Delay In Maturation Research Articles

Effect of the alveolate parasite Perkinsus olseni infection on sexual maturation and spawning efficiency of the clam Ruditapes decussatus.

The effect of Perkinsus olseni infection on the reproduction ability of clams has been underestimated so far. Although some studies found evidence of reduction of egg production and delay in gonad maturation after infection, the total effect of the infection is still unclear. In this study, Ruditapes decussatus clams from a naïve population were injected with two different doses of P. olseni parasites, a low dose leading to a light infection and a high dose leading to a heavy infection. Clams were maintained during 2 months for maturation, and at the end of the experiment, the spawning was induced, the number of larvae release and mortality were evaluated. During the maturation period, infection level, gonadal stage, condition index, gross biochemical composition and oxidative status of progenitors were evaluated at days 0, 30 and 60 post-injection. The effects of P. olseni infection on clams showed alterations on biochemical parameters, namely lipid peroxidation, a significant mortality and a delayed gonad maturation, with a greater effect in the highly infected individuals. The reproductive capacity of the clams was impaired in both infected groups showing a lower production and a higher mortality rate of larvae. Finally, this study indicates that the production of natural beds with a high prevalence of P. olseni could be compromised by a deregulation of the natural reproduction cycle and a decrease in larvae production by infected animals, probably due to a combination of lower egg production and lower lipid reserves in larvae from infected clams.

Dynamic Behaviors of a COVID-19 and Influenza Co-Infection Model with Time Delays and Humoral Immunity

Co-infections with respiratory viruses were reported in hospitalized patients in several cases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) are two respiratory viruses and are similar in terms of their seasonal occurrence, clinical manifestations, transmission routes, and related immune responses. SARS-CoV-2 is the cause of coronavirus disease 2019 (COVID-19). In this paper, we study the dynamic behaviors of an influenza and COVID-19 co-infection model in vivo. The role of humoral (antibody) immunity in controlling the co-infection is modeled. The model considers the interactions among uninfected epithelial cells (ECs), SARS-CoV-2-infected ECs, IAV-infected ECs, SARS-CoV-2 particles, IAV particles, SARS-CoV-2 antibodies, and IAV antibodies. The model is given by a system of delayed ordinary differential equations (DODEs), which include four time delays: (i) a delay in the SARS-CoV-2 infection of ECs, (ii) a delay in the IAV infection of ECs, (iii) a maturation delay of newly released SARS-CoV-2 virions, and (iv) a maturation delay of newly released IAV virions. We establish the non-negativity and boundedness of the solutions. We examine the existence and stability of all equilibria. The Lyapunov method is used to prove the global stability of all equilibria. The theoretical results are supported by performing numerical simulations. We discuss the effects of antiviral drugs and time delays on the dynamics of influenza and COVID-19 co-infection. It is noted that increasing the delay length has a similar influence to that of antiviral therapies in eradicating co-infection from the body.

Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis.

Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring's brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4-21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated Bdnf expression, together with changes in proBDNF/mBDNF balance, might affect neuronal cell viability, positioning, and maturation in PHHC pups. Reduced Kdr gene expression and the content of SEMA3E might lead to impaired brain development. In the brain tissue of E20 PHHC fetuses, the content of the procaspase-8 was decreased, and the activity level of the caspase-3 was increased; this may indicate the development of apoptosis. PHHC disturbs the mechanisms of early brain development leading to a delay in brain tissue maturation and formation of the motor reaction of pups.

An evolutionary explanation of female-biased sexual size dimorphism in North Sea plaice, Pleuronectes platessa L.

Sexual size dimorphism (SSD) is caused by differences in selection pressures and life-history trade-offs faced by males and females. Proximate causes of SSD may involve sex-specific mortality, energy acquisition, and energy expenditure for maintenance, reproductive tissues, and reproductive behavior. Using a quantitative, individual-based, eco-genetic model parameterized for North Sea plaice, we explore the importance of these mechanisms for female-biased SSD, under which males are smaller and reach sexual maturity earlier than females (common among fish, but also arising in arthropods and mammals). We consider two mechanisms potentially serving as ultimate causes: (a) Male investments in male reproductive behavior might evolve to detract energy resources that would otherwise be available for somatic growth, and (b) diminishing returns on male reproductive investments might evolve to reduce energy acquisition. In general, both of these can bring about smaller male body sizes. We report the following findings. First, higher investments in male reproductive behavior alone cannot explain the North Sea plaice SSD. This is because such higher reproductive investments require increased energy acquisition, which would cause a delay in maturation, leading to male-biased SSD contrary to observations. When accounting for the observed differential (lower) male mortality, maturation is postponed even further, leading to even larger males. Second, diminishing returns on male reproductive investments alone can qualitatively account for the North Sea plaice SSD, even though the quantitative match is imperfect. Third, both mechanisms can be reconciled with, and thus provide a mechanistic basis for, the previously advanced Ghiselin-Reiss hypothesis, according to which smaller males will evolve if their reproductive success is dominated by scramble competition for fertilizing females, as males would consequently invest more in reproduction than growth, potentially implying lower survival rates, and thus relaxing male-male competition. Fourth, a good quantitative fit with the North Sea plaice SSD is achieved by combining both mechanisms while accounting for sex-specific costs males incur during their spawning season. Fifth, evolution caused by fishing is likely to have modified the North Sea plaice SSD.

Design of Oscillatory Networks through Post-Translational Control of Network Components.

Many essential functions in biological systems, including cell cycle progression and circadian rhythm regulation, are governed by the periodic behaviors of specific molecules. These periodic behaviors arise from the precise arrangement of components in biomolecular networks that generate oscillatory output signals. The dynamic properties of individual components of these networks, such as maturation delays and degradation rates, often play a key role in determining the network's oscillatory behavior. In this study, we explored the post-translational modulation of network components as a means to generate genetic circuits with oscillatory behaviors and perturb the oscillation features. Specifically, we used the NanoDeg platform-A bifunctional molecule consisting of a target-specific nanobody and a degron tag-to control the degradation rates of the circuit's components and predicted the effect of NanoDeg-mediated post-translational depletion of a key circuit component on the behavior of a series of proto-oscillating network topologies. We modeled the behavior of two main classes of oscillators, namely relaxation oscillator topologies (the activator-repressor and the Goodwin oscillator) and ring oscillator topologies (repressilators). We identified two main mechanisms by which non-oscillating networks could be induced to oscillate through post-translational modulation of network components: an increase in the separation of timescales of network components and mitigation of the leaky expression of network components. These results are in agreement with previous findings describing the effect of timescale separation and mitigation of leaky expression on oscillatory behaviors. This work thus validates the use of tools to control protein degradation rates as a strategy to modulate existing oscillatory signals and construct oscillatory networks. In addition, this study provides the design rules to implement such an approach based on the control of protein degradation rates using the NanoDeg platform, which does not require genetic manipulation of the network components and can be adapted to virtually any cellular protein. This work also establishes a framework to explore the use of tools for post-translational perturbations of biomolecular networks and generates desired behaviors of the network output.

An epidemiological multi-delay model on Cassava Mosaic disease with delay-dependent parameters

Knowledge of the timing of the incubation period in plant and maturation period of vector are crucial in our understanding of vector born viral diseases and in the design of appropriate prevention. In this paper, we have formulated a model on the dynamics for Cassava Mosaic diseases considering incubation period in plant and maturation period of vectors as time delay factors. The mathematical model includes susceptible vectors, infected vectors, healthy plant, and infected plant populations. Depending on the system parameters, we identify conditions for biological viability and stability of different steady states of the non-delay model. We perform stability analysis and numerical simulation to evaluate the various parameters? role and demonstrate model behavior in different dynamical regimes. We suggest that incubation delay may destabilize epidemiological dynamics. A coexistence equilibrium can lose stability at a moderate level of maturation delay and restore stability if the maturation delay is significant.

A stage-structured predator-prey model with Crowley-Martin functional response

<p style='text-indent:20px;'>A stage-structured predator-prey model with Crowley-Martin functional response is formulated and analyzed to investigate the impaction of predator maturity delay and predator interference on the dynamics of the system. It is shown that the net reproduction number of the system determines its threshold dynamics: the system is permanent if and only if the net reproduction number is larger than one unit, otherwise the predators go extinct; Moreover, given that the system is permanent, the unique coexistence equilibrium is shown to be globally asymptotically stable provided that the predator's interference is large enough; Numerical simulations are also performed to explore the effects of predator maturity delay and predator's interference on the stability of interior equilibrium. It is indicated that an increase of maturity delay of the predator will enlarge its extinction risk and may also enrich dynamics of the system in the sense of bringing stability switches of the coexistence equilibrium; and that an increase of predator's interference may lead to stability switch of coexistence equilibrium from unstable to stable, implying that a large predator's interference can be stabilizing.</p>

Dynamics of a periodic stage-structure competitive model with two maturation delays

Dynamics of a periodic stage-structure competitive model with two maturation delays

Influence of Preharvest Bagging on Maturity Indices and Postharvest Quality of Cherry Tomato (Solanum lycopersicum var. cerasiforme)

The production of cherry tomato (Solanum lycopersicum var. cerasiforme) is negatively affected by harsh environmental conditions such as extremely high and low temperatures, wind and hail damage, and pest and disease infestation. These factors delay maturity and cause uneven ripening, fruit abrasion, and blemishes, which consequently result in poor fruit quality and reduced shelf life. Preharvest bagging is an environmentally friendly alternative technique for enhancement of fruit quality and hence alleviates the stated problems. The study evaluated the physico-chemical quality of ‘Tinker’ and ‘Roma VF’ cherry tomato as influenced by preharvest bagging (transparent and blue plastics) during 8 days of shelf life at ambient conditions. Five clusters of fruit per plant per cultivar with a diameter of 1.5 to 2.0 cm were bagged after 16 days of fruit set and harvested at the green maturity stage, 12 days after preharvest bagging for the assessment of postharvest quality. Preharvest bagging effectively accelerated fruit maturity and ripening as indicated by enhanced fruit size, uniform color development, high pH, dry matter (DM) content, soluble solid content (SSC), and low titratable acidity (TA) during shelf life. Bagged fruit had higher loss of firmness and weight mainly due to ripening and showed very slight incidence of diseases during shelf life of 8 days. Unbagged cherry tomato had delayed maturity and ripening; small-sized fruit; uneven color development; low pH, SSC, and DM; and high TA. Although unbagged cherry tomato had lower firmness and weight loss due to delayed ripening, fruit showed moderate to severe incidence of tomato bacterial canker disease (Clavibacter michiganensis subsp. michiganensis) during shelf life. These results indicated that preharvest bagging accelerated fruit maturity and ripening, improved physico-chemical quality, and reduced disease infestation on cherry tomato during shelf life.

Prenatal and Perinatal Antibiotic Exposure and Long-Term Outcome.

Antibiotics are frequently administered during pregnancy. Although necessary to address acute infections, their use facilitates antibiotic resistance. Other associations have also been found with the use of antibiotics, such as perturbations of gut bacteria, delays in microbial maturation, and increased risks of allergic and inflammatory diseases. Little is known about how the prenatal and perinatal administration of antibiotics to mothers affects the clinical outcomes of their offspring. A literature search was conducted of the Cochrane, Embase, and PubMed engines. The retrieved articles were reviewed by two authors and verified for relevance. The primary outcome was the effect of pre- and perinatal maternal antibiotic use on clinical outcomes. Thirty-one relevant studies were included in the meta-analysis. Various aspects are discussed, including infections, allergies, obesity, and psychosocial factors. In animal studies, antibiotic intake during pregnancy has been suggested to cause long-term alterations in immune regulation. In humans, associations have been found between antibiotic intake during pregnancy and different types of infections and an increased risk of pediatric infection-related hospitalization. A dose-dependent positive association between pre- and perinatal antibiotic use and asthma severity has been reported in animal and human studies, while positive associations with atopic dermatitis and eczema were reported by human studies. Multiple associations were identified between antibiotic intake and psychological problems in animal studies; however, relevant data from human studies are limited. However, one study reported a positive association with autism spectrum disorders. Multiple animal and human studies reported a positive association between pre- and perinatal antibiotic use by mothers and diseases in their offspring. Our findings have potentially significant clinical relevance, particularly considering the implications for health during infancy and later in life as well as the related economic burden.

Variation in the Oxidative Status of Testicular Tissues During Critical Pubertal Age Under Influence of Bisphenol A

Pubertal development of testis requires stringent regulations and precise expansion of germ cells. Reactive oxygen species (ROS) are involved in regulation and proliferation of spermatogonia. Bisphenol A (BPA) is well known for the induction of oxidative stress in testicular tissues leading to major adversities including reduced fertility in male. In the present study, BPA led response of antioxidants was assessed during critical period of pubertal maturation of testis. Four groups of Wistar albino rats were formed containing 15 animals each; Group I-Control, Group II-administered with 5 mg/kg/d BPA, Group III- administered with 25 mg/kg/d BPA and Group IV- administered with 50 mg/kg/d BPA. These groups were further bifurcated into three distinct periods of exposure i.e. 42-63 PND, 42-91 PND and 42-105 PND, containing 5 animals each. Level of CAT, SOD, GSH, GPx, and LPO was analysed. Linear regression for individual antioxidants and Pearson’s correlation between antioxidants were applied for age-wise analysis of variance. Results showed that during first three weeks (i.e. 42-63 PND) of BPA administration were better tolerated, irrespective of doses. Later intervals indicated significant decline (p<0.05) in the activity and level of antioxidants. Relatedness between variables of antioxidants following BPA exposure and control were extremely low (R2<0.1) indicating differential activity. Nonetheless, between antioxidants strong strength of association (r>0.9) was evident. Although initial toleration against BPA’s oxidative insult was evident, it could not be sustained following 91 or 105 PND. Extremely lower activity of antioxidant at later stage suggested potential delay in testicular maturity.

Lifespan extension in female mice by early, transient exposure to adult female olfactory cues.

Several previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation. We hypothesized that olfactory information might also have a sex-specific effect on lifespan, and we show here that the lifespan of female mice can be increased significantly by odors from adult females administered transiently, that is from 3 days until 60 days of age. Female lifespan was not modified by male odors, nor was male lifespan susceptible to odors from adults of either sex. Conditional deletion of the G protein Gαo in the olfactory system, which leads to impaired accessory olfactory system function and blunted reproductive priming responses to male odors in females, did not modify the effect of female odors on female lifespan. Our data provide support for the idea that very young mice are susceptible to influences that can have long-lasting effects on health maintenance in later life, and provide a potential example of lifespan extension by olfactory cues in mice.

Identifying the hydrocarbon potential from seismic, geochemical, and wireline data of the Sallum intra-basin, North Western Desert of Egypt

ABSTRACT The current study's objectives are to identify the primary source rock's hydrocarbon potential and, using various approaches, examine the Sallum Concession's petroleum system, which lies in the extreme northwestern part of the Western Desert of Egypt. We integrated seismic, geochemical, and well logging data. As a result, the structure analysis indicates that the area is elevated topographic land, representing a high intra-basin about the surrounding Faghour, Matrouh, and Shushan basins. Therefore, the site is a significant concession with various source rocks; Khatatba (Safa member) and Alam El-Buieb (AEB-3A member) are the oil-prone source rocks of the northern and southern parts of the area with high TOC (up to 11.3%) and mid-mature stage (0.7-1.0% Ro) at depth below 8000 ft. On the other hand, the Paleozoic Desouqy, Zeitoun, and Shiffah formations, located below 12000 ft, are gas-prone source rocks with high organic contents (TOC 1.41-4.64%) and fair potential for gas generation and are currently in the mid-mature stage (0.7-1.0% Ro). We concluded that the concession's low oil production might result from a delay in Kerogen maturity and hydrocarbon migration. Finally, the East of Sallum concession is the only potential area because the wells in the west do not show reservoirs characteristics.

Global Stability of Delayed SARS-CoV-2 and HTLV-I Coinfection Models within a Host

The aim of the present paper is to formulate two new mathematical models to describe the co-dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human T-cell lymphotropic virus type-I (HTLV-I) in a host. The models characterizes the interplaying between seven compartments, uninfected ECs, latently SARS-CoV-2-infected ECs, actively SARS-CoV-2-infected ECs, free SARS-CoV-2 particles, uninfected CD4+T cells, latently HTLV-I-infected CD4+T cells and actively HTLV-I-infected CD4+T cells. The models incorporate five intracellular time delays: (i) two delays in the formation of latently SARS-CoV-2-infected ECs and latently HTLV-I-infected CD4+T cells, (ii) two delays in the reactivation of latently SARS-CoV-2-infected ECs and latently HTLV-I-infected CD4+T cells, and (iii) maturation delay of new SARS-CoV-2 virions. We consider discrete-time delays and distributed-time delays in the first and second models, respectively. We first investigate the properties of the model’s solutions, then we calculate all equilibria and study their global stability. The global asymptotic stability is examined by constructing Lyapunov functionals. The analytical findings are supported via numerical simulation. The impact of time delays on the coinfection progression is discussed. We found that, increasing time delays values can have an antiviral treatment-like impact. Our developed coinfection model can contribute to understand the SARS-CoV-2 and HTLV-I co-dynamics and help to select suitable treatment strategies for COVID-19 patients with HTLV-I.

Prenatal maternal depression predicts neural maturation and negative emotion in infants

Despite widespread acceptance that prenatal symptoms of depression in mothers are detrimental to infants’ long-term emotional and cognitive development, little is known about the mechanisms that may integrate outcomes across these domains. Rooted in the integrative perspective that emotional development is grounded in developing cognitive processes, we hypothesized that prenatal symptoms of depression in mothers would be associated with delays in neural maturation that support sociocognitive function in infants, leading to more problematic behaviors. We used a prospective longitudinal study of mothers (N = 92) and their infants to test whether self-reported symptoms of depression in mothers during the second and third trimesters were associated with neural development and infant outcomes at 4 months of age. While controlling for postpartum symptoms of depression, more prenatal symptoms of depression in mothers predicted less neural maturation in the parietal region of 4-month-old infants. Less neural maturation, in turn, was associated with greater infant negativity, suggesting neural maturation as a putative mechanism linking maternal symptoms of depression with infant outcomes. Differences in neural regions and developmental timing are also discussed.

BENIGN ENLARGEMENT OF SUBARACHNOID SPACES IN INFANTS

Benign enlargement of subarachnoid spaces (BESS) constitutes is one of the most frequent neurosonographic findings in infancy and is considered to regress spontaneously by the age of 2 years. Although the majority of children with BESS demonstrate normal developmental milestones, some patients may experience a transient psychomotor delay under the age of 2 year. Besides clinical andneuroimaging findings, the long-term impact of BESS is of great interest (learning difficulties at school, language delay, impairmentsin social-cognitive abilities, reduced quality of life, decreased attention skills and poor visual-motor performance, increased risk ofautism spectrum disorders as well as a higher incidence of epilepsy). It is considered that the risk of long-term consequences may be associated with pathogenetic features of dilation of extra-axial cerebrospinal fluid spaces. In this review, we describe potentialpathogenetic mechanisms of dilatation of the subarachnoid space and its pathological sequelae in children. Generally, numerous pathogenetic hypotheses about developing BESS have been proposed as follows: remarkable physiological imbalance between the skull and brain growth in infants aged from three months to one year; manifestation of cerebral trophy; communicating hydrocephalus due to a distal block with a valve mechanism; a delay in maturation of arachnoid villi/granulations until two years of age; the result of abusive head trauma in infants. However, the hypothesis about pathological consequences of BESS in the long run due to abnormalvenous hemodynamics has emerged in recent years. Impaired venous outflow is the main driving factor of subarachnomegaly and the more severe pathological changes the more significant symptoms of subarachnomegaly. We also highlight the role of impaired cerebralvenous circulation in the development of subarachnomegaly. Further studies are needed to investigate the clinical relevance of chronic increased intracranial pressure due to venous outflow disturbance in infants with enlarged subarachnoid spaces.Тhe subject for future research should be to determine a diagnostic algorithm to help distinguish patients with BESS from those who are at risk of impairedneurological development and require additional diagnostic and therapeutic interventions.

Preliminary evidence for a lower brain age in children with attention-deficit/hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in abnormal brain development. Here, we quantified the level of individual brain maturation in children with ADHD using structural neuroimaging and a recently developed machine learning algorithm. More specifically, we compared the BrainAGE index between three groups matched for chronological age (mean ± SD: 11.86 ± 3.25 years): 89 children diagnosed with ADHD, 34 asymptomatic siblings of those children with ADHD, and 21 unrelated healthy control children. Brains of children with ADHD were estimated significantly younger (-0.85 years) than brains of healthy controls (Cohen's d = -0.33; p = 0.028, one-tailed), while there were no significant differences between unaffected siblings and healthy controls. In addition, more severe ADHD symptoms were significantly associated with younger appearing brains. Altogether, these results are in line with the proposed delay of individual brain maturation in children with ADHD. However, given the relatively small sample size (N = 144), the findings should be considered preliminary and need to be confirmed in future studies.

Dinâmica da maturação nuclear e citoplasmática de oócitos bovinos cultivados in vitro em meio suplementado com fulerol

ABSTRACT The aim of this work was to evaluate, in vitro, the dynamics of nuclear and cytoplasmic maturation of bovine oocytes in traditional IVM medium (CT) and supplemented with fullerol (MF50), for 36 hours. The nuclear maturation of CT (n=300) and MF50 (n=270) every 6 hours, stained with Hoechst33342 and cytoplasmic, the mitochondrial distribution of CT (n=197) and MF50 (n=159) at every 12 hours, stained with Mitotracker Orange. At 6 hours, CT oocytes (19%) were in MI (metaphase I), while in MF50 they were in GV (germ vesicle) or GVB (GV breakeage), repeating at 12 hours. At 18 hours, 46.3% were matured in CT, and 20% in MF50. At 24 hours, 43.9% of maturation was observed in the MF50 group, and 63.8% in the CT. At 30 and 36 hours, the maturation pattern was stable, but with the onset of oocyte degeneration. There was a delay in cytoplasmic maturation with 36 hours (P<0.05) in MF50 (53.9% of mature gametes), compared to CT (69.8%). With immature cytoplasm, they were 10.4% and 31.7% for CT and MF50 (P<0.05), respectively. It was concluded that fullerol possibly interfered in the expansion of cumulus oophorus cells, as well as delayed the meiotic progression and cytoplasmic maturation.

Manipulating plasma thyroid hormone levels alters development of endothermy and ventilation in nestling red-winged blackbirds.

Thyroid hormones are key regulators of development and metabolism in vertebrates. During the nestling period, young of altricial species transition from an ectothermic phenotype to an endothermic phenotype. Red-winged blackbirds are an altricial species that exhibit an increase in plasma 3,3', 5-triiodo-L-thyronine (T3) levels during the first 5days post-hatch (dph), begin to develop endothermic metabolic responses by 7 dph, and fledge within 10 days of hatching. We propose that thyroid hormones play an important role in regulating development of endothermy during the nestling period in altricial birds. To better understand the effects of thyroid hormones on endothermic metabolic development in an altricial species, we treated nestling red-winged blackbirds on 2, 3, and 5 dph with either methimazole (MMI) to induce hypothyroidism or supplemental T3 to induce hyperthyroidism. We then measured on 5, 7, and 9 dph morphology and whole animal O2 consumption ( ) and ventilation in the thermal neutral zone and during gradual cooling. Treatment of nestlings with MMI resulted in lower plasma T3 levels on 5 dph that recovered by 7 dph, while supplementing with T3 did not affect plasma T3 levels on 5, 7 and 9 dph. Treatment with MMI resulted in smaller nestlings with smaller hearts and structural characters such as wing chord and femur length, but larger lungs and kidneys. Treatment with T3 produced smaller nestlings with smaller body masses and shorter femur and tarsus lengths. The development of and ventilation endothermic responses to gradual cooling in MMI treated nestlings were delayed when compared with control nestlings. In 9 dph nestlings, hypothyroidism resulted in alterations in the responses of ventilation frequency and tidal volume to cooling when compared with the control nestlings. Supplemental T3 had no effect on the development of and ventilation in the thermal neutral zone or in response to cooling. Our data suggest plasma thyroid hormone levels play an active role in the systemic development of endothermic capacity and the development of ventilatory control. In the nestling avian, multiple systems develop in concert to produce an endothermic phenotype, but reduced thyroid hormone delays maturation of endothermic capacity.

TNFα stimulates the proliferation of immature Sertoli cells by attenuating UPS-degradation of cyclin D1 and leads to the delay of BTB maturation in pubertal rats.

The Sertoli cell that plays a vital role during spermatogenesis is a known target of physiological and pathological factors affecting testicular development. Tumor necrosis factor alpha (TNFα) participates in the blood-testis barrier reconstruction, cell apoptosis, and inflammatory response by recognizing receptors on Sertoli cell. TNFα has also been shown to induce the proliferation of immature Sertoli cell in vitro, yet the mechanism still remains unclarified. This study was designed to investigate the effect of TNFα on blood-testis barrier development during puberty and the underlying mechanisms of TNFα-induced immature Sertoli cell proliferation. Immature male Sprague-Dawley rats of postnatal day 12 were intraperitoneally injected with TNFα. Biotin-labeled method was used to detect permeability of the developing blood-testis barrier after TNFα treatment, and the distribution of occludin and junctional adhesion molecule-A (JAM-A) were detected by immunofluorescence. Sertoli cells isolated from Sprague-Dawley rats of postnatal day 10 were cultured in vitro and treated with TNFα. Cell proliferation rate was reflected by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay. Immunoblot and quantitative polymerase chain reaction were used to detect the expression of proliferating cell nuclear antigen, Fbxo4, and cyclin D1. Immunoprecipitation was used to detect the ubiquitination of cyclin D1 and the interaction between Fbxo4 and cyclin D1. Ammonium pyrrolidinedithiocarbamate (PDTC) was applied to detect the effect of nuclear factor kappaB (NFκB) activity inhibition on TNFα-induced Sertoli cell proliferation. The adenoviral recombinant plasmid containing rat Fbxo4 gene was constructed to investigate the effect of Fbxo4 overexpression on Sertoli cell proliferation promoted by TNFα. The in vivo experiment revealed a significant delay of blood-testis barrier maturation in pubertal rats caused by exogenous TNFα. TNFα (10ng/ml) treatment in vitro was found to promote the proliferation of immature Sertoli cells, accompanied with increased NFκB activity and cyclin D1 protein level. The level of Fbxo4 and ubiquitination of cyclin D1 were decreased after TNFα treatment. Inhibitor of NFκB or overexpression of Fbxo4 could both reverse the TNFα-induced proliferation of immature Sertoli cells, meanwhile restore the ubiquitin-proteasome system-dependent degradation of cyclin D1. Overexpression of Fbxo4 could not affect the activation of NFκB caused by TNFα. These results indicate that TNFα inhibits the ubiquitination and degradation of cyclin D1 through the NFκB pathway, thereby promoting the proliferation of immature Sertoli cell in vitro and inducing the delay of blood-testis barrier maturation in pubertal rats.