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[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans

Influence of Repeated-Sprint Bout Duration in Sprint Interval Training Intervention on Physical Performance Adaptations of Young Volleyball Players.

The objective of this study was to examine the effects of repeated-sprint training (RST) with varying bout durations on the physical fitness adaptations of young male volleyball players. Forty athletes were randomly allocated to one of three intervention groups performing RST with varying bout durations and similar repetition volumes, all executed at maximal effort. The 3-sec group (n = 10) completed two sets of 30 bouts, the 6-sec group (n = 10) performed two sets of 15 bouts, and the 9-sec group (n = 10) carried out two sets of 10 bouts, each adhering to a 1:3 work to rest ratio. An active control group (n = 10) engaged solely in regular volleyball training without the RST intervention. Physical fitness measures-including countermovement vertical jump (CMVJ), 10-m and 20-m linear sprints, T-test change-of-direction speed (T-CODS), reactive strength index (RSI), and the Wingate anaerobic power test-were assessed pre- and post-a 6-week training intervention (i.e., 18 sessions). All RST groups showed significant post-intervention improvements in physical fitness (main effect of time, p = 0.001), with greater adaptations compared with the control group and effect sizes ranging from small to very large. The 3-sec bout group demonstrated greater gains in CMVJ, 10-m and 20-m sprint performance, RSI, and peak power output compared with the 9-sec group (all, p < 0.05). Conversely, the 9-sec group exhibited superior adaptations in T-CODS and mean power output relative to the 3-sec group (all, p < 0.05). In conclusion, the 3-sec group experienced greater enhancements in explosive and sprint performances, while the 9-sec group showed superior gains in change of direction and mean power output. These findings indicate that manipulation of sprint-bout duration in RST can be used to optimize distinct performance adaptations in young volleyball players.

Humans

A Duty to Act.

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healthcare

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n&#x202f;=&#x202f;8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n&#x202f;=&#x202f;4) and 181 in low motile (n&#x202f;=&#x202f;4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7&#x202f;&#xd7; 10&#x207b;2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9&#x202f;&#xd7; 10&#x207b;2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0&#x202f;&#xd7; 10&#x207b;2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3&#x202f;&#xd7; 10&#x207b;1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3&#x202f;&#xd7; 10&#x207b;2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals

A Duty to Act.

Explore the source record for details and available documents.

healthcare

Base editing reversal of radiation sensitivity in NHEJ1 immunodeficiency.

Inherited defects of DNA double-stranded break (DSB) repair can result in radiosensitive/radiation-sensitive (RS) SCID (RS-SCID). We applied base editing to reverse NHEJ1 mutations in patient fibroblasts, exemplifying how this technology can help interrogate RS sequence variants.

Journal Article

Randomized study of the effects of testosterone administration on severity of asthma in horses.

BACKGROUND: Low testosterone concentrations are associated with poor lung function in human asthmatics, and androgen administration improves airway obstruction in women with asthma. HYPOTHESIS/OBJECTIVES: Testosterone improves clinical scores, lung function, airway neutrophilia, and airway remodeling in horses with severe asthma. ANIMALS: Ten horses affected by severe asthma from a research herd. METHODS: In a randomized, blinded, crossover study, horses received dexamethasone (0.06&#xa0;mg/kg PO q24h for 10&#xa0;days) or a single intramuscular injection of testosterone cypionate (0.35&#xa0;mg/kg), with a 2-week washout period. Clinical respiratory scores were assessed at days 0, 2, 5, and 10; lung function was evaluated at days 0, 5, and 10; and bronchoalveolar lavage fluid cytology and central airway remodeling at days 0 and 10. Mixed linear models were used for analysis. RESULTS: The respiratory clinical scores improved with dexamethasone administration (median [95% CI], from 12 (9-13) to 5 (3-6), P&#xa0;<&#xa0;.001), and remained unchanged with testosterone administration (from 10 [8-12] to 9 [8-11], P&#xa0;=&#xa0;.6). Pulmonary elastance improved with both treatments, but the effect was more pronounced with dexamethasone administration (from 5.1&#xa0;cm H2O/L [2.4-5.8] to 0.5 [0.4-0.8], P&#xa0;<&#xa0;.001) than with testosterone administration (from 4.5&#xa0;cm H2O/L [1.6-8.5] to 3.0 [1.0-4.1], P&#xa0;=&#xa0;.04). Pleural pressure and pulmonary resistance decreased only with dexamethasone. Neither treatment altered airway neutrophilia or bronchial remodeling. CONCLUSIONS AND CLINICAL IMPORTANCE: Testosterone is less effective than dexamethasone and only mildly improves pulmonary elastance in horses with severe asthma.

Animals

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1&#x2011;chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals