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PLoS Genetics Apr 2024Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure...
Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by which Drosophila larvae adapt their development in low oxygen (hypoxia). During normal development, larvae grow and increase in mass until they reach critical weight (CW), after which point a neuroendocrine circuit triggers the production of the steroid hormone ecdysone from the prothoracic gland (PG), which promotes maturation to the pupal stage. However, when raised in hypoxia (5% oxygen), larvae slow their growth and delay their maturation to the pupal stage. We find that, although hypoxia delays the attainment of CW, the maturation delay occurs mainly because of hypoxia acting late in development to suppress ecdysone production. This suppression operates through a distinct mechanism from nutrient deprivation, occurs independently of HIF-1 alpha and does not involve dilp8 or modulation of Ptth, the main neuropeptide that initiates ecdysone production in the PG. Instead, we find that hypoxia lowers the expression of the EGF ligand, spitz, and that the delay in maturation occurs due to reduced EGFR/ERK signaling in the PG. Our study sheds light on how animals can adjust their development rate in response to changing oxygen levels in their environment. Given that hypoxia is a feature of both normal physiology and many diseases, our findings have important implications for understanding how low oxygen levels may impact animal development in both normal and pathological situations.
Topics: Animals; Ecdysone; Signal Transduction; Larva; Drosophila Proteins; Epidermal Growth Factor; Drosophila melanogaster; Hypoxia; Gene Expression Regulation, Developmental; ErbB Receptors; Oxygen; Pupa
PubMed: 38669270
DOI: 10.1371/journal.pgen.1011232 -
PLoS Pathogens Apr 2024The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple...
The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans, Cryptosporidium spp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate macrogamont differentiation and maturation. RNA-seq studies confirmed selective modulation of macrogamont differentiation for 10 identified compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompanies Cryptosporidium sexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in differentiation into macrogamonts. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for macrogamont formation.
Topics: Cryptosporidiosis; Protozoan Proteins; Life Cycle Stages; Cryptosporidium; Transcription Factors; Animals; Humans; Small Molecule Libraries
PubMed: 38669269
DOI: 10.1371/journal.ppat.1011906 -
Animal Reproduction Science Apr 2024Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are... (Review)
Review
Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are still considered sub-fertile, escaping current assessment methods for sperm quality and resilience to preservation. As end-product, the ejaculate (emitted spermatozoa sequentially exposed to the composite seminal plasma, the SP) ought to define the homeostasis of the testes, the epididymis, and the accessory sexual glands. Yet, linking findings in the ejaculate to sperm production biology and fertility is suboptimal. The present essay critically reviews how the ejaculate of a fertile boar can help us to diagnose both reproductive health and resilience to semen handling, focusing on methods -available and under development- to identify suitable biomarkers for cryotolerance and fertility. Bulk SP, semen proteins and microRNAs (miRNAs) have, albeit linked to sperm function and fertility after AI, failed to enhance reproductive outcomes at commercial level, perhaps for just being components of a complex functional pathway. Hence, focus is now on the interaction sperm-SP, comparing in vivo with ex vivo, and regarding nano-sized lipid bilayer seminal extracellular vesicles (sEVs) as priority. sEVs transport fragile molecules (lipids, proteins, nucleic acids) which, shielded from degradation, mediate cell-to-cell communication with spermatozoa and the female internal genital tract. Such interaction modulates essential reproductive processes, from sperm homeostasis to immunological female tolerance. sEVs can be harvested, characterized, stored, and manipulated, e.g. can be used for andrological diagnosis, selection of breeders, and alternatively be used as additives to improve cryosurvival and fertility.
PubMed: 38664134
DOI: 10.1016/j.anireprosci.2024.107476 -
Journal of Immunology (Baltimore, Md. :... Jun 2024The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although...
The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although their functions are less clear. During "thymic involution," a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ∼1% of human neonatal thymocytes but up to ∼10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells. In this article, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- versus postinvolution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells postinvolution. We also performed RNA sequencing on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is, to our knowledge, the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution and establishing the highly genetically manipulatable zebrafish model as a template for involution studies.
Topics: Animals; Zebrafish; Thymus Gland; B-Lymphocytes; Animals, Genetically Modified; T-Lymphocytes; Humans; Cell Differentiation; Models, Animal
PubMed: 38656392
DOI: 10.4049/jimmunol.2300495 -
European Journal of Endocrinology May 2024Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology.
CONTEXT
Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology.
OBJECTIVES
This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison.
METHODS
First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches.
RESULTS
Lower limit of quantification was 11 pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192 pmol/L; boys up to 225 pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638 pmol/L). However, boys' RIs (up to 259 pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours.
CONCLUSIONS
Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding.
Topics: Humans; Male; Tandem Mass Spectrometry; Child; Estradiol; Female; Reference Values; Child, Preschool; Adolescent; Infant; Chromatography, Liquid; Puberty; Infant, Newborn; Sexual Maturation
PubMed: 38652605
DOI: 10.1093/ejendo/lvae046 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Mar 2024Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. 1 gene mutation plays an essential pathogenic role in the... (Review)
Review
Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. 1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.
Topics: Core Binding Factor Alpha 2 Subunit; Humans; Animals; Cell Differentiation; Bone Development; Chondrocytes; Osteoblasts; Osteoclasts; Mesenchymal Stem Cells; Mice; Bone Diseases; Osteoporosis; Osteoarthritis
PubMed: 38645858
DOI: 10.12182/20240360103 -
Developmental Psychobiology May 2024Most studies of adolescent and adult behavior involved one age group of each, whereas the dynamic changes in brain development suggest that there may be behavioral flux...
Most studies of adolescent and adult behavior involved one age group of each, whereas the dynamic changes in brain development suggest that there may be behavioral flux in adolescence. In two studies, we investigated developmental changes in social reward motivation in female and male Long-Evans rats from prepuberty to early adulthood in a social operant conditioning task. Given the earlier onset of puberty in females than in males, we predicted the course of social reward development would differ between the sexes. Overall, the pattern of results from both studies suggests that the trajectory of social motivation across adolescence is characterized by upward and downward shifts that do not depend on the sex of the rats. During training, in both studies, the mean number of social gate openings and percentage of social gate openings was higher at P30 (prepubertal, early adolescence) and P50 (late adolescence) than at P40 (mid adolescence) and P70 (adulthood) irrespective of sex. Nevertheless, the specific age comparisons that were significant depended on the study. In both studies, P30 rats had greater levels of social motivation than did adults in accessing a social reward when increased effort was required (progressive ratio tests). In an extinction test, only P30 and P50 rats continued to show more nose-pokes at the previously social gate than at the nonsocial gate, suggesting resistance to extinction. The results highlight the importance of characterizing behavior at several timepoints in adolescence to understand the neural mechanisms, many of which show similar discontinuities as they develop across adolescence.
Topics: Male; Rats; Female; Animals; Motivation; Rats, Long-Evans; Sexual Maturation; Reward; Conditioning, Operant
PubMed: 38643359
DOI: 10.1002/dev.22495 -
Journal of Cosmetic Dermatology Apr 2024During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in...
BACKGROUND
During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region.
METHODS
This study has been performed using 7 T-magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed.
RESULTS
The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles.
CONCLUSIONS
This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology.
PubMed: 38638000
DOI: 10.1111/jocd.16314 -
Disability and Health Journal Jul 2024Thanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of...
BACKGROUND
Thanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of sexual desires. However, access to reproductive counselling and contraceptive use has been reported to be lower for women with physical and intellectual disabilities compared to the general population.
OBJECTIVE
We investigated oral contraceptive use in women with SB, residing in Sweden and how use varies based on the level of lesion and demographic factors.
METHODS
This was a population-based case-control study using annual data from national registers from 2006 to 2015. The sample consisted of 7045 women aged 15-49 years, of which 1173 had a diagnosis of SB. χ tests and logistic regression were used to investigate the study objective.
RESULTS
The rate of oral contraceptive use in women with SB was 24.6 % compared to 34.5 % among the general population. After adjusting for potential confounders women with SB were found to have a lower probability of using oral contraceptives (OR 0.63 95 % CI 0.56-0.71) compared to women without SB. Among women with SB, those with diagnoses Q05.8 (Sacral SB without hydrocephalus) and Q05.9 (SB unspecified) had a higher likelihood of using oral contraceptives compared to other Q05 diagnoses.
CONCLUSION
Women with SB had a lower likelihood of being on oral contraceptives compared to the control group. Further research should investigate if the lower use indicates that oral contraceptives are not an inappropriate method of contraception for women with SB.
Topics: Humans; Female; Sweden; Spinal Dysraphism; Adult; Adolescent; Case-Control Studies; Young Adult; Middle Aged; Contraceptives, Oral; Contraception Behavior; Disabled Persons; Logistic Models; Registries; Contraception
PubMed: 38637232
DOI: 10.1016/j.dhjo.2024.101627 -
Bulletin of Entomological Research Apr 2024The continuous utilisation of an alternative host may influence parasitoid performance across successive generations due to conditioning in natal hosts. (Olliff) has...
The continuous utilisation of an alternative host may influence parasitoid performance across successive generations due to conditioning in natal hosts. (Olliff) has successfully been reared using L. pupae as a feasible alternative host. However, the extended rearing of on this alternative host may impact the biological features of the parasitoids. Parasitoids were reared using pupae for 30 consecutive generations. Quality criteria were assessed during the generations F5, F15, and F30, offering pupae of the target pest, (Fabr.), and compared with the F0 generation (parasitoids reared in pupae). Criteria included assessments of parasitism performance, host selection, and wing form variation in the parasitoid wasps. Additionally, we examined the fecundity of females that emerged from both hosts, considering their age, egg loading before and after one oviposition, as well as parasitism of sugarcane stalk borer pupae. Rearing using pupae of did not affect its biological traits or preference for the target pest for 30 generations. After parasitism, the parasitoid left the host pupa inside the stalk, and one oviposition was enough to kill pupae and obtain viable parasitoid progeny. Female sexual maturation and egg loading occurred 72 and 96 h after parasitoid emergence. Egg-loading recovery after parasitism did not happen within 24 h. can be reared for up to 30 generations using alternative hosts without compromising its parasitism performance or egg loading.
PubMed: 38629310
DOI: 10.1017/S0007485324000129