(A) Characteristics of spermatozoa in asthenoteratozoospermia affected man. (B) Pedigree and Sanger sequencing analysis of the family. (C) The effect of the missense variant in the CCIN gene.
Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to ...play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma.
We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample.
In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8
T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis.
We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Male infertility due to spermatogenesis defects affects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. Here we describe three men with primary ...infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) from two unrelated Han Chinese families. We performed whole-exome sequencing (WES) and Sanger sequencing on the proband of family 1, and found that he carried novel compound heterozygous missense mutations in dynein axonemal heavy chain 6 (DNAH6) that resulted in the substitution of a conserved amino acid residue and co-segregated with the MMAF phenotype in this family. Papanicolaou staining and transmission electron microscopy analysis revealed morphological and ultrastructural abnormalities in the sperm flagella in carriers of these genetic variants. Immunostaining experiments showed that DNAH6 was localized in the sperm tail. This is the first report identifying novel recessive mutations in DNAH6 as a cause of MMAF. These findings expand the spectrum of known MMAF mutations and phenotypes and provide information that can be useful for genetic and reproductive counseling of MMAF patients.
Subjective cognitive decline (SCD) represents a cognitively normal state but at an increased risk for developing Alzheimer's disease (AD). Recognizing the glucose metabolic biomarkers of SCD could ...facilitate the location of areas with metabolic changes at an ultra-early stage. The objective of this study was to explore glucose metabolic biomarkers of SCD at the region of interest (ROI) level.
This study was based on cohorts from two tertiary medical centers, and it was part of the SILCODE project (NCT03370744). Twenty-six normal control (NC) cases and 32 SCD cases were in cohort 1; 36 NCs, 23 cases of SCD, 32 cases of amnestic mild cognitive impairment (aMCIs), 32 cases of AD dementia (ADDs), and 22 cases of dementia with Lewy bodies (DLBs) were in cohort 2. Each subject underwent 18Ffluoro-2-deoxyglucose positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), and subjects from cohort 1 additionally underwent amyloid-PET scanning. The ROI analysis was based on the Anatomical Automatic Labeling (AAL) template; multiple permutation tests and repeated cross-validations were conducted to determine the metabolic differences between NC and SCD cases. In addition, receiver operating characteristic curves were used to evaluate the capabilities of potential glucose metabolic biomarkers in distinguishing different groups. Pearson correlation analysis was also performed to explore the correlation between glucose metabolic biomarkers and neuropsychological scales or amyloid deposition.
Only the right middle temporal gyrus (RMTG) passed the methodological verification, and its metabolic levels were correlated with the degrees of complaints (R = - 0.239, p = 0.009), depression (R = - 0.200, p = 0.030), and abilities of delayed memory (R = 0.207, p = 0.025), and were weakly correlated with cortical amyloid deposition (R = - 0.246, p = 0.066). Furthermore, RMTG metabolism gradually decreased across the cognitive continuum, and its diagnostic efficiency was comparable (NC vs. ADD, aMCI, or DLB) or even superior (NC vs. SCD) to that of the metabolism of the posterior cingulate cortex or precuneus.
These findings suggest that the hypometabolism of RMTG could be a typical feature of SCD, and the large-scale hypometabolism in patients with symptomatic stages of AD may start from the RMTG, which gradually progresses starting in the preclinical stage. The specificity of identifying SCD from the perspective of self-perceived symptoms is likely to be increased by the detection of RMTG metabolism.
Primordial follicle assembly in the mouse occurs during perinatal ages and largely determines the ovarian reserve that will be available to support the reproductive life span. The development of ...primordial follicles is controlled by a complex network of interactions between oocytes and ovarian somatic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time series on murine ovaries, coupled with several bioinformatics analyses, the complete dynamic genetic programs of germ and granulosa cells from E16.5 to postnatal day (PD) 3 were reported. Along with confirming the previously reported expression of genes by germ cells and granulosa cells, our analyses identified 5 distinct cell clusters associated with germ cells and 6 with granulosa cells. Consequently, several new genes expressed at significant levels at each investigated stage were assigned. By building single-cell pseudotemporal trajectories, 3 states and 1 branch point of fate transition for the germ cells were revealed, as well as for the granulosa cells. Moreover, Gene Ontology (GO) term enrichment enabled identification of the biological process most represented in germ cells and granulosa cells or common to both cell types at each specific stage, and the interactions of germ cells and granulosa cells basing on known and novel pathway were presented. Finally, by using single-cell regulatory network inference and clustering (SCENIC) algorithm, we were able to establish a network of regulons that can be postulated as likely candidates for sustaining germ cell-specific transcription programs throughout the period of investigation. Above all, this study provides the whole transcriptome landscape of ovarian cells and unearths new insights during primordial follicle assembly in mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Manipulated rainfall reduction lowered transpiration and growth of black locust trees.•Simulated drought weakened the response of sap flow to meteorological variables.•It showed different behavior ...under long or severe drought from short term drought.•The plantations in semiarid area tend to suffer from future precipitation decrease.
Black locust (Robinia pseudoacacia) plantations have been widely established in the semiarid and sub-humid areas of central China. Under the condition of global climate change, which is introducing much uncertainty of precipitation patterns in this region, it is of special significance to investigate their responses to precipitation. Here, we investigated sap flow response to reduced throughfall. Stem sap flow was measured from 2011 to 2017 using Granier-type sensors. By placing waterproof panels within tree rows, about 47.5% precipitation was excluded from treated plots since April 2015. Differences in soil water content gradually increased to 4.3% between treated and control plots with continued throughfall exclusion. Decreased precipitation input significantly reduced the average sap flux density in treated plots by 9.1%–45.3%. The extent of this reduction depended on precipitation in the previous and current years. Transpiration and forest growth were negatively affected by the treatment. Furthermore, sap flow response to environmental factors became insensitive, with the discrepancy increasing with increasing drought duration, but was regained by rainfall recharge to soil water in the first two treatment years. However, prolonged drought might damage transpiration resilience capacity, as the saturated sap flux after soil water recharging during the wet period was still lower than that in the control plot in the latter year. Predawn leaf water potential was significantly lower in the treated plot compared to the control plot, whereas midday leaf water potential was similar. Whole tree hydraulic conductance (GP) was also similar between the two plots, except in extreme drought months when GP was much lower in the treated plot. In addition, the specific leaf area and stomatal density decreased in the treated plot. Therefore, decreases in precipitation would cause a transpiration reduction, weakening the tree’s response to meteorological variables and lowering growth and productivity, potentially damaging transpiration resilience. These results suggest that black locust is sensitive to water changes, its capacity of drought tolerant is restrained by the drought time scale or drought severity, the use of such species in reforestation in semiarid regions should be implemented with caution.
Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting ...spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non‐obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole‐exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S‐phase kinase‐associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1.
The nonsense variant of BCORL1 damaged the normal interaction between BCORL1 and SKP1, thereby resulted in impaired spermatogenesis.
Constrained spin systems and KNdS black holes Chakrabhavi, Vivek; Etheredge, Muldrow; Qiu, Yue ...
The journal of high energy physics,
02/2024, Letnik:
2024, Številka:
2
Journal Article
Recenzirano
Odprti dostop
A
bstract
Kerr-Newman de Sitter (KNdS) spacetimes have a rich thermodynamic structure that involves multiple horizons, and so differs in key respects from asymptotically flat or AdS black holes. In ...this paper, we show that certain features of KNdS spacetimes can be reproduced by a constrained system of
N
non-interacting spins in a magnetic field. Both the KNdS and spin systems have bounded energy and entropy, a maximum of the entropy in the interior of the energy range, and a symmetry that maps lower energy states to higher energy states with the same entropy. Consequently, both systems have a temperature that can be positive or negative, where the gravitational temperature is defined analogously to that of the spins. We find that the number of spins
N
corresponds to 1/Λ for black holes with very small charge
q
and rotation parameter
a
, and scales like
a
2
+
q
2
/
Λ
for larger values of
a
and
q
. These comparisons show that certain key features of the complex thermodynamics of KNdS spacetimes are reproduced by a simple system of noninteracting spins, suggesting that there may be a relatively simple effective description of quantum de Sitter black holes in terms of a finite dimensional Hilbert space.
•C sequestration and mineralization showed negative correlations at 0–10 cm layer.•Macro-aggregates (>2 mm) were the main carriers of SOC sequestration.•No-till improved C stock in macro-aggregates ...due to less mineralization.•Straw returning increased C concentration due to low mineralization quotient.
Understanding the process of soil organic carbon (SOC) sequestration and mineralization in aggregates is pertinent to mitigate climate change and minimize risks of soil degradation. Thus, soil samples were obtained after a 10-year field experiment to identify the influences of tillage on aggregate-associated SOC sequestration and mineralization in the North China Plain (NCP). Four tillage practices investigated were as follows: no-till with straw retention (NTS, conservation tillage), rotary tillage with straw incorporation (RTS), conventional tillage with straw incorporation (CTS), and conventional tillage with straw removal (CT). Significantly negative correlations were observed between SOC concentration and potentially mineralized carbon in aggregates under different treatments for the 0–10 cm soil layer. The large macro-aggregates (>2 mm) with the highest proportion of size distribution represented the major pool of SOC stock (47.3–51.2%) and mineralization amount (38.2–43.6%) in the 0–30 cm layer, followed by that in the small macro-aggregates (0.25–2 mm), regardless of tillage practices. However, the mineralization quotient (mineralization per unit SOC concentration) of macro-aggregates (>0.25 mm) was lower than that for the other size classes. The NTS enhanced the macro-aggregate formation in the 0–20 cm layer and associated SOC concentration in the 0–10 cm layer. Furthermore, NTS decreased total potential mineralization in the 0–30 cm layer compared with the other tillage practices, attributed to decrease in the large macro-aggregates (30.0–51.4%) with low particulate organic carbon (POC) concentration. The NTS with low straw inputs had higher incremental efficiency with straw incorporation than that in the RTS and CTS by 45.0% and 13.5%, respectively (P < 0.05). Overall, the higher proportion of macro-aggregates recorded under NTS decreased carbon mineralization, and consequently, increased incremental efficiency with straw incorporation, and improved SOC sequestration in the surface soil layer in the NCP.
Severe oligozoospermia (SO) is an important cause of male infertility. Its etiology and pathogenesis are associated with genetic abnormalities; however, the genetic causes of the majority of ...idiopathic human SO remain unclear. Here, we report a homozygous splice‐site mutation in M1AP (meiosis 1 associated protein; NM_138804, c.1435‐1G>A) observed in a patient with SO from a consanguineous Han Chinese family. His parents and fertile brother were heterozygous for the mutation. The splice variant led to a lack of M1AP protein in the patient's spermatozoa. Ultrastructural and immunostaining analyses of patient's spermatozoa showed highly aberrant swollen mitochondrial sheaths with normal axonemal structures. Subsequent mutation screening identified three additional heterozygous M1AP variants in 4/243 subjects with idiopathic SO, but no M1AP variants among 223 fertile subjects. Additionally, a previously study reported that M1ap knock‐out mice exhibited SO due to meiotic arrest. Hence, our findings indicate that M1AP mutation might represent novel genetic alteration responsible for human SO.
(A) Pedigree and Sanger sequencing analysis of the family. (B) The effect of the splice‐split variant in the M1AP gene. (C) Aberrant swollen mitochondrial sheath in sperm flagella of M1AP mutant spermatozoa.
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