bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of psychological interventions for anxiety in the perinatal period: A systematic review and meta-analysis
Authors: Clinkscales Natalie , Golds Lisa , Berlouis Katherine , MacBeth Angus
Published: January 2022

Background

Anxiety disorders are a relatively common occurring mental health issue during pregnancy and the perinatal period. There is evidence that untreated perinatal anxiety is a risk factor for adverse outcomes for mother and infant. Despite their potential acceptability to users, psychological interventions research for this population is still in its infancy. This systematic review and meta-analysis aimed to comprehensively evaluate the evidence of the effectiveness of psychological interventions for reducing perinatal anxiety.

Method

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched included EMBASE, MEDLINE, PsychINFO, MIDIRS, CINAHL and the Cochrane Library. Search terms included: Psychological Therapy, Perinatal Period, Antenatal, Postnatal, Anxiety, Obsessive Compulsive Disorder and Phobia.

Results

The search strategy identified 2,025 studies. A total of 21 studies published between 2004 and 2021 fulfilled inclusion criteria. Of those, 17 were included in the meta-analysis. Overall results indicated that psychological interventions were more effective than control conditions in reducing symptoms of perinatal anxiety with a medium post treatment effect size. Significant effect sizes were also identified for online, face-to-face, group and guided self-help treatment modalities.

Limitations

A small sample of studies are represented and limited to articles published in English. The review was unable to draw specific conclusions about what works (i.e. therapeutic modality/delivery) for whom (i.e. specific diagnoses) due to purposefully broad inclusion criteria. The longer-term effects of psychological interventions for perinatal anxiety and infant outcomes could not be established.

Conclusions

This review demonstrates that psychological interventions are effective in reducing symptoms of both anxiety and comorbid anxiety and depression in the antenatal and postnatal periods. The results also demonstrate the efficacy of delivering such interventions in multiple settings, including online, and in group format. Further research is required to optimise treatment delivery to individual needs.
Students as Community Vaccinators: Implementation of a Service-Learning COVID-19 Vaccination Program
Authors: Griswold Andrew R. , Klein Julia , Dusaj Neville , Zhu Jeff , Keeler Allegra , Abramson Erika L. , Gurvitch Dana
Published: January 2022

Background

Service-learning is an integral component of medical education. While the COVID-19 pandemic has caused massive educational disruptions, it has also catalyzed innovation in service-learning as real-time responses to pandemic-related problems. For example, the limited number of qualified providers was a potential barrier to local and national SARS-CoV-2 vaccination efforts. Foreseeing this hurdle, New York State temporarily allowed healthcare professional trainees to vaccinate, enabling medical students to support an overwhelmed healthcare system and contribute to the community. Yet, it was the responsibility of medical schools to interpret these rules and implement the vaccination programs. Here the authors describe a service-learning vaccination program directed towards underserved communities.

Methods

Weill Cornell Medicine (WCM) rapidly developed a faculty-led curriculum to prepare students to communicate with patients about the COVID-19 vaccines and to administer intramuscular injections. Qualified students were deployed to public vaccination clinics located in underserved neighborhoods across New York City in collaboration with an established community partner. The educational value of the program was evaluated with retrospective survey.

Results

Throughout the program, which lasted from February to June 2021, 128 WCM students worked at 103 local events, helping to administer 26,889 vaccine doses. Analysis of student evaluations revealed this program taught fundamental clinical skills, increasing comfort giving intramuscular injection from 2% to 100% and increasing comfort talking to patients about the COVID-19 vaccine from 30% to 100%. Qualitatively participants described the program as a transformative service-learning experience.

Conclusion

As new virus variants emerge, nations battle recurrent waves of infection, and vaccine eligibility expands to include children and boosters, the need for effective vaccination plans continues to grow. The program described here offers a novel framework that academic medical centers could adapt to increase vaccine access in their local community and provide students with a uniquely meaningful educational experience.
The C-terminal domain of SEC-10 is fundamental for exocyst function, Spitzenkörper organization and cell morphogenesis in Neurospora crassa
Authors: Figueroa-Meléndez Alfredo , Martínez-Núñez Leonora , Rico-Ramírez Adriana M. , Martínez-Andrade Juan M. , Munson Mary , Riquelme Meritxell
Published: January 2022

The exocyst is a conserved multimeric complex that participates in the final steps of the secretion of vesicles. In the filamentous fungus Neurospora crassa, the exocyst is crucial for polar growth, morphology, and the organization of the Spitzenkörper (Spk), the apical body where secretory vesicles accumulate before being delivered to the plasma membrane. In the highly polarized cells of N. crassa, the exocyst subunits SEC-3, SEC-5, SEC-6, SEC-8, and SEC-15 were previously found localized at the plasma membrane of the cells’ apices, while EXO-70 and EXO-84 occupied the frontal outer layer of the Spk, occupied by vesicles. The localization of SEC-10 had remained so far elusive. In this work, SEC-10 was tagged with the green fluorescent protein (GFP) either at its N- or C-terminus and found localized at the plasma membrane of growing hyphal tips, similar to what was previously observed for some exocyst subunits. While expression of an N-terminally tagged version of SEC-10 at its native locus was fully viable, expression of a C-terminally tagged version at its native locus resulted in severe hyphal growth and polarity defects. Additionally, a sec-10 knockout mutant in a heterokaryotic state (with genetically different nuclei) was viable but showed a strongly aberrant phenotype, confirming that this subunit is essential to maintain hyphal morphogenesis. Transmission electron microscopy analysis revealed the lack of a Spk in the SEC-10-GFP strain, suggesting a critical role of the exocyst in the vesicular organization at the Spk. Mass spectrometry analysis revealed fewer peptides of exocyst subunits interacting with SEC-10-GFP than with GFP-SEC-10, suggesting an essential role of the C-terminus of SEC-10 in exocyst assembly and/or stability. Altogether, our data suggest that an unobstructed C-terminus of SEC-10 is indispensable for the exocyst complex function and that a GFP tag could be blocking important subunit-subunit interactions.
Red harvester ant (Order: Hymenoptera) preference for cover crop seeds in South Texas
Authors: Elliott Lilly , Rivera Daniella , Noval Adrian , Choudhury Robin A. , Penn Hannah J.
Published: January 2022

Harvester ants are known to selectively forage seeds, potentially impacting nearby plant community composition. In agricultural areas, harvester ants may be viewed as pests by foraging on crop seeds or as beneficials by preferentially removing weed seeds. However, little work has been done on harvester ant preferences for cover crop seeds. Local observations suggest that ants may take cover crop seeds, but no studies have evaluated ant agricultural impacts or seed preferences in the Lower Rio Grande Valley (LRGV). We examined red harvester ant (Pogonomyrmex barbatus Smith) preferences for commonly used cover crop seeds in the LRGV (vetch, oat, fescue, sunn hemp, and radish with wheatgrass as a control) and a commonly used bacterial seed inoculation treatment meant to increase root nodulation. We tested seed sets using choice tests housed in seed depots located within the foraging range of ant colonies with no prior exposure to the selected seeds. Of the evaluated cover crop seeds, wheatgrass and oat were the first to be removed entirely from the depot, with vetch remaining after 24 h. When we inoculated the two most preferred seeds to determine if there was a preference for non-inoculated seeds, we found no difference between inoculated and non-inoculated seeds. There were also significant changes in activity over time for both trials. These data indicate that harvester ant foraging preferences and activity can inform grower management recommendations regarding the risks of using certain cover crops and months sowing should be conducted in fields with known harvester ant presence.
Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant
Authors: Mould Dallas L. , Stevanovic Mirjana , Ashare Alix , Schultz Daniel , Hogan Deborah A
Published: January 2022

Microbes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation explain the frequent presence of lasR loss-of-function mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR- derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR- lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR- lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR- cells in a CbrB-controlled manner. We propose that in vivo metabolomes are a major driver of pathogen evolution, which may influence the progression of disease and its treatment.
Limb Specific Failure of Proliferation and Translation in the Mesenchyme Leads to Skeletal Defects in Diamond Blackfan Anemia
Authors: Hom Jimmy , Karnavas Theodoros , Hartman Emily , Papoin Julien , Tang Yuefeng , Dulmovits Brian M. , Khan Mushran , Patel Hiren , Bondy Jedediah , Edelman Morris , Touraine Renaud , Chanoz-Poulard Geneviève , Ottenberg Gregory , Maynard Robert , Adams Douglas J. , Robledo Raymond F. , Grande Daniel A , Marambaud Philippe , Barnes Betsy J , Durand Sébastien , Narla Anupama , Ellis Steven , Zon Leonard I. , Peters Luanne L. , Da Costa Lydie , Lipton Jeffrey M. , Ackert-Bicknell Cheryl L. , Blanc Lionel
Published: January 2022

Abstract

Ribosomopathies are a class of disorders caused by defects in the structure or function of the ribosome and characterized by tissue-specific abnormalities. Diamond Blackfan anemia (DBA) arises from different mutations, predominantly in genes encoding ribosomal proteins (RPs). Apart from the anemia, skeletal defects are among the most common anomalies observed in patients with DBA, but they are virtually restricted to radial ray and other upper limb defects. What leads to these site-specific skeletal defects in DBA remains a mystery. Using a novel mouse model for RP haploinsufficiency, we observed specific, differential defects of the limbs. Using complementary in vitro and in vivo approaches, we demonstrate that reduced WNT signaling and subsequent increased β-catenin degradation in concert with increased expression of p53 contribute to mesenchymal lineage failure. We observed differential defects in the proliferation and differentiation of mesenchymal stem cells (MSCs) from the forelimb versus the hind limbs of the RP haploinsufficient mice that persisted after birth and were partially rescued by allelic reduction of Trp53. These defects are associated with a global decrease in protein translation in RP haploinsufficient MSCs, with the effect more pronounced in cells isolated from the forelimbs. Together these results demonstrate translational differences inherent to the MSC, explaining the site-specific skeletal defects observed in DBA.
Structure of theLysinibacillus sphaericusTpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX
Authors: Williamson Lainey J. , Galchenkova Marina , Best Hannah L. , Bean Richard J. , Munke Anna , Awel Salah , Pena Gisel , Knoska Juraj , Schubert Robin , Doerner Katerina , Park Hyun-Woo , Bideshi Dennis K. , Henkel Alessandra , Kremling Viviane , Klopprogge Bjarne , Lloyd-Evans Emyr , Young Mark , Valerio Joana , Kloos Marco , Sikorski Marcin , Mills Grant , Bielecki Johan , Kirkwood Henry , Kim Chan , de Wijn Raphael , Lorenzen Kristina , Xavier P. Lourdu , Rahmani Aida , Gelisio Luca , Yefanov Oleksandr , Mancuso Adrian P. , Federici Brian , Chapman Henry N. , Crickmore Neil , Rizkallah Pierre J. , Berry Colin , Oberthür Dominik
Published: January 2022

Tpp49Aa1 fromLysinibacillus sphaericusis a Toxin_10 family protein that – in combination with Cry48Aa1, a 3-domain crystal protein - has potent mosquitocidal activity, specifically againstCulex quinquefasciatusmosquitoes. MHz serial femtosecond crystallography at a nano-focused X-ray free electron laser, allowed rapid and high-quality data collection to determine the Tpp49Aa1 structure at 1.62 Å resolution from native nanocrystals. This revealed the packing of Tpp49Aa1 within these nanocrystals, isolated from sporulated bacteria, as a homodimer with a large intermolecular interface, shedding light on natural crystallization. Complementary experiments conducted at varied pH also enabled investigations of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals. Using modelling, we propose a potential interaction between Tpp49Aa1 and Cry48Aa1 that may play a role in their codependency and broaden our understanding of this two-component system. We expand the known target range, demonstrating Tpp49Aa1/Cry48Aa1 susceptibility of larvae fromAnopheles stephensi, Aedes albopictusandCulex tarsalis– substantially increasing the potential use of this toxin pair in mosquito control. Further functional insights are gained usingCulexcell lines to characterise cellular models for future investigations into Cry48Aa1/Tpp49Aa1 mechanism of action and to demonstrate transient detrimental effects of individual toxin components.

Significance Statement

The Tpp49Aa1/Cry48Aa1 protein pair kills mosquito larvae. Innovative use of nano-focused X-ray free electron laser to match the size of natural Tpp49Aa1 nanocrystals and the highest beam intensity available in any XFEL for high-throughput data collection, allowed structural resolution to 1.62 Å.

Tpp proteins show a range of interactions with different partners to elicit toxicity. To gain insight into Tpp49Aa1, its interaction with Cry48Aa1 was modelled. We also establish cell-based assays of Tpp49Aa1/Cry48Aa1 activity.

We expand the known target range to include three more mosquito species:Anopheles stephensi, Aedes albopictusandCulex tarsalis. This study will underpin future Tpp mode of action investigations and aid insecticide optimization against mosquito vectors of emerging diseases such as West Nile Virus and malaria.
Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation
Authors: Stieger Kevin C. , Eles James R. , Ludwig Kip A. , Kozai Takashi D.Y.
Published: January 2022

Background

Neural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz).

Objective

We hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent.

Methods

We quantified how asymmetric stimulation waveforms delivered at 10 Hz or 100 Hz for 30s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the leading phase to the return phase of charge-balanced cathodal- and anodal-first waveforms.

Results

Neurons within 40-60μm of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20-90 % of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity increased over time for some waveforms at 10 Hz, but decreased more at 100 Hz than other waveforms.

Conclusion

These data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.
FRaeppli, a multispectral imaging toolbox for cell tracing and dense tissue analysis in zebrafish
Authors: Caviglia Sara , Unterweger Iris A. , Gasiūnaitė Akvilė , Vanoosthuyse Alexandre E. , Cutrale Francesco , Trinh Le A. , Fraser Scott E. , Neuhauss Stephan C. F. , Ober Elke A.
Published: January 2022

Visualizing cell shapes, interactions and lineages of differentiating cells is instrumental for understanding organ development and repair. Across species, strategies for stochastic multicolour labelling have greatly facilitated tracking cells in in vivo and mapping neuronal connectivity. Nevertheless, integrating multi-fluorophore information into the context of developing tissues in zebrafish is challenging given their cytoplasmic localization and spectral incompatibility with commonly used fluorescent markers. Here, we developed FRaeppli (Fish-Raeppli) expressing bright membrane-or nuclear-targeted fluorescent proteins for efficient cell shape analysis and tracking. High spatiotemporal activation flexibility is provided by the Gal4/UAS system together with Cre/lox and/or PhiC31integrase. The distinct spectra of the FRaeppli fluorescent proteins allow simultaneous imaging with GFP and infrared subcellular reporters or tissue landmarks. By tailoring hyperspectral protocols for time-efficient acquisition, we demonstrate FRaeppli’s suitability for live imaging of complex internal organs, like the liver. Combining FRaeppli with polarity markers revealed previously unknown canalicular topologies between differentiating hepatocytes, reminiscent of the mammalian liver, suggesting shared developmental mechanisms. The multispectral FRaeppli toolbox thus enables the comprehensive analysis of intricate cellular morphologies, topologies and tissue lineages at single-cell resolution in zebrafish.
SLiMAn: an integrative web server for exploring short linear motif-mediated interactions in interactomes
Authors: Reys Victor , Labesse Gilles
Published: January 2022

Cells express thousands of macromolecules, and their functioning relies on multiple networks of intermolecular interactions. These interactions can be experimentally determine at different spatial and temporal resolutions. But, physical interfaces are not often delineated directly especially in high-throughput experiments. However, numerous three-dimensional structures of complexes have been already solved and sequence conservation allows comparative modeling of additional complexes. A large fraction of protein-protein interactions involves domain and so-called SLiMs (for Short Linear Motifs). Often, SLiMs lie in disordered regions or loops. Their small size and loosely folded nature prevent straightforward detection. SLiMAn (Short Linear Motif Analysis), a new web server is provided to help thorough analysis of interactomics data. Starting from a list of putative interactants such as the output of an interactomics study, SLiMs (from ELM) and SLiM-recognition domains (from Pfam) are extracted and potential pairing are displayed. Additionally, filters are available to dig into the predicted results such as the motif E-value, IUpred2 scoring functions for disorder or BioGRID interaction matches. When structural templates are available, a given SLiM and its recognition domain can be modeled using SCWRL. We illustrate, here, the use of SLiMAn on three distinct examples including one real-case study. We oversee wide-range applications for SLiMAn in the context of massive analysis of protein-protein interactions at proteome-wide scale. This new web server is made freely available at http://sliman.cbs.cnrs.fr.
Mechanisms of A-type lamin targeting to nuclear ruptures are disrupted in LMNA- and BANF1-associated progerias
Authors: Sears Rhiannon M. , Roux Kyle J.
Published: January 2022

Mutations in the genes LMNA and BANF1 can lead to accelerated aging syndromes called progeria. The protein products of these genes, A-type lamins and BAF, respectively, are nuclear envelope (NE) proteins that interact and participate in various cellular processes, including nuclear envelope rupture and repair. BAF localizes to sites of nuclear rupture and recruits NE-repair machinery, including the LEM-domain proteins, ESCRT-III complex, A-type lamins, and membranes. Here, we show that it is a mobile, nucleoplasmic population of A-type lamins that is rapidly recruited to ruptures in a BAF-dependent manner via BAF’s association with the Ig-like β fold domain of A-type lamins. These initially mobile lamins become progressively stabilized at the site of rupture. Farnesylated prelamin A and lamin B1 fail to localize to nuclear ruptures, unless that farnesylation is inhibited. Progeria-associated LMNA mutations inhibit the recruitment affected A-type lamin to nuclear ruptures, due to either permanent farnesylation or inhibition of BAF binding. A progeria-associated BAF mutant targets to nuclear ruptures but is unable to recruit A-type lamins. Together, these data reveal the mechanisms that determine how lamins respond to nuclear ruptures and how progeric mutations of LMNA and BANF1 impair recruitment of A-type lamins to nuclear ruptures.
Assessing the global impact of targeted conservation actions on species abundance
Authors: Jellesmark Sean , Blackburn Tim M. , Dove Shawn , Geldmann Jonas , Visconti Piero , Gregory Richard D. , McRae Louise , Hoffmann Mike
Published: January 2022

In recent years, vertebrate population abundance has declined at unprecedented rates (WWF 2020). In response, targeted conservation measures – such as breeding programs or species-specific habitat management – have been applied to halt population declines, aid population recovery, and reduce and reverse the loss of biodiversity (Salafsky et al. 2008; Bolam et al. 2020). Until now, assessments of conservation actions have focused on the extent to which they reduce extinction risk, impact populations within protected areas, or increase the global area of land under protection (Hoffmann et al. 2010, 2015; Barnes et al. 2016; Maxwell et al. 2020; Bolam et al. 2020; Grace et al. 2021a). Here, we record and analyze conservation actions for 26,904 vertebrate populations from 4,629 species, to measure the impact of targeted conservation on vertebrate abundance. Using a counterfactual approach to represent population trends in the absence of conservation, we demonstrate that targeted actions have delivered substantial positive effects on the abundance of recipient vertebrate populations worldwide. We show that, in the absence of conservation, a global indicator of vertebrate abundance would have declined even more. Positive population trends were associated with vertebrate populations subject to species or habitat management. We demonstrate that targeted conservation actions can help to reverse global biodiversity loss and show the value of counterfactual analysis for impact evaluation – an important step towards reversing biodiversity declines.
Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP- 2ε in vomeronasal sensory neurons
Authors: Lin Jennifer M. , Mitchell Tyler A. , Rothstein Megan , Pehl Alison , Taroc Ed Zandro M. , Katreddi Raghu Ram , Parra Katherine E. , Zuloaga Damian G. , Simoes-Costa Marcos , Forni Paolo E.
Published: January 2022

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remains a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing vomeronasal sensory neurons (VSNs), and vomeronasal dependent behaviors can be reprogrammed through the rescue of tfap2e/AP-2ε expression in the AP-2ε mice, and partially reprogrammed by inducing ectopic AP-2ε expression in mature apical VSNs. We suggest that the transcription factor AP-2ε can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.

GRAPHICAL ABSTRACT
Allometric tissue-scale forces activate mechanoresponsive immune cells to drive pathological foreign body response to biomedical implants
Authors: Padmanabhan Jagannath , Chen Kellen , Sivaraj Dharshan , Kuehlmann Britta A. , Bonham Clark A. , Dohi Teruyuki , Henn Dominic , Stern-Buchbinder Zachary A. , Than Peter A. , Hosseini Hadi S. , Barrera Janos A. , Kussie Hudson C. , Magbual Noah J. , Borrelli Mimi R. , Trotsyuk Artem A. , Kwon Sun Hyung , Dunn James C.Y. , Maan Zeshaan N. , Januszyk Michael , Prantl Lukas , Gurtner Geoffrey C.
Published: January 2022

For decades, it has been assumed that the foreign body response (FBR) to biomedical implants is primarily a reaction to the chemical and mechanical properties of the implant. Here, we show for the first time that a third independent variable, allometric tissue-scale forces (which increase exponentially with body size), can drive the biology of FBR in humans. We first demonstrate that pathological FBR in humans is mediated by immune cell-specific Rac2 mechanotransduction signaling, independent of implant chemistry or mechanical properties. We then show that mice, which are typically poor models of human FBR, can be made to induce a strikingly human-like pathological FBR by altering these extrinsic tissue forces. Altering these extrinsic tissue forces alone activates Rac2 signaling in a unique subpopulation of immune cells and results in a human-like pathological FBR at the molecular, cellular, and local tissue levels. Finally, we demonstrate that blocking Rac2 signaling negates the effect of increased tissue forces, dramatically reducing FBR. These findings highlight a previously unsuspected mechanism for pathological FBR and may have profound implications for the design and safety of all implantable devices in humans.

One-Sentence Summary

Allometric tissue-scale forces at the implant-tissue interface drive pathological foreign body response.
dsRNA-induced condensation of antiviral proteins promotes PKR activation
Authors: Corbet Giulia A. , Burke James M. , Bublitz Gaia R. , Parker Roy
Published: January 2022

Mammalian cells respond to dsRNA in multiple manners. One key response to dsRNA is the activation of PKR, an eIF2α kinase, which triggers translational arrest and the formation of stress granules. However, the process of PKR activation in cells is not fully understood. In response to increased endogenous or exogenous dsRNA, we observed that PKR forms novel cytosolic condensates, referred to as dsRNA-induced foci (dRIFs). dRIFs contain dsRNA, form in proportion to dsRNA, and are enhanced by longer dsRNAs. dRIFs also enrich several other dsRNA-binding proteins including ADAR1, Stau1, NLRP1, and PACT. Strikingly, dRIFs correlate with and form prior to translation repression by PKR and localize to regions of cells where PKR activation is initiated. We suggest that dRIF formation is a mechanism cells utilize to enhance the sensitivity of PKR activation in response to low levels of dsRNA, or to overcome viral inhibitors of PKR activation.
ART duration and immunometabolic state determine efficacy of DC-based treatment restoring functional HIV- specific CD8+ T cells in PLWH
Authors: Calvet-Mirabent Marta , Sánchez-Cerrillo Ildefonso , Martín-Cófreces Noa , de la Fuente Hortensia , Tsukalov Ilya , Delgado-Arévalo Cristina , Calzada María José , de los Santos Ignacio , Sanz Jesús , García-Fraile Lucio , Sánchez-Madrid Francisco , Alfranca Arantzazu , Muñoz-Fernández María Ángeles , Buzón Maria J. , Martín-Gayo Enrique
Published: January 2022

Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated in detail. Here, we studied the association of ART duration with memory subsets, exhaustion and metabolic profiles of CD8+ T cells from PLWH and improvement of polyfunctional and effector HIV-1 specific responses after stimulation with Gag-adjuvant-primed DC. HIV-1-specific CD8+ T cell responses from a larger proportion PLWH on ART for more than 10 years (LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cellsin vitro. In contrast, CD8+ T cells from PLWH on ART for less than a decade (ST-ARTp) were less responsive to DC treatment and functional improvement was limited in this group. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolytic induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+PD1-cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines.
Metabolomic, photoprotective, and photosynthetic acclimatory responses to post-flowering drought in sorghum
Authors: Baker Christopher R. , Patel Dhruv , Cole Benjamin J. , Ching Lindsey G. , Dautermann Oliver , Kelikian Armen C. , Allison Cayci , Pedraza Julie , Sievert Julie , Bilbao Aivett , Lee Joon-Yong , Kim Young-Mo , Kyle Jennifer E. , Bloodsworth Kent J. , Paurus Vanessa , Hixson Kim K. , Hutmacher Robert , Dahlberg Jeffery , Lemaux Peggy G. , Niyogi Krishna K.
Published: January 2022

Climate change is globally affecting rainfall patterns, necessitating the improvement of drought tolerance in crops. Sorghum bicolor is a drought-tolerant cereal capable of producing high yields under water scarcity conditions. Functional stay-green sorghum genotypes can maintain green leaf area and efficient grain filling in terminal post-flowering water deprivation, a period of ~10 weeks. To obtain molecular insights into these characteristics, two drought-tolerant genotypes, BTx642 and RTx430, were grown in control and terminal post-flowering drought field plots in the Central Valley of California. Photosynthetic, photoprotective, water dynamics, and biomass traits were quantified and correlated with metabolomic data collected from leaves, stems, and roots at multiple timepoints during drought. Physiological and metabolomic data was then compared to longitudinal RNA sequencing data collected from these two genotypes. The metabolic response to drought highlights the uniqueness of the post-flowering drought acclimation relative to pre-flowering drought. The functional stay-green genotype BTx642 specifically induced photoprotective responses in post-flowering drought supporting a putative role for photoprotection in the molecular basis of the functional stay-green trait. Specific genes are highlighted that may contribute to post-flowering drought tolerance and that can be targeted in crops to maximize yields under limited water input conditions.

Highlight

Pathways contributing to the long-term maintenance of photosynthetic activity in terminal post-flowering drought are revealed by a comprehensive approach combining in-field photosynthetic physiological analysis, metabolomics, and transcriptomics.
Absence of the fragile X mental retardation protein alters response patterns to sounds in the auditory midbrain
Authors: Sibille Jérémie , Kremkow Jens , Koch Ursula
Published: January 2022

Among the different autism spectrum disorders, Fragile X Syndrome (FXS) is the most common inherited cause of mental retardation. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/- mouse model. However, the physiological mechanisms underlying FXS’s acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the Inferior Colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of WT and Fmr1 -/- mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we were surprised to notice that all neuron response types in Fmr1 -/- mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.
Microbiomes of hadal fishes contain similar taxa, obligate symbionts, and known piezophiles across trench habitats
Authors: Blanton Jessica M. , Peoples Logan M. , Gerringer Mackenzie E. , Iacuniello Caroline M. , Gallo Natalya D. , Linley Thomas D. , Jamieson Alan J. , Drazen Jeffrey C. , Bartlett Douglas H. , Allen Eric E.
Published: January 2022

Hadal snailfishes are the deepest-living fishes in the ocean, inhabiting trenches from depths of ∼6,000 to 8,000 m. While the microbial communities in trench environments have begun to be characterized, the microbes associated with hadal megafauna remain relatively unknown. Here, we describe the gut microbiomes of two hadal snailfishes, Pseudoliparis swirei (Mariana Trench) and Notoliparis kermadecensis (Kermadec Trench) using 16S rRNA gene amplicon sequencing. We contextualize these microbiomes with comparisons to the abyssal macrourid Coryphaenoides yaquinae and the continental shelf-dwelling snailfish Careproctus melanurus. The microbial communities of the hadal snailfishes were distinct from their shallower counterparts and were dominated by the same sequences related to the Mycoplasmataceae and Desulfovibrionaceae. These shared taxa indicate that symbiont lineages may have remained similar to the ancestral symbiont since their geographic separation or that they are dispersed between geographically distant trenches and subsequently colonize specific hosts. The abyssal and hadal fishes contained sequences related to known, cultured piezophiles, microbes that grow optimally under high hydrostatic pressure, including Psychromonas, Moritella, and Shewanella. These taxa are adept at colonizing nutrient-rich environments present in the deep ocean, such as on particles and in the guts of hosts, and we hypothesize they could make a dietary contribution to deep-sea fishes by degrading chitin and producing fatty acids. We characterize the gut microbiota within some of the deepest fishes to provide new insight into the diversity and distribution of host-associated microbial taxa and the potential of these animals, and the microbes they harbor, for understanding adaptation to deep-sea habitats.

Importance

Hadal trenches, characterized by high hydrostatic pressures and low temperatures, are one of the most extreme environments on our planet. By examining the microbiome of abyssal and hadal fishes, we provide insight into both the physiology of the deepest-living vertebrates and the microbes which colonize them. Our findings show that there are similar microbial populations in fishes geographically separated by thousands of miles, reflecting strong selection for specific microbial lineages. Only a handful of psychropiezophilic taxa, which do not reflect the diversity of microbial life at great depth, have been successfully isolated in the laboratory. Our examination of deep-sea fish microbiomes shows that typical high-pressure culturing methodologies, which have largely remained unchanged since the pioneering work of Claude ZoBell in the 1950s, may simulate the chemical environment found in animal guts and helps explain why the same deep-sea genera are consistently isolated.
IL-33 regulates age-dependency of long-term immune dysfunction induced by sepsis
Authors: Colon David F. , Wanderley Carlos W. , Turato Walter M. , Borges Vanessa F. , Franchin Marcelo , Castanheira Fernanda V. S. , Nascimento Daniele , Prado Douglas , de Lima Mikhael Haruo Fernandes , Volpon Leila C , Kavaguti Silvia K. , Ramalho Fernando , Carlotti Ana P. , Carmona Fabio , Franklin Bernardo S , Alves-Filho Jose C. , Cunha Fernando Q.
Published: January 2022

Sepsis survival in adults is commonly followed by immunosuppression and increased susceptibility to secondary infections. However, the long-term immune consequences of pediatric sepsis are unknown. Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages, and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. In contrast to adults, infant mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in post-septic adults but not infant mice. Impaired IL-33 production in post-septic infant mice was associated with increased DNA-methylation on lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in infant mice. Clinically, adults but not pediatric post-septic patients exhibited higher counts of Tregs and sera IL-33 levels. Hence, we describe a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression.
Culture and genomic analysis of Symbiopectobacterium purcellii, gen.nov. sp. nov., isolated from the leafhopper Empoasca decipiens
Authors: Nadal-Jimenez Pol , Siozios Stefanos , Halliday Nigel , Cámara Miguel , Hurst Gregory D.D.
Published: January 2022

Bacterial endosymbionts are found in multiple arthropod species, where they play crucial roles as nutritional symbionts, defensive symbionts or reproductive parasites. Recent work has highlighted a new clade of heritable microbes within the gammaproteobacteria that enter into both obligate and facultative symbioses, with an obligately required unculturable symbiont recently given the name Cand. Symbiopectobacterium. In this study, we describe a culturable rod shaped non-flagellated bacterial symbiont from this clade isolated from the leafhopper Empoasca decipiens. The symbiont is related to the transovarially-transmitted ‘BEV’ bacterium that was first isolated from the leafhopper Euscelidius variegatus by Alexander Purcell, and we therefore name the symbiont Symbiopectobacterium purcellii sp. nov. gen. nov. We further report the closed genome sequence for S. purcellii. The genome is atypical for a heritable microbe, being large in size, without profound AT bias and with little evidence of pseudogenization. The genome is predicted to encode Type II, III and VI secretion systems and associated effectors and a non-ribosomal peptide synthase array likely to produce bioactive small molecules. Predicted metabolism is more complete than for other symbionts in the Symbiopectobacterium clade, and the microbe is predicted to synthesize a range of B vitamins. However, Biolog plate analysis indicate metabolism is depauperate compared to the sister clade, represented by Pectobacterium carotovorum. A quorum-sensing pathway related to that of Pectobacterium spp. (containing an overlapping expI-expR1 pair in opposite directions and a “solo” expR2) is evidenced, and LC-MS/MS analysis reveals the presence of 3-hydroxy-C10-HSL as the sole N-acylhomoserine lactone (AHL) in our strain. This AHL profile is profoundly divergent from that of other Erwinia and Pectobacterium spp., which produce mostly 3-oxo-C6- and 3-oxo-C8-HSL and could aid group identification. Thus, this microbe denotes one that has lost certain pathways associated with a saprophytic lifestyle but represents an important baseline against which to compare other members of the genus Symbiopectobacterium that show more profound integration into host biology.
MeShClust v3.0: High-quality clustering of DNA sequences using the mean shift algorithm and alignment-free identity scores
Authors: Girgis Hani Z.
Published: January 2022

Background

Tools for accurately clustering biological sequences are among the most important tools in computational biology. Two pioneering tools for clustering sequences are CD-HIT and UCLUST, both of which are fast and consume reasonable amounts of memory; however, there is a big room for improvement in terms of cluster quality. Motivated by this opportunity for improving cluster quality, we applied the mean shift algorithm in MeShClust v1.0. The mean shift algorithm is an instance of unsupervised learning. Its strong theoretical foundation guarantees the convergence to the true cluster centers. Our implementation of the mean shift algorithm in MeShClust v1.0 was a step forward; however, it was not the original algorithm. In this work, we make progress toward applying the original algorithm while utilizing alignment-free identity scores in a new tool: MeShClust v3.0.

Results

We evaluated CD-HIT, MeShClust v1.0, MeShClust v3.0, and UCLUST on 22 synthetic sets and five real sets. These data sets were designed or selected for testing the tools in terms of scalability and different similarity levels among sequences comprising clusters. On the synthetic data sets, MeShClust v3.0 outperformed the related tools on all sets in terms of cluster quality. On two real data sets obtained from human microbiome and maize transposons, MeShClust v3.0 outperformed the related tools by wide margins, achieving 55%—300% improvement in cluster quality. On another set that includes degenerate viral sequences, MeShClust v3.0 came third. On two bacterial sets, MeShClust v3.0 was the only applicable tool because of the long sequences in these sets. MeShClust v3.0 requires more time and memory than the related tools; almost all personal computers at the time of this writing can accommodate such requirements. MeShClust v3.0 can estimate an important parameter that controls cluster membership with high accuracy.

Conclusions

These results demonstrate the high quality of clusters produced by MeShClust v3.0 and its ability to apply the mean shift algorithm to large data sets and long sequences. Because clustering tools are utilized in many studies, providing high-quality clusters will help with deriving accurate biological knowledge.
Forecasting the next revolution: food technology’s impact on consumers' acceptance and satisfaction
Authors: Recuero-Virto Nuria , Valilla-Arróspide Cristina
Published: January 2022

Purpose

In a sector that needs to satisfy a fast-increasing population, advancements like cultivated meat and bio-circular economy are basic to sustain the industry and the society. As innovations are key for economic and social progress, it is crucial to understand consumers' position on this matter.

Design/methodology/approach

Based on text data mining, 7,030 tweets were collected and organised into 14 different food-related topics. Of the total, 6 of these categories were positive, 5 were negative and 3 were neutral.

Findings

In total, 6 categories related to food technologies were positively perceived by Twitter users, such as innovative solutions and sustainable agriculture, while 5 like the virtual dimensions of the industry or crisis-related scenarios were negatively perceived. It is remarkable that 3 categories had a neutral sentiment, which gives ground to improvement before consumers have a negative opinion and consequently will be more complicated to change their minds.

Originality/value

Technological innovations are becoming predominant in the food industry. The SARS-CoV-2 pandemic has made the sector improve even faster. Traditional methods needed to be substituted and technologies such as robots, artificial intelligence, blockchain and genetics are here to stay.
Exploring the university research scholars’ information literacy competency: a focus on the knowledge and skills
Authors: Senthur Selvi Kalai , Ganesan Perumal
Published: January 2022

Purpose

This study aims to determine the level of knowledge in searching, evaluating, information management competency and to find differences among research scholars’ in terms of their information literacy (IL) competency with regards to gender and academic designation.

Design/methodology/approach

A survey method was conducted to collect the data from the research scholars’ pursuing their doctoral degrees in Manonmaniam Sundaranar University, Tamil Nadu, India.

Findings

The results of this study revealed that the majority have used simple search and were not using the Online Public Access Catalogue. They were not able to assess the information retrieved and the assistance from the library staff to locate the resources was found to be minimal. This study also highlighted some of the problems faced by the research scholars and provided some suggestions based on the findings. This study highlights the need to adopt a new IL framework and conduct user literacy training programmes for effective use of the resources.

Practical implications

This study also has practical implications in terms of assessing the IL competency among the research scholars and significant variations which identified through demographics and assessment of IL competency will enable policymakers to develop a framework for brand new literacy instructions. The results may help to frame long-term strategies to motivate and train the research scholars in the effective use of technologies for improving their academic performance.

Originality/value

This study used a questionnaire as tool to collect the data. The outcome of the results will help the librarians and authorities to discuss research scholars’ IL competency and take appropriate decisions to improve their IL skills.