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Actinomycetales, such as the genus Streptomyces, are well-known cell factories employed to produce a wide variety of secondary metabolites for industrial use. However, not only is the genetic engineering of Streptomyces more complicated and tedious than other model laboratory species, such as Escherichia coli, there is also a considerable lack of genetic tools, hindering its adoption as a common chassis for synthetic biology. In this work, 23 novel shuttle vectors are presented that follow the canonical SEVA (Standard European Vector Architecture) common architecture with the goal of increasing the genetic toolbox repertoire for Streptomyces and other actinomycetes. The ORI module of these plasmids is composed of the combination of two origins of replication, one for Gram-negative bacteria and the other for Streptomyces, a Gram-positive bacteria. Origins of replication have been included in the collection for integrative, low-copy number, and medium-to-high-copy number vectors for Streptomyces. Also, a new selection marker has been developed that confers resistance to apramycin. The functionality of these plasmids was tested via the heterologous expression of GFP and the heterologous production of the plant flavonoid apigenin in Streptomyces albus J1074, with successful results in both cases, therefore expanding the current repertoire of genetic manipulation tools in Streptomyces species. © 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.BACKGROUND The N3 wave is a vestibular evoked neurogenic potential detected in some patients with profound sensorineural hearing loss (PSNHL) during brainstem auditory evoked potential (BAEP) analysis. In 1998, Kato et al. mentioned two electropositive waves preceding N3, which we named p1-p2, but no further description was given. OBJECTIVE We sought to demonstrate the reproducibility of these waves and hypothesize on their anatomic origin. METHODS We used two cohorts of patients with PSNHL. The first cohort comprised 10 patients with N3, allowing us to establish a new test with adequate electrophysiological conditions headed to detect p1-p2 waves (PN3EP). The second cohort consisted of two groups group A comprised 10 patients in whom N3 was not detected; and group B comprised 20 patients presenting N3. PN3EP was performed in both groups, of which 50% had cervical myogenic vestibular evoked potentials (cVEMPs). RESULTS Only group B presented p1-p2. The PN3EP facilitated the identification of p1-p2 over BAEP analysis, and their presence correlated well with cVEMPs. CONCLUSIONS P1-p2 may be covered due to inadequate BAEP setting conditions, and could be generated in the distal neural path that generates the N3 wave. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.INTRODUCTION Rigorous research in the last few years has shown that in addition to the classical mechanism of neurodegeneration, certain unconventional mechanisms may also lead to neurodegenerative disease. One of them is a widely studied metabolic disorder type 2 diabetes mellitus (T2DM). We now have a clear understanding of glucose-mediated neurodegeneration, mostly from studies in Alzheimer's disease (AD) models. AD is recognized to be significantly associated with hyperglycemia, even earning the term "type 3 diabetes." Here, we review first the pathophysiology of AD, both from the perspective of classical protein accumulation, as well as the newer T2DM-dependent mechanisms supported by findings from patients with T2DM. Secondly, we review the different pathways through which neurodegeneration is aggravated in hyperglycemic conditions taking AD as a case study. Finally, some of the current advances in AD management as a result of recent research developments in metabolic disorders-driven neurodegeneration are also discussed. METHODS Relevant literatures found from PubMed search were reviewed. RESULTS Apart from the known causes of AD, type 2 diabetes opens a new window to the AD pathology in several ways. It is a bidirectional interaction, of which, the molecular and signaling mechanisms are recently studied. click here This is our attempt to connect all of them to draw a complete mechanistic explanation for the neurodegeneration in T2DM. Refer to Figure 3. CONCLUSION The perspective of AD as a classical neurodegenerative disease is changing, and it is now being looked at from a zoomed-out perspective. The correlation between T2DM and AD is something observed and studied extensively. It is promising to know that there are certain advances in AD management following these studies. © 2020 Indian Institute of Science Education and Research (IISER), Tirupati. Brain and Behavior published by Wiley Periodicals, Inc.Although outcomes of hematopoietic stem cell transplantation from alternative donors have been improved, it has not yet challenged the precedence of Human leukocyte antigen (HLA)-matched or a few loci-mismatched donors. Since the availabilities of these donors among non-sibling relatives has been scarcely discussed, we analyzed them using a large Japanese dataset of HLA typing. Dataset included HLA data from 2838 patients and their relatives, distributed in all parts of Japan. Antigen-mismatches at the HLA-A, -B, -DR loci and allele-mismatches at the HLA-A, -B, -C, -DRB1 loci were examined. The availabilities of 0-1/6 antigen-mismatched donors among 1 parent-candidate and 1 sibling-candidate were 24.3% and 33.9%, and those of 0-2/8 allele-mismatched donors were 18.6% and 32.1%, respectively. Additional HLA-C antigen-mismatches (18.1% vs 0.0%) along with the possession of 1-3/8 allele-mismatches (31.3% vs 3.0%) were more frequently observed in parent-candidates than in sibling-candidate. Most multiple allele-mismatched pairs had HLA-B allele-mismatches. In conclusion, expanding donor searches to include non-sibling relatives could widen the availability of conventional relative donors with 0-1/6 antigen-mismatch or 0-2/8 allele-mismatch to 20-30%. High-resolution typing including HLA-C locus examination should be performed, since additional mismatches at HLA-C loci along with multiple allele-mismatches were often observed, especially among non-sibling-pairs. This article is protected by copyright. All rights reserved. This article is protected by copyright. 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