Regulatory roles of ephrinA5 and its novel signaling pathway in mouse primary granulosa cell apoptosis and proliferation

Recent findings suggest that ephrinA5 (Efna5) has a novel role in female mouse fertility, in addition to its well-defined role as a neurogenesis factor. Nevertheless, its physiological roles in ovarian granulosa cells (GC) have not been determined. In this study, mouse GC were cultured and transfected with ephrin A5 siRNA and negative control to determine the effects of Efna5 on GC apoptosis, proliferation, cell cycle progression, and related signaling pathways. To understand the mode signaling, the mRNA expression levels of Efna5 receptors (Eph receptor A5, Eph receptor A3, Eph receptor A8, and Eph receptor B2) were examined. Both mRNA and protein expressions of apoptosis-related factors (Bax, Bcl-2, Caspase 8, Caspase 3, and Tnfα) and a proliferation marker, Pcna, were investigated. Additionally, the role of Efna5 on paracrine oocyte-secreted factors and steroidogenesis hormones were also explored. Efna5 silencing suppressed GC apoptosis by downregulating Bax and upregulating Bcl-2 in a Caspase 8-dependent manner. Efna5 knockdown promoted GC proliferation via p-Akt and p-ERK pathway activation. The inhibition of Efna5 enhanced BMH15 and estradiol expression, but suppressed GDF9, while progesterone level remained unaltered. These results demonstrated that Efna5 is a pro-apoptotic agent in GC and plays important role in folliculogenesis by mediating apoptosis, proliferation, and steroidogenesis in female mouse. Therefore Efna5 might be potential therapeutic target for female fertility disorders.     

A Maize (Zea mays L.) BIK1-Like Receptor-Like Cytoplasmic Kinase Contributes to Disease Resistance

Plant Molecular Biology Reporter - Receptor-like cytoplasmic kinases (RLCKs) form a large subfamily of proteins in plants. RLCKs are known to regulate plant immunity to bacterial and fungal...     

Regeneration of seven indigenous tree species in a dry Afromontane forest,southern Ethiopia

Regeneration of seven indigenous tree species having significant ecological and economic importance was investigated in the Munessa-Shashemene dry Afromontane forest (MSF), southern Ethiopia. Densities and distributions of seedlings, saplings and trees were assessed along gradients of altitude, light and disturbance using quadrat sizes of 10×5 m (for seedlings) and 20×20 m (saplings and trees) following line transects. The number of individuals, frequency and height of the study species were recorded in the quadrats at every 100 m drop in altitude. Seedling densities varied markedly among the species and altitudes. Mean densities (number of individuals ha⁻¹) of seedlings ranged from zero (Polyscias fulva) to 5334 (Prunus africana), and from three (Polyscias fulva) to 102 (Podocarpus falcatus) for trees and saplings. Canonical Correspondence Analysis revealed that seedlings of Celtis africana and Croton macrostachyus were highly favored by disturbance and, hence, were concentrated in canopy gaps within the forest. Based on their population structures, the study species could be categorized into three groups: (1) Species that showed the highest proportion of individuals in the lowest height class and with a gradual decrease towards the upper height classes, which suggests good regeneration; Podocarpus falcatus, C. africana, C. macrostachys and P. africana belonged to this group. (2) Species that showed higher proportions of individuals in the lowest height class and with missing individuals in the subsequent middle height classes, indicative of hampered regeneration; Syzygium guineense and Pouteria adolfi-friederici belonged to this group. (3) Species with no individuals in the lowest and middle height classes but represented by individuals in upper height classes; P. fulva belonged to this group. The species categorized in the last two groups exhibited hampered regeneration, and P. fulva is in the verge of local extermination. High seedling densities (e.g. C. africana and P. africana) and/or adaptive defense mechanisms to herbivory (e.g. P. falcatus and C. macrostachyus) were common attributes of species, which exhibited good regeneration. Regeneration problems were largely attributed to human disturbance, lack of suitable habitat for seed germination or problems associated to seed set (seed predation or abortion). Our study indicated that P. fulva, P. adolfi-friederici and S. guineense require the highest immediate attention for conservation in the MSF.     

Miltefosine for the treatment of cutaneous leishmaniasis—A pilot study from Ethiopia

BackgroundCutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.Methodology and principal findingsIn an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.Conclusions/SignificanceBased on miltefosine’s good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04004754","term_id":"NCT04004754"}}NCT04004754.