The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate

Protein phosphatase 1 (PP1) binding proteins are quintessential regulators, determining substrate specificity and defining subcellular localization and activity of the latter. Here, we describe a novel PP1 binding protein, the nuclear membrane protein lamina associated polypeptide 1B (LAP1B), which interacts with the DYT1 dystonia protein torsinA. The PP1 binding domain in LAP1B was here identified as the REVRF motif at amino acids 55-59. The LAP1B:PP1 complex can be immunoprecipitated from cells in culture and rat cortex and the complex was further validated by yeast co-transformations and blot overlay assays. PP1, which is enriched in the nucleus, binds to the N-terminal nuclear domain of LAP1B, as shown by immunocolocalization and domain specific binding studies. PP1 dephosphorylates LAP1B, confirming the physiological relevance of this interaction. These findings place PP1 at a key position to participate in the pathogenesis of DYT1 dystonia and related nuclear envelope-based diseases.publishe

Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a “shift” of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis

Governance and sustainable development at higher education institutions

© 2020, Springer Nature B.V. Governance issues, here interpreted as the provisions of adequate policy frameworks characterized by reliability and accountability, coupled with resources to support their implementation, are known to be the basis for the implementation of sustainable development measures. This paper discusses the influence of governance in the ways sustainability is perceived and practiced in a higher education context. Apart from due considerations to the role of governance as the basis for regulation and institutional actions and management decisions, this paper reports on an empirical study undertaken in a sample of higher education institutions. This study entailed an analysis of sustainable development policies, certification, organizational structure, budget, reports, team for sustainability, staff training, and challenges for the integration of sustainability and governance. The results suggest that even though there are different opinions and attitudes on the role of governance, it is regarded as an important component in supporting efforts by higher education institutions to include considerations on sustainable development as part of their strategies

Decubital ischemic fasciitis

A 77-year-old immobilized woman presented with a hard, palpable and fixed mass over the greater trochanter. Subsequent Magnetic Resonance Imaging (MRI) revealed a subcutaneous mass lesion abutting the iliotibial band. On T1-weighted images (WI), the lesion was isointense to muscle (white arrow), with a central focus of high signal intensity (SI) (Fig. A, axial T1-WI). Fat suppressed (FS) T2-WI showed predominantly hyperintense signal (black arrowheads) with intralesional foci of low SI, adjacent to the right greater trochanter (white asterisk) (Fig. B, axial FS T2-WI). After intravenous administration of gadolinium contrast, marked enhancement was seen with small areas of non enhancement, in keeping with necrotic foci (white arrow) (Fig. C, coronal contrast-enhanced FS T1-WI.). Neither invasion of the gluteus muscles nor the bone marrow of the greater trochanter was seen. Solely based on the MRI findings, malignancy could not be excluded. Therefore, wide surgical resection of the lesion was performed. Histological examination revealed the diagnosis of ischemic fasciitis, with a central hypo - cellular area surrounded by a fibroblastic (white asterisk) and vascular proliferating outer zone (Fig. D)

The therapeutic implications of an abdominal aortic aneurysm with coincident horseshoe kidney

Two male patients were admitted to the department of vascular surgery for treatment of a large infrarenal abdominal aortic aneurysm (AAA) and an associated horseshoe kidney (HSK). Both patients were successfully treated by endovascular aneurysm repair (EVAR). Horseshoe kidney is a rare and complex congenital anomaly, which increases significantly the technical difficulty of conventional surgical repair of an associated AAA. Appropriate preoperative evaluation of the vascular supply of the HSK by CT- angiography and renal function is mandatory for optimal planning of the treatment strategy. EVAR is regarded as a valuable alternative to open surgical therapy, in the absence of renal failure and provided that accessory renal arteries are absent or small

Popliteal arteriovenous fistula following total knee arthroplasty

Postoperative popliteal arteriovenous fistula is a very rare complication. We report a unique asymptomatic fistula in a 77-year-old male patient, seven months after total knee replacement. The diagnosis was suspected by a clinical palpable thrill and confirmed with a typical doppler ultrasound signaling. This vascular malformation was successfully treated by surgical resection of the fistula. Referring to the literature, considering the management of popliteal aneurysms, we suggest to prefer an open procedure in patients who are in good general condition