Cytochalasin D restores nuclear size acting on F-actin and IZUMO1 localization in low-quality spermatozoa

In spermatozoa, the nuclear F-actin supports the acroplaxome, a subacrosomal structure involved in the correct exposure of several acrosomal membrane proteins; among them, the glycoprotein IZUMO1 is the major protein involved in sperm-oocyte fusion. Nuclear F-actin is also involved in sperm head shaping and chromosome compartmentalization. To date, few notions regarding the bivalent role of F-actin on sperm chromatin organization and IZUMO1 positioning have been reported. In our work, we characterized subcellular organization of F-actin in human high- and low-quality spermatozoa (A- and B-SPZ), respectively, showing that F-actin over-expression in sperm head of B-SPZ affected IZUMO1 localization. A correct IZUMO1 repositioning following in vitro induction of F-actin depolymerization, by cytochalasin D treatment, occurred. Interestingly, F-actin depolymerization was also associated with a correct acrosome repositioning, thus to favor a proper acrosome reaction onset, with changes in sperm nuclear size parameters and histone acetylation rate reaching high-quality conditions. In conclusion, the current work shows a key role of F-actin in the control of IZUMO1 localization as well as chromatin remodeling and acetylation events

High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

Metopic synostosis

Premature closure of the metopic suture results in a growth restriction of the frontal bones, which leads to a skull malformation known as trigonocephaly. Over the course of recent decades, its incidence has been rising, currently making it the second most common type of craniosynostosis. Treatment consists of a cranioplasty, usually preformed before the age of 1 year. Metopic synostosis is linked with an increased level of neurodevelopmental delays. Theories on the etiology of these delays range from a reduced volume of the anterior cranial fossa to intrinsic malformations of the brain. This paper aims to provide an overview of this entity by giving an update on the epidemiology, etiology, evolution of treatment, follow-up, and neurodevelopment of metopic synostosis

Resolution of acute acquired comitant esotropia after suboccipital decompression for Chiari I malformation.

International audiencePURPOSE: To report a case of acute comitant esotropia successfully treated with suboccipital decompression in a 9-year-old male patient with Chiari I malformation. DESIGN: Interventional case report. METHODS: A 9-year-old male with Chiari I malformation had acute onset of diplopia, headache, and comitant esotropia. RESULTS: About 9 months after suboccipital decompression, diplopia resolved and there was near orthophoria on examination 15 months after surgery. CONCLUSION: In view of our case and after a review of literature, we advocate primary suboccipital decompression to treat acute comitant esotropia in patients with Chiari I malformation. A follow-up period of at least 1 year rather than 6 months seems necessary to assess surgery effects

Body size scaling of space use in coastal pike (Esox lucius) in brackish lagoons of the southern Baltic Sea

The northern pike (Esox lucius) has been intensively studied in terms of behaviour due to its relevance to fisheries and its importance for structuring fish communities in freshwater ecosystems. However, little is known about the behaviour of coastal pike living in brackish lagoons. Freshwater ecosystems, particularly lakes and small rivers, are usually finite in space, which can limit the expression of space use as a function of body size and other traits. Better understanding the spatial behaviour shown by coastal pike in extended brackish lagoons and its relationship to body size, sex, season and vulnerability to fishing is an important step to further our knowledge on brackish pike populations and can inform management. Here, we present two years of acoustic telemetry data acquired on a large sample of coastal pike (n = 210) with an extended size range (480 to 1.210 mm total length) inhabiting six interconnected coastal lagoons bordered by the islands of Fischland-Darß-Zingst, Hiddensee, Rügen and Usedom in the Baltic Sea (area ca. 1.200 km²). Overall, the space used by coastal pike (50 % and 95 % utilization distribution, UD) scaled positively with body size, with larger fish using significantly more space after controlling for co-variates, but this effect was mainly observed at the between lagoon level. Within a given lagoon, body size scaling of space use was only observed for the 50 % UD of males. We also found the ratio of 50 % UD on 95 % UD to scale negatively with size, meaning that larger-sized pike used areas out of their core ranges more intensively regardless of sex. Space use also differed between seasons, with activity spaces being elevated in spring likely due to spawning migrations and increased reproduction-related activity. Study design was an important co-variate for our space use proxies, as we collected proportionally more data on pike that used less space, but fish recaptured by fisheries did not differ in space use from those that were not recaptured. All space use proxies were found to be repeatable, suggesting an influence of pike personalities on their individual spatial behaviour. This study provides an updated understanding of spatial behaviour in Brackish water-adapted pike and its ties to body size, highlighting how body size in interaction with biotic and abiotic factors drives space use patterns.We wish to thank the European Union and State of Mecklenburg-Vorpommern, Ministry of Agriculture and Environment, for funding our project via the European Maritime and Fisheries Fund (Grant/Award numbers MV-I.18-LM-004 and B730117000069;BODDENHECHT).Peer reviewe