bluuebunny/crossref_metadata_2025 huggingface dataset:
Concatenator, a user-friendly program to concatenate DNA sequences, implementing graphical user interfaces for MAFFT and FastTree
Authors: Vences Miguel , Patmanidis Stefanos , Kharchev Vladimir , Renner Susanne S
Published: July 2022

Motivation

Phylogenetic and phylogenomic analyses require multi-gene input files in different formats, but there are few user-friendly programs facilitating the workflow of combining, concatenating or separating, aligning and exploring multi-gene datasets.

Results

We present Concatenator, a user-friendly GUI-driven program that accepts single-marker and multi-marker DNA sequences in different input formats, including Fasta, Phylip and Nexus, and that outputs concatenated sequences as single-marker or multi-marker Fasta, interleaved nexus or Phylip files, including command files for downstream model selection in IQ-TREE. It includes the option to (re)align markers with MAFFT and produces exploratory trees with FastTree. Although tailored for medium-sized phylogenetic projects, Concatenator is able to process phylogenomic datasets of up to 30 000 markers.

Availability and implementation

Concatenator is written in Python, with C extensions for MAFFT and FastTree. Compiled stand-alone executables of Concatenator for MS Windows and Mac OS along with a detailed manual can be downloaded from www.itaxotools.org; the source code is openly available on GitHub (https://github.com/iTaxoTools/ConcatenatorGui).
Predicting and explaining the impact of genetic disruptions and interactions on organismal viability
Authors: Al-Anzi Bader F , Khajah Mohammad , Fakhraldeen Saja A
Published: July 2022

Motivation

Existing computational models can predict single- and double-mutant fitness but they do have limitations. First, they are often tested via evaluation metrics that are inappropriate for imbalanced datasets. Second, all of them only predict a binary outcome (viable or not, and negatively interacting or not). Third, most are uninterpretable black box machine learning models.

Results

Budding yeast datasets were used to develop high-performance Multinomial Regression (MN) models capable of predicting the impact of single, double and triple genetic disruptions on viability. These models are interpretable and give realistic non-binary predictions and can predict negative genetic interactions (GIs) in triple-gene knockouts. They are based on a limited set of gene features and their predictions are influenced by the probability of target gene participating in molecular complexes or pathways. Furthermore, the MN models have utility in other organisms such as fission yeast, fruit flies and humans, with the single gene fitness MN model being able to distinguish essential genes necessary for cell-autonomous viability from those required for multicellular survival. Finally, our models exceed the performance of previous models, without sacrificing interpretability.

Availability and implementation

All code and processed datasets used to generate results and figures in this manuscript are available at our Github repository at https://github.com/KISRDevelopment/cell_viability_paper. The repository also contains a link to the GI prediction website that lets users search for GIs using the MN models.

Supplementary information

Supplementary data are available at Bioinformatics online.
REALGAR: a web app of integrated respiratory omics data
Authors: Kan Mengyuan , Diwadkar Avantika R , Saxena Supriya , Shuai Haoyue , Joo Jaehyun , Himes Blanca E
Published: July 2022

Motivation

In the post genome-wide association study (GWAS) era, omics techniques have characterized information beyond genomic variants to include cell and tissue type-specific gene transcription, transcription factor binding sites, expression quantitative trait loci (eQTL) and many other biological layers. Analysis of omics data and its integration has in turn improved the functional interpretation of disease-associated genetic variants. Over 170 000 transcriptomic and epigenomic datasets corresponding to studies of various cell and tissue types under specific disease, treatment and exposure conditions are available in the Gene Expression Omnibus resource. Although these datasets are valuable to guide the design of experimental validation studies to understand the function of disease-associated genetic loci, in their raw form, they are not helpful to experimental researchers who lack adequate computational resources or experience analyzing omics data. We sought to create an integrated re-source of tissue-specific results from omics studies that is guided by disease-specific knowledge to facilitate the design of experiments that can provide biologically meaningful insights into genetic associations.

Results

We designed the Reducing Associations by Linking Genes and omics Results web app to provide multi-layered omics information based on results from GWAS, transcriptomic, epigenomic and eQTL studies for gene-centric analysis and visualization. With a focus on asthma datasets, the integrated omics results it contains facilitate the formulation of hypotheses related to airways disease-associated genes and can be addressed with experimental validation studies.

Availability and implementation

The REALGAR web app is available at: http://realgar.org/. The source code is available at: https://github.com/HimesGroup/realgar.

Supplementary information

Supplementary data are available at Bioinformatics online.
Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue
Authors: Monogue Brendan , Chen Yixi , Sparks Hadrian , Behbehani Ranya , Chai Andrew , Rajic Alexander J , Massey Aaron , Kleinschmidt-Demasters B K , Vermeren Matthieu , Kunath Tilo , Beckham J David
Published: July 2022

The protein alpha-synuclein is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson’s disease and dementia with Lewy bodies. However, the normal function of alpha-synuclein in neurons is not clearly defined. We have previously shown that mice lacking alpha-synuclein expression exhibit markedly increased viral growth in the brain, increased mortality and increased neuronal cell death, implicating alpha-synuclein in the neuronal innate immune response.

To investigate the mechanism of alpha-synuclein-induced immune responses to viral infections in the brain, we challenged alpha-synuclein knockout mice and human alpha-synuclein knockout dopaminergic neurons with RNA virus infection and discovered that alpha-synuclein is required for neuronal expression of interferon-stimulated genes. Furthermore, human alpha-synuclein knockout neurons treated with type 1 interferon failed to induce a broad range of interferon stimulated genes, implying that alpha-synuclein interacts with type 1 interferon signalling. We next found that alpha-synuclein accumulates in the nucleus of interferon-treated human neurons after interferon treatment and we demonstrated that interferon-mediated phosphorylation of STAT2 is dependent on alpha-synuclein expression in human neurons. Next, we found that activated STAT2 co-localizes with alpha-synuclein following type 1 interferon stimulation in neurons. Finally, we found that brain tissue from patients with viral encephalitis expresses increased levels of phospho-serine129 alpha-synuclein in neurons.

Taken together, our results show that alpha-synuclein expression supports neuron-specific interferon responses by localizing to the nucleus, supporting STAT2 activation, co-localizing with phosphorylated STAT2 in neurons and supporting expression of interferon-stimulated genes. These data provide a novel mechanism that links interferon activation and alpha-synuclein function in neurons.
Disentangling the effects of Alzheimer’s and small vessel disease on white matter fibre tracts
Authors: Dewenter Anna , Jacob Mina A , Cai Mengfei , Gesierich Benno , Hager Paul , Kopczak Anna , Biel Davina , Ewers Michael , Tuladhar Anil M , de Leeuw Frank-Erik , Dichgans Martin , Franzmeier Nicolai , Duering Marco ,   for the SVDs@target Consortium and Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: July 2022

Alzheimer’s disease and cerebral small vessel disease are the two leading causes of cognitive decline and dementia and coexist in most memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature in both Alzheimer’s and cerebral small vessel disease. However, disease-specific biomarkers of white matter alterations are missing. Recent advances in diffusion MRI operating on the fixel level (fibre population within a voxel) promise to advance our understanding of disease-related white matter alterations. Fixel-based analysis allows derivation of measures of both white matter microstructure, measured by fibre density, and macrostructure, measured by fibre-bundle cross-section. Here, we evaluated the capacity of these state-of-the-art fixel metrics to disentangle the effects of cerebral small vessel disease and Alzheimer’s disease on white matter integrity.

We included three independent samples (total n = 387) covering genetically defined cerebral small vessel disease and age-matched controls, the full spectrum of biomarker-confirmed Alzheimer’s disease including amyloid- and tau-PET negative controls and a validation sample with presumed mixed pathology. In this cross-sectional analysis, we performed group comparisons between patients and controls and assessed associations between fixel metrics within main white matter tracts and imaging hallmarks of cerebral small vessel disease (white matter hyperintensity volume, lacune and cerebral microbleed count) and Alzheimer’s disease (amyloid- and tau-PET), age and a measure of neurodegeneration (brain volume).

Our results showed that (i) fibre density was reduced in genetically defined cerebral small vessel disease and strongly associated with cerebral small vessel disease imaging hallmarks; (ii) fibre-bundle cross-section was mainly associated with brain volume; and (iii) both fibre density and fibre-bundle cross-section were reduced in the presence of amyloid, but not further exacerbated by abnormal tau deposition. Fixel metrics were only weakly associated with amyloid- and tau-PET.

Taken together, our results in three independent samples suggest that fibre density captures the effect of cerebral small vessel disease, while fibre-bundle cross-section is largely determined by neurodegeneration. The ability of fixel-based imaging markers to capture distinct effects on white matter integrity can propel future applications in the context of precision medicine.
A right to memory and communication policy: safeguarding the capability of remembrance
Authors: Tirosh Noam , Schejter Amit M
Published: July 2022

Can a right to memory be counted among the rights society needs to safeguard, if so, what are its theoretical and conceptual foundations, and how do they relate to communications? We answer these questions by offering a new perspective regarding the right’s components, origin and justifications, the mechanisms needed to realize it and the legal framework required for such realization. We begin by first recognizing the fundamental role of memory in human life, in particular as it pertains to the creation, preservation, and endowment of identity, which justifies the need to protect it. We then discuss memory’s four elements—remembering, forgetting, being remembered, and being forgotten—and their dependence on communications. We follow by describing the nature of rights and the distinction between different types of rights. This helps us claim that recognizing the right to memory requires ensuring the capability to communicate by designing appropriate communication policies.
Cooperative National Regulation to Secure Transnational Public Goods: A Reply to Nico Krisch
Authors: O’Keefe Roger
Published: July 2022

There is no doubt, as vividly highlighted in Nico Krisch’s ‘Jurisdiction Unbound: (Extra)territorial Regulation as Global Governance’, that in certain sectors some economically weighty states seek to take advantage of the international law of jurisdiction with a view to determining unilaterally how particular transnational economic activities are conducted. This same law, however, particularly the jurisdictional obligations provided for among states parties by multilateral treaties, is not only capable of serving cooperative national regulation to secure transnational public goods but in respect of a wide range of activities is already doing so. Rather than a fundamental ‘reorientation of jurisdiction towards the solution of common problems and the protection of global interests’, what is needed is political will and diplomatic agreement to use even further the existing law, especially the treaty-based possibilities that it offers, to these ends.
Alternative Modes of Introgression-Mediated Selection Shaped Crop Adaptation to Novel Climates
Authors: Blanco-Pastor José Luis
Published: July 2022

Recent plant genomic studies provide fine-grained details on the evolutionary consequences of adaptive introgression during crop domestication. Modern genomic approaches and analytical methods now make it possible to better separate the introgression signal from the demographic signal thus providing a more comprehensive and complex picture of the role of introgression in local adaptation. Adaptive introgression has been fundamental for crop expansion and has involved complex patterns of gene flow. In addition to providing new and more favorable alleles of large effect, introgression during the early stages of domestication also increased allelic diversity at adaptive loci. Previous studies have largely underestimated the effect of such increased diversity following introgression. Recent genomic studies in wheat, potato, maize, grapevine, and ryegrass show that introgression of multiple genes, of as yet unknown effect, increased the effectiveness of purifying selection, and promoted disruptive or fluctuating selection in early cultivars and landraces. Historical selection processes associated with introgression from crop wild relatives provide an instructive analog for adaptation to current climate change and offer new avenues for crop breeding research that are expected to be instrumental for strengthening food security in the coming years.
Peering in: youth perspectives on Health Promoting Schools and youth engagement in Nova Scotia, Canada
Authors: Kontak Julia C , Caldwell Hilary A T , Kay-Arora Margaret , Hancock Friesen Camille L , Kirk Sara F L
Published: July 2022

Health Promoting Schools (HPS) is a whole-school approach that shapes the conditions necessary to support student health and well-being. Youth engagement is recognized as key to HPS implementation, yet research related to the involvement of youth voice in school health promotion initiatives is limited. The purpose of this study was to understand youth perspectives on HPS and school youth engagement. Ten youth (grades 9–10, ages 14–16) were trained as peer researchers using a Youth Participatory Action Research approach. The peer researchers interviewed 23 of their peers (grades 7–10, ages 12–16) on perspectives related to HPS and school youth engagement. All interviews were audio-recorded, transcribed and data were analysed using inductive ‘codebook’ thematic analysis. Themes related to a healthy school community were mapped onto the pillars of HPS: (i) Social and Physical Environment, (ii) Teaching and Learning, (iii) Partnerships and Services and (iv) School Policies. Participants placed more importance on the social and physical environment of the school including respect, inclusivity, supportive relationships and the design of spaces. Key factors for youth engagement were: (i) safe and supportive spaces, (ii) passion and interest, (iii) using their voice, (iv) power dynamics, (v) accessibility and (vi) awareness. With recognition that youth engagement is a crucial part of HPS, this work provides relevant and applicable information on areas of the healthy school community that are important to youth, and if/how they are meaningfully engaged in school decision-making.
A Mendelian randomization study to assess the genetic liability of gastroesophageal reflux disease for cardiovascular diseases and risk factors
Authors: Sun Xingang , Chen Lu , Zheng Liangrong
Published: July 2022

Observational studies have reported that gastroesophageal reflux disease (GERD) is a risk factor for cardiovascular diseases (CVD); however, the causal inferences between them remain unknown. We conducted a Mendelian randomization (MR) study to estimate the causal associations between GERD and 10 CVD outcomes, as well as 14 cardiovascular risk factors. We used summary statistics from genome-wide association studies for GERD and the FinnGen consortium for CVD. We further investigated whether GERD correlated with cardiovascular risk factors and performed multivariable MR and mediation analyses to estimate the mediating effects of these risk factors on GERD–CVD progression. Sensitivity analyses and replication analyses were also performed. Our results indicated that GERD was positively associated with seven CVD outcomes with odds ratios of 1.26 [95% confidence interval (CI), 1.15, 1.37] for coronary artery disease, 1.41 (95% CI, 1.28, 1.57) for myocardial infarction, 1.34 (95% CI, 1.19, 1.51) for atrial fibrillation, 1.34 (95% CI, 1.21, 1.50) for heart failure, 1.30 (95% CI, 1.18, 1.43) for any stroke, 1.19 (95% CI, 1.06, 1.34) for ischemic stroke and 1.29 (95% CI, 1.16, 1.44) for venous thromboembolism. Furthermore, GERD was associated with nine cardiovascular risk factors and major depressive disorder demonstrated significant mediation effects on the causal pathway linking GERD and any stroke. This study demonstrates that GERD is associated with seven CVD outcomes and nine cardiovascular risk factors. Importantly, GERD treatment may help prevent common CVD events.
Behavioral impulsivity is associated with pupillary alterations and hyperactivity in CDKL5 mutant mice
Authors: Viglione Aurelia , Sagona Giulia , Carrara Fabio , Amato Giuseppe , Totaro Valentino , Lupori Leonardo , Putignano Elena , Pizzorusso Tommaso , Mazziotti Raffaele
Published: July 2022

Cyclin-dependent kinase-like 5 (Cdkl5) deficiency disorder (CDD) is a severe neurodevelopmental condition caused by mutations in the X-linked Cdkl5 gene. CDD is characterized by early-onset seizures in the first month of life, intellectual disability, motor and social impairment. No effective treatment is currently available and medical management is only symptomatic and supportive. Recently, mouse models of Cdkl5 disorder have demonstrated that mice lacking Cdkl5 exhibit autism-like phenotypes, hyperactivity and dysregulations of the arousal system, suggesting the possibility to use these features as translational biomarkers. In this study, we tested Cdkl5 male and female mutant mice in an appetitive operant conditioning chamber to assess cognitive and motor abilities, and performed pupillometry to assess the integrity of the arousal system. Then, we evaluated the performance of artificial intelligence models to classify the genotype of the animals from the behavioral and physiological phenotype. The behavioral results show that CDD mice display impulsivity, together with low levels of cognitive flexibility and perseverative behaviors. We assessed arousal levels by simultaneously recording pupil size and locomotor activity. Pupillometry reveals in CDD mice a smaller pupil size and an impaired response to unexpected stimuli associated with hyperlocomotion, demonstrating a global defect in arousal modulation. Finally, machine learning reveals that both behavioral and pupillometry parameters can be considered good predictors of CDD. Since early diagnosis is essential to evaluate treatment outcomes and pupillary measures can be performed easily, we proposed the monitoring of pupil size as a promising biomarker for CDD.
The influence of regulation of medically assisted reproduction on the risk of hospitalization in the first 2 years of life
Authors: Basso Olga , Shapiro Gabriel D , Twardowski Sarah E , Monnier Patricia , Buckett William , Tamblyn Robyn
Published: July 2022

STUDY QUESTION

Do publicly funded fertility treatment and single embryo transfer (SET) result in lower hospitalization rates of children of parents with infertility?

SUMMARY ANSWER

Following the 2010 Quebec law introducing free fertility treatment and SET, neonatal intensive care unit (NICU) admissions decreased among all children born to parents with infertility, but not among singletons, whose risk remained slightly higher than that of children of parents without infertility, even accounting for treatment and maternal age.

WHAT IS KNOWN ALREADY

Previous studies reported lower NICU admission rates among children conceived with ART after the 2010 law; however, children conceived without ART by parents with infertility were not considered.

STUDY DESIGN, SIZE, DURATION

Cohort study of children born in 1997–2017 to patients evaluated for infertility (‘exposed’) at an academic fertility center in Montreal (Canada) in 1996–2015. A random sample of births to Montreal residents served as comparison. Outcomes were identified from Quebec administrative databases.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We compared children’s healthcare utilization before and after the 2010 law in 6273 exposed and 12 583 randomly sampled births (6846 and 12 775 children, respectively). We repeated the analysis among children conceived in the 63 months before and after the law (‘restricted period’), and examined whether differences in twinning, fertility treatment, and maternal age explained the higher risk of NICU admission among children of parents with infertility.

MAIN RESULTS AND THE ROLE OF CHANCE

In the exposed cohort, the proportion of twin births and of several adverse outcomes declined after the law. NICU admission and duration of NICU stay decreased overall, but not in singletons. Both measures remained higher in exposed children. Except for NICU admission, hospitalization rates were similar in exposed and random sample children. After accounting for fertility treatment and maternal age, exposed singletons were 17% more likely to be admitted to the NICU than children of parents with no medical history of infertility.

LIMITATIONS, REASONS FOR CAUTION

Sample size was relatively small; infertile patients were from a single center and the random sample from one city. Despite some limitations, administrative databases are likely to accurately reflect healthcare utilization.

WIDER IMPLICATIONS OF THE FINDINGS

Universal access to treatment and, particularly, SET results in an overall reduction of adverse outcomes among children conceived with treatment; however, children of parents with infertility are at a slightly higher risk, regardless of treatment.

STUDY FUNDING/COMPETING INTEREST(S)

This study was funded by the Canadian Institutes for Health Research (CIHR, grant no. 123362). No competing interests.

TRIAL REGISTRATION NUMBER

N/A.
Two unusual variants of pulmonary intra-lobar sequestration
Authors: Pauels Laura , De Waele Michèle , Medart Laurent , Debruche Mathieu
Published: July 2022

A pulmonary sequestration is a congenital malformation characterized by non-functional lung tissue with abnormal arterial systemic supply and abnormal connection to the bronchial tree. This may lead to recurrent infections rendering a surgical intervention more demanding. Because of multiple anatomic variations, it is important to obtain high-quality preoperative radiological clarification to determine the most suitable surgical approach. Although a non-surgical technique, consisting of embolization of the aberrant artery has been described, a surgical technique remains the treatment of choice in operable patients. Preoperative embolization of the aberrant artery may reduce the risk of haemorrhage but could cause technical challenges in a hybrid approach and therefore unforeseen peroperative stress to the surgical team. We report 2 adult patients with unusual intra-lobar sequestration with aberrant vascular rare anatomy. Both were treated by surgery. In the latter patient, we performed a hybrid approach. This was complicated by peroperative coils exposure making it a technical challenge to proceed.
Tipping Points: Challenges in Analyzing International Crisis Escalation
Authors: Chen Chong , Roberts Jordan , Adhikari Shikshya , Asal Victor , Beardsley Kyle , Gonzalez Edward , Jahanbani Nakissa , James Patrick , Lobell Steven E , Ripsman Norrin M , Silverstone Scott , van Wijk Anne
Published: July 2022

Why do some near crises tip over into full-blown crisis and others do not? This paper considers existing scholarship and identifies four key barriers to using quantitative analysis for tipping-point analyses: strategic indeterminacy; the incentives for conflict parties to avoid inefficiencies; the paucity of cases; and the availability of quality data. Due to these challenges, many do not perform well as immediate causes for crisis escalation. We also argue and demonstrate through two quantitative models of crisis escalation that some variables, particularly related to domestic politics, can do well in explaining why some disputes tip into crisis and others do not. As we illustrate with reference to the 1995–1996 Third Taiwan Straits Crisis, qualitative approaches that analyze the processes by which leaders and foreign policy institutions make decisions add needed explanatory power to purely quantitative models of the potential for near crises to tip into crisis.
Conventional papillary thyroid carcinoma with intraglandular lymphatic dissemination shows more aggressive features
Authors: Lei Yuanyuan , Feng Sha , Yu Qiuxiao , Shen Guihua , Yuan Lijuan , Huang Wenting
Published: July 2022

Objective

To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intraglandular lymphatic dissemination.

Methods

Seventy-three conventional papillary thyroid carcinoma patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining. The results were evaluated by two pathologists and were statistically analyzed. The rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intraglandular dissemination, multifocal non-intraglandular dissemination-CVPTC and single focus-CVPTC were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density, microvessel density and the clinicopathological characteristics of conventional papillary thyroid carcinoma were assessed.

Results

Twenty-five intraglandular dissemination-CVPTC, 17 multifocal non-intraglandular dissemination-CVPTC and 31 single focus-CVPTC cases were included in this study. The results showed that BRAF-V600E expression was independently correlated with intraglandular dissemination, age and pN staging (P < 0.05). The lymphatic vessel density in the intraglandular dissemination-CVPTC group was higher than that in the non-intraglandular dissemination-CVPTC group (P < 0.05). Compared with cases without intraglandular dissemination, intraglandular dissemination-CVPTC was associated with a younger age, higher lymph node metastasis rate, pN staging, the expression of BRAF-V600E and increased Capsule invasion and lymphovascular tumor thrombus (P < 0.05). During the follow-up of 30 months (median 15 months), two patients in the intraglandular dissemination-CVPTC group had cervical lymph node metastasis after the first operation.

Conclusions

Intraglandular dissemination-CVPTC shows more aggressive features, and intraglandular lymphatic dissemination may be a potential biological indicator of poor prognosis.
Structures of multisubunit membrane complexes with the CRYO ARM 200
Authors: Gerle Christoph , Kishikawa Jun-ichi , Yamaguchi Tomoko , Nakanishi Atsuko , Çoruh Orkun , Makino Fumiaki , Miyata Tomoko , Kawamoto Akihiro , Yokoyama Ken , Namba Keiichi , Kurisu Genji , Kato Takayuki
Published: July 2022

Progress in structural membrane biology has been significantly accelerated by the ongoing ‘Resolution Revolution’ in cryo-electron microscopy (cryo-EM). In particular, structure determination by single-particle analysis has evolved into the most powerful method for atomic model building of multisubunit membrane protein complexes. This has created an ever-increasing demand in cryo-EM machine time, which to satisfy is in need of new and affordable cryo-electron microscopes. Here, we review our experience in using the JEOL CRYO ARM 200 prototype for the structure determination by single-particle analysis of three different multisubunit membrane complexes: the Thermus thermophilus V-type ATPase VO complex, the Thermosynechococcus elongatus photosystem I monomer and the flagellar motor lipopolysaccharide peptidoglycan ring (LP ring) from Salmonella enterica.
Compartmentalization, a key mechanism controlling the multitasking role of the SnRK1 complex
Authors: Gutierrez-Beltran Emilio , Crespo Jose L
Published: July 2022

SNF1-related protein kinase 1 (SnRK1), the plant ortholog of mammalian AMP-activated protein kinase/fungal (yeast) Sucrose Non-Fermenting 1 (AMPK/SNF1), plays a central role in metabolic responses to reduced energy levels in response to nutritional and environmental stresses. SnRK1 functions as a heterotrimeric complex composed of a catalytic α- and regulatory β- and βγ-subunits. SnRK1 is a multitasking protein involved in regulating various cellular functions, including growth, autophagy, stress response, stomatal development, pollen maturation, hormone signaling, and gene expression. However, little is known about the mechanism whereby SnRK1 ensures differential execution of downstream functions. Compartmentalization has been recently proposed as a new key mechanism for regulating SnRK1 signaling in response to stimuli. In this review, we discuss the multitasking role of SnRK1 signaling associated with different subcellular compartments.
KMT-2021-BLG-0171Lb and KMT-2021-BLG-1689Lb: two microlensing planets in the KMTNet high-cadence fields with followup observations
Authors: Yang Hongjing , Zang Weicheng , Gould Andrew , Yee Jennifer C , Hwang Kyu-Ha , Christie Grant , Sumi Takahiro , Zhang Jiyuan , Mao Shude ,   (Leading Authors), Albrow Michael D , Chung Sun-Ju , Han Cheongho , Jung Youn Kil , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Cha Sang-Mok , Kim Dong-Jin , Kim Hyoun-Woo , Kim Seung-Lee , Lee Chung-Uk , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W ,   (The KMTNet Collaboration), Drummond John , Maoz Dan , McCormick Jennie , Natusch Tim , Penny Matthew T , Zhu Wei ,   (The MAP, μFUN Follow-up Teams), Bond Ian A , Abe Fumio , Barry Richard , Bennett David P , Bhattacharya Aparna , Donachie Martin , Fujii Hirosane , Fukui Akihiko , Hirao Yuki , Itow Yoshitaka , Kirikawa Rintaro , Kondo Iona , Koshimoto Naoki , Li Man Cheung Alex , Matsubara Yutaka , Muraki Yasushi , Miyazaki Shota , Olmschenk Greg , Ranc Clément , Rattenbury Nicholas J , Satoh Yuki , Shoji Hikaru , Silva Stela Ishitani , Suzuki Daisuke , Tanaka Yuzuru , Tristram Paul J , Yamawaki Tsubasa , Yonehara Atsunori ,   (The MOA Collaboration)
Published: July 2022

Follow-up observations of high-magnification gravitational microlensing events can fully exploit their intrinsic sensitivity to detect extrasolar planets, especially those with small mass ratios. To make followup observations more uniform and efficient, we develop a system, HighMagFinder, to automatically alert possible ongoing high-magnification events based on the real-time data from the Korea Microlensing Telescope Network (KMTNet). We started a new phase of follow-up observations with the help of HighMagFinder in 2021. Here we report the discovery of two planets in high-magnification microlensing events, KMT-2021-BLG-0171 and KMT-2021-BLG-1689, which were identified by the HighMagFinder. We find that both events suffer the ‘central-resonant’ caustic degeneracy. The planet-host mass-ratio is q ∼ 4.7 × 10−5 or q ∼ 2.2 × 10−5 for KMT-2021-BLG-0171, and q ∼ 2.5 × 10−4 or q ∼ 1.8 × 10−4 for KMT-2021-BLG-1689. Together with two other events, four cases that suffer such degeneracy have been discovered in the 2021 season alone, indicating that the degenerate solutions may have been missed in some previous studies. We also propose a quantitative factor to weight the probability of each solution from the phase space. The resonant interpretations for the two events are disfavoured under this consideration. This factor can be included in future statistical studies to weight degenerate solutions.
Uncovering Signals of Positive Selection in Peruvian Populations from Three Ecological Regions
Authors: Caro-Consuegra Rocio , Nieves-Colón Maria A , Rawls Erin , Rubin-de-Celis Verónica , Lizárraga Beatriz , Vidaurre Tatiana , Sandoval Karla , Fejerman Laura , Stone Anne C , Moreno-Estrada Andrés , Bosch Elena
Published: July 2022

Peru hosts extremely diverse ecosystems which can be broadly classified into the following three major ecoregions: the Pacific desert coast, the Andean highlands, and the Amazon rainforest. Since its initial peopling approximately 12,000 years ago, the populations inhabiting such ecoregions might have differentially adapted to their contrasting environmental pressures. Previous studies have described several candidate genes underlying adaptation to hypobaric hypoxia among Andean highlanders. However, the adaptive genetic diversity of coastal and rainforest populations has been less studied. Here, we gathered genome-wide single-nucleotide polymorphism-array data from 286 Peruvians living across the three ecoregions and analyzed signals of recent positive selection through population differentiation and haplotype-based selection scans. Among highland populations, we identify candidate genes related to cardiovascular function (TLL1, DUSP27, TBX5, PLXNA4, SGCD), to the Hypoxia-Inducible Factor pathway (TGFA, APIP), to skin pigmentation (MITF), as well as to glucose (GLIS3) and glycogen metabolism (PPP1R3C, GANC). In contrast, most signatures of adaptation in coastal and rainforest populations comprise candidate genes related to the immune system (including SIGLEC8, TRIM21, CD44, and ICAM1 in the coast; CBLB and PRDM1 in the rainforest; and BRD2, HLA-DOA, HLA-DPA1 regions in both), possibly as a result of strong pathogen-driven selection. This study identifies candidate genes related to human adaptation to the diverse environments of South America.
COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease
Authors: Avanoglu Guler Aslihan , Yuce Inel Tuba , Kasifoglu Timucin , Coskun Cansu , Karadeniz Hazan , Yildirim Derya , Bilici Reyhan , Satis Hasan , Kucuk Hamit , Haznedaroglu Seminur , Goker Berna , Ozturk Mehmet Akif , Sari Ismail , Tufan Abdurrahman
Published: July 2022

Objectives

To evaluate the impact of familial Mediterranean fever (FMF) features on the clinical course and outcomes of coronavirus disease 2019 (COVID-19) and clinical course of FMF after COVID-19.

Methods

Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records.

Results

Seventy-three FMF patients were included in the study. 94.5% of patients had clinical symptoms of COVID-19. We found 24.7% hospitalization, 12.3% respiratory support, 4.1% intensive care unit admission, 6.8% complication, and 1.4% mortality rate in patients. The risk factors of hospitalization for respiratory support were male gender [OR: 7.167 (95% CI: 1.368–37.535)], greater age [OR: 1.067 (95% CI: 1.016–1.121)], and non-adherence to colchicine treatment before the infection [OR: 7.5 (95% CI: 1.348–41.722)]. One-third of patients had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia.

Conclusions

FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased, with some of them being protracted and destructive.
Optical and near-infrared photometric and polarimetric monitoring at flaring state of BL Lacertae in 2020–2021
Authors: Hazama Natsuko , Sasada Mahito , Imazawa Ryo , Fukazawa Yasushi , Kawabata Koji S , Nakaoka Tatsuya , Akitaya Hiroshi
Published: July 2022

BL Lacertae (BL Lac) was in an unprecedented bright state since 2020 August. We have conducted long-term photometric and polarimetric observations of BL Lac in optical and near-infrared (NIR) bands using the Kanata telescope in the Higashi-Hiroshima Observatory. BL Lac had simultaneously brightened in the NIR, optical, X-ray, and gamma-ray bands during the brightening period. There were two peaks of brightness in the optical and NIR bands. The degree of polarization and electric-vector position angle (EVPA) were also found to have fluctuated in the optical and NIR bands. A bluer-when-brighter trend was observed between the optical and NIR bands during the entire period of our observation. Furthermore, during the first bright period, the EVPA became parallel to the position angle of the jet. On the other hand, the polarization during the second brightening showed a different behavior from that during the first brightening. The brightenings can be explained by a combination of a shock acceleration in which a shock was generated with the perpendicular-direction shock front of the jet and a variation of the inclination angle.
Beneficial BacteriumAzospirillum brasilenseInduces Morphological, Physiological and Molecular Adaptation to Phosphorus Deficiency inArabidopsis
Authors: Sun Nan , Huang Lin , Zhao Hongcheng , Zhang Nan , Lin Xianyong , Sun Chengliang
Published: July 2022

Although most cultivated soils have high levels of total phosphorus (P), the levels of bioavailable inorganic P (Pi) are insufficient. The application of plant-growth-promoting rhizobacteria (PGPR) is an eco-friendly strategy for P utilization; however, PGPR-mediated plant responses that enhance Pi acquisition remain unexplored. Here, we investigated the effect of Azospirillum brasilense on Arabidopsis adaptation to Pi deficiency. Results showed that A. brasilense inoculation alleviated Pi-deficiency-induced growth inhibition and anthocyanin accumulation and increased the total P content in Arabidopsis plants. A comprehensive analysis of root morphology revealed that A. brasilense increased root hair density and length under Pi-limited conditions. We further demonstrated that A. brasilense enhanced the acid phosphatase activity and upregulated the expression of several Pi transporter genes, such as PHOSPHATE1 (PHO1), PHOSPHATE TRANSPORTER 1:(PHT1:1) and PHT1;4. However, A. brasilense did not enhance the growth o total P content in pht1;1, pht1;4 and pht1;1pht1;4 mutants. Moreover, A. brasilense could not increase the P content and PHT1;1 expression in the root hairless mutant rsl4rsl2, because of the occurrence of low-Pi-induced PHT1;1 and PHT1;4 in root hairs. These results indicate that A. brasilense can promote root hair development and enhance acid phosphatase activity and Pi transporter expression levels, consequently improving the Pi absorption capacity and conferring plant tolerance to Pi deficiency.
A Role for Allantoate Amidohydrolase (AtAAH) in the Germination of Arabidopsis thaliana Seeds
Authors: Yazdanpanah Farzaneh , Willems Leo A J , He Hanzi , Hilhorst Henk W M , Bentsink Leónie
Published: July 2022

Seed dormancy is a very complex trait controlled by interactions between genetic and environmental factors. Nitrate is inversely correlated with seed dormancy in Arabidopsis. This is explained by the fact that seed dry storage (after-ripening) reduces the need for nitrogen for germination. When nitrate is absorbed by plants, it is first reduced to nitrite and then to ammonium for incorporation into amino acids, nucleic acids and chlorophyll. Previously, we showed that ALLANTOATE AMIDOHYDROLASE (AtAAH) transcripts are up-regulated in imbibed dormant seeds compared with after-ripened seeds. AAH is an enzyme in the uric acid catabolic pathway which catalyzes the hydrolysis of allantoate to yield CO2, NH3 and S-ureidoglycine. This pathway is the final stage of purine catabolism, and functions in plants and some bacteria to provide nitrogen, particularly when other nitrogen sources are depleted. Ataah mutant seeds are more dormant and accumulate high levels of allantoate, allantoin and urea, whereas energy-related metabolites and several amino acids are lower upon seed imbibition in comparison with Columbia-0. AtAAH expression could be detected during the early stages of seed development, with a transient increase around 8 d after pollination. AtAAH expression is the highest in mature pollen. The application of exogenous potassium nitrate can partly complement the higher dormancy phenotype of the Ataah mutant seeds, whereas other nitrogen sources cannot. Our results indicate that potassium nitrate does not specifically overcome the alleviated dormancy levels in Ataah mutant seeds, but promotes germination in general. Possible pathways by which AtAAH affects seed germination are discussed.
Communication network within the essential AAA-ATPase Rix7 drives ribosome assembly
Authors: Kocaman Seda , Lo Yu-Hua , Krahn Juno M , Sobhany Mack , Dandey Venkata P , Petrovich Matthew L , Etigunta Suhas K , Williams Jason G , Deterding Leesa J , Borgnia Mario J , Stanley Robin E
Published: July 2022

Rix7 is an essential AAA+ ATPase that functions during the early stages of ribosome biogenesis. Rix7 is composed of three domains including an N-terminal domain (NTD) and two AAA+ domains (D1 and D2) that assemble into an asymmetric stacked hexamer. It was recently established that Rix7 is a presumed protein translocase that removes substrates from preribosomes by translocating them through its central pore. However, how the different domains of Rix7 coordinate their activities within the overall hexameric structure was unknown. We captured cryo-electron microscopy (EM) structures of single and double Walker B variants of full length Rix7. The disordered NTD was not visible in the cryo-EM reconstructions, but cross-linking mass spectrometry revealed that the NTD can associate with the central channel in vitro. Deletion of the disordered NTD enabled us to obtain a structure of the Rix7 hexamer to 2.9 Å resolution, providing high resolution details of critical motifs involved in substrate translocation and interdomain communication. This structure coupled with cell-based assays established that the linker connecting the D1 and D2 domains as well as the pore loops lining the central channel are essential for formation of the large ribosomal subunit. Together, our work shows that Rix7 utilizes a complex communication network to drive ribosome biogenesis.
Prevention of suicidal behavior in diabetes: the role of primary care
Authors: Sher L
Published: July 2022

Studies in different countries suggest that the rates of suicide ideation, attempts and death are increased in patients with diabetes in comparison to the general population. Suicidal behavior in patients with diabetes is a significant but underappreciated problem. Elevated suicide risk in individuals with diabetes may be related to comorbid psychiatric disorders, particularly depression. Considerable evidence suggests a bidirectional relationship between diabetes and depression: individuals with diabetes are at elevated risk of developing depression and patients with depression are more likely to develop diabetes. Frequent comorbidity of diabetes and depression may be related to psychosocial and neurobiological factors. Other comorbid psychiatric conditions including anxiety and alcohol use disorders may also increase suicide risk in diabetes. Primary care physicians are likely the key to suicide prevention efforts in individuals with diabetes since they see almost half of individuals who die by suicide within 1 month of their suicide. The management of potentially suicidal patients with diabetes in primary care comprises six major components: management of diabetes and its complications, especially conditions associated with pain; diagnosis and treatment of comorbid psychiatric disorders; frequent assessment of suicide risk; restricting access to the means of suicide; specific treatments to reduce the predisposition to attempt suicide; and referral to psychiatric care. Suicide prevention in individuals with diabetes and other medical disorders is a difficult but critically important task.
Addressing the Needs of People with Schizophrenia in South Africa During the COVID-19 Pandemic
Authors: Thela Lindokuhle , Talatala Mvuyiso , Chiliza Bonginkosi
Published: July 2022

Research indicates that most people with Schizophrenia from low to middle-income countries do not receive adequate healthcare. Inadequate policies, lack of funding, poor service planning and neglect are some barriers to adequate care. Intrinsic barriers to care include stigma, lack of insight, and pathways to care that are often driven by cultural beliefs, and many systemic challenges. South Africa was not spared from the scourge of COVID-19, hosting a third of all reported cases in Africa. In a country with disparities, it would be of interest to get insight into the situation concerning the healthcare needs of people with Schizophrenia during the pandemic. A pandemic such as COVID-19 placed enormous strains on already limited and unequally distributed health care resources. In this paper, we discuss: (1) The South African healthcare system (with respect to Schizophrenia care). (2) COVID-19 policies related to the care of people with Schizophrenia (testing, access to vaccine). (3) Managing people with Schizophrenia amid the COVID-19 pandemic. (4) Recommendations.
CE: Original Research: Cognitive Behavioral Therapy for Symptom Management in Treatment-Resistant Schizophrenia
Authors: Ryan Matilda , Sattenspiel Dina , Chianese Alexander , Rice Helen
Published: July 2022

Background:

Treatment-resistant schizophrenia (TRS) comes with significant medical comorbidities, including heart disease, liver disease, and diabetes—all of which contribute to higher mortality rates and shortened life expectancy. Second-generation antipsychotic medications do not consistently alleviate psychotic symptoms, especially among patients with TRS. Clozapine, the gold standard of pharmacological treatment for TRS, offers only partial relief for many patients. Additional treatment approaches, which include cognitive behavioral therapy (CBT), are often necessary.

Purpose:

The aim of this integrative review was to assess the efficacy of CBT as an adjunctive treatment for TRS in various study populations.

Methods:

The Johns Hopkins Nursing Evidence-Based Practice Model and Guidelines were used to guide the review. A literature search of PubMed, CINAHL, Scopus, and PsycInfo was conducted, and a total of 66 articles were identified. Strong inclusion and exclusion criteria were applied to ensure that only high-quality studies were included for analysis.

Results:

Of the eight studies that met the eligibility criteria, five indicated that CBT has statistically significant efficacy in reducing positive psychotic symptoms of TRS. There was also evidence that in implementing CBT, a follow-up period of at least six months helps to sustain improvements.

Conclusions:

CBT can be a safe and effective adjunctive treatment for patients with this illness. We recommend that nurses who work in psychiatric settings, EDs, and home health or community care settings obtain training in CBT.
New Drug Treats Rare Genetic Overgrowth Disorder
Authors: Aschenbrenner Diane S.
Published: July 2022

The Food and Drug Administration has approved alpelisib (Vijoice) to treat a rare noninherited genetic disorder called PIK3CA-related overgrowth spectrum.
High Stress Levels Among Families of ICU Patients Critically Ill with COVID-19
Authors: Rosenberg Karen
Published: July 2022

According to this study:

Many family members of patients admitted to the ICU with COVID-19 during the early months of the pandemic reported significant symptoms of posttraumatic stress disorder, more than before the crisis.