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Future Science OA Oct 2023There are various reasons for drug failure in the developmental stage including toxicity, adverse effects and inefficacy. This is likely due to the differences in drug... (Review)
Review
There are various reasons for drug failure in the developmental stage including toxicity, adverse effects and inefficacy. This is likely due to the differences in drug behavior between a simple and controlled cell culture system to that of a more complex whole organism environment. While the use of human phenotypical cells relevant to the condition may provide more accurate screening results, they are susceptible to producing false positives as cells are continuously influenced by constant chemical and physical interaction with the surrounding microenvironment. Therefore, several microenvironmental and pharmacomechanical aspects must be factored in during tissue culture drug screening.
PubMed: 37752922
DOI: 10.2144/fsoa-2023-0027 -
Environmental Science and Pollution... Dec 2023The pattern of arsenic (As) uptake at different developmental stages in plants and its consequent influence on the growth of plants was investigated in bean and lettuce....
The pattern of arsenic (As) uptake at different developmental stages in plants and its consequent influence on the growth of plants was investigated in bean and lettuce. Further, the human health risk from the consumption of these As-laced vegetables was determined. The irrigation water was contaminated with As at concentrations of 0.1, 0.25, and 0.5 mg/L. The As concentration in the plant parts (root, stem, leaves, and flower/fruit) was determined in bean at the young, flowering, and fruiting stages and lettuce at the young and mature stages. At the different growth stages, As had an impact on the biomass of bean and lettuce plant parts, but none of the biomass changes were significant (p>0.05). The increase in As concentration of the irrigation water elevated the As concentration of plant parts of both plants at all growth stages, with the exception of the bean fruit. The As concentration in the developmental stages was in the order: lettuce (young>mature) and bean (fruiting>young>flowering). In lettuce, the transfer factor was higher at the young stage (0.09-0.19, in the control and 0.1 mg/L As treatment), while in bean, it was highest at the flowering stage (0.09-0.41, in all treatments). In the edible part, lettuce possessed substantially elevated As concentrations (0.30, 0.61, and 1.21 mg/kg DW) compared to bean (0.008, 0.005, and 0.022 mg/kg DW) at As treatments of 0.1, 0.25, and 0.5 mg/L, respectively, and posed significant health risks at all applied As concentrations.
Topics: Humans; Lactuca; Arsenic; Vegetables; Plant Leaves; Water
PubMed: 37917265
DOI: 10.1007/s11356-023-30593-7 -
Frontiers in Psychology 2023In birds, parental care and attachment period differ widely depending on the species (altricial or precocial), developmental strategies, and life history traits. In most... (Review)
Review
In birds, parental care and attachment period differ widely depending on the species (altricial or precocial), developmental strategies, and life history traits. In most bird species, parental care can be provided by both female and male individuals and includes specific stages such as nesting, laying, and hatching. During said periods, a series of neuroendocrine responses are triggered to motivate parental care and attachment. These behaviors are vital for offspring survival, development, social bonding, intergenerational learning, reproductive success, and ultimately, the overall fitness and evolution of bird populations in a variety of environments. Thus, this review aims to describe and analyze the behavioral and endocrine systems of parental care and newborn attachment in birds during each stage of the post-hatching period.
PubMed: 37599744
DOI: 10.3389/fpsyg.2023.1183554 -
Cell Genomics Jan 2024Gene duplication produces the material that fuels evolutionary innovation. The "out-of-testis" hypothesis suggests that sperm competition creates selective pressure...
Gene duplication produces the material that fuels evolutionary innovation. The "out-of-testis" hypothesis suggests that sperm competition creates selective pressure encouraging the emergence of new genes in male germline, but the somatic expression and function of the newly evolved genes are not well understood. We systematically mapped the expression of young duplicate genes throughout development in Caenorhabditis elegans using both whole-organism and single-cell transcriptomic data. Based on the expression dynamics across developmental stages, young duplicate genes fall into three clusters that are preferentially expressed in early embryos, mid-stage embryos, and late-stage larvae. Early embryonic genes are involved in protein degradation and develop essentiality comparable to the genomic average. In mid-to-late embryos and L4-stage larvae, young genes are enriched in intestine, epidermal cells, coelomocytes, and amphid chemosensory neurons. Their molecular functions and inducible expression indicate potential roles in innate immune response and chemosensory perceptions, which may contribute to adaptation outside of the sperm.
Topics: Animals; Male; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Genes, Duplicate; Semen; Gene Expression Profiling; Larva
PubMed: 38190105
DOI: 10.1016/j.xgen.2023.100467 -
Cell Reports Mar 2024The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development,...
The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key transcription factor responding to the reduced nutrition. By integrating temporal and nutritional signaling, the DR response regulates many development-related genes, including gska-3/GSK3β, through BLMP-1-PHA-4 at the onset of adulthood. Upon DR, a precocious activation of BLMP-1 in early larval stages impairs neuronal development through gska-3, whereas the increase of gska-3 by BLMP-1-PHA-4 at the last larval stage suppresses WNT signaling in adulthood for DR-induced longevity. Our findings reveal a temporal checkpoint of the DR response that protects larval development and promotes adult health.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Caloric Restriction; Gene Expression Regulation; Longevity; Transcription Factors; Wnt Signaling Pathway
PubMed: 38483903
DOI: 10.1016/j.celrep.2024.113959 -
Radiotherapy and Oncology : Journal of... Jan 2024Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton...
BACKGROUND AND PURPOSE
Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment.
MATERIALS AND METHODS
Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients.
RESULTS
271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0-4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9-12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16-0.79, P = 0.01).
CONCLUSION
IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.
Topics: Humans; Male; Aged; Female; Protons; Positron Emission Tomography Computed Tomography; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Proton Therapy; Lung Neoplasms; Lymphopenia; Anemia; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 38000689
DOI: 10.1016/j.radonc.2023.110019 -
Cell Proliferation May 2024Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To...
Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To address this problem, it is necessary to induce functional granulosa cells at different stages in vitro. In this study, we established a reprogramming method to induce early- and late-stage granulosa cells with different steroidogenic abilities. We used an AMH-fluorescence-reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa-like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH-EGFP hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late-stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early-stage granulosa cells. CD55 AMH-EGFP hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early-stage granulosa cells. More importantly, CD55 hiGC transplantation alleviated polycystic ovary syndrome (PCOS) in a mouse model. Therefore, hiGC provides a cellular model to study the developmental program of human granulosa cells and has potential to treat PCOS.
Topics: Female; Humans; Forkhead Box Protein L2; Granulosa Cells; Animals; Mice; Fibroblasts; Steroidogenic Factor 1; Progesterone; Polycystic Ovary Syndrome; Cellular Reprogramming; Cells, Cultured
PubMed: 38192172
DOI: 10.1111/cpr.13589 -
Physiological and Biochemical Zoology :... 2023AbstractTrade-offs between life history traits are context dependent; they vary depending on environment and life stage. Negative associations between development and...
AbstractTrade-offs between life history traits are context dependent; they vary depending on environment and life stage. Negative associations between development and growth often characterize larval life stages. Both growth and development consume large parts of the energy budget of young animals. The metabolic rate of animals should reflect differences in growth and developmental rates. Growth and development can also have negative associations with immune function because of their costs. We investigated how intraspecific variation in growth and development affected the metabolism of larval amphibians and whether intraspecific variation in growth, development, and metabolic rate could predict mortality and viral load in larvae infected with ranavirus. We also compared the relationship between growth and development before and after infection with ranavirus. We hypothesized that growth and development would affect metabolism and predicted that each would have a positive correlation with metabolic rate. We further hypothesized that allocation toward growth and development would increase ranavirus susceptibility and therefore predicted that larvae with faster growth, faster development, and higher metabolic rates would be more likely to die from ranavirus and have higher viral loads. Finally, we predicted that growth rate and developmental rate would have a negative association. Intraspecific variation in growth rate and developmental rate did not affect metabolism. Growth rate, developmental rate, and metabolism did not predict mortality from ranavirus or viral load. Larvae infected with ranavirus exhibited a trade-off between developmental rate and growth rate that was absent in uninfected larvae. Our results indicate a cost of ranavirus infection that is potentially due to both the infection-induced anorexia and the cost of infection altering priority rules for resource allocation.
Topics: Animals; DNA Virus Infections; Larva; Ranavirus; Life History Traits; Amphibians
PubMed: 38237190
DOI: 10.1086/727729 -
Developmental Biology Sep 2024Regeneration, regrowing lost and injured body parts, is an ability that generally declines with age or developmental transitions (i.e. metamorphosis, sexual maturation)....
Regeneration, regrowing lost and injured body parts, is an ability that generally declines with age or developmental transitions (i.e. metamorphosis, sexual maturation). Regeneration is also an energetically costly process, and trade-offs occur between regeneration and other costly processes such as growth, or sexual reproduction. Here we investigate the interplay of regeneration, reproduction, and developmental stage in the segmented worm Platynereis dumerilii. P. dumerilii can regenerate its whole posterior body axis, along with its reproductive cells, thereby having to carry out the two costly processes (somatic and germ cell regeneration) after injury. We specifically examine how developmental stage affects the success of germ cell regeneration and sexual maturation in developmentally young versus developmentally old organisms. We hypothesized that developmentally younger individuals (i.e. with gametes in early mitotic stages) will have higher regeneration success than the individuals at developmentally older stages (i.e. with gametes undergoing meiosis and maturation). Surprisingly, older amputated worms grew faster and matured earlier than younger amputees. To analyze germ cell regeneration during and after posterior regeneration, we used Hybridization Chain Reaction for the germline marker vasa. We found that regenerated worms start repopulating new segments with germ cell clusters as early as 14 days post amputation. In addition, vasa expression is observed in a wide region of newly-regenerated segments, which appears different from expression patterns during normal growth or regeneration in worms before gonial cluster expansion.
Topics: Animals; Germ Cells; Regeneration; Sexual Maturation; Polychaeta
PubMed: 38797257
DOI: 10.1016/j.ydbio.2024.05.013 -
NeuroImmune Pharmacology and... Dec 2023Researchers have found considerable evidence in the past 20 years that perinatal opioid exposure leads to an increased risk of developmental disorders in offspring that... (Review)
Review
Researchers have found considerable evidence in the past 20 years that perinatal opioid exposure leads to an increased risk of developmental disorders in offspring that persist into adulthood. The use of opioids to treat pain concerning pregnancy, delivery, and postpartum complications has been rising. As a result, communities have reported a 300-400 % increase in Neonatal Opioid Withdrawal Syndrome (NOWS). NOWS represents the initial stage of several behavioral, phenotypic, and synaptic deficits. This review article summarizes the Developmental Outcomes of Perinatal Exposure (DOPE) to prescription opioids. Moreover, we also seek to connect these findings to clinical research that describes DOPE at multiple stages of life. Since specific mechanisms that underlie DOPE remain unclear, this article aims to provide a framework for conceptualizing across all ages and highlight the implications they may have for longevity.
PubMed: 38058996
DOI: 10.1515/nipt-2023-0017