Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters

A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. We found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, our data indicate that EphBs control axon guidance and synaptogenesis by distinct mechanisms and provide a new mouse model for dissecting EphB function in development and disease

Selective Remodeling: Refining Neural Connectivity at the Neuromuscular Junction

A primer on new research by Fuentes-Medel and colleagues explains the important role of non-neural cells in clearing neural debris, which is continuously produced during the normal remodeling processes that establish and maintain neural connectivity

A Chemical Genetic Approach Reveals Distinct Mechanisms of EphB Signaling During Brain Development

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, as EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knockin mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly, and specifically blocked. Using these mice we demonstrate that the tyrosine kinase activity of EphBs is required for axon guidance in vivo. By contrast, EphB-mediated synaptogenesis occurs normally when the kinase activity of EphBs is inhibited suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, these experiments reveal that EphBs control axon guidance and synaptogenesis by distinct mechanisms, and provide a new mouse model for dissecting EphB function in development and disease

Aesthetics of self-scaling: parallaxed transregionalism and Kutluğ Ataman's art practice

This article examines relations of ethnography, contemporary art-practice, globalisation and scalar geopolitics with particular reference to Kutluğ Ataman’s artworks. Having been shortlisted for the Turner Prize at the Tate and awarded the prestigious international Carnegie Prize in 2004 with his forty-screen video installation Küba (2004), Ataman became an extremely well-known, globally acclaimed artist and filmmaker. Self-conscious of their global travel and critically attentive to the contemporary ethnographic turn in the visual arts scene, Ataman’s video-works perform a conscientious failure of representing cultural alterity as indigeneity. Concentrating on the artist’s engagement with ethnography, this article contains three main parts. Analyses of the selection of videos in each part will give an account of different scalar aspects of Ataman’s artworks. It will first revisit a previous study (Çakirlar 2011) on the artist’s earlier work of video-portraits including Never My Soul! (2002) and Women Who Wear Wigs (1999). A detailed discussion of Küba follows, which may be taken as the ‘hinge - work’ in Ataman’s oeuvre that marks a scalar transition in his critical focus - from body and identity to community and geopolitics. The discussion will then move to a brief analysis of the series Mesopotamian Dramaturgies, including the screen-based sculptures Dome (2009), Column (2009), Frame (2009), English as a Second Language (2009), and The Complete Works of William Shakespeare (2009). Rather than addressing scale as a differential concept, this article aims to demonstrate the ways in which Ataman’s art-practice produces self-scaling, self-regioning subjects that unsettle the hierarchical constructions of scale and facilitates a critique of the scalar normativity within the global art world’s regionalisms and internationalisms

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics. © 2020 The Royal Society of Chemistry

Appropriate waist circumference cut points for identifying insulin resistance in black youth: a cross sectional analysis of the 1986 Jamaica birth cohort

Background While the International Diabetes Federation (IDF) has ethnic specific waist circumference (WC) cut-points for the metabolic syndrome for Asian populations it is not known whether the cut-points for black populations should differ from those for European populations. We examined the validity of IDF WC cut points for identifying insulin resistance (IR), the underlying cause of the metabolic syndrome, in predominantly black, young Jamaican adults. Methods Participants from a 1986 birth cohort were evaluated between 2005 and 2007 when they were 18-20 years old. Trained observers took anthropometric measurements and collected a fasting blood sample. IR was assessed using the homeostasis model assessment computer programme (HOMA-IR). Sex specific quartiles for IR were generated using HOMA-IR values and participants in the highest quartile were classified as "insulin resistant". Receiver operator characteristic (ROC) curves were used to estimate the best WC to identify insulin resistance. The sensitivity and specificity of these values were compared with the IDF recommended WC cut-points. Results Data from 707 participants (315 males; 392females) were analysed. In both sexes those with IR were more obese, had higher mean systolic blood pressure, glucose and triglycerides and lower mean HDL cholesterol. The WC was a good predictor of IR with an ROC area under the curve (95% CI) of 0.71(0.64,0.79) for men and 0.72(0.65,0.79) for women. Using the Youden Index (J) the best WC cut point for identifying IR in male participants was 82 cm (sensitivity 45%, specificity 93%, J 0.38) while the standard cut point of 94 cm had a sensitivity of 14% and specificity of 98% (J 0.12). In the female participants 82 cm was also a good cut point for identifying IR (sensitivity 52%, specificity 87%, J 0.39) and was similar to the standard IDF 80 cm cut point (sensitivity 53%, specificity 82%, J 0.35). Conclusions The WC that identified IR in young black men is lower than the IDF recommended WC cut point. Sex differences in WC cut points for identifying IR were less marked in this population than in other ethnic groups

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and Harvar