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Stem Cell Research Dec 2023Congenital Disorders of Glycosylation (CDG) are rare inherited metabolic diseases caused by genetic defects in the glycosylation of proteins and lipids. In this study,...
Generation of human induced pluripotent stem cell line (AOUMEYi001-A) from a patient affected by Congenital disorders of glycosylation (ALG8-CDG) using self-replicating RNA vector.
Congenital Disorders of Glycosylation (CDG) are rare inherited metabolic diseases caused by genetic defects in the glycosylation of proteins and lipids. In this study, we describe the generation and characterization of one human induced pluripotent stem cell (hiPSC) line from a 15-year-old male patient with CDG. The patient carried three variants, one (c.122G > A; p.Arg41Gln) inherited from his father and two (c.445 T > G; p.Leu149Arg and the novel c.980C > G; p.Thr327Arg) inherited from his mother in the ALG8 gene (OMIM #608103). The generated hiPSC line shows a normal karyotype, expresses pluripotency markers, and is able to differentiate into the three germ layers.
Topics: Male; Humans; Adolescent; Congenital Disorders of Glycosylation; Induced Pluripotent Stem Cells; Glycosylation; Glucosyltransferases; Mutation
PubMed: 38323760
DOI: 10.1016/j.scr.2023.103235 -
BMC Plant Biology Feb 2024Mounting evidence recognizes structural variations (SVs) and repetitive DNA sequences as crucial players in shaping the existing grape phenotypic diversity at intra- and...
Mounting evidence recognizes structural variations (SVs) and repetitive DNA sequences as crucial players in shaping the existing grape phenotypic diversity at intra- and inter-species levels. To deepen our understanding on the abundance, diversity, and distribution of SVs and repetitive DNAs, including transposable elements (TEs) and tandemly repeated satellite DNA (satDNAs), we re-sequenced the genomes of the ancient grapes Aglianico and Falanghina. The analysis of large copy number variants (CNVs) detected candidate polymorphic genes that are involved in the enological features of these varieties. In a comparative analysis of Aglianico and Falanghina sequences with 21 publicly available genomes of cultivated grapes, we provided a genome-wide annotation of grape TEs at the lineage level. We disclosed that at least two main clusters of grape cultivars could be identified based on the TEs content. Multiple TEs families appeared either significantly enriched or depleted. In addition, in silico and cytological analyses provided evidence for a diverse chromosomal distribution of several satellite repeats between Aglianico, Falanghina, and other grapes. Overall, our data further improved our understanding of the intricate grape diversity held by two Italian traditional varieties, unveiling a pool of unique candidate genes never so far exploited in breeding for improved fruit quality.
Topics: Humans; Vitis; Plant Breeding; DNA Transposable Elements; DNA, Satellite
PubMed: 38317087
DOI: 10.1186/s12870-024-04778-2 -
Public Health Research & Practice Jun 2024Skin cancer is highly preventable through primary prevention activities such as avoiding ultraviolet radiation exposure during peak times and regular use of sun... (Review)
Review
OBJECTIVES
Skin cancer is highly preventable through primary prevention activities such as avoiding ultraviolet radiation exposure during peak times and regular use of sun protection. General practitioners (GPs) and primary care nurses have key responsibilities in promoting sustained primary prevention behaviour. We aimed to review the evidence on skin cancer primary prevention activities in primary care settings, including evidence on feasibility, effectiveness, barriers and enablers.
STUDY TYPE
Rapid review and narrative synthesis.
METHODS
We searched published literature from January 2011 to October 2022 in Embase, Medline, PsychInfo, Scopus, Cochrane Central and CINAHL. The search was limited to skin cancer primary prevention activities within primary care settings, for studies or programs conducted in Australia or countries with comparable health systems. Analysis of barriers and enablers was informed by an implementation science framework.
RESULTS
A total of 31 peer-reviewed journal articles were included in the review. We identified four main primary prevention activities: education and training programs for GPs; behavioural counselling on prevention; the use of novel risk assessment tools and provision of risk-tailored prevention strategies; and new technologies to support early detection that have accompanying primary prevention advice. Enablers to delivering skin cancer primary prevention in primary care included pairing preventive activities with early detection activities, and access to patient resources and programs that fit with existing workflows and systems. Barriers included unclear requirements for skin cancer prevention counselling, competing demands within the consultation and limited access to primary care services, especially in regional and remote areas.
CONCLUSIONS
These findings highlight potential opportunities for improving skin cancer prevention activities in primary care. Ensuring ease of program delivery, integration with early detection and availability of resources such as risk assessment tools are enablers to encourage and increase uptake of primary prevention behaviours in primary care, for both practitioners and patients.
Topics: Humans; Skin Neoplasms; Primary Health Care; Primary Prevention; Australia
PubMed: 38316050
DOI: 10.17061/phrp34012401 -
Annals of Clinical and Translational... Mar 2024ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal...
OBJECTIVE
ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series.
METHODS
We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant.
RESULTS
We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing.
INTERPRETATION
This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease.
Topics: Adult; Humans; Muscular Diseases; Muscle, Skeletal; Actinin; Phenotype; Cardiomyopathies
PubMed: 38311799
DOI: 10.1002/acn3.51983 -
Pulmonology Feb 2024
PubMed: 38309994
DOI: 10.1016/j.pulmoe.2024.01.003 -
Life (Basel, Switzerland) Jan 2024Chickpeas ( L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and...
Application of Biostimulant in Seeds and Soil on Three Chickpea Varieties: Impacts on Germination, Vegetative Development, and Bacterial Facilitation of Nitrogen and Phosphorus.
Chickpeas ( L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and plant processes, it is crucial to address demand. Achieving this necessitates implementing sustainable agricultural practices incorporating the use of biostimulants, adaptable crops for arid conditions, as well as pest and disease-resistant crops that are sustainable over time. Three varieties of chickpeas were analysed to determine the effect of two different biostimulant application methods on both germination and vegetative growth. Possible effects due to location were also examined by conducting tests at two different sites. Significant variations in biostimulant response were evident only during the germination period, but not during the vegetative development stage, where the observed statistical differences were influenced more by the location or variety of chickpeas employed. Furthermore, this study examined the effect of biostimulants on nutrient cycling within the soil-plant microbiota system. Nitrogen-fixing bacteria (NFB) are present in the soil of chickpea crops at an order of magnitude of 10 CFU/g DS. Additionally, an average concentration of 10 CFU/g DS of phosphorus-mobilising bacteria was observed. Applying biostimulants (BioE) to seeds resulted in a successful germination percentage (GP) for both Amelia (AM) and IMIDRA 10 (IM) varieties.
PubMed: 38276277
DOI: 10.3390/life14010148 -
Journal of Anatomy Jun 2024The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular...
The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies.
Topics: Humans; Male; Ectromelia; Female; Magnetic Resonance Imaging; Abnormalities, Multiple; Pregnancy; Fetus
PubMed: 38267217
DOI: 10.1111/joa.14015 -
Cells Jan 2024P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in a variety of cells. Five of the family members... (Review)
Review
P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in a variety of cells. Five of the family members are sensitive to low concentrations of extracellular ATP, while the P2X6 receptor has an unknown affinity. The last subtype, the P2X7 receptor, is unique in requiring millimolar concentrations to fully activate in humans. This low sensitivity imparts the agonist with the ability to act as a damage-associated molecular pattern that triggers the innate immune response in response to the elevated levels of extracellular ATP that accompany inflammation and tissue damage. In this review, we focus on microglia because they are the primary immune cells of the central nervous system, and they activate in response to ATP or its synthetic analog, BzATP. We start by introducing purinergic receptors and then briefly consider the roles that microglia play in neurodevelopment and disease by referencing both original works and relevant reviews. Next, we move to the role of extracellular ATP and P2X receptors in initiating and/or modulating innate immunity in the central nervous system. While most of the data that we review involve work on mice and rats, we highlight human studies of P2X7R whenever possible.
Topics: Rats; Mice; Humans; Animals; Microglia; Central Nervous System; Adenosine Triphosphate; Alarmins; Receptors, Purinergic P2X7
PubMed: 38247852
DOI: 10.3390/cells13020161 -
Journal of Assisted Reproduction and... Mar 2024To examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital...
PURPOSE
To examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital deliveries.
METHODS
We conducted a retrospective cohort study using medical health records of deliveries occurring in 2016-2022 at a women's specialty hospital in a southern state of the Unites States (US). Pregnancies achieved using medically assisted reproductive (MAR) techniques were compared with unassisted pregnancies using propensity score matching (PSM), based on demographic, preexisting health, and reproductive factors. Study outcomes included cesarean delivery, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), delivery complications, and postpartum readmission. We used Poisson regression with robust standard errors to generate risk ratios (RRs) and 95% confidence intervals (CIs) for all study outcomes.
RESULTS
Among 57,354 deliveries, 586 (1.02%) pregnancies were achieved using MAR and 56,768 (98.98%) were unassisted ("non-MAR"). Compared to the non-MAR group, MAR pregnancies had significantly higher prevalence of all study outcomes, including GDM (15.9% vs. 11.2%, p < 0.001), HDP (28.2% vs. 21.1%, p < 0.001), cesarean delivery (56.1% vs. 34.6%, p < 0.001), delivery complications (10.9% vs. 6.8%, p = 0.03), and postpartum readmission (4.3% vs. 2.7%, p = 0.02). In a PSM sample of 584 MAR and 1,727 unassisted pregnancies, MAR was associated with an increased risk of cesarean delivery (RR = 1.11, 95% CI = 1.01-1.22); whereas IVF was associated with an increased risk of cesarean delivery (RR = 1.15, 95% CI = 1.03-1.28) and delivery complications (RR = 1.44, 95% CI = 1.04-2.01).
CONCLUSIONS
Women who conceived with MAR were at increased risk of cesarean deliveries, and those who conceived with IVF were additionally at risk of delivery complications.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Fertilization; Fertility; Diabetes, Gestational; Pre-Eclampsia; Cardiovascular Diseases; Pregnancy Outcome
PubMed: 38244153
DOI: 10.1007/s10815-024-03025-9 -
Public Health Feb 2024To update an earlier review, published in 2016, on the health and other outcomes associated with children and young people's consumption of energy drinks (EDs). (Review)
Review
OBJECTIVE
To update an earlier review, published in 2016, on the health and other outcomes associated with children and young people's consumption of energy drinks (EDs).
STUDY DESIGN
Review article.
SYSTEMATIC REVIEW
Systematic searches of nine databases (ASSIA, CINAHL, Cochrane Library, DARE, Embase, ERIC, MEDLINE, PsycINFO and Web of Science) retrieved original articles reporting the effects of EDs experienced by children and young people up to the age of 21 years. Searches were restricted by publication dates (January 2016 to July 2022) and language (English). Studies assessed as being weak were excluded from the review. Included studies underwent narrative synthesis.
RESULTS
A total of 57 studies were included. Boys consumed EDs more than girls. Many studies reported a strong positive association between ED consumption and smoking, alcohol use, binge drinking, other substance use and the intentions to initiate these behaviours. Sensation-seeking and delinquent behaviours were positively associated with ED consumption, as were short sleep duration, poor sleep quality and low academic performance. Additional health effects noted in the updated review included increased risk of suicide, psychological distress, attention-deficit hyperactivity disorder symptoms, depressive and panic behaviours, allergic diseases, insulin resistance, dental caries and erosive tooth wear.
CONCLUSIONS
This review adds to the growing evidence that ED consumption by children and young people is associated with numerous adverse physical and mental health outcomes. Where feasible and ethical, additional longitudinal studies are required to ascertain causality. The precautionary principle should be considered in regulatory policy and restriction of ED sales to this population.
PROSPERO REGISTRATION
CRD42021255484.
Topics: Child; Male; Female; Humans; Adolescent; Young Adult; Adult; Energy Drinks; Dental Caries; Alcohol Drinking; Substance-Related Disorders; Smoking
PubMed: 38228408
DOI: 10.1016/j.puhe.2023.08.024