[The Molecular and Genetic Mechanisms of Sex Determination in Poplar].

The study of molecular and genetic mechanisms of sex determination in the poplar is of interest not only in the fundamental science, but also in the applied research. In landscaping of large settlements, it is advisable to use male individuals of the Populus genus due to their hypoallergenicity and increased resistance to environmental pollution, stress conditions, and pathogens. However, sex determination in poplars is complicated by the complex genetic structure of the sex-determining region of the genome (SDR). In this review, the emergence, evolution, structure, and function of the SDR in the genus Populus are discussed. Current insights into the structure and function of the key regulator of sex selection in poplars, orthologue of the ARR16/ARR17 gene and the possible roles of other genes that are differentially expressed between male and female plants, including microRNAs, in this process are discussed in detail. The great diversity of species and the high complexity of SDR organization justify the need for further study of the molecular mechanisms of sex determination in poplars.

Personal Genetic-Hypertension Odyssey From Phenotypes to Genotypes and Targets.

Hypertension requires increased systemic vascular resistance. Thus far, Mendelian hypertension-related genes are related to salt retention, an indirect regulatory effect. With the identification of mutated, overactive, PDE3A (phosphodiesterase 3A), we have uncovered a more direct vasoconstrictive mechanism. The autosomal-dominant syndrome features another specific phenotype, brachydactyly type E. Hypertension and the bony phenotype invariably occur together. We distinguished between these phenotypes by examining individual pedigrees. We implicated the gene encoding the parathyroid hormone-related peptide in the brachydactyly. We identified the hypertensive mechanisms as involving regulatory-region, gain-of-function, exon 4 rare pathogenic variants, in the cAMP-cGMP-catabolizing enzyme, PDE3A. We generated rodent models that recapitulate all human phenotypes. Comparisons not only allowed pathogenic insights into the human condition but also provided intervention models. Moreover, we identified rare pathogenic variants in exon 13 encoding the enzymatic pocket. These patients had identical phenotypes, also corroborated in a rodent model, which produced the same human phenotypes. These data could allow the differentiation between a target organ and blood pressure phenotype. The research allows visualization of enzymatic processes at the intracellular nanodomain level. The scope of this project has elucidated genetic mechanisms important to cartilage development, possibly cancer metastases, and findings relevant to cardiovascular regulation via systemic vascular resistance. For our team, the project was an educational/scientific adventure over a professional lifetime.

Examining Roles, Challenges, and Opportunities Within the Metabolic Genetics Workforce.

The metabolic genetics clinic is a crucial hub for the management of patients with inborn errors of metabolism and other complex genetic conditions. Because more patients are being identified due to the expanded diagnostics, including newborn screening, and living longer with the advent of improved therapies, the multidisciplinary metabolic genetics team has been challenged in growing proportionally to meet patients' needs. Insufficient rates of recruitment to the field and increased levels of attrition have led to concerns about a rising shortage of metabolic genetics health care providers and necessitate creative solutions to grow the workforce. Here, we describe the roles and responsibilities of the multidisciplinary metabolic genetics team and describe opportunities to support patient care and promote clinician work-life balance in a rapidly changing field.

Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes.

BACKGROUND: Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. METHODS: This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. RESULTS: GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). CONCLUSIONS: GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Classification of PTEN germline non-truncating variants: a new approach to interpretation.

BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) encompasses distinct syndromes, including Cowden syndrome resulting from PTEN pathogenic variants. Missense variants account for 30% of PHTS cases, but their classification remains challenging. To address these difficulties, guidelines were published by the Clinical Genome Resource PTEN Variant Curation Expert Panel. METHODS: Between 2010 and 2020, the Bergonie Institute reference laboratory identified 76 different non-truncating PTEN variants in 166 patients, 17 of which have not previously been reported. Variants were initially classified following the current guidelines. Subsequently, a new classification method was developed based on four main criteria: functional exploration, phenotypic features and familial segregation, in silico modelling, and allelic frequency. RESULTS: This new method of classification is more discriminative and reclassifies 25 variants, including 8 variants of unknown significance. CONCLUSION: This report proposes a revision of the current PTEN variant classification criteria which at present rely on functional tests evaluating only the phosphatase activity of PTEN and apply a particularly stringent clinical PHTS score.The classification of non-truncating variants of PTEN is facilitated by taking into consideration protein stability for variants with intact phosphatase activity, clinical and segregation criteria adapted to the phenotypic variability of PHTS and by specifying the allelic frequency of variants in the general population. This novel method of classification remains to be validated in a prospective cohort.

Biology and genetic diversity of Candida krusei isolates from fermented vegetables and clinical samples in China.

Candida krusei, also known as Pichia kudriavzevii, is an emerging non-albicans Candida (NAC) species causing both superficial and deep-seated infections in humans. This fungal pathogen is inherently resistant to the first-line antifungal drug, fluconazole, and is widely distributed in natural environments such as soil, foods, vegetables, and fruits. In this study, we collected 86 C. krusei strains from clinical settings and traditional fermented vegetables from different areas of China. Compared to C. krusei strains from fermented vegetables, clinical isolates exhibited a higher ability to undergo filamentation and biofilm development, which could facilitate its host colonization and infections. Isolates from fermented vegetables showed higher resistance to several antifungal drugs including fluconazole, voriconazole, itraconazole, amphotericin B, and caspofungin, than clinical strains, while they were more susceptible to posaconazole than clinical strains. Although C. krusei has been thought to be a diploid organism, we found that one-fourth of clinical strains and the majority of isolates from fermented vegetables (87.5%) are triploid. Whole-genome sequencing and population genetic analyses demonstrated that isolates from clinical settings and fermented food are genetically associated, and distributed across a wide range of genetic clusters. Additionally, we found that six nucleotide substitutions at the promoter region of the ABC11 gene, encoding a multidrug efflux pump, could play a critical role in antifungal resistance in this species. Given the ubiquitous distribution of C. krusei strains in fermented vegetables and their genetic association with clinical strains, a One Health approach will be necessary to control the prevalence of this pathogen.

Prospective Evaluation of Extubation Failure in Neonates and Infants After Cardiac Surgery.

Background: Extubation failure and its associated complications are not uncommon after pediatric cardiac surgery, especially in neonates and young infants. We aimed to identify the frequency, etiologies, and clinical characteristics associated with extubation failure after cardiac surgery in neonates and young infants. Methods: We conducted a single center prospective observational study of patients ≤180 days undergoing cardiac surgery between June 2022 and May 2023 with at least one extubation attempt. Patients who failed extubation, defined as reintubation within 72 h of first extubation attempt, were compared with patients extubated successfully using χ2, Fisher exact, or Wilcoxon rank-sum tests as appropriate. Results: We prospectively enrolled 132 patients who met inclusion criteria, of which 11 (8.3%) failed extubation. Median time to reintubation was 25.5 h (range 0.4-55.8). Extubation failures occurring within 12 h (n = 4) were attributed to upper airway obstruction or apnea, whereas extubation failures occurring between 12 and 72 h (n = 7) were more likely to be due to intrinsic lung disease or cardiac dysfunction. Underlying genetic anomalies, greater weight relative to baseline at extubation, or receiving positive end expiratory pressure (PEEP) > 5 cmH2O at extubation were significantly associated with extubation failure. Conclusions: In this study of neonates and young infants recovering from cardiac surgery, etiologies of early versus later extubation failure involved different pathophysiology. We also identified weight relative to baseline and PEEP at extubation as possible modifiable targets for future investigations of extubation failure in this patient population.

A review of porcine skeletal muscle plasticity and implications for genetic improvement of carcass and meat quality.

Skeletal muscle is characterized by a remarkable plasticity to adapt to stimuli such as contractile activity, loading conditions, substrate supply or environmental factors. The existing knowledge of muscle plasticity along with developed genetic and genomic technologies, have enabled creating animal breeding strategies and allowed for implementing agriculturally successful porcine genetic improvement programs. The primary focus of this review paper is on pig skeletal muscle plasticity as it relates to genetic improvement of desirable carcass composition and pork quality traits. Biological constraints between practically realized breeding objectives, pig skeletal muscle biology, and pork quality are also discussed. Future applications of genetic and genomic technologies and plausible focus on new breeding objectives enhancing pork production sustainability are proposed as well.

Evolution of a large periplasmic disk in Campylobacterota flagella enables both efficient motility and autoagglutination.

The flagellar motors of Campylobacter jejuni (C. jejuni) and related Campylobacterota (previously epsilonproteobacteria) feature 100-nm-wide periplasmic "basal disks" that have been implicated in scaffolding a wider ring of additional motor proteins to increase torque, but the size of these disks is excessive for a role solely in scaffolding motor proteins. Here, we show that the basal disk is a flange that braces the flagellar motor during disentanglement of its flagellar filament from interactions with the cell body and other filaments. We show that motor output is unaffected when we shrink or displace the basal disk, and suppressor mutations of debilitated motors occur in flagellar-filament or cell-surface glycosylation pathways, thus sidestepping the need for a flange to overcome the interactions between two flagellar filaments and between flagellar filaments and the cell body. Our results identify unanticipated co-dependencies in the evolution of flagellar motor structure and cell-surface properties in the Campylobacterota.

Genetic variants associated with cardiac hypertrophy-related sudden cardiac death and cardiovascular outcomes in a Finnish population.

BACKGROUND: Hypertrophic cardiomyopathy is a common cause of non-ischaemic sudden cardiac death (SCD). Left ventricular hypertrophy (LVH) without cardiomyopathy-related myocardial disarray is a common autopsy finding and is often associated with prior hypertension in SCD subjects. Our aim was to investigate novel rare gene variants among SCD subjects with presumably hypertension-related LVH and myocardial fibrosis at autopsy. METHODS: Whole exome sequencing was used to study rare variants (minor allele frequency<0.005) estimated to be deleterious in 96 non-ischaemic SCD subjects with presumably hypertension-related LVH and myocardial fibrosis. Associations of the identified variants with cardiac disease endpoints were replicated in the Finnish national genetic study (FinnGen) dataset. RESULTS: 18 variants were estimated likely to affect protein function and 14 of these were associated with cardiomyopathies, heart failure, conduction abnormalities, hypertension and/or cardiac arrest in Finnish population (FinnGen). Three of the variants were classified as pathogenic or likely pathogenic. These include the splice site variant NM_000449.3:c.234-1G>A in regulatory factor X5 and frameshift variants NM_000449.3:c.234-1G>A in dehydrogenase/reductase 7C and NM_015873.3:c.1164del in villin like. CONCLUSIONS: We identified rare deleterious variants associated with LVH in SCD subjects. Several of the identified rare variants associated with cardiovascular endpoints including heart failure, cardiomyopathies, cardiac arrest and hypertension in general population.

The extraordinary "ordinary magic" of resilience.

In this essay, I will briefly sample different instances of the utilization of the concept of resilience, attempting to complement a comprehensive representation of the field in the special issue of Development and Psychopathology inspired by the 42nd Minnesota Symposium on Child Psychology, hosted by the Institute of Child Development at the University of Minnesota and held in October of 2022. Having established the general context of the field, I will zoom in on some of its features, which I consider "low-hanging fruit" and which can be harvested in a systematic way to advance the study of resilience in the context of the future of developmental psychopathology.

Corrigendum: Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

[This corrects the article DOI: 10.1177/15353702231198068.].

The importance of integrating phycological research, teaching, outreach, and engagement in a changing world.

The ecological, evolutionary, economic, and cultural importance of algae necessitates a continued integration of phycological research, education, outreach, and engagement. Here, we comment on several topics discussed during a networking workshop-Algae and the Environment-that brought together phycological researchers from a variety of institutions and career stages. We share some of our perspectives on the state of phycology by examining gaps in teaching and research. We identify action areas where we urge the phycological community to prepare itself to embrace the rapidly changing world. We emphasize the need for more trained taxonomists as well as integration with molecular techniques, which may be expensive and complicated but are important. An essential benefit of these integrative studies is the creation of high-quality algal reference barcoding libraries augmented with morphological, physiological, and ecological data that are important for studies of systematics and crucial for the accuracy of the metabarcoding bioassessment. We highlight different teaching approaches for engaging undergraduate students in algal studies and the importance of algal field courses, forays, and professional phycological societies in supporting the algal training of students, professionals, and citizen scientists.

Transcriptomic data sets for Novosphingobium aromaticivorans grown with the ß-5-linked aromatic dimer dehydrodiconiferyl alcohol and the related G-aromatic monomers vanillin and ferulic acid.

The transcriptomes of a 2-pyrone-4,6-dicarboxylic acid-producing strain of Novosphingobium aromaticivorans DSM12444 were determined when grown in minimal medium containing glucose alone or glucose plus vanillin, ferulic acid, or the ß-5-linked aromatic dimer dehydrodiconiferyl alcohol as carbon sources. Here, we present the RNA-sequencing data we obtained.

Family Screening in Hypertrophic Cardiomyopathy: Identification of Relatives With Low Yield From Systematic Follow-Up.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease, and clinical and genetic family screening is recommended by guidelines. OBJECTIVES: This study sought to investigate the diagnostic yield of screening relatives of HCM patients and identify predictive factors for HCM development during long-term follow-up in relatives from gene-elusive families. METHODS: This was a retrospective cohort study of families screened at clinics for inherited cardiomyopathies in Eastern Denmark, from 2006 to 2023. RESULTS: We included 1,230 relatives (55% female; age: 42 ± 17 years) from 531 families. The combined clinical and genetic yield at baseline was 26% (n = 321). After 7 years (mean) of follow-up (6,762 person-years), 43 (4%) additional relatives developed HCM. The strongest predictors of developing HCM were carrying a likely pathogenic/pathogenic variant (HR: 4.58; 95% CI: 2.50-8.40; P < 0.001) and larger left ventricular maximum wall thickness (MWT) (HR: 2.21 per mm; 95% CI: 1.76-2.77 per mm; P < 0.001). In gene-elusive families, we found that an MWT of ≥10 mm represented the optimal classification threshold for developing HCM (area under the curve: 0.80), with only 2 (0.4%) relatives from gene-elusive families with an MWT of <10 mm developing HCM during follow-up. CONCLUSIONS: In HCM, the diagnostic yield of a single screening visit was 1 in 4, and the additional yield during 7 years of follow-up was 4%. Gene carriers and relatives from gene-elusive families with a baseline MWT of ≥10 mm were at the highest risk of developing HCM during follow-up. These findings may inform future recommendations on the management of relatives of HCM patients.

Genetic predisposition to childhood cancer.

The etiology of childhood cancer remains largely unknown. Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis. Unlike adult cancers, pediatric cancers typically have a higher prevalence of germline pathogenic variants in cancer predisposition genes. Inherited cancer predisposition syndromes account for approximately 10% of all childhood cancers. Over the years, the diagnosis of cancer predisposition syndromes was based on clinical suspicion prompting referral to a specialized geneticist. However, advances in molecular technologies have led to a shift toward a "genotype-first" approach. Identification of genetic variants related to cancer predisposition enables tailored treatment, improves clinical outcome, optimizes surveillance, and facilitates genetic counseling of the affected child and the family.