Fetal androgen action is an important determinant of Sertoli cell (SC) number at birth. Androgens “program” reproductive tract development in rats between embryonic d (e) 15.5 and e17.5 (“male ...programming window”), and this is reflected for life by anogenital distance (AGD). We investigated if androgen regulation of SC number/proliferation was also programmed by androgens in this window. Pregnant rats were treated in various fetal time windows with vehicle (control) or 500 mg/kg·d di(n-butyl) phthalate (DBP), which suppresses fetal intratesticular testosterone (ITT). ITT and SC number/proliferation index were determined at e17.5 or e21.5; AGD was also determined at e21.5. In controls, SC number increased 11-fold and ITT by 10-fold from e17.5–e21.5. In animals exposed daily to DBP from e13.5, SC number was reduced by approximately 50% at e21.5, but increased 6-fold, as did ITT, from e17.5–e21.5; DBP had no effect on ITT at e15.5, reduced ITT by 50% at e17.5, and by more than 75% at e19.5–21.5. DBP exposure just in the male programming window did not alter SC number at e17.5 or 21.5 but reduced AGD. DBP treatment beyond e19.5 caused major reductions in SC number/proliferation index and ITT at e21.5. Only DBP treatments that included the male programming window led to reduced AGD at e21.5, but SC number was clearly not programmed in this window. Nevertheless, testis weight correlated highly (P < 0.001) with AGD at e21.5, and postnatal d 25 and 90 in animals exposed in utero to vehicle or DBP (e13.5–e21.5). Thus, AGD may predict adult testis size but probably not through a direct relationship with SC number.
East Africa hosts significant reserves of untapped geothermal energy. Exploration has focused on geologically young (<1 Ma) silicic calderas, yet there are many sites of geothermal potential where ...there is no clear link to an active volcano. The origin and architecture of these systems are poorly understood. Here, we combine remote sensing and field observations to investigate a fault‐controlled geothermal play located north of Lake Abaya in the Main Ethiopian Rift. Soil gas CO2 and temperature surveys were used to examine permeable pathways and showed elevated values along a ∼110 m high fault, which marks the western edge of the Abaya graben. Ground temperatures are particularly elevated where multiple intersecting faults form a wedged horst structure. This illustrates that both deep penetrating graben bounding faults and near‐surface fault intersections control the ascent of hydrothermal fluids and gases. Total CO2 emissions along the graben fault are ∼300 t d−1; a value comparable to the total CO2 emission from silicic caldera volcanoes. Fumarole gases show δ13C of −6.4‰ to −3.8‰ and air‐corrected 3He/4He values of 3.84–4.11 RA, indicating a magmatic source originating from an admixture of upper mantle and crustal helium. Although our model of the North Abaya geothermal system requires a deep intrusive heat source, we find no ground deformation evidence for volcanic unrest or recent volcanism along the graben fault. This represents a key advantage over the active silicic calderas that typically host these resources and suggests that fault‐controlled geothermal systems offer viable prospects for geothermal exploration.
Key Points
First conceptual model of a fault‐controlled magmatic geothermal resource in the East African Rift
Focus on North Abaya in the Main Ethiopian Rift and show that deep hydrothermal upflow is concentrated along a major graben bounding fault
Magmatic CO2 emissions along this fault are ∼300 t d−1 and comparable to average values from the world's subaerial volcanoes
Phthalate exposure induces germ cell effects in the fetal rat testis. Although experimental models have shown that the human fetal testis is insensitive to the steroidogenic effects of phthalates, ...the effects on germ cells have been less explored.
We sought to identify the effects of phthalate exposure on human fetal germ cells in a dynamic model and to establish whether the rat is an appropriate model for investigating such effects.
We used immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction to examine Sertoli and germ cell markers on rat testes and human fetal testis xenografts after exposure to vehicle or di(n-butyl) phthalate (DBP). Our study included analysis of germ cell differentiation markers, proliferation markers, and cell adhesion proteins.
In both rat and human fetal testes, DBP exposure induced similar germ cell effects, namely, germ cell loss (predominantly undifferentiated), induction of multinucleated gonocytes (MNGs), and aggregation of differentiated germ cells, although the latter occurred rarely in the human testes. The mechanism for germ cell aggregation and MNG induction appears to be loss of Sertoli cell-germ cell membrane adhesion, probably due to Sertoli cell microfilament redistribution.
Our findings provide the first comparison of DBP effects on germ cell number, differentiation, and aggregation in human testis xenografts and in vivo in rats. We observed comparable effects on germ cells in both species, but the effects in the human were muted compared with those in the rat. Nevertheless, phthalate effects on germ cells have potential implications for the next generation, which merits further study. Our results indicate that the rat is a human-relevant model in which to explore the mechanisms for germ cell effects.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The increasing demand for low-latency, high-bandwidth connectivity has introduced novel challenges to delivering strong resilience guarantees in production network environments. Closed hardware ...platforms, known as middleboxes, that lack visibility and support for state retention remain a key challenge for continuous service delivery during network failures. These middleboxes rarely employ recovery mechanisms of their own, inspiring renewed interest in the field of NFV in recent years due to this gap within the industry. The increasing availability of VNF capabilities in modern infrastructures offers an opportunity to exploit the flexibility of software and use hybrid architectures to improve resilience. Katoptron is a high-availability service that propagates state between unmodified hardware middleboxes and backup PNF or VNF appliances. The platform utilises targeted packet mirroring to allow network devices to organically construct equivalent state and thus allow an easy transition between hardware and software. To demonstrate its viability, we have evaluated Katoptron against a wide range of common hardware middlebox use cases built using multiple open-source packet processing frameworks. Results show upwards of 90% matching state with no observable delay to normal traffic or impact on its functionality.
For hospitalized children admitted outside of a critical care unit, the location, mode of death, "do-not-resuscitate" order (DNR) use, and involvement of palliative care teams have not been described ...across high-income countries.
To describe location of death, patient and terminal care plan characteristics of pediatric inpatient deaths inside and outside the pediatric intensive care unit (PICU).
Secondary analysis of inpatient deaths in the Evaluating Processes of Care and Outcomes of Children in Hospital (EPOCH) randomized controlled trial.
Twenty-one centers from Canada, Belgium, the United Kingdom, Ireland, Italy, the Netherlands, and New Zealand.
Descriptive statistics were used to compare patient and terminal care plan characteristics. A multivariable generalized estimating equation examined if palliative care consult during hospital admission was associated with location of death.
A total of 365 of 144,539 patients enrolled in EPOCH died; 219 (60%) died in PICU and 143 (40%) died on another inpatient unit. Compared with other inpatient wards, patients who died in PICU were less likely to be expected to die, have a DNR or palliative care consult. Hospital palliative care consultation was more common in older children and independently associated with a lower adjusted odds (95% confidence interval) of dying in PICU 0.59 (0.52-0.68).
Most pediatric inpatient deaths occur in PICU where patients were less likely to have a DNR or palliative care consult. Palliative care consultation could be better integrated into end-of-life care for younger children and those dying in PICU.
Introduction to the Special Issue Curtis, Jessie Hutchison; Zhang-Wu, Qianqian; Chang-Bacon, Chris K.
Journal of language, identity, and education,
07/2023, Letnik:
22, Številka:
4
Journal Article
Introduction to the Special Issue Curtis, Jessie Hutchison; Zhang-Wu, Qianqian; Chang-Bacon, Chris K.
Journal of language, identity, and education,
07/04/2023, Letnik:
22, Številka:
4
Journal Article
Introduction to the Special Issue Jessie Hutchison Curtis; Zhang-Wu, Qianqian; Chang-Bacon, Chris K
Journal of language, identity, and education,
07/2023, Letnik:
22, Številka:
4
Journal Article
The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of ...unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities.
•Most mouse Cre driver lines tested exhibited variable rates of germline recombination•Germline recombination exhibits parental sex bias and target locus selectivity•Similar principles apply to multiple organisms and recombinase systems•Guidelines are provided for detecting and minimizing unwanted germline recombination
Luo et al. report variable rates of germline recombination in commonly used mouse Cre driver lines, influenced by sex of Cre-carrying parents and target loci. Guidelines are provided to optimize cell-type-specific recombination in genetically targeted organisms expressing site-specific recombinases.
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