Training effectiveness evaluation: Advancing a Kirkpatrick model based composite framework.

The present study aims at ideating a quantitative protocol to evaluate effectiveness of training programmes especially meant for farmers, farm women, and rural youth. The specific objective was to develop a robust framework for measuring the effectiveness of rural training programmes organized by the Farmers Training Centres (FTCs) of India. Kirkpatrick's training evaluation model provides us the foundation to design a four-dimensional composite framework based on range-based indicator normalization, principal component analysis based indicator weight estimation, and rank correlation based framework sensitivity testing. We used cross-sectional primary data generated through household survey and personal interviews with randomly selected one thousand trainees to test and validate our proposed protocol. Applying it on our evaluation target we find that the degree of effectiveness of the training programmes varies; one in every four training programmes may not be effective. Trainees' reactions on various aspects of the training programmes may have positive and significant influence on learning. Training outcomes may be linked with the trainees' post-training changes in behaviour. A sensitivity test confirms that the proposed framework is not susceptible to changes in weighting schemes, implying robustness of indicator selection. The findings offer dissection of individual training programmes guiding policy decisions for a training organization. The proposed framework enriches the Kirkpatrick's training evaluation model by offering standardized indicators for training effectiveness evaluation.

Involvement of PI3 kinase and MAP kinase in IGF-I and insulin-induced ovarian steroidogenesis in common carp Cyprinus carpio.

Previously, we observed that in vitro steroidogenesis in intact ovarian follicles of common carp Cyprinus carpio can alone be induced by recombinant human insulin-like growth factor (IGF-I) and bovine insulin (b-insulin) and this induction was gonadotropin-independent. To investigate early signal transduction components involved in this process, the possible role of phosphatidylinositol 3-kinase (PI3 kinase) during ovarian steroidogenesis was examined. IGF-I and b-insulin induced testosterone and 17ß-estradiol production in carp ovarian theca and granulosa cells in short-term coincubation and this induction was significantly inhibited by Wortmannin and LY294002, two mechanistically different specific inhibitors of PI3 kinase. IGF-I and b-insulin were shown to activate PI3 kinase from 30 min onwards with a maximum at 90 min. In this study, we found the involvement of mitogen-activated protein kinase (MAP kinase) in the regulation of IGF-I- and b-insulin-induced steroidogenesis in carp ovary. An antagonist of mitogen-activated protein kinase kinase1/2 (MEK1/2) markedly attenuated IGF-I- and b-insulin-induced steroid production. Cells treated with IGF-I and b-insulin stimulated ERK1/2-dependent phosphorylation of extracellular signal regulated protein kinase1/2 (ERKs1/2) in a time-dependent manner, which was significantly attenuated in presence of MEK1/2 inhibitor. PI3 kinase inhibitors strongly attenuated phosphorylation and activation of MAP kinase, which was increased during IGF-I and b-insulin-induced steroidogenesis. Taken together, these results suggest that PI3 kinase is an initial component of the signal transduction pathway which precedes the MAP kinase during IGF-I- and b-insulin-induced steroidogenesis in C. carpio ovarian follicles.

Application of conventional metallic nanoparticles on male reproductive system - challenges and countermeasures.

The application of nanotechnology in the present era has substantial impact on different industrial and medical fields. However, the advancement in nanotechnology for potential therapeutic and consumer benefits has been an anxious cause regarding the probable hazardous consequences of these molecules in biological systems and the environment. The toxic effects can perturb the physiologic system broadly and reproductive function and fertility specifically. Despite engineered nanomaterials (ENMs) having a wide range of applications, toxicological investigations of the probable ramifications of ENMs on the reproductive systems of mammals and fertility remains in its nascence. Complication in the male reproductive system is quite a pertinent issue in today's world which comprises of benign prostatic enlargement, prostate cancer, and unhealthy sperm production. The therapeutic drugs should not only be active in minimum dose but also site-specific in action, criteria being met by nanomedicines. Nanomedicine therapy is promising but encompasses the chances of adverse effects of being cytotoxic and generating oxidative stress. These hurdles can be overcome by creating coated nanoparticles with organic substances, modification of shape and size, and synthesizing biocompatible green nanoparticles. This review attempts to look into the applications of most widely used metals like zinc, titanium, silver, and gold nanoparticles in the therapy of the male reproductive system, their prospective harmful effects, and the way out to create a safe therapeutic system by specific modifications of these metal and metal oxide nanoparticles.

Efficacy of phytochemicals as immunomodulators in managing COVID-19: a comprehensive view.

Throughout history, disease outbreaks have worked havoc upon humanity, sometimes reorienting the history and at times, signaling the end of entire civilizations and the modern pandemic that the world is dealing with, is COVID-19 or SARS-CoV-2. A healthy immunity could be an ideal gear for resisting COVID-19 for neither medicines nor vaccines have been ascertained till date. In view of the present scenario, there is a demanding necessity to analyze innovative and valid techniques for forestalling and cure of COVID-19 by re-evaluating the structure of the natural compounds for drug designing. The Ayurveda has come forward by prescribing a lot of medicinal herbs for combating this dreaded disease. We have searched from sources in Pubmed and Google Scholar and found 1509 items. The search criteria were limited to the effect of phytochemicals in certain immunomodulatory aspects of viral infection. The original research papers related to the works on phytochemicals in the down regulation of NF-kB, activation of NK and CD8+ cells, inhibition of inflammatory cytokine release and ROS scavenging were included in our study. Here, we try to focus on the immunoregulatory cells which have a vital aspect in COVID-19 and highlight the potential effects of the restorative use of phytochemicals as drugs or dietary supplements. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00706-2.

Text-Based Localization of Moments in a Video Corpus.

Prior works on text-based video moment localization focus on temporally grounding the textual query in an untrimmed video. These works assume that the relevant video is already known and attempt to localize the moment on that relevant video only. Different from such works, we relax this assumption and address the task of localizing moments in a corpus of videos for a given sentence query. This task poses a unique challenge as the system is required to perform: 2) retrieval of the relevant video where only a segment of the video corresponds with the queried sentence, 2) temporal localization of moment in the relevant video based on sentence query. Towards overcoming this challenge, we propose Hierarchical Moment Alignment Network (HMAN) which learns an effective joint embedding space for moments and sentences. In addition to learning subtle differences between intra-video moments, HMAN focuses on distinguishing inter-video global semantic concepts based on sentence queries. Qualitative and quantitative results on three benchmark text-based video moment retrieval datasets - Charades-STA, DiDeMo, and ActivityNet Captions - demonstrate that our method achieves promising performance on the proposed task of temporal localization of moments in a corpus of videos.

Steroid-induced oocyte maturation in Indian shad Tenualosa ilisha (Hamilton, 1822) is dependent on phosphatidylinositol 3 kinase but not MAP kinase activation.

Fully grown fish and amphibian oocytes exposed to a maturation-inducing steroid (MIS) activates multiple signal transduction pathways, leading to formation and activation of maturation-promoting factor (MPF) and induction of germinal vesicle breakdown (GVBD). The present study was to investigate if phosphatidylinositol 3 kinase (PI3 kinase) and mitogen-activated protein kinase (MAP kinase) activation are required for naturally occurring MIS, 17α,20ß-dihydroxy-4-pregnen-3-one (17,20ß-P)-induced cdc2 activation and oocyte maturation (OM) in Tenualosa ilisha. We observed that 17,20ß-P-induced OM was significantly inhibited by PI3 kinase inhibitors Wortmannin and LY29400. 17,20 ß-P was shown to activate PI3 kinase maximally at 90 min and cdc2 kinase at 16 h of treatment. Relative involvement of PI3 kinase, MAP kinase and cdc2 kinase in 17,20ß-P-induced OM was examined. MAP kinase was rapidly phosphorylated and activated (60-120 min) after MIS treatment and this response preceded the activation of cdc2 kinase by several hours. A selective inhibitor of MAP kinase (MEK), PD98059, sufficiently blocked the phosphorylation and activation of MAP kinase. Inhibition of MAP kinase activity using PD98059 however, had no effect on MIS-induced cdc2 kinase activation and GVBD. These results demonstrate that activation of the PI3 kinase is required for 17,20ß-P-induced cdc2 kinase activation and OM in T. ilisha. MAP kinase although was activated in response to 17,20ß-P and PI3 kinase activation, it is not necessary for cdc2 activation and OM in this species.

Changes in plasma steroid levels during oocyte development in Indian shad, Tenualosa ilisha (Hamilton, 1822): role of gonadotropins on in vitro steroid production and development of oocyte maturational competence.

Circanual variations in plasma testosterone (T), 17-estradiol (E2), and 17,20-dihydroxy-4-pregnen-3-one (17,20-P) levels and ovarian steroid synthetic potential of Tenualosa ilisha of river Hooghly, West Bengal, India were examined. This fish exhibited bi-annual spawning; one during April-May and another during August-September. Coinciding with the GSI values, present study recorded a decline in plasma T and E2 levels from October, reaching their lowest values in January followed by a rapid rise in March when the ovary contained mostly vitellogenic follicles and remained high up to April (postvitellogenic stage). Plasma 17,20ß-P level was detected in March and reached peak value in April during oocyte maturation. After spawning, all the steroid levels declined to reach lowest values in June. From June onwards, T and E2 levels again increased for the next cycle and peaked at the end of vitellogenesis. Plasma 17,20ß-P was reappeared in August and reached maximum in September during oocyte maturation and spawning. Of the two gonadotropins tested, in vitro production of both T and E2 by the vitellogenic and postvitellogenic follicles was regulated by FSH and LH respectively. Production of 17,20-P by the post-vitellogenic follicles was regulated by LH only. Acquisition of in vitro oocyte maturational competence (OMC) was developed by the addition of HCG in culture medium. Treatment of a 3ß-HSD inhibitor blocked LH-induced steroid production, but not development of OMC. Both Cycloheximide and actinomycin D inhibited LH-induced development of OMC, indicating the requirement of de novo protein synthesis for this process.

Expression of LH receptor in nonpregnant mouse endometrium: LH induction of 3ß-HSD and de novo synthesis of progesterone.

In mouse uterus, at the late diestrus stage LH binding sites have previously been described. The aim of our study was to confirm the existence of LH receptor (Lhr (Lhcgr)) mRNA and its protein in mouse endometrium. Endometrium at all stages of the estrous cycle contained Lhr mRNA, essentially identical to that found in mouse ovary. Endometrium also contained a 72  kDa immunoreactive receptor protein that bound to mouse anti-LHR antibody in western blot. Both receptor mRNA and protein were maximally expressed in the endometrium at metestrus and LH caused a significant increase in their expression levels. Endometrium also contained 3ß-hydroxy steroid dehydrogenase (3ß-hsd) mRNA and 3ß-HSD protein. LH addition elevated their expression and activity as evident from increased conversion of labeled pregnenolone to progesterone (P(4)) and de novo P(4) synthesis. LH-induced endometrial P(4) synthesis is mediated through expression of steroidogenic acute regulatory (Star) gene. Results demonstrated that LH-induced P(4) synthesis in endometrium is possibly mediated through the cAMP pathway. Involvement of a MAPK pathway was also evident. Gonadotropin-stimulated endometrial P(4) synthesis was markedly attenuated by an antagonist of MEK1/2, PD98059. LH-stimulated MEK1/2-dependent phosphorylation of ERK1/2 in a concentration- and time-dependant manner in cultured endometrial tissues. Moreover, involvement of cAMP in LH-stimulated activation of ERK1/2 was also evident. It is therefore possible that the major signaling pathways regulating endometrial steroidogenesis in mouse, including the adenylate cyclase and MAP kinase pathways, converge at a point distal to activation of protein kinase A and ERK1/2.

Regulation of ovarian steroidogenesis in vitro by gonadotropin in common carp Cyprinus carpio: interaction between calcium- and adenylate cyclase-dependent pathways and involvement of ERK signaling cascade.

Multiple signal transduction pathways mediating gonadotropin-induced testosterone and 17ß-estradiol (E(2)) production were identified in carp ovarian theca and granulosa cells in short-term co-incubation. Inhibitors of voltage-sensitive calcium channels (VSCCs) and calmodulin attenuated human chorionic gonadotropin (HCG)-induced steroid production, whereas modulators of adenylate cyclase and protein kinase A (PKA) increased their production, indicating that both calcium- and PKA-dependent pathways are involved in the regulation of gonadotropin-induced steroidogenesis in carp ovary. Interactions between these two pathways are evident from the positive effect of elevated intracellular calcium on HCG-induced steroid production and the reduction of forskolin (FK)- and dibutyryl cAMP (dbcAMP)-induced steroidogenesis by inhibitors of VSCCs and calmodulin. In this study, we found the involvement of a third signaling pathway, a mitogen-activated protein kinase (MAP kinase), in the regulation of gonadal steroidogenesis in this fish. An antagonist of mitogen-activated protein kinase kinases 1/2 (MEK1/2; also known as MAP2K1/MAP2K2) markedly attenuated HCG-induced steroid production. Cells treated with HCG stimulated MEK1/2-dependent phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERKs1/2) in a concentration and time-dependent manner. Moreover, ERK1/2 activation in cells was mimicked by FK and dbcAMP suggesting that ERK1/2 transduce signal downstream of PKA in HCG-induced ovarian steroidogenesis. Evidence for presence of cross talk between calcium-dependent pathways and this MAP kinase cascade has been shown by demonstrating the inhibitory effects of verapamil and calmodulin on ERK1/2 activation after HCG stimulation. Our results suggest that activation of ERK1/2 by HCG as well as other agents may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis in carp ovary.

Regulation of ovarian steroidogenesis in vitro by IGF-I and insulin in common carp, Cyprinus carpio: stimulation of aromatase activity and P450arom gene expression.

Regulation of ovarian steroidogenesis in vitro by recombinant human insulin-like growth factor-I (IGF-I) and bovine insulin (b-insulin) was investigated in intact follicles and isolated follicular cells of carp, Cyprinus carpio at vitellogenic stage of oocyte maturation. In intact follicles, IGF-I and b-insulin stimulated testosterone and 17beta-estradiol production in vitro. In isolated theca cells, IGF-I and b-insulin stimulated testosterone production, whereas in granulosa cells, they stimulated 17beta-estradiol production when testosterone was added in the incubation medium as precursor substrate. In intact follicles and in theca cells, IGF-I and b-insulin had no effect on HCG-stimulated testosterone production. HCG-stimulated 17beta-estradiol production, however, was significantly increased by IGF-I and b-insulin. To clarify the mechanism of 17beta-estradiol production by the ovarian follicles during vitellogenic stage of carp, effects of IGF-I and b-insulin either alone or in combination with HCG on aromatase activity (conversion of testosterone to 17beta-estradiol) and cytochrome P450 aromatase (P450arom) gene expression were investigated in vitro. IGF-I and b-insulin alone stimulated aromatase activity and P450arom gene expression and significantly enhanced HCG-induced enzyme activity and P450arom gene expression. Our results thus indicate that IGF-I and b-insulin alone can stimulate testosterone and 17beta-estradiol production in vitellogenic follicles of C. carpio by stimulating aromatase activity and P450arom gene expression. Evidence also provided for the modulation of HCG-induced aromatase activity and P450arom gene expression by IGF-I and b-insulin in such follicles.

Involvement of PI3 kinase and MAP kinase in IGF-I- and insulin-induced oocyte maturation in Cyprinus carpio.

Previously, we observed that in vitro germinal vesicle breakdown (GVBD) in Cyprinus carpio oocytes was induced by recombinant human insulin-like growth factor-I (IGF-I) and bovine insulin (b-insulin) and this induction was steroid-independent. To investigate further the early signal transduction components involved in this process, the possible role of phosphatidylinositol 3-kinase (PI3 kinase) during oocyte maturation was examined. IGF-I- and b-insulin-induced oocyte maturation was significantly inhibited by Wortmannin and LY294002, two mechanistically different specific inhibitors of PI3 kinase. IGF-I and b-insulin were shown to activate PI3 kinase after 90 min of their treatment. Both IGF-I and b-insulin were found to activate cdc2 kinase at 21h of treatment. We examined the relative involvement of PI3 kinase, MAP kinase and cdc2 kinase in IGF-I- and b-insulin-induced oocyte maturation in C. carpio. MAP kinase was rapidly phosphorylated and activated (30-150 min) in response to exposure of the oocytes with IGF-I and b-insulin. This response preceded the phosphorylation and activation of cdc2 by several hours (almost 19h). A potent and selective inhibitor of MEK, PD98059, the protein kinase that phosphorylates and activate MAP kinase, blocked the phosphorylation and activation of MAP kinase and cdc2 kinase and GVBD induction. Likewise, PI3 kinase inhibitors strongly inhibited phosphorylation and activation of MAP kinase, which was increased during oocyte maturation. Taken together, these results suggest that PI3 kinase is an initial component of the signal transduction pathway which precedes MAP kinase, and MPF activation during IGF-I- and b-insulin-induced oocyte maturation in C. carpio.

Stimulation of salmon calcitonin on secretion of 17beta-estradiol by the ovarian follicles of common carp, Cyprinus carpio.

The effects of salmon calcitonin (sCT) on the secretion of 17beta-estradiol (E(2)) were examined in female common carp, Cyprinus carpio. Vitellogenic stage fish adapted to high-Ca water were i.p. injected with vehicle, sCT, human chorionic gonadotropin (hCG), or hCG plus sCT. To determine whether ovarian follicles are equipped with CT receptors, a CT binding assay was conducted. In the in vitro experiments, vitellogenic follicles were incubated with stimulators and inhibitors. Administration of sCT increased the basal and hCG-stimulated E(2) release in vivo and in vitro. Binding characteristics of [(125)I]sCT to plasma membrane preparation of carp ovarian follicles showed saturability with high-affinity (K(d)=48.48 pmol/l and B(max)=1.2 pmol/mg protein). To clarify the mechanism of E(2) production by sCT, in vitro effect of sCT and hCG on aromatase activity (conversion of testosterone to E(2)) and cytochrome P450 aromatase (P450arom) gene expression in carp ovarian follicles were investigated. Salmon CT-stimulated both aromatase activity and P450arom gene expression in ovarian follicles of carp. sCT-stimulated E(2) release by the ovarian follicles in vitro was augmented in the presence of dibutyryl cAMP. Inhibitor of protein kinase A (PKA), SQ 22536 inhibited sCT-stimulated steroid production in a dose-dependent manner. Specific inhibitor of protein kinase C (PKC), NPC-15437 dihydrochloride had no inhibitory effects on sCT-induced E(2) release. The present study indicates that sCT binds specifically to carp ovary and stimulates E(2) production by increasing the activity of cytochrome P450 aromatase and P450arom gene expression. The results further suggest that stimulatory action of sCT on E(2) production is mediated through cAMP pathway.

In vitro effects of insulin-like growth factors and insulin on oocyte maturation and maturation-inducing steroid production in ovarian follicles of common carp, Cyprinus carpio.

In vitro germinal vesicle breakdown (GVBD) in Cyprinus carpio oocytes was induced by recombinant human insulin-like growth factor-I and -II (IGF-I and IGF-II) and bovine insulin (b-insulin). Treatment of postvitellogenic ovarian follicles with IGF-I and b-insulin increased concentration of maturation-inducing hormone (MIH), 17alpha,20beta-dihydroxy-4-pregnane-3-one (DHP) in the medium. IGF-I and IGF-II both and b-insulin induced GVBD in denuded oocytes. IGF-I analogue R3 IGF-I was more potent than IGF-I in inducing GVBD of postvitellogenic follicles suggesting that ovarian IGF binding proteins may inhibit IGF-I action. Vitellogenic follicles, which were immature for oocytes to complete GVBD in response to DHP or HCG, underwent GVBD by IGF-I, not by b-insulin. IGF-I was also able to stimulate DHP production in such follicles. Addition of DHP and HCG to the culture of vitellogenic follicles containing IGF-I or b-insulin did neither potentiate the stimulation of GVBD induced by IGF-I nor initiate the same in response to b-insulin. Incubation of postvitellogenic follicles with trilostane (3beta-HSD inhibitor) had no inhibitory effects on IGF-I- and b-insulin-induced GVBD but attenuated the same under HCG stimulation. Trilostane, however, strongly inhibited DHP production induced by all these effectors. Induction of GVBD by IGF-I and b-insulin was not altered in the presence of actinomycin D. However, it significantly blocked the HCG-induced GVBD. Cycloheximide was shown to inhibit the induction of GVBD and DHP production by IGF-I, b-insulin and HCG. Both actinomycin D and cycloheximide were found to inhibit DHP production stimulated by all the three effectors. Collectively, these observations indicate that IGF-I and b-insulin can induce GVBD via MIH- and transcription-independent pathway. Incubation of the follicles with gap junction uncouplers, 1-heptanol or 1-octanol, had no effect on IGF-I- and b-insulin-induced GVBD, but attenuated the same induced by HCG. These uncouplers, however, inhibited DHP production induced by IGF-I, b-insulin and HCG. This result suggests that both IGF-I and b-insulin can induce oocyte maturation without coupled gap junction between oocytes and granulosa cells, while homologous gap junctions are required for DHP production. Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase), wortmannin and LY294002 inhibited GVBD by IGF-I and b-insulin. These two inhibitors also attenuated HCG-induced GVBD. These data suggest that PI-3 kinase activity is required for IGF-I, b-insulin and HCG induction of GVBD in C. carpio.