Participation of epididymal cysteine-rich secretory proteins in sperm egg fusion and their potential use for male fertility regulation

Rat protein DE is an androgen-dependent cysteine-rich secretory protein (CRISP) synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted spermatozoa and participates in gamete fusion through binding to egg complementary sites. Immunization of rats with DE inhibits fertility and sperm fusion ability, suggesting that DE represents a good epididymal contraceptive target. Recombinant DE fragments and synthetic peptides revealed that DE binds to the egg via a 12-amino acid region of an evolutionarily conserved motif, Signature 2 (S2). The ability of other CRISP to bind to the rat egg was correlated with their S2 amino acid sequences. Although testicular protein Tpx-1 (CRISP-2) was capable of binding to rodent eggs, human epididymal AEG-related protein (ARP) and helothermine (from lizard saliva) were not. The S2 region presented only two substitutions in Tpx-1 and four in ARP and helothermine, compared with the DE S2, suggesting that this amino acid sequence was relevant for egg interaction. Studies with Tpx-1 and anti-Tpx-1 revealed the participation of this protein in gamete fusion through binding to complementary sites in the egg. In competition studies, DE reduced binding of Tpx-1 dose-dependently, indicating that both CRISP share the egg complementary sites. That anti-DE and anti-Tpx-1 inhibit sperm-egg fusion while recognizing only the corresponding proteins, suggests functional cooperation between these homologous CRISP to ensure fertilization success. These results increase our understanding of the molecular mechanisms of gamete fusion and contribute to the development of new and safer fertility regulating methods.Fil: Cohen, Debora Juana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Busso. Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ellerman, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Maldera, Julieta Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Goldweic, Nadia Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

An Empirical Validation of Cognitive Complexity as a Measure of Source Code Understandability

Background: Developers spend a lot of their time on understanding source code. Static code analysis tools can draw attention to code that is difficult for developers to understand. However, most of the findings are based on non-validated metrics, which can lead to confusion and code, that is hard to understand, not being identified. Aims: In this work, we validate a metric called Cognitive Complexity which was explicitly designed to measure code understandability and which is already widely used due to its integration in well-known static code analysis tools. Method: We conducted a systematic literature search to obtain data sets from studies which measured code understandability. This way we obtained about 24,000 understandability evaluations of 427 code snippets. We calculated the correlations of these measurements with the corresponding metric values and statistically summarized the correlation coefficients through a meta-analysis. Results: Cognitive Complexity positively correlates with comprehension time and subjective ratings of understandability. The metric showed mixed results for the correlation with the correctness of comprehension tasks and with physiological measures. Conclusions: It is the first validated and solely code-based metric which is able to reflect at least some aspects of code understandability. Moreover, due to its methodology, this work shows that code understanding is currently measured in many different ways, which we also do not know how they are related. This makes it difficult to compare the results of individual studies as well as to develop a metric that measures code understanding in all its facets.Comment: 12 pages. To be published at ESEM '20: ACM / IEEE International Symposium on Empirical Software Engineering and Measuremen

Cardiac rhabdomyomas in tuberous sclerosis patients: A case report and review of the literature

SummaryRhabdomyomas are the most common benign cardiac tumours. They are often associated with tuberous sclerosis and can be diagnosed antenatally and postnatally by echocardiography. Rhabdomyomas tend to regress spontaneously and are not usually operated upon, unless they become obstructive or cause severe arrhythmias. We describe the case of a child with tuberous sclerosis who was admitted for the resection of a subependymal giant cell astrocytoma, in whom cardiac rhabdomyomas in the right ventricular outflow tract were diagnosed. These two kinds of tumours are well known in the setting of tuberous sclerosis

A Pilot Survey for the H2_2O Southern Galactic Plane Survey (HOPS)

We describe observations with the Mopra radiotelescope designed to assess the feasibility of the H$_2$O maser southern Galactic plane survey (HOPS). We mapped two one-square-degree regions along the Galactic plane using the new 12 mm receiver and the UNSW Mopra spectrometer (MOPS). We covered the entire spectrum between 19.5 and 27.5 GHz using this setup with the main aims of finding out which spectral lines can be detected with a quick mapping survey. We report on detected emission from H$_2$O masers, NH$_3$ inversion transitions (1,1), (2,2) and (3,3), HC$_3$N (3-2), as well as several radio recombination lines.Comment: accepted by PAS

Sweet's syndrome in a patient with Crohn's disease: a case report

<p>Abstract</p> <p>Background</p> <p>Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, has been associated with malignancy, autoimmune disease and collagen vascular disease. The association of Crohn's disease and Sweet's syndrome is rare. We report a case of Sweet's syndrome in a patient with Crohn's disease.</p> <p>Case presentation</p> <p>A 63-year-old man with a history of Crohn's disease presented with one-week duration of abdominal pain, diarrhea and hematochezia. He also noticed eruption of painful skin rashes all over his body at the same time. Colonoscopy and esophagogastroduodenoscopy (EGD) showed inflammation involving different parts of the gastrointestinal tract consistent with Crohn's disease. Punch biopsy of the skin lesion was consistent with Sweet's syndrome, which has a rare association with Crohn's disease.</p> <p>Conclusion</p> <p>Crohn's disease should be excluded in patients presenting with Sweet's syndrome and diarrhea. Alternatively, Sweet's syndrome should be considered as a diagnosis when a patient with Crohn's disease develops skin lesions.</p

Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled iNKT cell gene expression during ontogeny and in peripheral subsets as part of the Immunological Genome Project (ImmGen). High-resolution comparative transcriptional analyses defined developmental and subset-specific iNKT cell gene expression programs. In addition, iNKT cells were found to share an extensive transcriptional program with natural killer (NK) cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Strikingly, the NK- iNKT program also operated constitutively in γδT cells and in adaptive T cells following activation. Together, our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes

Effects of Somatosensory Stimulation on the Excitability of the Unaffected Hemisphere in Chronic Stroke Patients

INTRODUCTION: Somatosensory stimulation of the paretic upper limb enhances motor performance and excitability in the affected hemisphere, and increases activity in the unaffected hemisphere, in chronic stroke patients. We tested the hypothesis that somatosensory stimulation of the paretic hand would lead to changes in excitability of the unaffected hemisphere in these patients, and we investigated the relation between motor function of the paretic hand and excitability of the unaffected hemisphere. METHODS: Transcranial magnetic stimulation was administered to the unaffected hemisphere of nine chronic stroke patients. Patients were submitted to 2-h somatosensory stimulation in the form of median nerve stimulation and control stimulation using a cross-over design. Baseline Jebsen-Taylor test scores were evaluated. Resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, and visual analog scores for attention, fatigue and drowsiness were measured across conditions. RESULTS: Better pre-stimulation baseline motor function was correlated with deeper SICI in the unaffected hemisphere. We found no overt changes in any physiological marker after somatosensory stimulation. There was increased drowsiness in the control session, which may have led to changes in intracortical facilitation. CONCLUSIONS: Our results do not support an overt effect of a single session of somatosensory stimulation of the paretic hand on motor cortical excitability of the unaffected hemisphere as measured by motor threshold, short-interval intracortical inhibition or intracortical facilitation. It remains to be determined if other markers of cortical excitability are modulated by somatosensory stimulation, and whether repeated sessions or lesion location may lead to different effects