21 research outputs found

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

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    : The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

    Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay

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    The atypical amino acid d-aspartate (d-Asp) occurs at considerable amounts in the developing brain of mammals. However, during postnatal life, d-Asp levels diminish following the expression of d-aspartate oxidase (DDO) enzyme. The strict control of DDO over its substrate d-Asp is particularly evident in the hippocampus, a brain region crucially involved in memory, and highly vulnerable to age-related deterioration processes. Herein, we explored the influence of deregulated higher d-Asp brain content on hippocampus-related functions during aging of mice lacking DDO (Ddo(-/-)). Strikingly, we demonstrated that the enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old Ddo(-/-) mice is followed by an accelerated decay of basal glutamatergic transmission, NMDAR-dependent LTP and hippocampus-related reference memory at 13/14 months of age. Therefore, the precocious deterioration of hippocampal functions observed in mutants highlights for the first time a role for DDO enzyme in controlling the rate of brain aging process in mammals

    Intrasplenic hepatocyte transplantation in the pig: new technical aspects

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    0 RTHOTOPIC liver transplantation (OLT) is the only clinically effective treatment for fulminant or chronic liver failure, whether genetic in origin or due to acquired hepatocellular dysfunction. However, wider application of OLT is limited by organ shortage and a relatively high mortality rate. Consequently, there is increasing interest in hepatocyte transplantation, especially in the treatment of metabolic disorders, or, in combination with plasmapheresis, of fulminant hepatic failure (bioartificial liver).’ With genetic defects, it may be possible to introduce genes into hepatocytes before autotransplantation. In recent years, the spleen has been the most popular site for inoculation of hepatocytes in experimental studies. Several authors have reported good survival and function,‘.” but problems remain in respect to long-term survival, ccl1 proliferation and differentiation, and the provision of sufficient number of cells to support failing liver function. Additionally, with one exception,4 most studies have been performed in the rat, and there has been little work carried out in large mammals. In order to address these concerns, we describe a method of autotransplantation in the pig which simplifies the surgical procedures and allows estimation of hepatocyte proliferation and survival in the spleen

    Enterprise Risk Management measurement: Insights from an interdisciplinary literature review

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    Enterprise Risk Management (ERM) represents a paradigm envisioned to provide an organization both resilience and opportunity in the face of uncertainty. The de-bate around ERM\u2019s value contribution to the organization has led to key ERM re-search questions arising, highlighting the need for further investigation of empiri-cal measurement of ERM and its implementation. Calls from several scholars specifically request extending the academic body of knowledge on ERM meas-urement. Motivated by the above calls, this study presents the findings of a systematic review of the ERM literature. The review examines the academic discipline of journals existing ERM studies are published in, these journals\u2019 H-indices, the lo-cation of the studies, and the methodology of how ERM is measured in the stud-ies. The review establishes that the ERM literature cuts across several academic research disciplines such as accounting, finance and strategy. Moreover, the ex-tant literature underscores that it is very difficult to quantify and measure ERM in practice within organizations. Consequential to this, most empirical studies of ERM have emphasized either a qualitative approach focusing in depth on specific organizations, or a quantitative approach relying on accessible, basic secondary data available in company reports. A gap in knowledge is presented around ex-tending ERM measurement, in particular in terms of a methodology based on primary data collection and analysis. This paper concludes that further development of empirical measurement scales based on primary data, whereby direct, first-hand input from members of organi-zations implementing ERM is collected, will augment the ERM body of knowledge. Such scales will allow for important aspects of ERM as it is imple-mented in the organization to be empirically measured
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