Modeling-Dependent Protein Characterization of the Rice Aldehyde Dehydrogenase (ALDH) Superfamily Reveals Distinct Functional and Structural Features

The completion of the rice genome sequence has made it possible to identify and characterize new genes and to perform comparative genomics studies across taxa. The aldehyde dehydrogenase (ALDH) gene superfamily encoding for NAD(P)+-dependent enzymes is found in all major plant and animal taxa. However, the characterization of plant ALDHs has lagged behind their animal- and prokaryotic-ALDH homologs. In plants, ALDHs are involved in abiotic stress tolerance, male sterility restoration, embryo development and seed viability and maturation. However, there is still no structural property-dependent functional characterization of ALDH protein superfamily in plants. In this paper, we identify members of the rice ALDH gene superfamily and use the evolutionary nesting events of retrotransposons and protein-modeling–based structural reconstitution to report the genetic and molecular and structural features of each member of the rice ALDH superfamily in abiotic/biotic stress responses and developmental processes. Our results indicate that rice-ALDHs are the most expanded plant ALDHs ever characterized. This work represents the first report of specific structural features mediating functionality of the whole families of ALDHs in an organism ever characterized

Global Perspectives on Task Shifting and Task Sharing in Neurosurgery.

BACKGROUND: Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. METHODS: The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018-January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. RESULTS: Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). CONCLUSIONS: Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons

In Huntington's disease (HD), whether transneuronal spreading of mutant huntingtin (mHTT) occurs and its contribution to non-cell autonomous damage in brain networks is largely unknown. We found mHTT spreading in three different neural network models: human neurons integrated in the neural network of organotypic brain slices of HD mouse model, an ex vivo corticostriatal slice model and the corticostriatal pathway in vivo. Transneuronal propagation of mHTT was blocked by two different botulinum neurotoxins, each known for specifically inactivating a single critical component of the synaptic vesicle fusion machinery. Moreover, healthy human neurons in HD mouse model brain slices displayed non-cell autonomous changes in morphological integrity that were more pronounced when these neurons bore mHTT aggregates. Altogether, our findings suggest that transneuronal propagation of mHTT might be an important and underestimated contributor to the pathophysiology of HD

Continuous quality improvement in intensive care medicine. The GiViTI Margherita project - Report 2005

Aim. The assessment of the quality of intensive care medicine is mandatory in the modern healthcare system. In Italy, the GiViTI (Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva) network is working in this field since 1991 and it now involves 295 out of the about 450 Italian intensive care units (ICU). In 2002 GiViTI launched a project for the continuous quality assessment and improvement that is now joined by 180 ICUs. Data collected in 2005 are analyzed and presented. Methods. All admitted patients were entered in a validated software, which performs a multitude of validity checks during the data entry. Data were further reviewed by the co-ordinating center; patients admitted in months with more than 10% of incomplete or inconsistent records in each ICU were excluded from the analysis. Each year, a multivariate logistic regression model is fitted to identify predictors of hospital mortality. Starting from the SAPS 2 and the 2004 GiViTI model predictions of hospital mortality, two calibration tables and curves are presented. Results. In 2005, 180 Italian ICUs collected data on 55 246 patients. After excluding those admitted in months with an unjustified lower recruitment rate or with less than 90% of complete and consistent data, we had 52 816 (95.6%) valid cases. Although the rough hospital mortality in 2005 was 1% higher than in 2004 (22.6% vs 21.5%), the adjusted mortality shows a statistically significant 4% reduction (obser-ved-to-expected ratio: 0.96; 95% CI: 0.94-0.97). Conclusion. Italian ICUs in 2005 performed better than in 2004, at a parity of patient severity