BMP signaling: at the gate between activated melanocyte stem cells and differentiation.

Through recurrent bouts synchronous with the hair cycle, quiescent melanocyte stem cells (McSCs) become activated to generate proliferative progeny that differentiate into pigment-producing melanocytes. The signaling factors orchestrating these events remain incompletely understood. Here, we use single-cell RNA sequencing with comparative gene expression analysis to elucidate the transcriptional dynamics of McSCs through quiescence, activation, and melanocyte maturation. Unearthing converging signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated. Employing conditional lineage-specific genetic ablation studies in mice, we found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation. We show that interestingly, BMP signaling functions downstream from activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, and chromatin landscaping, we show that following WNT-mediated activation of McSCs, BMP and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation. Our findings shed light upon the signaling interplay and timing of cues that orchestrate melanocyte lineage progression in the hair follicle and underscore a key role for BMP signaling in driving complete differentiation.

Trunk distortion weakens the tree productivity revealed by half-sib progeny determination of Pinus yunnanensis.

Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1-3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79-0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families' genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.

Genetic parameter changes and age-age correlations in Pinus koraiensis growth over 40-year progeny testing.

BACKGROUND: Early selection in tree breeding could be achieved by addressing the longevity of tree improvement activities. Genetic parameter changes and age-age correlations are essential for determining the optimal timing of early selection. Practical tracking of genetic parameters of Pinus koraiensis, a major timber species with economic and ecological value, has become feasible as its progeny testing has entered the mid-term age in Korea. However, research on the age-age correlation of P. koraiensis as progeny trials approach rotation age is limited. This study aimed to investigate genetic parameter trends and age-age correlations in P. koraiensis progeny. P. koraiensis progeny were assessed at two sites using a linear mixed-effects model with two-dimensional spatial autoregressive structure. Height, diameter, and volume growth were measured in 11 assessments over 40 years. RESULTS: Genetic parameters, such as height and diameter, showed different patterns of change. The heritability ranged for the three growth traits in 0.083-0.710, 0.288-0.781, and 0.299-0.755 across the sites and age. Height heritability and its coefficient of variance decreased, whereas the diameter and volume estimates remained relatively constant. Correlations with Age 40 for phenotypic, genetic, and rank of breeding values ranged between 0.16 and 0.92, 0.594 and 0.988, and 0.412 and 0.965, respectively. These correlations generally increased as the age approached Age 40, with particularly high levels observed at Age 26 and Age 30. CONCLUSION: The observed genetic trends in P. koraiensis progeny testing offer valuable insights for early and precise selection. Notably, selecting superior genotypes at Ages 26-30 is supported by discernible genetic gains and robust correlations. Future research should integrate unbalanced data for selecting mother trees or families and conduct a comprehensive economic analysis of early selection to validate its practical benefits.

Examination of the PET in vivo generator 134Ce as a theranostic match for 225Ac.

PURPOSE: The radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of 134Ce offer perspectives for developing innovative in vivo investigations that are not possible with 225Ac. In this work, 225Ac- and 134Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, 134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging. METHODS: The precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with 225Ac or 134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The 225Ac and 134Ce-labelled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody. RESULTS: In vitro and in vivo studies with both 225Ac and 134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the 134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of 134Ce's PET-compatible daughter 134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing 225Ac-labelled tracers are not quantitatively represented by 134Ce PET imaging. CONCLUSION: When employing slow-internalizing vectors, 134Ce might not be an ideal match for 225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of 134La. However, this same characteristic makes it possible to estimate the redistribution of 225Ac's progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment.

Inbreeding in Chinese fir: Insights into the adaptive growth traits of selfed progeny from mRNA, miRNA, and copy number variation.

PREMISE: The impact of inbreeding on biological processes is well documented in individuals with severe inbreeding depression. However, the biological processes influencing the adaptive growth of normal selfed individuals are unknown. Here, we aimed to investigate how inbreeding affects gene expression for adaptive growth of normal selfed seedlings from a self-fertilizing parent in Chinese fir (Cunninghamia lanceolata). METHODS: Using RNA-seq data from above- and underground tissues of abnormal and normal selfed seedlings, we analyzed GO biological processes network. We also sequenced small RNAs in the aboveground tissues and measured the copy number variations (CNV) of the hub genes. RESULTS: Phenotypic fitness analysis revealed that the normal seedlings were better adapted than their abnormal counterparts. Upregulated differentially expressed genes (DEGs) were associated with development processes, and downregulated DEGs were mainly enriched in fundamental metabolism and stress response. Results of mRNA-miRNA parallel sequencing revealed that upregulated target genes were predominantly associated with development, highlighting their crucial role in phosphorylation in signal transduction networks. We also discovered a moderate correlation (0.1328 < R2 < 0.6257) between CNV and gene expression levels for three hub genes (TMKL1, GT2, and RHY1A). CONCLUSIONS: We uncovered the key biological processes underpinning the growth of normal selfed seedlings and established the relationship between CNV and the expression levels of hub genes in selfed seedlings. Understanding the candidate genes involved in the growth of selfed seedlings will help us comprehend the genetic mechanisms behind inbreeding depression in the evolutionary biology of plants.

Spatial transcriptomics reveals gene interactions and signaling pathway dynamics in rat embryos with anorectal malformation.

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.

Effective dose assessment due to inhalation of 222Rn, 220Rn, and their progeny: highlighting the major contribution of thoron in a thoron-prone area in Cameroon.

To assess public exposure to radon, thoron, and their progeny, measurements were conducted in 50 dwellings within the bauxite-rich area of Fongo-Tongo in western Cameroon. Passive integrating radon-thoron discriminative detectors (specifically RADUET) were employed for radon and thoron measurements. Additionally, concentrations of short-lived radon and thoron progeny were estimated using Direct Radon Progeny Sensors (DRPSs) and Direct Thoron Progeny Sensors (DTPSs) based on LR-115 detectors. The findings revealed indoor radon concentrations ranging from 31 to 123 Bq m-3 with a geometric mean (GM) of 62 Bq m-3, and indoor thoron concentrations ranging from 36 to 688 Bq m-3 with a GM of 242 Bq m-3. The Equilibrium Equivalent Radon Concentration (EERC) ranged from 3 to 86 Bq m-3 with a GM of 25 Bq m-3, while the Equilibrium Equivalent Thoron Concentration (EETC) ranged from 1.2 to 12.5 Bq m-3 with a GM of 7.6 Bq m-3. Notably, all dwellings recorded radon concentrations below 100 Bq m-3. Arithmetic means of radon and thoron equilibrium factors were calculated as 0.47 and 0.04, respectively. To assess annual effective doses from radon and thoron inhalation, equilibrium factors were used along with direct measurements of EERC and EETC. The differences observed in annual effective doses were 4.5% for radon and 42.5% for thoron. Furthermore, the contribution of thoron and its decay products to the annual effective dose from radon, thoron, and their progeny ranged from 12 to 94%, with an average contribution of 58%. Thus, this study found that the effective dose due to thoron inhalation in the study area exceeded that due to radon inhalation. It is concluded that, when evaluating radiation doses and health risks, it is crucial to consider both thoron and its progeny alongside radon and its progeny. This underscores the importance of considering direct measurements for accurately estimating radiation doses.

Programming effects of intrauterine hyperthermia on adrenal gland development.

Maternal heat stress during late pregnancy can lead to intrauterine hyperthermia and affect fetal hypothalamic-pituitary-adrenal axis development and function. Herein, we investigated the effects of chronic environmental heat stress exposure of Holstein cows in the last 2 mo of gestation on their offspring's adrenal gland histomorphology and transcriptome. Cows in their last 54 ± 5 d of gestation were either heat stressed (housed under the shade of a freestall barn) or provided heat stress abatement via active cooling (via water soakers and fans) during a subtropical summer (temperature-humidity index >68). Respiration rate (RR) and skin temperature (ST) were elevated in heat-stressed dams relative to the cows with access to heat abatement (23 breaths/min and 2°C higher for RR and ST, respectively). Heifers born to heat-stressed cows experienced heat stress in utero (HS), whereas heifers born to actively cooled cows did not (CL). The adrenal gland was harvested from 6 heifers per group that were euthanized at birth (d 0; n = 12) or 1 wk after weaning (d 63; n = 12). Circulating cortisol was measured from blood samples collected weekly throughout the preweaning period. At d 63, heifers that experienced HS while developing in utero had heavier adrenal glands, with a greater total tissue surface area and thickness of the zona glomerulosa (ZG), fasciculata (ZF), and reticularis (ZR), compared with CL heifers. In addition, the adrenal gland of HS heifers had fewer cells in the ZG, more and larger cells in the ZF, and larger cells in the ZR, relative to CL heifers. Although no changes in circulating cortisol were observed through the preweaning period, the transcriptomic profile of the adrenal tissue was altered by fetal exposure to hyperthermia. Both at birth and on d 63, approximately 30 pathways were differentially expressed in the adrenal glands of HS heifers relative to CL. These pathways were associated with immune function, inflammation, prolactin signaling, cell function, and calcium transport. Upstream regulators significantly activated or inhibited in the adrenal glands of heifers exposed to intrauterine hyperthermia were identified. Maternal exposure to heat stress during late gestation caused an enlargement of their offspring's adrenal glands by inducing ZG and ZF cell hypertrophy, and caused gene expression changes. These phenotypic, histological, and molecular changes in the adrenal gland might lead to alterations in stress, immune, and metabolic responses later in life.

Stress decreases spermatozoa quality and induces molecular alterations in zebrafish progeny.

BACKGROUND: Chronic stress can produce a severe negative impact on health not only in the exposed individuals but also in their offspring. Indeed, chronic stress may be contributing to the current worldwide scenario of increasing infertility and decreasing gamete quality in human populations. Here, we evaluate the effect of chronic stress on behavior and male reproductive parameters in zebrafish. Our goal is to provide information on the impact that chronic stress has at molecular, histological, and physiological level in a vertebrate model species. RESULTS: We evaluated the effects of a 21-day chronic stress protocol covering around three full waves of spermatogenesis in Danio rerio adult males. The induction of chronic stress produced anxiety-like behavior in stressed males as assessed by a novel tank test. At a molecular level, the induction of chronic stress consistently resulted in the overexpression of two genes related to endoplasmic reticulum (ER) stress in the brain. Gene set enrichment analysis (GSEA) of testes suggested a dysregulation of the nonsense-mediated decay (NMD) pathway, which was also confirmed on qPCR analysis. Histological analysis of the testicle did not show significant differences in terms of the relative proportions of each germ-cell type; however, the quality of sperm from stressed males was compromised in terms of motility. RNA-seq analysis in stress-derived larval progenies revealed molecular alterations, including those predicted to affect translation initiation, DNA repair, cell cycle control, and response to stress. CONCLUSIONS: Induction of chronic stress during a few cycles of spermatogenesis in the vertebrate zebrafish model affects behavior, gonadal gene expression, final gamete quality, and progeny. The NMD surveillance pathway (a key cellular mechanism that regulates the stability of both normal and mutant transcripts) is severely affected in the testes by chronic stress and therefore the control and regulation of RNAs during spermatogenesis may be affected altering the molecular status in the progeny.

Multivariate analysis of herd structure and genetic resource indicators in seedstock beef cattle herds.

Genetic, environmental, technological and financial resources are used differently in cattle herds that participate in the same breeding programme. The percentages of calves sired by sires within their own herd or from external herds vary across herds, as do the intensities of use of reproductive biotechnologies. These divergences may be related to differences in the indicators of genetic performance for economic traits. The aim of this study was to determine the factors related to herd structure and genetic resource utilization that exert the greatest influence on the genetic merit of seedstock herds within a Nellore breeding programme. The database comprised 21 factors, along with genomic-enhanced expected progeny differences (GE-EPDs) for growth, reproductive and carcass traits, as well as a selection index of animals from 128 herds. By combining principal component analysis and cluster analysis, we were able to group the herds. We identified statistically significant differences (p < 0.05) in the mean values of the factors, GE-EPDs and genetic trends among the groups of herds. Differences in the percentage of sires from external herds and in sire age between the groups of herds were the factors most associated with differences in mean GE-EPDs and genetic trends. Using young sires from other herds or lineages is an effective strategy in animal breeding. By enhancing genetic variability, this approach does not only improve the genetic quality of herds but also accelerates genetic progress in desired traits over time. Therefore, to ensure the success of this strategy, it is crucial that seedstock herds undergo a thorough selection process aimed at maximizing the genetic potential of future generations of beef cattle.

Relevance of radon progeny measurements for the assessment of inhalation doses in groundwater utilities.

The high radon concentrations measured in the indoor air of groundwater facilities and the prevalence of the problem have been known for several years. Unlike in other workplaces, in groundwater plants, radon is released into the air from the water treatment processes. During the measurements of this study, the average radon concentrations varied from 500 to 8800 Bq m-3. In addition, the indoor air of the treatment plants is filtered and there are no significant internal aerosol sources. However, only a few published studies on groundwater plants have investigated the properties of the radon progeny aerosol, such as the equilibrium factor (F) or the size distribution of the aerosol, which are important for assessing the dose received by workers. Moreover, the International Commission on Radiological Protection has not provided generic aerosol parameter values for dose assessment in groundwater treatment facilities. In this study, radon and radon progeny measurements were carried out at three groundwater plants. The results indicate surprisingly high unattached fractions (fp= 0.27-0.58), suggesting a low aerosol concentration in indoor air. The correspondingFvalues were 0.09-0.42, well below those measured in previous studies. Based on a comparison of the effective dose rate calculations, either the determination of thefpor, with certain limitations, the measurement of radon is recommended. Dose rate calculation based on the potential alpha energy concentration alone proved unreliable.

Origin and Emergence of Microglia in the CNS-An Interesting (Hi)story of an Eccentric Cell.

Microglia belong to tissue-resident macrophages of the central nervous system (CNS), representing the primary innate immune cells. This cell type constitutes ~7% of non-neuronal cells in the mammalian brain and has a variety of biological roles integral to homeostasis and pathophysiology from the late embryonic to adult brain. Its unique identity that distinguishes its "glial" features from tissue-resident macrophages resides in the fact that once entering the CNS, it is perennially exposed to a unique environment following the formation of the blood-brain barrier. Additionally, tissue-resident macrophage progenies derive from various peripheral sites that exhibit hematopoietic potential, and this has resulted in interpretation issues surrounding their origin. Intensive research endeavors have intended to track microglial progenitors during development and disease. The current review provides a corpus of recent evidence in an attempt to disentangle the birthplace of microglia from the progenitor state and underlies the molecular elements that drive microgliogenesis. Furthermore, it caters towards tracking the lineage spatiotemporally during embryonic development and outlining microglial repopulation in the mature CNS. This collection of data can potentially shed light on the therapeutic potential of microglia for CNS perturbations across various levels of severity.

Deletion of the H240R Gene of African Swine Fever Virus Decreases Infectious Progeny Virus Production Due to Aberrant Virion Morphogenesis and Enhances Inflammatory Cytokine Expression in Porcine Macrophages.

African swine fever virus (ASFV) is a complex nucleocytoplasmic large DNA virus that causes African swine fever, a lethal hemorrhagic disease that currently threatens the pig industry. Recent studies have identified the viral structural proteins of infectious ASFV particles. However, the functional roles of several ASFV structural proteins remain largely unknown. Here, we characterized the function of the ASFV structural protein H240R (pH240R) in virus morphogenesis. pH240R was identified as a capsid protein by using immunoelectron microscopy and interacted with the major capsid protein p72 by pulldown assays. Using a recombinant ASFV, ASFV-ΔH240R, with the H240R gene deleted from the wild-type ASFV (ASFV-WT) genome, we revealed that the infectious progeny virus titers were reduced by approximately 2.0 logs compared with those of ASFV-WT. Furthermore, we demonstrated that the growth defect was due to the generation of noninfectious particles with a higher particle-to-infectious titer ratio in ASFV-ΔH240R-infected primary porcine alveolar macrophages (PAMs) than in those infected with ASFV-WT. Importantly, we found that pH240R did not affect virus-cell binding, endocytosis, or egress but did affect ASFV assembly; noninfectious virions containing large aberrant tubular and bilobulate structures comprised nearly 98% of all virions observed in ASFV-ΔH240R-infected PAMs by electron microscopy. Notably, we demonstrated that ASFV-ΔH240R infection induced high-level expression of inflammatory cytokines in PAMs. Collectively, we show for the first time that pH240R is essential for ASFV icosahedral capsid formation and infectious particle production. Also, these results highlight the importance of pH240R in ASFV morphogenesis and provide a novel target for the development of ASF vaccines and antivirals. IMPORTANCE African swine fever is a lethal hemorrhagic disease of global concern that is caused by African swine fever virus (ASFV). Despite extensive research, there exist relevant gaps in knowledge of the fundamental biology of the viral life cycle. In this study, we identified pH240R as a capsid protein that interacts with the major capsid protein p72. Furthermore, we showed that pH240R was required for the efficient production of infectious progeny virions as indicated by the H240R-deleted ASFV mutant (ASFV-ΔH240R). More specifically, pH240R directs the morphogenesis of ASFV toward the icosahedral capsid in the process of assembly. In addition, ASFV-ΔH240R infection induced high-level expression of inflammatory cytokines in primary porcine alveolar macrophages. Our results elucidate the role of pH240R in the process of ASFV assembly, which may instruct future research on effective vaccines or antiviral strategies.

Asexual reproduction through seeds: the complex case of diplosporous apomixis.

Apomixis is considered a potentially revolutionary tool to generate high-quality food at a lower cost and shorter developmental time due to clonal seed production through apomeiosis and parthenogenesis. In the diplosporous type of apomixis, meiotic recombination and reduction are circumvented either by avoiding or failing meiosis or by a mitotic-like division. Here, we review the literature on diplospory, from early cytological studies dating back to the late 19th century to recent genetic findings. We discuss diplosporous developmental mechanisms, including their inheritance. Furthermore, we compare the strategies adopted to isolate the genes controlling diplospory with those to produce mutants forming unreduced gametes. Nowadays, the dramatically improved technologies of long-read sequencing and targeted CRISPR/Cas mutagenesis justify the expectation that natural diplospory genes will soon be identified. Their identification will answer questions such as how the apomictic phenotype can be superimposed upon the sexual pathway and how diplospory genes have evolved. This knowledge will contribute to the application of apomixis in agriculture.

Circulatory system disease mortality and occupational exposure to radon progeny in the cohort of Newfoundland Fluorspar Miners between 1950 and 2016.

OBJECTIVES: Exposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up. METHODS: The cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily. RESULTS: Relative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74-0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76-1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66-1.48), and 1.39 (95% CI 0.84-2.30), respectively. CONCLUSIONS: Our findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease.

Radon exposure and risk of neurodegenerative diseases among male miners in Ontario, Canada: A cohort study.

BACKGROUND: Environmental radon has been examined as a risk factor for neurodegenerative diseases in a small number of previous studies, but the findings have been inconsistent. This study aims to investigate the association between occupational radon exposure and neurodegenerative disease in a cohort of male miners with work experience in multiple ore types in Ontario, Canada. METHODS: Radon exposure (1915-1988) was assessed using two job-exposure matrices (JEM) constructed from using historical records for 34,536 Ontario male miners. Neurodegenerative outcomes were ascertained between 1992 and 2018. Poisson regression models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between cumulative radon exposure in working level months (WLM) and each neurodegenerative outcome. RESULTS: Levels of cumulative radon exposure showed variability among cohort members with a mean of 7.5 WLM (standard deviation 24.4). Miners in uranium mines or underground jobs had higher levels and more variability in exposure than workers in non-uranium work or surface jobs. Compared to the reference group (radon < 1 WLM), increased rates of Alzheimer's (RR 1.23, 95% CI 1.05-1.45) and Parkinson's disease (RR 1.43, 95% CI 1.08-1.89) were observed among workers with >1-5 WLM and >5-10 WLM, respectively, but not among higher exposed workers (>10 WLM). CONCLUSION: This study did not observe a positive monotonic dose-response relationship between cumulative radon exposure and Alzheimer's or Parkinson's disease in Ontario mining workers. There was no association observed with motor neuron disease.

Genome-Wide Association Analysis of Heat Tolerance in F2 Progeny from the Hybridization between Two Congeneric Oyster Species.

As the world's largest farmed marine animal, oysters have enormous economic and ecological value. However, mass summer mortality caused by high temperature poses a significant threat to the oyster industry. To investigate the molecular mechanisms underlying heat adaptation and improve the heat tolerance ability in the oyster, we conducted genome-wide association analysis (GWAS) analysis on the F2 generation derived from the hybridization of relatively heat-tolerant Crassostrea angulata ♀ and heat-sensitive Crassostrea gigas ♂, which are the dominant cultured species in southern and northern China, respectively. Acute heat stress experiment (semi-lethal temperature 42 °C) demonstrated that the F2 population showed differentiation in heat tolerance, leading to extremely differentiated individuals (approximately 20% of individuals die within the first four days with 10% survival after 14 days). Genome resequencing and GWAS of the two divergent groups had identified 18 significant SNPs associated with heat tolerance, with 26 candidate genes located near these SNPs. Eleven candidate genes that may associate with the thermal resistance were identified, which were classified into five categories: temperature sensor (Trpm2), transcriptional factor (Gata3), protein ubiquitination (Ube2h, Usp50, Uchl3), heat shock subfamily (Dnajc17, Dnaja1), and transporters (Slc16a9, Slc16a14, Slc16a9, Slc16a2). The expressional differentiation of the above genes between C. gigas and C. angulata under sublethal temperature (37 °C) further supports their crucial role in coping with high temperature. Our results will contribute to understanding the molecular mechanisms underlying heat tolerance, and provide genetic markers for heat-resistance breeding in the oyster industry.

Assessment of radon, thoron, and their progeny concentrations in the dwellings of Shivalik hills of Jammu and Kashmir, India.

The present work determines the contents of active and passive indoor 222Rn, 220Rn, and their daughter in the 32 houses of the Reasi district of J&K, India. The passive 222Rn and 220Rn concentration was measured by dosimeters, whereas the active content was measured by active radon monitor. Progeny sensors and integrated samplers were operated for the evaluation of passive and active daughter contents of 222Rn and 220Rn. The measured averaged values of indoor 220Rn and 222Rn were 73 ± 40 and 22 ± 8 Bqm-3, respectively. The radon and thoron equilibrium factor has varied from 0.3 to 1.7 and from 0.006 to 0.6. The fine fraction of the above-mentioned gases was also calculated. The results of Mann-Whitney test statistically demonstrated significant differences between the content of indoor 222Rn, 220Rn, and their daughter for different seasons. The values of 222Rn, 220Rn, and their daughter content were appeared to be elevated in set of mud houses among all sets of houses. The values of all daughter concentration and indoor 222Rn were appeared to lie within the limit proposed by various agencies. The total doses were detected less than range commended by ICRP that suggested the district is safe as a health hazard point of view.

Evaluation of indoor 222Rn and 220Rn concentrations in Dakshina Kannada, Karnataka, India.

Naturally occurring radioactive gases which tend to build up (radon and thoron) in indoor environs can cause deleterious health effects including the development of lung cancer. The present study aims to measure 222Rn and 220Rn levels in dwellings in different seasons in the environs of Dakshina Kannada region of India. The 222Rn and 220Rn concentrations were measured in the monsoon, autumn, winter, and summer seasons using Solid State Nuclear Track Detector (SSNTD, LR-115 type II) films fixed in single-entry pinhole cylindrical twin-cup dosimeters. The higher 222Rn levels in indoors were observed during winter with an average concentration of 38.8 Bq m-3 and lower during summer with an average of 14.1 Bq m-3. The average indoor thoron concentration was also highest in winter with an average value of 25.5 Bq m-3 and lowest in summer with 8.8 Bq m-3. The annual inhalation dose ranged from 0.44 to 1.06 mSv year-1 with a mean value of 0.66 mSv year-1. The annual effective dose varied from 1.03 to 2.57 mSv year-1 with an average value of 1.59 mSv year-1. The assessed values have been contrasted with the limit suggested by the UNSCEAR and the ICRP and were found to be within the permissible level. The normality of frequency distribution curves of 222Rn and 220Rn concentrations was assessed by the Kolmogorov-Smirnov test.

Pedigree reconstruction and spatial analysis for genetic testing and selection in a Larix kaempferi (Lamb.) Carrière plantation.

BACKGROUND: Larix kaempferi is one of the major timber species in Northeast Asia. Demand for the reforestation of the species is rising in South Korea due to an increase in large timber production and utilization. However, progeny trials for the species have not been explored, making it challenging to foster advanced generations of tree improvement. In the present study, genetic testing and selection for diameter growth were conducted using pedigree reconstruction and phenotypic spatial distribution analysis in a plantation of L. kaempferi. The aim of the present study was to select the superior larch individuals using the pedigree reconstruction and phenotypic spatial distribution to substitute progeny trials. The plantation of seed orchard crops was established in 1990 and one-hundred and eighty-eight trees were selected as the study material. Genetic variation was investigated first to validate its adequacy as breeding material. Genetic testing was carried out using a model considering pedigree information and spatial autoregression of the phenotypes. RESULTS: The expected heterozygosity of the mother trees and offspring were 0.672 and 0.681 presenting the corresponding level of genetic variation between two groups. The pedigree reconstruction using maternity analysis assigned one to six progenies to ninety-two candidate mothers. The accuracy of genetic testing was exceedingly increased with the animal model considering AR1 ⊗ AR1 structure compared to the animal model only. The estimated genetic variance of the former was 9.086 whereas that of the latter was 4.9E-5 for DBH. The predicted breeding values of the offspring for DBH were ranged from -5.937 cm to 5.655 cm and the estimated heritability of diameter growth was 0.344. CONCLUSIONS: The genetic testing approach based on pedigree reconstruction and phenotypic spatial distribution analysis was considered a useful analytical scheme that could replace or supplement progeny trials.