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

Structural dynamics of the RNA dependent RNA polymerase of H1N1 strain affecting humans: a bioinformatics approach

The Influenza flu is a pandemic disease that renders the highest risk factor to the society due to its efficient ability of airborne transmission. Studies on the H1N1 strain gained significant focus, since its pandemic outbreak in 2009 and particularly the computational studies on its structural elements significantly aided in revealing their functional uniqueness. Among the 10 structural proteins of H1N1, the RNA-dependent RNA polymerase (RdRp) heterotrimeric protein complex, which is responsible for the synthesis of viral RNA (vRNA) from the negative-sense RNA genome of the virus, is the focus of the present study. This study aimed to investigate the structural dynamics of the RdRp complex with particular emphasis on the reported 17 mutations. The mutant strain is more stabilized by strong concerted residue-residue interactions at both intra- and inter- monomeric levels. In comparison, the mutant strain is structurally flexible with enhanced stabilizing interactions. The structural dynamics of RdRp are significantly governed by the dynamics of the (i) endonuclease domain of PA, (ii) RNA-entry region of PB1 and (iii) cap-binding region of PB2. Explicitly, the cap binding region of PB2 expresses (i) a concerted motion with the RNA-entry region, along with (ii) an anti-correlated motion with the endonuclease domain of the PA subunit, which further supports the stable dynamics of cap-binding towards RNA binding. These findings contribute to the understanding of the structural dynamics associated with the pandemic and mutant structures of RdRp and render a basic knowledge for further development of novel inhibitors towards influenza flu affected humans. Communicated by Ramaswamy H. Sarma</p

Regulation of Cyclic AMP Response Element Binding and Hippocampal Plasticity-Related Genes by Peroxisome Proliferator-Activated Receptor α

SummaryPeroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates genes involved in fatty acid catabolism. Here, we provide evidence that PPARα is constitutively expressed in nuclei of hippocampal neurons and, surprisingly, controls calcium influx and the expression of various plasticity-related genes via direct transcriptional regulation of cyclic AMP response element binding (CREB). Accordingly, Pparα-null, but not Pparβ-null, mice are deficient in CREB and memory-associated proteins and have decreased spatial learning and memory. Small hairpin RNA knockdown of PPARα in the hippocampus suppressed CREB and NR2A, rendering wild-type animals markedly poor in consolidating spatial memory, whereas introduction of PPARα to the hippocampus of Pparα-null mice increased hippocampal CREB and NR2A and improved spatial learning and memory. Through detailed analyses of CREB and NR2A activity, as well as spatial learning and memory in bone marrow chimeric animals lacking PPARα in the CNS, we uncover a mechanism for transcriptional control of Creb and associated plasticity genes by PPARα

HYALINE CELL–RICH CHONDROID SYRINGOMA OF THE FINGER

A mixed tumor is a neoplasm that has microscopic features of both epithelial and mesenchymal differentiation. Such mixed tumors are known as pleomorphic adenomas in the salivary glands, and their cutaneous counterparts are called chondroid syringomas. These tumors commonly occur in the head and neck region of middle-aged men. Hyaline cell–rich chondroid syringoma is a rare benign variant of chondroid syringoma composed of cells with eosinophilic hyaline cytoplasm and plasmacytoid features, the origin of which remains elusive. Although very few cases have been reported in literature, it is important to be aware of this entity so as to avoid misdiagnosis on histopathological examination. In this report we present a case of hyaline cell-rich chondroid syringoma occurring in the finger

Patient experience and perceived acceptability of whole-body magnetic resonance imaging for staging colorectal and lung cancer compared with current staging scans: a qualitative study

OBJECTIVE: To describe the experience and acceptability of whole-body magnetic resonance imaging (WB-MRI) staging compared with standard scans among patients with highly suspected or known colorectal or lung cancer. DESIGN: Qualitative study using one-to-one interviews with thematic analysis. SETTING: Patients recruited from 10 hospitals in London, East and South East England between March 2013 and July 2014. PARTICIPANTS: 51 patients (31 male, age range 40-89 years), with varying levels of social deprivation, were recruited consecutively from two parallel clinical trials comparing the diagnostic accuracy and cost-effectiveness of WB-MRI with standard scans for staging colorectal and lung cancer ('Streamline-C' and 'Streamline-L'). WB-MRI was offered as an additional scan as part of the trials. RESULTS: In general WB-MRI presented a greater challenge than standard scans, although all but four patients completed the WB-MRI. Key challenges were enclosed space, noise and scan duration; reduced patient tolerance was associated with claustrophobia, pulmonary symptoms and existing comorbidities. Coping strategies facilitated scan tolerance and were grouped into (1) those intended to help with physical and emotional challenges, and (2) those focused on motivation to complete the scan, for example focusing on health benefit. Our study suggests that good staff communication could reduce anxiety and boost coping strategies. CONCLUSIONS: Although WB-MRI was perceived as more challenging than standard scans, it was sufficiently acceptable and tolerated by most patients to potentially replace them if appropriate. TRIAL REGISTRATION NUMBER: ISRCTN43958015 and ISRCTN50436483

Additional file 12: Table S5. of Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties

Repeat elements identified in Tulsi genome assembly and classified in different groups of repeats

Additional file 25: Table S11. of Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties

Metabolites with unknown pathways with their disease implications. There are 15 medicinally relevant metabolites in Ocimum sp. with unknown pathways