Drosophila expressing human SOD1 successfully recapitulates mitochondrial phenotypic features of familial amyotrophic lateral sclerosis

Mitochondrial pathology is a seminal pathogenic hallmark of familial amyotrophic lateral sclerosis (FALS) which is extensively manifested by human patients and mutant SOD1G93A mammalian models. Rodents expressing human FALS-associated mutations successfully mimic several human disease features; although they are not as amenable to genetic and therapeutic compound screenings as non-mammalian models. In this study, we report a newly generated and characterized Drosophila model that expresses human SOD1G93A in muscle fibers. Presence of SOD1G93A in thoracic muscles causes mitochondrial pathology and impairs normal motor behavior in these flies. Use of this new FALS-24B-SOD1G93A fly model holds promise for better understanding of the mitochondrial affectation process in FALS and for the discovery of novel therapeutic compounds able to reverse mitochondrial dysfunction in this fatal disease

Parkin Mediates Apparent E2-Independent Monoubiquitination In Vitro and Contains an Intrinsic Activity That Catalyzes Polyubiquitination

10.1371/journal.pone.0019720PLoS ONE65

The CRISPR/Cas9 System for Crop Improvement: Progress and Prospects

The global demand for high-quality crops is continuously growing with time. Crop improvement techniques have a long history and they had been applied since the beginning of domestication of the first agricultural plants. Since then, various new techniques have and are being developed to further increase the commercial value and yield of crops. The latest crop improvement technique known as genome editing is a technique that enables precise modification of the plant genome via knocking out undesirable genes or enabling genes to gain new function. The variants generated from the genome editing are indistinguishable from naturally occurring variation. It is also less time-consuming and more readily accepted in the market commercially. The usage of genome editing has proven to be advantages and plays a promising role in future crop improvement efforts. Therefore, in this chapter, we aim to highlight the progress and application of genome editing techniques, in particular, the CRISPR/Cas9 system as a powerful genome editing tool for crop improvement. In addition, the challenges and future prospects of this technology for crop improvement will also be discussed

Disease-causing mutations in Parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy

Parkin catalyzes mitochondrial ubiquitination, recruiting autophagic components that clear damaged mitochondria. Defects in this pathway are implicated in Parkinson's disease

Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.

Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate the expression of EMT markers, phenocopying NELF ablation. Elevated expression of NELF-E and KAT2B is associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Taken together, we uncover a crucial role of the NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis

Impact of cardiac arrest centers on the survival of patients with nontraumatic out‐of‐hospital cardiac arrest : a systematic review and meta‐analysis

Background The role of cardiac arrest centers (CACs) in out‐of‐hospital cardiac arrest care systems is continuously evolving. Interpretation of existing literature is limited by heterogeneity in CAC characteristics and types of patients transported to CACs. This study assesses the impact of CACs on survival in out‐of‐hospital cardiac arrest according to varying definitions of CAC and prespecified subgroups. Methods and Results Electronic databases were searched from inception to March 9, 2021 for relevant studies. Centers were considered CACs if self‐declared by study authors and capable of relevant interventions. Main outcomes were survival and neurologically favorable survival at hospital discharge or 30 days. Meta‐analyses were performed for adjusted odds ratio (aOR) and crude odds ratios. Thirty‐six studies were analyzed. Survival with favorable neurological outcome significantly improved with treatment at CACs (aOR, 1.85 [95% CI, 1.52–2.26]), even when including high‐volume centers (aOR, 1.50 [95% CI, 1.18–1.91]) or including improved‐care centers (aOR, 2.13 [95% CI, 1.75–2.59]) as CACs. Survival significantly increased with treatment at CACs (aOR, 1.92 [95% CI, 1.59–2.32]), even when including high‐volume centers (aOR, 1.74 [95% CI, 1.38–2.18]) or when including improved‐care centers (aOR, 1.97 [95% CI, 1.71–2.26]) as CACs. The treatment effect was more pronounced among patients with shockable rhythm ( P =0.006) and without prehospital return of spontaneous circulation ( P =0.005). Conclusions were robust to sensitivity analyses, with no publication bias detected. Conclusions Care at CACs was associated with improved survival and neurological outcomes for patients with nontraumatic out‐of‐hospital cardiac arrest regardless of varying CAC definitions. Patients with shockable rhythms and those without prehospital return of spontaneous circulation benefited more from CACs. Evidence for bypassing hospitals or interhospital transfer remains inconclusive