bluuebunny/crossref_metadata_2025 huggingface dataset:
Hip thrust and back squat training elicit similar gluteus muscle hypertrophy and transfer similarly to the deadlift
Authors: Plotkin Daniel L. , Rodas Merlina A. , Vigotsky Andrew D. , McIntosh Mason C. , Breeze Emma , Ubrik Rachel , Robitzsch Cole , Agyin-Birikorang Anthony , Mattingly Madison L. , Michel J. Max , Kontos Nicholas J. , Frugé Andrew D. , Wilburn Christopher M. , Weimar Wendi H. , Bashir Adil , Beyers Ronald J. , Henselmans Menno , Contreras Bret M. , Roberts Michael D.
Published: June 2023

Purpose

We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes.

Methods

Untrained college-aged participants were randomized into HT or SQ groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed nine weeks of supervised training (15–17 sessions), before and after which we assessed muscle cross-sectional area (mCSA) via magnetic resonance imaging and strength via three-repetition maximum (3RM) testing and an isometric wall push test.

Results

Glutei mCSA growth was similar across both groups. Estimates [(−) favors HT; (+) favors SQ] modestly favored the HT compared to SQ for lower [effect ± SE, −1.6 ± 2.1 cm2], mid [−0.5 ± 1.7 cm2], and upper [−0.5 ± 2.6 cm2], but with appreciable variance. Gluteus medius+minimus [−1.8 ± 1.5 cm2] and hamstrings [0.1 ± 0.6 cm2] mCSA demonstrated little to no growth with small differences between groups. Thigh mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm2] and adductors [2.5 ± 0.7 cm2]. Squat 3RM increases favored SQ [14 ± 2.5 kg] and hip thrust 3RM favored HT [−26 ± 5 kg]. 3RM deadlift [0 ± 2 kg] and wall push strength [−7 ± 13 N] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes.

Conclusion

Nine weeks of squat versus hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar strength transfers to the deadlift and wall push.
Site-specific acetylation of polynucleotide kinase 3’-phosphatase (PNKP) regulates its distinct role in DNA repair pathways
Authors: Islam Azharul , Chakraborty Anirban , Sarker Altaf H , Aryal Uma K , Sharma Gulshan , Boldogh Istvan , Hazra Tapas
Published: June 2023

Mammalian polynucleotide kinase 3’-phosphatase (PNKP) is a dual-function DNA end-processing enzyme with 3’-phosphatase and 5’-kinase activities, which generate 3’-OH and 5’-phosphate termini respectively, as substrates for DNA polymerase and DNA ligase to complete DNA repair. PNKP is thus involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes, which involve distinct sets of proteins. In this study, we report that PNKP is acetylated at two lysine (K142 and K226) residues. While K142 (AcK142) is constitutively acetylated by p300, CBP acetylates K226 (AcK226) only after DSB induction. Co-immunoprecipitation analysis using antibodies specific for PNKP peptides containing AcK142 or AcK226 of PNKP showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP only with DSBR proteins. Although acetylation at these residues did not significantly affect the enzymatic activity of PNKPin vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage, specifically in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington’s Disease (HD)-based mouse model, K142, but not K226, was acetylated. This observation is consistent with the reported degradation of CBP but not p300 in HD cells. Moreover, genomes of HD cells progressively accumulated DSBs specifically in the transcribed genes. Chromatin-immunoprecipitation analysis using anti-AcK142 or anti-AcK226 antibodies demonstrated an association of Ac-PNKP with the transcribed genes, consistent with PNKP’s role in transcription-coupled repair. Thus, our findings collectively demonstrate that acetylation at two lysine residues located in different domains of PNKP regulates its functionally distinct role in BER/SSBR vs. DSBR.
Lineage-specific intolerance to oncogenic drivers restricts histological transformation
Authors: Gardner Eric E. , Earlie Ethan M. , Li Kate , Thomas Jerin , Hubisz Melissa J. , Stein Benjamin D. , Zhang Chen , Cantley Lewis C. , Laughney Ashley M. , Varmus Harold
Published: June 2023

Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial cell types in the lung. Intriguingly, LUAD can histologically transform into SCLC following treatment with targeted therapies. Here we designed models to follow the conversion of LUAD to SCLC and found the barrier to histological transformation converges on tolerance to Myc, which we implicate as a lineage-specific driver of the pulmonary neuroendocrine cell. Histological transformations are frequently accompanied by activation of the Akt pathway. Manipulating this pathway permitted tolerance to Myc as an oncogenic driver, producing rare, stem-like cells, transcriptionally resembling the pulmonary basal lineage. These findings suggest histological transformation may require the plasticity inherent to the basal stem cell, enabling tolerance to previously incompatible oncogenic driver programs.

One-Sentence Summary

By modeling histological transformation of lung cancer, we uncover neuroendocrine-specific tolerance to Myc as an oncogenic driver.
A large-scale bioinformatic study of graspimiditides and structural characterization of albusimiditide
Authors: Choi Brian , Acuna Arthur , Koos Joseph D. , Link A. James
Published: June 2023

Graspetides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that exhibits an impressive diversity in patterns of side chain-to-side chain ω-ester or ω-amide linkages. Recent studies have uncovered a significant portion of graspetides to contain an additional post-translational modification involving aspartimidylation catalyzed by anO-methyltransferase, predominantly found in the genomes of Actinomycetota. Here, we present a comprehensive bioinformatic analysis focused on graspetides harboring aspartimide for which we propose the name graspimiditides. From Protein BLAST results of 5,000 methyltransferase sequences, we identified 962 unique putative graspimiditides, which we further classified into eight main clusters based on sequence similarity along with several smaller clusters and singletons. The previously studied graspimiditides, fuscimiditide and amycolimiditide, are identified in this analysis; fuscimiditide is a singleton while amycolimiditide is in the fifth largest cluster. Cluster 1, by far the largest cluster, contains 641 members, encoded almost exclusively in theStreptomycesgenus. To characterize an example of a graspimiditide in Cluster 1, we conducted experimental studies on the peptide fromStreptomyces albusJ1074, which we named albusimiditide. By tandem mass spectrometry, hydrazinolysis, and amino acid substitution experiments, we elucidated the structure of albusimiditide to be a large tetracyclic peptide with four ω-ester linkages generating a stem-loop structure with one aspartimide. The ester crosslinks form 22-, 46-, 22-, and 44-atom macrocycles, last of which, the loop, contains the enzymatically installed aspartimide. Furtherin vitroexperiments revealed that the aspartimide hydrolyzes in a 3:1 ratio of isoaspartate to aspartate residues. Overall, this study offers a comprehensive insight into the diversity and structural features of graspimiditides, paving the way for future investigations of this unique class of natural product.

Abstract Figure
In vivovisualization of intracellular pH gradient in brain using PET imaging
Authors: Yamasaki Tomoteru , Mori Wakana , Ohkubo Takayuki , Hiraishi Atsuto , Zhang Yiding , Kurihara Yusuke , Nengaki Nobuki , Tashima Hideaki , Fujinaga Masayuki , Zhang Ming-Rong
Published: June 2023

Intracellular pH (pHi) is a valuable index for predicting hypoxic brain damage. However, no positron emission tomography (PET) probe is currently available for monitoring pHiin vivo. In this study, we developed a new approach for visualizing monoacylglycerol lipase (MAGL) activity in the brain. This approach used PET with a new probe [11C]HC-A, an azetidine carbamate inhibitor, whose uptake and residence depended on the pHi gradient was evaluated within silico,in vitro, andin vivoassessments. Molecular dynamics simulations predicted that complex (complex-A) between HC-A and MAGL would be difficult to hydrolyze under acidic conditions.In vitroassessment using rat brain homogenate showed that [11C]HC-A reacted with MAGL to yield [11C]complex-A, which was rapidly hydrolyzed to liberate11CO2. The11CO2liberation rate was slower at lower pH. In PET with [11C]HC-A using ischemic rats, the radioactivity clearance rate, which reflects the production rate of11CO2in the brain, was lower in a remarkably hypoxic area than in the contralateral region. In conclusion, we successfully visualized the pHi gradient in the brain using PET imaging.
Review of spatial planning policy as an intervention for improving public health: protocol for a health-focused content review of local plans in England
Authors: Chang Michael , Carhart Neil
Published: June 2023

Introduction

Each local authority in England is required to create a statutory local plan that sets out their land use priorities as the basis of decision-making on urban development. Only recently has there been an explicit recognition the local plan is capable of being a legal determinant of and important public policy intervention in influencing population physical and mental health and wellbeing. But there is a lack of comprehensive understanding of whether and how local plans have integrated wider determinants of health. The objective of this research is to identify and understand the state of current local plans in relation to health by undertaking a census.

Methods and analysis

The review for England will involve a census of all local plans, and content and thematic analyses of a sample of local plans. This is subject to developing a review framework as the basis for gathering findings using a combination of query functions in PDF documents and data presentation in Excel, supported latterly by the computerassisted qualitative data analysis software, NVivo. The review framework will include a range of search parameters for identifying explicit health references across specified policy topics and wider determinants of health indicators as they relate to spatial planning based on an established evidence publication. A sampling strategy identifies inclusion and exclusion criteria to focus on local plans in England used in planning decision making. Results will be collected in qualitative and quantitative data formats. The results will be synthesised and discussed using a combination of qualitative data analytical strategies.

Ethics and dissemination

The review is desktop based using publicly available policy documents on local authority websites, so ethics approval is not required. The results of the review will be reported in journal articles and for policy makers to improve national and local policy development.
Single nucleotide variation catalogue from clinical isolates mapped on tertiary and quaternary structures of ESX-1 related proteins reveals critical regions as putative Mtb therapeutic targets
Authors: Tzfadia Oren , Siroy Axel , Vujkovic Alexandra , Gijsbers Abril , Snobre Jihad , Vargas Roger , Mulders Wim , Meehan Conor J. , Farhat Maha , Peters Peter J. , de Jong Bouke C. , Ravelli Raimond B.G.
Published: June 2023

Proteins encoded by the ESX-1 genes of interests are essential for full virulence in allMycobacterium tuberculosiscomplex (MTBc) lineages, the pathogens with the highest mortality worldwide. Identifying critical regions in these ESX-1 related proteins could provide preventive or therapeutic targets for MTB infection, the game changer needed for tuberculosis control. We analysed a compendium of whole genome sequences of clinical MTB isolates from all lineages from >32,000 patients and identified single nucleotide variations (SNV). When mutations corresponding to all nonsynonymous SNPs were mapped on the surface of known and AlphaFold-predicted ternary protein structures, fully conserved regions emerged. Some could be assigned to known quaternary structures, whereas others could be predicted to be involved in yet-to-be-discovered interactions. Some mutants had clonally expanded (found in >1% of the isolates): these were mostly located at the surface of globular domains, remote from known intra- and inter-molecular protein–protein interactions. Fully conserved intrinsically disordered regions (IDRs) of proteins were found, suggesting that these are crucial for the pathogenicity of the MTBc. Altogether, our findings provide an evolutionary structural perspective on MTB virulence and highlight fully conserved regions of proteins as attractive vaccine antigens and drug targets. Extending this approach to other pathogens can provide a novel critical resource for the development of innovative tools for pathogen control.
MX2 restricts HIV-1 and herpes simplex virus type 1 by forming cytoplasmic biomolecular condensates that mimic nuclear pore complexes
Authors: Moschonas George D. , Delhaye Louis , Cooreman Robin , Hüsers Franziska , Bhat Anayat , Sutter Delphine De , Parthoens Eef , Desmet Anne-Sophie , Maciejczuk Aleksandra , Grzesik Hanna , Lippens Saskia , Debyser Zeger , Sodeik Beate , Eyckerman Sven , Saelens Xavier
Published: June 2023

Human myxovirus resistance 2 (MX2) can potently restrict HIV-1 and herpesviruses at a post-entry step by a process that requires MX2 interaction with the capsids of these viruses. The involvement of other host cell factors in this process, however, remains poorly understood. Here, we mapped the proximity interactome of MX2 revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and -herpes simplex virus-1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region of MX2 and its dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates. Our results demonstrate that MX2 forms cytoplasmic condensates that act as nuclear pore decoys, which trap capsids and induce premature viral genome release, and thereby interfere with nuclear targeting of HIV-1 and HSV-1.
Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction
Authors: Zouaghi Yassine , Alpern Daniel , Gardeux Vincent , Russeil Julie , Deplancke Bart , Santoni Federico , Pitteloud Nelly , Messina Andrea
Published: June 2023

Gonadotropin-releasing hormone (GnRH) neurons play a crucial role in human reproduction and are associated with a spectrum of conditions. However, the underlying biological mechanisms remain elusive due to their small number and sparse distribution. We performed transcriptomic profiling of GnRH neurons during mouse embryonic development, revealing their molecular identity and gene expression dynamics. Our findings show that GnRH neurons undergo a profound transcriptional shift as they migrate from the nose to the brain and that distinct expression trajectories are associated with critical biological processes, including cell migration, neuronal projections, and synapse formation. Cell-to-cell communication analysis revealed timely and spatially restricted modulation of signaling pathways involving known molecules, such as Semaphorins and Plexins, and novel candidates, such as Neurexins and Endothelins. Using GWAS genes linked to human reproductive onset, we found a specific association with GnRH neuron trajectories rising in late developmental stages and involved in neuron maturation and connectivity. Finally, analysis of the genetic burden in a large cohort of patients with congenital GnRH deficiency revealed specific GnRH neuron trajectories with a significant mutation load compared to controls.

In conclusion, this study revealed the gene expression dynamics underlying GnRH neuron embryonic development and provides novel insights linking GnRH neuron biology to human reproduction.
The influence of diet on gut microbiome and body mass dynamics in a capital-breeding migratory bird
Authors: Jones Isabelle L , Marsh Kirsty J , Handby Tess , Hopkins K , Slezasek J , Bearhop Stuart , Harrison Xavier A
Published: June 2023

Gut-associated microbial communities are known to play a vital role in the health and fitness of their hosts. Though studies investigating the factors associated with among-individual variation in microbiome structure in wild animal species are increasing, knowledge of this variation at the individual level is scarce, despite the clear link between microbiome and nutritional status uncovered in humans and model organisms. Here, we combine detailed life history, foraging preference, and faecal microbiome data to investigate the relationship between diet, microbiome stability and rates of body mass gain in a migratory capital-breeding bird, the light-bellied Brent goose (Branta bernicla hrota). Our findings suggest that there is a significant relationship between foraging and the diversity, composition and stability of the faecal microbiome. We also suggest a link between foraging phenotype and the rates of mass gain during the spring staging of a capital breeder. This study offers rare insight into individual-level temporal dynamics of the gut microbiome of a wild host. Further work is needed to uncover the functional link between individual dietary choices, gut microbiome structure and stability, and the implications this has for the reproductive success of this capital breeder.
Tirzepatide inhibits tumor growth in mice with diet-induced obesity
Authors: Huang Linxuan , Zeng Jibin , Wang Ye , Pollak Michael
Published: June 2023

Tirzepatide, a drug used in management of type II diabetes, is an activator of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptors. Tirzepatide treatment leads to weight loss in murine models of obesity, and clinical trials have shown the drug can lead to weight loss up to ∼ 20% in overweight patients. Obesity has been shown to increase risk and/or to worsen prognosis of certain common cancers, including colon cancer, but the effect of tirzepatide on neoplasia has not been examined in detail. We studied the effects of this drug on the murine MC38 colon cancer model, which has previously shown to exhibit accelerated growth in hosts with diet-induced obesity. Tirzepatide did not cause tumor regression, but reduced tumor growth rates by ∼ 50%. This was associated with substantial reductions in food intake, and in circulating levels of insulin and leptin. Tirzepatide had no effect on MC38 cancer cell proliferationin vitro, and the effect of tirzepatide on tumor growthin vivocould be phenocopied in placebo treated mice simply by restricting food intake to the amount consumed mice receiving the drug. This provides evidence that the drug acts indirectly to inhibit tumor growth. Our findings raise the possibility that use of tirzepatide or similar agents may benefit patients with obesity-related cancers.
Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining cochlear hair cell survival
Authors: Wang Guangqin , Gu Yunpeng , Liu Zhiyong
Published: June 2023

Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly,Pou4f3-/-orGfi1-/-HCs form initially but then rapidly degenerate, whereasRbm24-/-HCs degenerate considerably later. However, the transcriptional cascades involving Pou4f3, Gfi1, and Rbm24 remains undescribed. Here, we demonstrate thatRbm24expression is completely repressed inPou4f3-/-HCs but unaltered inGfi1-/-HCs, and further that the expression of both POU4F3 and GFI1 is intact inRbm24-/-HCs. Moreover, by usingin vivomouse transgenic reporter assays, we identify threeRbm24enhancers to which POU4F3 binds. Lastly, throughin vivogenetic testing of whether Rbm24 restoration alleviates the degeneration ofPou4f3-/-HCs, we show that ectopic Rbm24 alone cannot preventPou4f3-/-HCs from degenerating. Collectively, our findings provide new molecular and genetic insights into how HC survival is regulated.
Ninein domains required for its localization, association with partners dynein and ensconsin, and microtubule organization
Authors: Tillery Marisa M. L. , Zheng Chunfeng , Zheng Yiming , Megraw Timothy L.
Published: June 2023

Ninein (Nin) is a microtubule (MT) anchor at the subdistal appendages of mother centrioles and the pericentriolar material (PCM) of centrosomes that also functions to organize microtubules at non-centrosomal microtubule-organizing centers (ncMTOCs). In humans, theNINgene is mutated in Seckel syndrome, an inherited developmental disorder. Here we dissect the protein domains involved in Nin’s localization and interactions with dynein and ensconsin (ens/MAP7) and show that the association with ens cooperatively regulates microtubule assembly inDrosophilafat body cells. We define domains of Nin responsible for its localization to the ncMTOC on the fat body cell nuclear surface, localization within the nucleus, and association with Dynein light intermediate chain (Dlic) and ens, respectively. We show that Nin’s association with ens synergistically regulates MT assembly. Together, these findings reveal novel features of Nin function and its regulation of a ncMTOC.
EARLY MATURITY 7modifies the circadian clock and photoperiod sensitivity in barley
Authors: Helmsorig Gesa , Walla Agatha , Rütjes Thea , Buchmann Gabriele , Schüller Rebekka , Hensel Götz , von Korff Maria
Published: June 2023

Breeding for variation in photoperiod response is crucial to adapt crop plants to novel environments. Plants measure changes in day length by the circadian clock, an endogenous timekeeper that allows plants to anticipate changes in diurnal and seasonal light-dark cycles. Here, we describe theearly maturity 7(eam7) mutation in barley, which interacts with natural variation atPHOTOPERIOD 1(Ppd-H1) to cause early flowering independent of the photoperiod. We identifyLIGHT-REGULATED WD 1 (LWD1)as a putative candidate to underly theeam7locus in barley as supported by genetic mapping and CRISPR-Cas9 generatedlwd1mutants. Mutations ineam7cause a significant phase advance and a misregulation of core clock and clock output genes under diurnal conditions. Early flowering correlated with an upregulation ofPpd-H1during the night and consequent induction of the florigenFLOWERING LOCUS T1under short days. We propose thatEAM7controls photoperiodic flowering in barley by controlling the light input into the clock and diurnal expression patterns of the major photoperiod response genePpd-H1.
African swine fever virus I196L is a virulence determinant and its deletant induces robust protection in Domestic pig
Authors: Fan Jiaqi , Zhu Rongnian , Li Nan , Yang Jinjin , Yue Huixian , Zhang Yanyan , Zhou Xintao , Ke Junnan , Wang Yu , Li Qixuan , Qi Yu , Miao Faming , Li Min , Chen Teng , Hu Rongliang
Published: June 2023

The worldwide pandemic of African swine fever virus (ASFV) has a profound impact on the global pig industry. ASFV is a complex multilayered structure and the functions of unknown genes are being revealed. Here we deleted I196L from virulent ASFV SY18 with different length and obtained two recombinant viruses. The replication efficiency of the two recombinant viruses were similar but significantly lower than parental SY18. The pigs all survived the two recombinant viruses with 106.0TCID50except one pig occurred sudden death and the suvived pigs all resisted the challenge without fever after intramuscularly injecting a lethal dose (102.0TCID50) of ASFV SY18. The recombinant viruses induced a strong anti-p54 humoral immune response. Meanwhile, the pigs also inevitably appeared moderate to high viremia throughout the observation period and presented a gradually downward trend. The results show that deleting I196L gene is a potential and effective vaccine that protects pigs from ASFV.

IMPORTANCE

The worldwide outbreak of African swine fever (ASF) cannot be effectively prevented due to no availably commercial vaccine. Many different types of vaccine candidates are researched and reported, which is a hopeful trend to develop safety and efficacy vaccine. Here we report on an unknown functional gene, I196L, which affects the virulence and replication of ASFV. When I196L was deleted from ASFV SY18, the recombinant virus decreased virulence and resisted the challenge of parental strain. This is a novel, effective, potential live attenuated vaccine (LAVs) for ASF.
Multi-omics analysis ofBacillus. subtilisspores formed at different environmental temperatures reveal differences at the morphological and molecular level
Authors: Huang Yixuan , Roseboom Winfried , Brul Stanley , Kramer Gertjan
Published: June 2023

Spore-forming bacteria play an essential role in the food industry and public health. Through sporulation, bacteria can withstand extreme environmental conditions that vegetative cells cannot survive. Although it is well established that the same environmental factors that affect the growth of vegetative cells also profoundly influence sporulation, the mechanisms of how growth conditions affect spore structure and function remain unknown. Prior research has shown that spores prepared at higher temperatures are more heat resistant than those prepared at lower temperatures. The present study examines, both at metabolomic and proteomic levels, the effect of different sporulation temperatures (25, 37 and 42°C) on the small molecule and protein composition of spores (strain PY79) of the model organismB. subtilis. Through differential harvesting times, spores of the same developmental stage were obtained for each temperature regime. The heat resistance, dipicolinic acid content, germination kinetics and spore morphology were assayed to compare spore properties. Metabolome and proteome analysis yielded unparalleled broad molecular detail of the spores formed at different environmental temperatures. Our findings indicate that peptidoglycan biosynthesis and 28 outer-layer proteins play a crucial role in the functional diversity of spores produced byB. subtilisunder varying temperatures.
Longitudinal development of thalamocortical functional connectivity in 22q11.2 deletion syndrome
Authors: Schleifer Charles H. , O’Hora Kathleen P. , Jalbrzikowski Maria , Bondy Elizabeth , Kushan-Wells Leila , Lin Amy , Uddin Lucina Q. , Bearden Carrie E.
Published: June 2023

Background

22q11.2 Deletion Syndrome (22qDel) is a genetic Copy Number Variant (CNV) that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youth at clinical high risk (CHR) for psychosis. Here, we use a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in 22qDel and typically developing (TD) controls.

Methods

TCC was calculated for nine functional networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) scans collected from n=65 22qDel participants (63.1% female) and n=69 demographically matched TD controls (49.3% female), ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Non-linear age trajectories were characterized with general additive mixed models (GAMMs).

Results

In 22qDel, TCC in the frontoparietal network increases until approximately age 13, while somatomotor and cingulo-opercular TCC decrease from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD controls. Somatomotor connectivity in 22qDel is significantly higher than TD in childhood, but lower in late adolescence. Frontoparietal TCC shows the opposite pattern.

Conclusions

22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than controls, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.
Catalytic bias and redox-driven inactivation of ancestral FeFe hydrogenases from group B2
Authors: Fasano Andrea , Bailly Aurore , Wozniak Jeremy , Fourmond Vincent , Léger Christophe
Published: June 2023

The biodiversity of hydrogenases, the enzymes that oxidize and produce H2, is only just beginning to be explored. Here we use direct electrochemistry to characterize two enzymes from a subgroup of ancestral FeFe hydrogenases, defined by the presence of three adjacent cysteine residues near the active site: the third FeFe hydrogenase fromClostridium pasteurianum(CpIII) and the second fromMegasphaera elsdenii(MeII). To examine the functional role of the unusual TSCCCP motif, which defines the group B2 and is replaced with TSCCP in group A hydrogenases, we also produced a CpIII variant where the supernumerary cysteine is deleted. CpIII and MeII inactivate under oxidative conditions in a manner that is distinct from all other previously characterized hydrogenases from group A. Our results suggest that the supernumerary cysteine allows the previously observed sulfide-independent formation of the Hinact state in these enzymes. We also evidence a second reversible, oxidative inactivation process. Because of their inactivation under oxidative conditions, these enzymes are inefficient H2oxidation catalysts, but their active site itself is not tuned to make them more active in one particular direction.
Fecal Virome of Southeastern Maned Sloth (Bradypus crinitus)
Authors: Coimbra Amanda , D’arc Mirela , Moreira Filipe Romero Rebello , Cosentino Matheus Augusto Calvano , Schiffler Francine Bittencourt , Miranda Thamiris dos Santos , Mouta Ricardo , Girardi Déa Luiza , Gomes de Matos Isabelle , Wanderkoke Victor , Medeiros Gabriel , Lima Monique , de Oliveira Thiago Henrique , Francisco Talitha Mayumi , Soffiati Flávio Landim , Ferreira Suelen Sanches , Ruiz-Miranda Carlos Ramon , Soares Marcelo Alves , Santos André Felipe Andrade dos
Published: June 2023

We report a viral metagenomic analysis of fecal samples fromBradypus crinitus, a recently described sloth species that occurs in the Atlantic Forest of Espírito Santo and Rio de Janeiro states, Southeast Brazil. Through Illumina sequencing, we generated a total of 2,065,344 raw reads, of which 945,386 reads (45.77%) passed the quality and size filter. The highest proportion of them was assigned to Eukarya, followed by Bacteria and only a small proportion to Virus. However, we identified 24 viral families using distinct taxonomic assignment tools, including phages and vertebrate viruses, such as retroviruses and papillomaviruses. Also, we identified four bacterial genus already associated with disease in sloths. Our study sheds light on the microbiome of a previously unexplored species, further contributing to the comprehension of metagenomic global diversity.
Photosynthetic acclimation mediates exponential growth of a desert plant in Death Valley summer
Authors: Prado Karine , Xue Bo , Johnson Jennifer E. , Field Sterling , Stata Matt , Hawkins Charles L. , Hsia Ru-Ching , Liu Hongbing , Cheng Shifeng , Rhee Seung Y.
Published: June 2023

Heat waves, now more frequent and longer due to climate change, devastate plant productivity. Although rare, thermophilic plants could hold keys to engineering heat resilience in crop plants.Tidestromia oblongifoliais a thermophilic flowering plant that thrives at temperatures above 45°C. When exposed to Death Valley summer conditions,T. oblongifoliaincreased its thermal optimum of photosynthesis within a day and accelerated growth within 10 days. The physiological changes were accompanied by morphological, anatomical, and gene expression changes revealed by a newly sequenced genome. In bundle sheath cells where Rubisco fixes CO2, mitochondria relocated to chloroplasts and novel, cup-shaped chloroplasts appeared. Understanding how this plant acclimates under heat may afford new ways of engineering heat tolerance in crop plants.

One-Sentence Summary

Tidestromia oblongifolia’s acclimation to Death Valley is accompanied by changes in gene expression, organellar dynamics, and photosynthesis.
Comparative genomics between Colombian clinical isolates of Monophasic VariantSalmonellaTyphimurium and international clonal lineages
Authors: Paloma Cuenca-Arias , Angeline Montaño Lucy , Catering Rodriguez Edna , Alejandro Ruiz-Moreno Héctor , Efraín Montilla-Escudero , Miguel Villarreal José , Magdalena Wiesner
Published: June 2023

In Colombia,SalmonellaTyphimurium monophasic variant (MVST) is the fourth serovar recovered in laboratory surveillance of acute diarrheal disease (ADD). Given its rapid worldwide dissemination, increasing multidrug-resistance, and the emergence of different endemic clones, it is considered an emerging public health problem. This study compared 21 Colombian clinical isolates and 27 MVST genomes from Europe, Asia, the United States, and Australia to know the gene pool and to define similarities with international clones. Eighty percent of the Colombian MVST isolates formed a lineage divided into 2 clones, while 4 genomes were associated with the European ST34 and USA lineages. These two Colombian clones emerged in relatively recent events, in which possible spread was established during 2011 and 2012, exhibiting a diversity of plasmids and prophages, adapting to the Colombian population after differentiation. These results are a clear example of the high plasticity of MVST, evidencing the need for active genomic surveillance to monitor the circulation of new clonal lineages.
Activation of Shh/Smo is sufficient to maintain oligodendrocyte precursor cells in an undifferentiated state but is not necessary for differentiation
Authors: Nocera Sonia , Marchena Miguel A. , Fernández-Gómez Beatriz , Laó Yolanda , Cordano Christian , Gómez-Torres Óscar , Luján Rafael , de Castro Fernando
Published: June 2023

Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2(control), Smofl/fl/NG2-CreERT2(loss of function) and SmoM2/NG2-CreERT2(gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (SAG or cyclopamine treatment respectively). To explore the effects of Shh/Smo on differentiation and myelination in vivo, we developed a highly quantifiable model by transplanting OPCs in the retina. We find that myelination is greatly enhanced upon cyclopamine treatment and hypothesize that Shh/Smo could promote OPC proliferation to subsequently inhibit differentiation. Consistent with this hypothesis, we find that the genetic activation of Smo significantly increased numbers of OPCs and decreased oligodendrocyte differentiation when we examined the corpus callosum during development and after cuprizone demyelination and remyelination. However, upon loss of function with the conditional ablation of Smo, myelination in the same scenarios are unchanged. Taken together, our present findings suggest that the Shh pathway is sufficient to maintain OPCs in an undifferentiated state, but is not necessary for myelination and remyelination.
The great divide: rhamnolipids mediate separation betweenP. aeruginosaandS. aureus
Authors: Bru Jean-Louis , Kasallis Summer , Chang Rendell , Zhuo Quantum , Nguyen Jacqueline , Pham Phillip , Warren Elizabeth , Whiteson Katrine , Høyland-Kroghsbo Nina Molin , Limoli Dominique H. , Siryaporn Albert
Published: June 2023

The coexistence of multiple bacterial species during infection can have significant impacts on pathogenesis.Pseudomonas aeruginosaandStaphylococcus aureusare opportunistic bacterial pathogens that can co-infect hosts and cause serious illness. The factors that dictate whether one species will outcompete the other or whether the two species can coexist are not fully understood. We investigated the role of surfactants in the interactions between these two species on a surface that enablesP. aeruginosato swarm. We found thatP. aeruginosaswarms are repelled by colonies of clinicalS. aureusisolates, creating physical separation between the two strains. This effect was abolished in mutants ofS. aureusthat were defective in the production of phenol-soluble modulins (PSMs), which form amyloid fibrils around wild-type colonies. We investigated the mechanism that establishes physical separation between the two species using the Imaging of Reflected Illuminated Structures (IRIS) method, which tracks the flow of the rhamnolipid surfactant layer produced byP. aeruginosa. We found that PSMs produced byS. aureusdeflected the rhamnolipid surfactant layer flow, which in turn, altered the direction ofP. aeruginosaswarms. These findings show that rhamnolipids mediate physical separation betweenP. aeruginosaandS. aureus, which enables these species to coexist in distinct microenvironments. Additionally, we found that aBacillus subtilissurfactant and abiotic hydrophobic molecules repelledP. aeruginosaswarms through surfactant deflection. Our results suggest that surfactant interactions could have major impacts on bacteria-bacteria and bacteria-host relationships. In addition, our findings uncover a mechanism responsible forP. aeruginosaswarm development that does not rely on sensing but instead is guided largely by the flow of the surfactant layer and its boundaries.
Rarefaction is currently the best approach to control for uneven sequencing effort in amplicon sequence analyses
Authors: Schloss Patrick D.
Published: June 2023

Considering it is common to find as much as 100-fold variation in the number of 16S rRNA gene sequences found across samples in a study, researchers need to control for the effect of uneven sequencing effort. How to do this has become a contentious question. Some have argued that rarefying or rarefaction is “inadmissible” because it omits valid data. A number of alternative approaches have been developed to normalize and rescale the data that purport to be invariant to the number of observations. I generated community distributions based on 12 published datasets where I was able to assess the ability of multiple methods to control for uneven sequencing effort. Rarefaction was the only method that could control for variation in uneven sequencing effort when measuring commonly used alpha and beta diversity metrics. Next, I compared the false detection rate and power to detect true differences between simulated communities with a known effect size using various alpha and beta diversity metrics. Although all methods of controlling for uneven sequencing effort had an acceptable false detection rate when samples were randomly assigned to two treatment groups, rarefaction was consistently able to control for differences in sequencing effort when sequencing depth was confounded with treatment group. Finally, the statistical power to detect differences in alpha and beta diversity metrics was consistently the highest when using rarefaction. These simulations underscore the importance of using rarefaction to normalize the number of sequences across samples in amplicon sequencing analyses.

Importance

Sequencing 16S rRNA gene fragments has become a fundamental tool for understanding the diversity of microbial communities and the factors that affect their diversity. Due to technical challenges, it is common to observe wide variation in the number of sequences that are collected from different samples within the same study. However, the diversity metrics used by microbial ecologists are sensitive to differences in sequencing effort. Therefore, tools are needed to control for the uneven levels of sequencing. This simulation-based analysis shows that despite a longstanding controversy, rarefaction is the most robust approach to control for uneven sequencing effort. The controversy started because of confusion over the definition of rarefaction and violation of assumptions that are made by methods that have been borrowed from other fields. Microbial ecologists should use rarefaction.
Do board gender diversity and remuneration impact earnings quality? Evidence from Spanish firms
Authors: Saona Paolo , Muro Laura , San Martín Pablo , McWay Ryan
Published: June 2023

Purpose

This study aims to investigate how gender diversity and remuneration of boards of directors’ influence earnings quality for Spanish-listed firms.

Design/methodology/approach

The sample includes 105 nonfinancial Spanish firms from 2013 to 2018, corresponding to an unbalanced panel of 491 firm-year observations. The primary empirical method uses a Tobit semiparametric estimator with firm- and industry-level fixed effects and an innovative set of measures for earnings quality developed by StarMine.

Findings

Results exhibit a positive correlation between increased gender diversity and a firm’s earnings quality, suggesting that a gender-balanced board of directors is associated with more transparent financial reporting and informative earnings. We also find a nonmonotonic, concave relationship between board remuneration and earnings quality. This indicates that beyond a certain point, excessive board compensation leads to more opportunistic manipulation of financial reporting with subsequent degradation of earnings quality.

Research limitations/implications

This study only covers nonfinancial Spanish listed firms and is silent about how alternative board features’ influence earnings quality and their informativeness.

Originality/value

This study introduces measures of earnings quality developed by StarMine that have not been used in the empirical literature before as well as measures of board gender diversity applied to a suitable Tobit semiparametric estimator for fixed effects that improves the precision of results. In addition, while most of the literature focuses on Anglo-Saxon countries, this study discusses board gender diversity and board remuneration in the underexplored context of Spain. Moreover, the hand-collected data set comprising financial reports provides previously untested board features as well as a nonlinear relationship between remuneration and earnings quality that has not been thoroughly discussed before.
Credit access and intensity of borrowing by irrigated rice farmers in Ghana: the role of extension services
Authors: Kyire Samuel Kwabena Chaa , Bannor Richard Kwasi , Kuwornu John K.M. , Oppong-Kyeremeh Helena
Published: June 2023

Purpose

Credit is essential in the farm business because it facilitates the adoption of productive technologies such as irrigation. However, access to credit remains a significant hurdle for sub-Saharan Africa, including Ghanaian farmers. Therefore, the authors assessed credit utilization and the intensity of borrowing by irrigated rice farmers in the Upper East region. In addition, how extension moderates the amount borrowed was analysed.

Design/methodology/approach

The multistage sampling approach was used in the study. The Tono and Vea irrigation schemes were purposively selected. Proportionally, 318 rice farmers were sampled from the Tono irrigation scheme and 159 from the Vea irrigation scheme. Cragg's double hurdle and moderation analysis were used.

Findings

It was uncovered that gender, age, years of farming, total farm size, rice farm size, contract farming and off-farm employment explain farmers' decision to borrow. On the other hand, the intensity of borrowing was influenced by gender, age, years of farming, rice farm size, contract farming and the number of extension contact. The moderation analysis revealed that extension contact improves the amount borrowed by farmers.

Research limitations/implications

While there are irrigated rice farmers in other regions of Ghana, this study was limited to rice farmers under the Tono and Vea Irrigation schemes in the Upper East region.

Originality/value

This study investigated the moderating role of extension contact on amount borrowed in Ghana. This makes a modest addition to the limited literature on the moderating role of extension and credit access.
A Juggler's manifesto: elevating creativity to stay productive amid uncertainty
Authors: Enstroem Rickard , Schmaltz Rodney
Published: June 2023

Purpose

The Industry 4.0 environment is characterized by fast data, vertically and horizontally interconnected systems, and human–machine interfaces. In the middle stands the manager, whose sustained performance is critical to the organization's success. Business disturbances—such as supply chain disruptions during the pandemic—can quickly test the manager's resiliency. While creativity and flexibility are critical for success in these situations, these skills are often not promoted directly. This paper will discuss strategies for enhancing managers' creativity and resiliency and give suggestions for improving professional development training and post-secondary business education.

Design/methodology/approach

A synthesis of the literature in business and psychology provides a foundation for creating a conceptual model incorporating strategies to promote managerial creativity and resiliency. While the model focuses on managerial performance under adverse conditions, the tenets of the model also apply during times of relative stability.

Findings

Findings based on a synthesis of the literature on creativity in business and psychology provide the foundation for a conceptual model to identify potential elements in training and curriculum design to further managers' creativity and resiliency. This model recommends clear, actionable training and program-level curriculum design suggestions for improved managerial performance.

Originality/value

This paper identifies a conceptual model to enhance managerial creativity leading to increased resiliency through professional development programs and suggestions for educators in post-secondary business education. This model provides tools for managers to deal with adverse and rapidly changing conditions flexibly, promoting employee productivity and satisfaction.