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Deubiquitination is crucial for the proper functioning of numerous biological pathways, such as DNA repair, cell cycle progression, transcription, signal transduction and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders and congenital abnormalities. ATXN7L3 is a component of the DUB module of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex and two other related DUB modules, and it serves as an obligate adaptor protein of three ubiquitin-specific proteases (USP22, USP27X or USP51). Through exome sequencing and by using GeneMatcher, we identified nine individuals with heterozygous variants in ATXN7L3. The core phenotype included global motor and language developmental delay, hypotonia and distinctive facial characteristics, including hypertelorism, epicanthal folds, blepharoptosis, a small nose and mouth, and low-set, posteriorly rotated ears. To assess pathogenicity, we investigated the effects of a recurrent nonsense variant [c.340C>T; p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired, as indicated by an increase in histone H2Bub1 levels. This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3- null mouse embryos, which have developmental delay and embryonic lethality. In conclusion, we present clinical information and biochemical characterization supporting ATXN7L3 variants in the pathogenesis of a rare syndromic neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

TMEM16F is a calcium-activated phospholipid scramblase and nonselective ion channel, which allows the movement of lipids bidirectionally across the plasma membrane. While the functions of TMEM16F have been extensively characterized in multiple cell types, the role of TMEM16F in the central nervous system remains largely unknown. Here, we sought to study how TMEM16F in the brain may be involved in neurodegeneration. Using a mouse model that expresses the pathological P301S human tau (PS19 mouse), we found reduced tauopathy and microgliosis in 6-to 7-mo-old PS19 mice lacking TMEM16F. Furthermore, this reduction of pathology can be recapitulated in the PS19 mice with TMEM16F removed from neurons, while removal of TMEM16F from microglia of PS19 mice did not significantly impact tauopathy at this time point. Moreover, TMEM16F mediated aberrant phosphatidylserine exposure in neurons with phospho-tau burden. These studies raise the prospect of targeting TMEM16F in neurons as a potential treatment of neurodegeneration. [ABSTRACT FROM AUTHOR]

Three-dimensional haptic matrices were pilot-tested as a nonvisual measure of cognitive ability. The results indicated that they correlated with convergent measures, with emphasis on spatial processing and that the participants who described items "visually" completed them more quickly and accurately and tended to have become visually impaired more recently than the other participants. (Contains 5 figures and 1 table.)

Replacing the active site arginine at position 166 with alanine slows the reaction 23-fold but does not change the magnitude of Bronsted beta(sub lg). This indicates that the transition state is the same.

Laparoscopy done in conjunction with vaginal hysterectomy may be more expensive than vaginal hysterectomy alone or abdominal hysterectomy. This was the conclusion of researchers who studied 1,049 women who had a hysterectomy at one hospital. Although laparoscopic vaginal hysterectomy reduced the hospital stay by an average of 1 day, it cost substantially more than the other two operative procedures. The operation also took longer because the combined approach required different sets of instruments and longer operating time. Vaginal hysterectomy alone was the least expensive procedure.

The coronavirus (COVID-19) pandemic created an unprecedented physical and mental health crisis on an international scale. Clients and therapists alike navigated the fears and uncertainty surrounding the virus, often in an environment of social isolation. The following paper presents a brief overview of the unique stressors and psychosocial factors impacting therapeutic work in the time of the coronavirus pandemic, including fears of the virus and social transmission, relational stressors due to isolation, grieving in isolation, fear of death, financial challenges, and the transition to telehealth. In addition, this paper aims to provide specific interventions and helpful approaches for psychotherapists navigating the novel challenges and demands to their clinical work through an AEDP (Accelerated Experiential Dynamic Psychotherapy) perceptive. This includes finding an entry point for accessing the pain: undoing aloneness; moving through the pain: dyadic affect regulation; and paying close attention to vitality within suffering: searching for transformance. Recommendations for the health and care of the clinician are also discussed, such as attuning to self-needs, anticipating and detecting dysregulation, staying with the good, meaning-making, identifying and responding to burnout, and the importance of receiving personal therapy and clinical supervision. [ABSTRACT FROM AUTHOR]

Mass spectrometry is commonly used in forensic chemistry laboratories for sensitive, definitive analysis. There have been significant efforts to bring mass spectrometry analysis on‐site through the development of ruggedized, fieldable instruments. Testing samples in the field is of particular interest in forensic science, homeland security, and defense applications. In forensic chemistry, testing seized drugs in the field can significantly improve efficiencies in processing of related criminal cases. The screening of passengers and luggage at transportation hubs is a critical need for homeland security for which mass spectrometry is well suited to provide definitive answers with low false positive rates. Mass spectrometry can yield reliable data for military personnel testing sites for potential chemical weapons release. To meet the needs of the forensic and security communities fieldable mass spectrometers based on membrane inlet systems and hybrid gas chromatography systems have been developed and commercialized. More recently developed ambient ionization mass spectrometry methods can eliminate the time, equipment, and expertise associated with sample preparation, and so are especially appealing for on‐site analysis. We describe the development of fieldable mass spectrometry systems, with emphasis on commercially available systems that have been deployed for on‐site analysis of seized drugs, chemical warfare agents, explosives, and other analytes of interest to the forensic and security communities. © 2020 John Wiley & Sons Ltd. Mass Spec Rev [ABSTRACT FROM AUTHOR]