bluuebunny/crossref_metadata_2025 huggingface dataset:
At least it is a dry cold: the global distribution of freeze–thaw and drought stress and the traits that may impart poly-tolerance in conifers
Authors: McCulloh Katherine A , Augustine Steven P , Goke Alex , Jordan Rachel , Krieg Christopher P , O’Keefe Kimberly , Smith Duncan D
Published: September 2022

Conifers inhabit some of the most challenging landscapes where multiple abiotic stressors (e.g., aridity, freezing temperatures) often co-occur. Physiological tolerance to multiple stressors (‘poly-tolerance’) is thought to be rare because exposure to one stress generally limits responses to another through functional trade-offs. However, the capacity to exhibit poly-tolerance may be greater when combined abiotic stressors have similar physiological impacts, such as the disruption of hydraulic function imposed by drought or freezing. Here, we reviewed empirical data in light of theoretical expectations for conifer adaptations to drought and freeze–thaw cycles with particular attention to hydraulic traits of the stem and leaf. Additionally, we examined the commonality and spatial distribution of poly-stress along indices of these combined stressors. We found that locations with the highest values of our poly-stress index (PSi) are characterized by moderate drought and moderate freeze–thaw, and most of the global conifer distribution occupies areas of moderate poly-stress. Among traits examined, we found diverse responses to the stressors. Turgor loss point did not correlate with freeze–thaw or drought stress individually, but did with the PSi, albeit inverse to what was hypothesized. Leaf mass per area was more strongly linked with drought stress than the poly-stress and not at all with freeze–thaw stress. In stems, the water potential causing 50% loss of hydraulic conductivity became more negative with increasing drought stress and poly-stress but did not correlate with freeze–thaw stress. For these traits, we identified a striking lack of coverage for substantial portions of species ranges, particularly at the upper boundaries of their respective PSis, demonstrating a critical gap in our understanding of trait prevalence and plasticity along these stress gradients. Future research should investigate traits that confer tolerance to both freeze–thaw and drought stress in a wide range of species across broad geographic scales.
A Systematic Survey on Prevalence of Grapevine Trunk Disease Pathogens in Oregon Vineyards
Authors: Hernandez Monica N. , KC Achala N.
Published: September 2022

Grapevine trunk diseases (GTDs) are found in vineyards worldwide and can be caused by different fungal pathogens. To characterize types of GTDs in Oregon vineyards, and how the GTD pathogens’ prevalence is affected by two geographical regions, a survey was conducted in which grapevine trunk samples were collected from 15 and 14 wine grape (Vitis vinifera) vineyards in southern and northern Oregon, respectively. Fungal species were identified through culture and PCR-based methods. GTD pathogens that were identified included Botryosphaeriaceae spp. and Phaeoacremonium spp. from 72 and 21% of the surveyed vineyards, respectively; Phaeomoniella chlamydospora, Cryptovalsa ampelina, Truncatella angustata, Seimatosporium lichenicola, Hormonema viticola from 7% of the surveyed vineyards; and Dactylonectria macrodidyma, and Pestaloptiopsis sp. from 3% of the surveyed vineyards. Pathogens were identified in both regions and in young and mature vineyards. The presence of GTD from the Botryosphaeria dieback complex was significantly affected by regions (P = 0.021), with pathogens being significantly more abundant in Willamette Valley (northern region) compared with Rogue Valley (southern region) vineyards. Some differences among other tested variables such as vineyard age, cultivars, rootstocks, and pruning methods were observed for all disease complexes; however, the differences were not statistically significant. Our study summarizes that Botryosphaeria dieback and Esca disease complexes are the most prevalent diseases infecting grapevines in Oregon vineyards and management practices need to be geared toward these economically important diseases. In addition, pathogens from other disease complexes are also present, suggesting a need for regular disease monitoring and following practices to limit the spread of these pathogens.
Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia
Authors: Suárez Santiago José Eduardo , Roldán Gabriel Roldán , Picazo Ofir
Published: September 2022

Schizophrenia is a serious neuropsychiatric disorder characterized by the presence of positive symptoms (hallucinations, delusions, and disorganization of thought and language), negative symptoms (abulia, alogia, and affective flattening), and cognitive impairment (attention deficit, impaired declarative memory, and deficits in social cognition). Dopaminergic hyperactivity seems to explain the positive symptoms, but it does not completely clarify the appearance of negative and cognitive clinical manifestations. Preclinical data have demonstrated that acute and subchronic treatment with NMDA receptor antagonists such as ketamine (KET) represents a useful model that resembles the schizophrenia symptomatology, including cognitive impairment. This latter has been explained as a hypofunction of NMDA receptors located on the GABA parvalbumin-positive interneurons (near to the cortical pyramidal cells), thus generating an imbalance between the inhibitory and excitatory activity in the corticomesolimbic circuits. The use of behavioral models to explore alterations in different domains of memory is vital to learn more about the neurobiological changes that underlie schizophrenia. Thus, to better understand the neurophysiological mechanisms involved in cognitive impairment related to schizophrenia, the purpose of this review is to analyze the most recent findings regarding the effect of KET administration on these processes.
Predatory Publications
Authors: Six-Means Amy
Published: September 2022

The most recognized route for authors to get their articles disseminated is through journals, which are then subscribed to by individuals and/or organizations who pay for these subscriptions. These subscriptions cover the cost of reviewing, editing, publishing, and archiving articles. Once a manuscript is accepted and published, authors usually give copyright ownership for their work to the publisher. Shortly after publishers moved to electronic formats and access, the era of “open access” journals began. Although there are different models of open access, the basic model, which allows anyone to read, download, and print articles freely, uses a different method to finance publication of articles. Rather than subscription based, authors pay for the cost of the publishers reviewing, editing, publishing, and archiving their manuscripts—which is practiced by both scholarly and predatory publishers. The primary purpose of scholarly publishing is to advance science, technology, and medicine; the purpose of predatory publishers is less ethical and more monetarily driven. Although knowledge of predatory practices is growing, many authors are unfamiliar with this, do not realize the consequences, and do not know how to recognize a predatory publisher. This has consequences to them professionally but, within health care, also has negative consequences to research, practice, and patient care. This article will briefly cover what the major differences between scholarly and predatory publications are, what impact they could have, and how to identify them for both researchers and authors.
Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated with the Microlesion Effect in Tourette Syndrome
Authors: Morishita Takashi , Sakai Yuki , Iida Hitoshi , Yoshimura Saki , Fujioka Shinsuke , Oda Kazunori , Tanaka Saori C. , Abe Hiroshi
Published: September 2022

Objectives

The microlesion effect is refers to the improvement of clinical symptoms after deep brain stimulation (DBS) lead placement and is suggested to indicate optimal lead placement. This phenomenon is well known for movement disorders, such as essential tremors and Parkinson disease, but very few studies have reported its implications in neuropsychiatric disorders. Our aim was to evaluate the magnitude of the microlesion effect in Tourette syndrome (TS) and the relationship between the microlesion effect and the anatomical location of implanted DBS leads.

Methods

This study included 6 consecutive patients who underwent DBS for severe TS. All patients were male and their mean age was 28.5 ± 10.5 years. All patients were videotaped at baseline and on postoperative day (POD) 7, and motor and phonic tic frequencies were recorded. We also analyzed the precision of lead placement in normalized brain space and evaluated the normative connectome associated with precise electrode positions for improvement of tics.

Results

The microlesion effect was observed as an improvement in tic symptoms in all patients. The median motor tic frequency was 20.2 tics/min (range, 9.7–60) at baseline and decreased to 3.2 tics/min (1.2–11.3) on POD 1 (z = −2.20, p = 0.028) and 5.7 tics/min (range, 1.9–16.6) on POD 7 (z = −2.20, p = 0.028). The median phonic tic frequency was 10.5 tics/min (range, 2.0−58.7) at baseline and decreased to 0.7 tics/min (range, 0−14.4) on POD 1 (z = −1.78, p = 0.075) and 2.25 tics/min (range, 1.3−13.7) on POD 7 (z = −1.57, p = 0.116). Image analyses revealed that the precise position of the electrode was directed toward the anteromedial centromedian nucleus. Normative connectome analysis demonstrated connections between improvement-related areas and wide areas of the prefrontal cortex.

Conclusion

This study shows that the microlesion effect may appear as an immediate improvement following DBS lead placement even in patients with TS. Our results support the existence of a “sweet spot” for tic suppression in patients with severe TS, and clinicians should pay attention to this phenomenon in the postoperative evaluation of the lead position.
Meta-analysis of the public RNA-Seq data of the Western honeybeeApis melliferato construct reference transcriptome data
Authors: Yokoi Kakeru , Wakamiya Takeshi , Bono Hidemasa
Published: September 2022

The Western honeybee (Apis mellifera) is valuable in biological research and agriculture. Its genome sequence was published before those for other insect species. RNA-Seq data forA. melliferahave been applied in several recently published studies. Nevertheless, these data have not been prepared for use in subsequent meta-analyses. To promoteA. melliferatranscriptome analysis, we constructed reference transcriptome data using the reference genome sequence and RNA-Seq data curated from about 1,000 runs of public databases. The new reference transcriptome data construct comprised 149,685 transcripts, and 194,174 protein sequences were predicted. About 50–60% of the predicted protein sequences were functionally annotated using the protein sequence data for several model and insect species. Novel candidate immune-related transcripts were searched by meta-analysis using immune response-related RNA-Seq and reference transcriptome data. Three to 20 candidate transcripts includingautophagy related protein 3were upregulated or downregulated in response to both viral and bacterial infections. The constructed reference transcriptome data may facilitate future transcriptome analyses ofA. mellifera.

Simple Summary

The honeybee is an economically and ecologically essential insect species and a critical social behavior model. It is vital to honey production and pollinates. Therefore, it has been studied extensively in entomological research. The Western honeybee (Apis mellifera) is a representative species of honeybees. The reference transcriptome data are required to perform the meta-analyses using public RNA-Seq data and transcriptome analysis using newly sequenced RNA-Seq data. The reference transcriptome sequences was constructed, which consisted of 149,685 transcripts, and 194,174 predicted amino acid sequences. Half the predicted protein sequences were functionally annotated using protein sequence datasets for several model and insect species. We performed meta-analysis to search for novel immune response-related transcripts. We identified 3–20 transcripts that were upregulated or downregulated in response to both viral and bacterial infections. However, the immune-related transcripts were not included among them. Autophagy related protein 3 was downregulated by viral infections. The results suggested that autophagy was implicated in the viral immune responses, and autophagy was not regulated by the canonical immune pathways inA. mellifera. The results of the meta-analysis suggested that the reference transcriptome data could be used for transcriptome analysis inA. mellifera.
Synthesizing Images of Tau Pathology from Cross-modal Neuroimaging using Deep Learning
Authors: Lee Jeyeon , Burkett Brian J. , Min Hoon-Ki , Senjem Matthew L. , Dicks Ellen , Corriveau-Lecavalier Nick , Mester Carly T. , Wiste Heather J. , Lundt Emily S. , Murray Melissa E. , Nguyen Aivi T. , Reichard Ross R. , Botha Hugo , Graff-Radford Jonathan , Barnard Leland R. , Gunter Jeffrey L. , Schwarz Christopher G. , Kantarci Kejal , Knopman David S. , Boeve Bradley F. , Lowe Val J. , Petersen Ronald C. , Jack Clifford R. , Jones David T.
Published: September 2022

Given the prevalence of dementia and the development of pathology-specific disease modifying therapies, high-value biomarker strategies to inform medical decision making are critical. In-vivo tau positron emission tomography (PET) is an ideal target as a biomarker for Alzheimer’s disease diagnosis and treatment outcome measure. However, tau PET is not currently widely accessible to patients compared to other neuroimaging methods. In this study, we present a convolutional neural network (CNN) model that impute tau PET images from more widely-available cross-modality imaging inputs. Participants (n=1,192) with brain MRI, fluorodeoxyglucose (FDG) PET, amyloid PET, and tau PET were included. We found that a CNN model can impute tau PET images with high accuracy, the highest being for the FDG-based model followed by amyloid PET and MRI. In testing implications of AI-imputed tau PET, only the FDG-based model showed a significant improvement of performance in classifying tau positivity and diagnostic groups compared to the original input data, suggesting that application of the model could enhance the utility of the metabolic images. The interpretability experiment revealed that the FDG- and MRI-based models utilized the non-local input from physically remote ROIs to estimate the tau PET, but this was not the case for the PiB-based model. This implies that the model can learn the distinct biological relationship between FDG PET, MRI, and tau PET from the relationship between amyloid PET and tau PET. Our study suggests that extending neuroimaging’s use with artificial intelligence to predict protein specific pathologies has great potential to inform emerging care models.
Localization of multiple hydrogels with MultiCUBE platform spatially guides 3D tissue morphogenesis in vitro
Authors: Suthiwanich Kasinan , Hagiwara Masaya
Published: September 2022

Localization of multiple hydrogels is expected to develop the structure of 3D tissue models in a location specific manner. Here, we successfully localize morphogenesis within individual tissues by exposing different hydrogel conditions to different parts of the tissues. We develop a unit-based scaffold with a unique frame design to trap hydrogel solutions inside their designated units. Interestingly, this unit-based scaffold within an optimal range of dimensional size and surface wettability can trap several cubic millimeters of hydrogels. This localization capability enables the spatial organization of hydrogel compositions, growth factors and physical conditions, as well as the position of biological samples (cells, spheroids, reconstituted tissues) relative to each hydrogel compartment. We succeed to localize the branching development of reconstituted human epithelial tissues according to the localized biomolecular and physical cues from hydrogels, regardless of the initial tissue configurations. Unlike 3D-bioprinting or microfluidics, the localization with this unit-based scaffold requires only manual pipetting and handling without any specialized equipment or skills, thus ready to use by researchers from any field. This scaffold-based localization provides a new promising route to spatially control morphogenesis, differentiation, and other developmental processes within organoids or other 3D tissues, resulting in 3D functional models for practical biomedical applications.
Heat dissipation drives the hump-shaped scaling of animal dispersal speed with body mass
Authors: Dyer Alexander , Brose Ulrich , Berti Emilio , Rosenbaum Benjamin , Hirt Myriam R.
Published: September 2022

Dispersal is critical to animal survival and thus biodiversity in fragmented landscapes. Increasing fragmentation in the Anthropocene necessitates predictions about the dispersal capabilities of the many species that inhabit natural ecosystems. This requires mechanistic, trait-based models of animal dispersal which are sufficiently general as well as biologically realistic. While larger animals should generally be able to travel greater distances, reported trends in their speeds across a range of body sizes suggest limited locomotor capacities among the largest species. Here, we show that this also applies to dispersal speeds and that this arises because of their limited heat-dissipation capacities. We derive a model considering how fundamental biophysical constraints of animal body mass associated with energy utilisation (i.e. larger animals have a lower metabolic energy cost of locomotion) and heat-dissipation (i.e. larger animals require more time to dissipate metabolic heat) limit sustained (i.e. aerobic) dispersal speeds. Using an extensive empirical dataset of animal dispersal speeds (531 species), we show that thisallometric heat-dissipation modelbest captures the hump-shaped trends in dispersal speed with body mass for flying, running and swimming animals. This implies that the inability to dissipate metabolic heat leads to the saturation and eventual decrease in dispersal speed with increasing body mass as larger animals must reduce their realised dispersal speeds in order to avoid hyperthermia during extended dispersal bouts. As a result, the highest dispersal speeds are achieved by animals of intermediate body mass, whereas the largest species might suffer from stronger dispersal limitations in fragmented landscapes than previously anticipated. Consequently, we provide a mechanistic understanding of animal dispersal speed that can be generalised across species, even when the details of an individual species’ biology are unknown, to facilitate more realistic predictions of biodiversity dynamics in fragmented landscapes.
Empirical methods for the validation of Time-To-Event mathematical models taking into account uncertainty and variability: Application to EGFR+ Lung Adenocarcinoma
Authors: Jacob Evgueni , Perrillat-Mercerot Angélique , Palgen Jean-Louis , L’Hostis Adèle , Ceres Nicoletta , Boissel Jean-Pierre , Bosley Jim , Monteiro Claudio , Kahoul Riad
Published: September 2022

Background

Over the past several decades, metrics have been defined to assess the quality of various types of models and to compare their performance depending on their capacity to explain the variance found in real-life data. However, available validation methods are mostly designed for statistical regressions rather than for mechanistic models. To our knowledge, in the latter case, there are no consensus standards, for instance for the validation of predictions against real-world data given the variability and uncertainty of the data. In this work, we focus on the prediction of time-to-event curves using as an application example a mechanistic model of non-small cell lung cancer. We designed four empirical methods to assess both model performance and reliability of predictions: two methods based on bootstrapped versions of parametric statistical tests: log-rank and combined weighted log-ranks (MaxCombo); and two methods based on bootstrapped prediction intervals, referred to here as raw coverage and the juncture metric. We also introduced the notion of observation time uncertainty to take into consideration the real life delay between the moment when an event happens, and the moment when it is observed and reported.

Results

We highlight the advantages and disadvantages of these methods according to their application context. We have shown that the context of use of the model has an impact on the model validation process. Thanks to the use of several validation metrics we have highlighted the limit of the model to predict the evolution of the disease in the whole population of mutations at the same time, and that it was more efficient with specific predictions in the target mutation populations. The choice and use of a single metric could have led to an erroneous validation of the model and its context of use.

Conclusions

With this work, we stress the importance of making judicious choices for a metric, and how using a combination of metrics could be more relevant, with the objective of validating a given model and its predictions within a specific context of use. We also show how the reliability of the results depends both on the metric and on the statistical comparisons, and that the conditions of application and the type of available information need to be taken into account to choose the best validation strategy.
Integrating gene annotation with orthology inference at scale
Authors: Kirilenko Bogdan M. , Munegowda Chetan , Osipova Ekaterina , Jebb David , Sharma Virag , Blumer Moritz , Morales Ariadna E. , Ahmed Alexis-Walid , Kontopoulos Dimitrios-Georgios , Hilgers Leon , Lindblad-Toh Kerstin , Karlsson Elinor K. ,   Zoonomia Consortium, Hiller Michael
Published: September 2022

Annotating coding genes and inferring orthologs are two classical challenges in genomics and evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA, a method that integrates structural gene annotation and orthology inference. TOGA implements a different paradigm to infer orthologous loci, improves ortholog detection and annotation of conserved genes compared to state-of-the-art methods, and handles even highly-fragmented assemblies. TOGA scales to hundreds of genomes, which we demonstrate by applying it to 488 placental mammal and 501 bird assemblies, creating the largest comparative gene resources so far. Additionally, TOGA detects gene losses, enables selection screens, and automatically provides a superior measure of mammalian genome quality. Together, TOGA is a powerful and scalable method to annotate and compare genes in the genomic era.
Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors
Authors: Rashmi Priyanka , Sigdel Tara K. , Rychkov Dmitry , Damm Izabella , Da Silva Andrea Alice , Vincenti Flavio , Lourenco Andre L. , Craik Charles S. , Reiser Jochen , Sarwal Minnie M
Published: September 2022

Focal segmental glomerulosclerosis (FSGS) is frequently associated with heavy proteinuria and progressive renal failure requiring dialysis or kidney transplantation. However, primary FSGS also has 40-80% risk of recurrence of disease in the transplanted kidney (rFSGS). Multiple circulating factors have been proposed to contribute to the pathogenesis of primary and rFSGS. However, neither the factors nor the downstream effectors specific to individual factors have been identified. The tumor necrosis factor, TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS has been supported by multiple studies. The proposed circulating factors include soluble urokinase-type plasminogen activator receptor (suPAR) and patient derived CD40 autoantibody (CD40autoAb) in the development and recurrence of FSGS. In a human in vitro model, using two novel human antibodies-anti uPAR (2G10) and anti CD40 antibody, we show that the podocyte injury caused by sera from FSGS patients is at least in part mediated by CD40 and suPAR. Additionally, we employ gene expression studies to compare the molecules and pathways activated in response to CD40 autoantibody from rFSGS patients (rFSGS/CD40autoAb) and suPAR, and delineate the unique pathways associated with FSGS injury and transcriptional podocyte alterations with targeted blockade of suPAR and CD40 pathways.

Clinical Impact

Focal Segmental Glomerulosclerosis remains a disease without specific therapy for primary disease and high rate of recurrence after kidney transplantation. Circulating factors are implicated in the pathogenesis of FSGS but targeting them for therapy has remained elusive. We propose two potential therapeutic molecules for rFSGS treatment-a human anti-uPAR antibody (2G10) and a humanized anti-CD40 blocking antibody (Bristol Meyer Squibb, 986090) that reverse podocyte injury associated with FSGS in cultured podocytes and can be further tested in pre-clinical and clinical models. Furthermore, we use microarray profiling to identify transcriptional pathways specific to podocyte injury from patient-derived CD40 autoantibodies (rFSGS/CD40autoAb) and suPAR and selective blockade of these pathways to abrogate podocyte injury.
MedDiC: high dimensional mediation analysis via difference in coefficients
Authors: Zhang Qi , Yang Zhikai , Yang Jinliang
Published: September 2022

High dimensional mediation analysis has been receiving increasing popularity, largely motivated by the scientific problems in genomics and biomedical imaging. Previous literature has primarily focused on mediator selection for high dimensional mediators. In this paper, we aim at the estimation and inference of overall indirect effect for high dimensional exposures and high dimensional mediators. We propose MedDiC, a novel debiased estimator of the high dimensional overall indirect effect based on difference-in-coefficients approach. We evaluate the proposed method using intensive simulations and find that MedDiC provides valid inference and offers higher power and shorter computing time than the competitors for both low dimensional and high dimensional exposures. We also apply MedDiC to a mouse f2 dataset for diabetes study and a dataset composed of diverse maize inbred lines for flowering time, and show that MedDiC yields more biologically meaningful gene lists, and the results are reproduciable across analyses using different measures of identical biological signal or related phenotype as the outcome.

Upon the acceptance of the paper, the code will be available on GitHub (https://github.com/QiZhangStat/MedDiC).
Injectable polymer-nanoparticle hydrogel for the sustained intravitreal delivery of bimatoprost
Authors: Meany Emily L. , Andaya Roxanne , Tang Shijia , Kasse Catherine M. , Fuji Reina N. , Grosskopf Abigail K. , d’Aquino Andrea l. , Bartoe Joshua T. , Ybarra Ryan , Shelton Amy , Pederson Zachary , Hu Chloe , Leung Dennis , Nagapudi Karthik , Ubhayakar Savita , Wright Matthew , Yen Chun-Wan , Appel Eric A.
Published: September 2022

Vision impairment resulting from chronic eye diseases, such as macular degeneration and glaucoma, severely impacts patients’ quality of life and poses an immense global financial burden. Current standard of care for such diseases includes daily eye drops or frequent intravitreal (ITV) injections, which are burdensome treatment modalities resulting in low patient compliance. There remains a growing need for easily administered long-acting delivery technologies for prolonging exposure of ocular therapeutics with each administration. Here, we deploy a supramolecular polymer-nanoparticle (PNP) hydrogel for ITV delivery of the glaucoma drug bimatoprost. PNP hydrogels are shear-thinning and self-healing, key properties for injectability, and enable slow release of molecular cargo in vitreous humor (VH) mimics. An in vivo study in New Zealand white rabbits demonstrated intravitreally injected PNP hydrogels form depots that degrade slowly over time, maintaining detectable levels of bimatoprost in the VH up to eight weeks following injection. Ophthalmic examinations and histopathology identified a mild foreign body response (FBR) to the hydrogel, characterized by rare clusters of foamy macrophages and giant cells associated with minimal, patchy fibroplasia. This work shows that PNP hydrogels exhibit numerous desirable traits for sustained drug delivery and further work will be necessary to optimize tolerability in the eye.
A high-quality chromosome-level genome assembly of rohu carp, Labeo rohita, and its utilization in SNP-based exploration of gene flow and sex determination
Authors: Arick Mark A. , Grover Corrinne E. , Hsu Chuan-Yu , Magbanua Zenaida , Pechanova Olga , Miller Emma R. , Thrash Adam , Youngblood Ramey C. , Ezzell Lauren , Alam Md Samsul , Benzie John A. H. , Hamilton Matthew G. , Karsi Attila , Lawrence Mark L. , Peterson Daniel G.
Published: September 2022

Labeo rohita (rohu) is a carp important to aquaculture in South Asia, with a production volume close to Atlantic salmon. While genetic improvements to rohu are ongoing, the genomic methods commonly used in other aquaculture improvement programs have historically been precluded in rohu, partially due to the lack of a high quality reference genome. Here we present a high-quality de novo genome produced using a combination of next-generation sequencing technologies, resulting in a 946 Mb genome consisting of 25 chromosomes and 2,844 unplaced scaffolds. Notably, while approximately half the size of the existing genome sequence, our genome represents 97.9% of the genome size newly estimated here using flow cytometry. Sequencing from 120 individuals was used in conjunction with this genome to predict the population structure, diversity, and divergence in three major rivers (Jamuna, Padma, and Halda), in addition to infer a likely sex determination mechanism in rohu. These results demonstrate the utility of the new rohu genome in modernizing some aspects of rohu genetic improvement programs.
Scaling protein-water interactions in the Martini 3 coarse-grained force field to simulate transmembrane helix dimers in different lipid environments
Authors: Cabezudo Ainara Claveras , Athanasiou Christina , Tsengenes Alexandros , Wade Rebecca C.
Published: September 2022

Martini 3, the latest version of the widely used Martini force field for coarse-grained molecular dynamics simulations, is a promising tool to investigate proteins in phospholipid bilayers. However, simulating other lipid environments, such as detergent micelles, presents challenges due to the absence of validated parameters for their constituent molecules. Here, we propose parameters for the micelle-forming surfactant, dodecylphosphocholine (DPC). These result in micelle assembly with aggregation numbers in agreement with experimental values. However, we identified a lack of hydrophobic interactions between transmembrane helix protein dimers and the tails of DPC molecules, preventing insertion and stabilization of the protein in the micelles. This problem was also observed for protein insertion by self-assembling 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or dipalmitoylphosphatidylcholine (DPPC) bilayers. We propose the reduction of the non-bonded interactions between protein and water beads by 10% as a simple and effective solution to this problem that enables protein encapsulation in phospholipid micelles and bilayers without altering protein dimerization or bilayer structure.

Abstract Figure
Conformational Changes Regulate Metal Coordination in the Catalytic Sites of Cas9
Authors: Das Anuska , Rai Jay , Roth Mitchell O. , Shu Yuerong , Medina Megan L. , Barakat MacKenzie R. , Li Hong
Published: September 2022

The control of CRISPR-Cas9 activities plays an essential role in its safe adoption for clinical and research applications. Previous studies have identified conformational dynamics of Cas9 as a key regulatory element for its enzymatic activity. The molecular basis for how conformations influence the catalytic processes at both nuclease domains, however, remains elusive. Here we present well-resolved cryo-EM structures of the activeAcidothermus cellulolyticusCas9 (AceCas9) complexes representing pre-cleavage (2.9 Å), two reaction intermediate (2.2 Å and 2.4 Å) and two post-cleavage (2.6 Å and 2.7 Å) states that reveal active site rearrangement during DNA binding and phosphodiester bond breakage by Cas9. Strikingly, large domain rearrangements in Cas9 triggered by the cognate DNA result in subtle changes in active sites that facilitate coordination of metal ions required for catalysis. The two reaction intermediate structures further reveal small oscillations in domain conformations, which alternates the reactive states of the two catalytic centers, thereby coupling cleavage of the two DNA strands. Consistent with the roles of conformations in organizing the active sites, adjustments of metal coordination ligands lead to altered metal specificity.
Cardiovascular risk in a rural psychiatric inpatient population: Retrospective case cohort study
Authors: Woodall Alan , Prosser Amy , Griffiths Millie , Shooter Ben , Garfitt Joy , Walker Lauren , Buchan Iain
Published: September 2022

Aims and Method

To evaluate cardiovascular risk in a rural inpatient psychiatric unit over a one-year period. Care records were analysed for risk factor recording, and cardiovascular risks estimated using the QRISK3 calculator, which estimates 10-year risk of myocardial infarction or stroke.

Results

Of eligible patients, risk factor recording as part of routine care was completed in 86% of possible QRISK3 inputs, enabling QIRSK3 estimation in all eligible patients. QRISK3 for this group was raised (Relative risk: 3.8, 95%CI: 2.5 – 5.0). High risk of cardiovascular disease (QRISK3 score >10%) was detected in 28% of patients.

Clinical Implications

This service evaluation demonstrated significant unmet need for cardiovascular risk reduction that could be identified as part of routine care. An opportunity exists to integrate mental and physical healthcare by routinely assessing cardiovascular risk in psychiatric inpatients. Resources and training are needed to produce this risk information and act on it.
The landscape of functional brain network impairments in late-onset GM2 gangliosidosis
Authors: Rangaprakash D , Rowe Olivia E , Stephen Christopher D , Eichler Florian S , Ratai Eva-Maria , Barry Robert L
Published: September 2022

Late-onset GM2 gangliosidosis (LOGG) is an ultra-rare neurological disease with motor, cognitive and psychiatric manifestations. It is caused by mutations in the HEXA or HEXB genes. Although cerebellar structural and metabolic impairments have been established, global brain functional impairments in this disease remain unknown. In this first functional MRI (fMRI) report on LOGG (N=14), we took an exploratory, multi-pronged approach by assessing impairments in several resting-state fMRI signal characteristics: fMRI signal strength, neurovascular coupling, static and time-varying functional connectivity, and network topology. Contrary to the predominance of cerebellar aberrations in prior non-functional studies, we found more widespread cortical aberrations (p<0.05, FDR-corrected) mainly in cognitive control networks but also in the default mode and somatomotor networks. There was reduced fMRI signal strength, enhanced neurovascular coupling, pathological hyper-connectivity, and altered temporal variability of connectivity in the LOGG cohort. We also observed an imbalance between functional segregation and integration as seen in other psychiatric/neurological disorders, with heightened segregation and suppressed integration (i.e., inefficient brain-wide communication). Some of these imaging markers were significantly associated with clinical measures, as well as with HEXA and HEXB gene expression. These aberrations might contribute to psychiatric symptoms (psychosis, mood disturbances), cognitive impairments (memory, attention, executive function), and oculomotor disturbances commonly seen in LOGG. Future LOGG imaging studies should probe brain function in addition to structure/metabolism while looking for mechanistic insights beyond the cerebellum.
Comparison of the effect of water jet cavitation peening on stress corrosion cracking behavior of nickel-based alloy 600 and alloy 182 in high temperature water
Authors: Ming Tingyun , Peng Qunjia , Han Yaolei , Zhang Tao
Published: September 2022

Purpose

This paper aims to understand the effect of water jet cavitation peening (WJP) on stress corrosion cracking (SCC) behavior of alloy 600 and alloy 182 in high temperature water.

Design/methodology/approach

Surface and cross-section morphology, grain boundary microstructure, residual stress and strain distribution, hardness and surface roughness in water jet cavitation peened alloy 600 and alloy 182 were characterized.

Findings

A superior stress corrosion cracking resistance was obtained in 600MA, which can be attributed to the formation of the ultrafine grain layer and the higher magnitude residual compressive stress.

Originality/value

Relationship between WJP-induced microstructure and stress state change and SCC susceptibility was conducted. It could provide a theoretical basis for developing application of WJP in nuclear power plants.
Actor engagement: origin, evolution and trends
Authors: Barrera Rodríguez Ana María , Duque Oliva Edison Jair , Vieira Salazar Jaime Andrés
Published: September 2022

Purpose

This paper aims to present the literature review on engagement in marketing, specifically on the concept of actor engagement (AE), to identify the most influential countries, authors, journals and institutions, their structure and research lines.

Design/methodology/approach

This review was carried out from a bibliometric and network analysis of documents published in the Scopus and Web of Science databases.

Findings

A total of 223 documents were found that were scientifically mapped in this field. The network analysis identified four perspectives or research clusters: customer engagement, the conceptualization, co-creation of value and service ecosystems. Finally, the agenda for future research is presented.

Originality/value

This paper carries out a bibliometric and network analysis, so far not done, of the literature on AE in which its perspectives and future lines of research were identified.
The journey of business transformation: unfreeze, change and refreeze – a multiple case study
Authors: Santos Edilson , Queiroz Maurício , Borini Felipe Mendes , Carvalho Daniel , Dutra Joel Souza
Published: September 2022

Purpose

The purpose of the study is to identify which factors facilitate and hinder change management in the business strategy execution journey and contribute to its transformation.

Design/methodology/approach

Companies that have implemented organizational transformation projects, as an adaptive response to their survival, were studied. The authors chose to work with three companies that went through strong changes in the period between 2014 and 2019. A total of 12 professionals were interviewed, encompassing top management and team members.

Findings

Cases were described, and the learning from them culminated in the recommendation of six managerial propositions, which should guide change agents in the planning and execution of their business transformation journeys.

Research limitations/implications

The findings were observed in the three case studies that implemented change management strategies. Failure case studies were not considered, which could present other managerial propositions.

Originality/value

The results of the article highlight the importance of coalition issue before the urgency in the organizational change model and also the importance of institutionalization along the change journey. As a managerial contribution is the model called “framework of the journey of execution and transformation of corporate strategy”, which serves as guidance for executives and agents of change in organizations.
The long-term relationship between the US housing market and HNWIs
Authors: Le Fur Eric
Published: September 2022

Purpose

The authors analyze the long-term relationship between the US housing market and the concentration of high net worth individuals.

Design/methodology/approach

The authors apply a cointegration and causality approach on a ten years database. The database includes by US state the density of high net worth individuals, the house price index, the homeownership rate, the number of housing units, and the privately-owned housing units authorized by building permits.

Findings

The results show a limited cointegration between the concentration of US wealthy households and the housing market. Thus, the authors can partly predict the fluctuations transmission from the housing market to wealthy households.

Originality/value

The authors suggest that our findings could be of interest to wealthy households, real estate professionals, and public authorities.
Foster carers' perceptions of the long‐term effectiveness of the Fostering Changes programme
Authors: Whitehead Loren , Barraclough Shanee , Tarren‐Sweeney Michael
Published: September 2022

The present article reports foster carer perceptions of the long‐term effectiveness of a carer‐focussed training intervention – the Fostering Changes (FC) programme. Five foster carers who completed FC at a not‐for‐profit child and family agency in New Zealand were interviewed 13–15 months post‐training about their experiences and perceptions of FC and its subsequent effectiveness. Interpretative phenomenological analysis (IPA) informed both data collection and analysis. Five superordinate themes were identified: (1) FC is perceived to be an effective training programme that provides sustained benefits; (2) foster carer training is crucially important; (3) the challenges of fostering continue, irrespective of training; (4) caregiver confidence gained from training wanes over time in the face of persistent challenges; (5) foster carers require ongoing therapeutic interventions and support because of their children's persistent behavioural and relational difficulties. The findings suggest that, while FC provides effective and relevant training, carers simultaneously require ongoing clinical services.

Practitioner points

Children in out‐of‐home care who have persistent relational and mental health difficulties require ongoing specialised therapeutic support

Foster carer group training (such as Fostering Changes) may help to stabilise children's placements and mental health recovery but does not replace the need for personalised, systemic interventions with caregivers

Foster carer group therapeutic training is preferably integrated within ongoing, systemic, multi‐component interventions, rather than offered as discrete, stand‐alone interventions
Experiences in successive forensic analysis of GSR and DNA traces collected on a single tape lift stub
Authors: Stamouli Amalia , van den Berge Margreet , Roepnarain Richard C. , Wesseling Vincent R. A. , Wiskerke Demi , Sijen Titia
Published: September 2022

Gunshot residue (GSR) and deoxyribonucleic acid (DNA) analyses are used in the reconstruction of shooting incidents involving firearms. In both fields, adhesive tapes are commonly applied to recover traces. Using a simultaneous sampling approach for retrieving both types of traces from objects related to a shooting can be powerful. We present the results for DNA testing and GSR analysis using “DNA stubs” to recover both types of traces in one sampling. The analyses are successive: stubs are first examined with scanning electron microscopy for the presence of GSR and next subjected to DNA extraction and short tandem repeat (STR) typing. The results show no negative effect on the DNA and GSR results. The risk of DNA contamination during GSR analysis is addressed, showing that it is negligible. Our experiences in casework show that the approach can be successfully implemented.
Effect of different activation methods on the intratubular penetration of CaOH2 paste: Ex‐vivo analysis by confocal laser scanning microscopy
Authors: Tadano João Pedro Gasparin , Bueno Carlos Eduardo da Silveira , Silveira Cláudia Fernandes de Magalhães , Yamanaka Tainara Bielecki , Piai Gabriela Gonçalez , Duarte Marco Antônio Húngaro , Vivan Rodrigo Ricci , De Martin Alexandre Sigrist
Published: September 2022

The aim of this study was to evaluate the maximum penetration depth (MPD) and penetration area (PA) of CaOH2 paste agitated by different methods and to measure the pH after performing these methods. Fifty‐five mandibular premolars were divided into control, GL and 4 experimental groups, GEC, GXP, GEDDY and GI (n = 11), where the paste was agitated with Easy Clean, XP‐endo Finisher, EDDY and Irrisonic, respectively. The canals were instrumented and irrigated with NaOCl. The paste was manipulated with propylene glycol and rhodamine B dye. Root sections were examined using confocal laser scanning microscopy. There was no difference between groups regarding PA (p > 0.05). At 5 mm, MPD was greater in GEC than in GL or GEDDY, and greater in GI than in GL (p < 0.05). At 2 mm, MPD was greater in GEC than in the other groups (p < 0.05). In conclusion, both Easy Clean and Irrisonic promoted deeper paste penetration and were associated with higher pH levels.
Prevention and treatment of pediatric pain and anxiety caused by botulinum neurotoxin A injections: Inadmissible without nitrous oxide analgesia and sedation?
Authors: Friedrichsdorf Stefan J.
Published: September 2022

This commentary is on the original article by Ostojic et al. on pages 1507–1516 of this issue.
Mechanisms underlying the blood pressure‐lowering effects of empagliflozin, losartan and their combination in people with type 2 diabetes: A secondary analysis of a randomized crossover trial
Authors: Scholtes Rosalie A. , Mosterd Charlotte M. , Hesp Anne C. , Smits Mark M. , Heerspink Hiddo J. L. , van Raalte Daniël H.
Published: September 2022

Aim

To study the effects of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved.

Methods

A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m2; estimated glomerular filtration rate: 90 ml/min/1.73m2) received a 1‐week treatment with empagliflozin 10 mg once daily, losartan 50 mg once daily, their combination, and placebo, in a randomized double‐blind crossover design, with 4‐week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed.

Results

Versus placebo (139 mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8 mmHg (P = .001), losartan by 12 mmHg (P = .001) and empagliflozin + losartan by 15 mmHg (P < .001). Combination therapy had a larger SBP‐lowering effect versus empagliflozin monotherapy (‐7 [95% CI ‐12; ‐2] mmHg) and numerically larger effects versus losartan monotherapy (‐3 [‐8; 2] mmHg). Empagliflozin reduced sympathetic nervous system (SNS) activity, arterial stiffness and extracellular fluid, while increasing serum albumin. Losartan reduced SNS activity and arterial stiffness. Combination therapy induced volume contraction variables, together with a reduction in SNS activity and arterial stiffness.

Conclusion

In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure‐lowering effect versus placebo than either of the drugs alone. Our data further suggest that the mechanisms underlying these blood pressure reductions at least partially differ between these agents.