-outcome model, this study aims to examine the impact of different information sources on information behavior among the Pakistani Z generation during the pandemic.

Design/methodology/approach

The study was quantitative, with 344 responses collected from Gen Z (those born in the late 1990s) using an online survey. The proposed structural model was tested with the help of SmartPLS 3.3. Information sources were divided into four categories, i.e. conventional media, personal networks, social media and Internet use through official health websites.

Findings

In the Pakistani context, conventional media was found to develop information overload among Zers, whereas social media and personal networks were positively associated with information anxiety. However, Internet use (official and medical websites) for health-related information-seeking significantly reduced information anxiety among people. None of these information sources are the reason for information avoidance but the sources affect either the independent predictor of information avoidance or the mediators. Whereas information overload is a predictor of information anxiety and information, anxiety is a mediator between information overload and avoidance behavior.

Research limitations/implications

To avoid the negative consequences of abundant information, the authors need to promote and encourage the use of authentic information sources to make Gen Z skeptical, independent, critical and scientific thinkers.

Originality/value

Information sources' dynamics in terms of negative consequences of abundant information has not been explored previously at this magnitude, particularly from the perspective of a developing country.
Mental health and character strengths: the dual role of boosting well-being and reducing suffering
Authors: Niemiec Ryan M.
Published: March 2023

Purpose

This paper aims to examine how character strengths have an important dual role in mental health in both promoting well-being and mental wellness and also in reducing symptoms and suffering. While there are many studies that have touched upon variables that character strengths can enhance for mental well-being or reduce for suffering, the author actually knows very little about how character strengths might relate to or impact mental health.

Design/methodology/approach

A large-scale study of 12,050 individuals was conducted to explore the self-perceived character strengths that are most helpful for mental health, for handling physical adversity, for handling social adversity and for fostering psychological well-being.

Findings

Some character strengths showed a general effect – showing a strong perceived impact across multiple domains – such as love, perspective, kindness, hope, humor and curiosity. Other character strengths showed a specific effect in that there was a strong perceived impact in one domain, such as perseverance and self-regulation for physical health, spirituality and social intelligence for social health and creativity for mental health. A strength-based approach to understanding and managing emotions was substantially more preferred than cognitive or behavioral approaches. Other findings examined the character strengths most desired to be improved upon for mental health.

Research limitations/implications

The research strategy was cross-sectional, thereby causality cannot be determined. Because of the large sample size, researchers are encouraged to consider examining the findings in intervention studies.

Practical implications

This study indicates that character strengths are highly relevant for mental health, all 24 character strengths are possible pathways to impact mental health (some more than others) and individuals can readily connect ways they can use their character strengths to positively improve their well-being and manage their suffering.

Social implications

Character strengths and their substantial positive potential provide an avenue for public impact on a large scale.

Originality/value

To the best of the author’s knowledge, this is the first known study to directly examine multiple intersections among mental health and character strengths in a large sample.
The longevity response to warm temperature is neurally controlled via the regulation of collagen genes
Authors: Palani Sankara Naynar , Sellegounder Durai , Wibisono Phillip , Liu Yiyong
Published: March 2023

Studies in diverse species have associated higher temperatures with shorter lifespan and lower temperatures with longer lifespan. These inverse effects of temperature on longevity are traditionally explained using the rate of living theory, which posits that higher temperatures increase chemical reaction rates, thus speeding up the aging process. Recent studies have identified specific molecules and cells that affect the longevity response to temperature, indicating that this response is regulated, not simply thermodynamic. Here, we demonstrate that in Caenorhabditis elegans, functional loss of NPR‐8, a G protein‐coupled receptor related to mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C, and that the lifespan extension at 25°C is regulated by the NPR‐8‐expressing AWB and AWC chemosensory neurons as well as AFD thermosensory neurons. Integrative transcriptomic analyses revealed that both warm temperature and old age profoundly alter gene expression and that genes involved in the metabolic and biosynthetic processes increase expression at 25°C relative to 20°C, indicating elevated metabolism at warm temperature. These data demonstrate that the temperature‐induced longevity response is neurally regulated and also provide a partial molecular basis for the rate of living theory, suggesting that these two views are not mutually exclusive. Genetic manipulation and functional assays further uncovered that the NPR‐8‐dependent longevity response to warm temperature is achieved by regulating the expression of a subset of collagen genes. As increased collagen expression is a common feature of many lifespan‐extending interventions and enhanced stress resistance, collagen expression could be critical for healthy aging.
Description and shaping factors of diet and feeding ecology of neotropical tadpoles: A case study and a comprehensive review
Authors: Gonçalves Iara Matias , Kloh Jéssica Stephanie , Ruthsatz Katharina , Figueredo Cleber Cunha , Eterovick Paula Cabral
Published: March 2023

Tadpoles are important components of many aquatic food webs as they influence populations at other trophic levels and, ultimately, energy transfer between aquatic and terrestrial ecosystems. What tadpoles consume is a key factor to their ecological functions. Neotropical anuran assemblages include many species with a larval stage, however, the diets of neotropical tadpoles are relatively poorly known. We performed a systematic review on the available literature on in situ studies of neotropical tadpole diets and found out that most studies are descriptive and temporally restricted, failing to consider seasonal variations. Studies frequently also fail to consider possible ontogenetic dietary variations or tadpoles' capacity to select food based on what is available to them in their habitats. We contributed to this topic by investigating seasonal variations and comparing the diets of two developmental stages of Scinax curicica tadpoles. Tadpole diet varied between dry and rainy seasons, but not between the studied developmental stages. These results, together with published studies, suggest that multiple ecological/physiological factors are likely to influence tadpole food intake and should not be overlooked. Studies on neotropical tadpole feeding ecology, digestion capacity, physiological effects of different diets and microbiome versus diet interactions are highly desirable but largely unexplored. Such studies are likely to add valuable information to understand tadpole roles in aquatic food webs, their growth and development performance resulting from food acquisition and assimilation, and consequently their effects on other species in aquatic and terrestrial ecosystems.
Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men
Authors: Rudman Yaron , Duskin‐Bitan Hadar , Richter Ilan , Tsvetov Gloria , Masri‐Iraqi Hiba , Akirov Amit , Shimon Ilan
Published: March 2023

Background

Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration.

Methods

We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded.

Results

Sixty‐one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with “informative” HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow‐up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median “low‐HB duration” (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3–8.8 years). In symptomatic patients, we identified a correlation between “low‐HB duration” and patient‐reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The “low‐HB duration” was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01).

Conclusions

In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.