Response from Varani et al. to “Comment on ‘the IS6 family, a clinically important group of insertion sequences including IS26’ by Ruth M. Hall”

The IS6 family of insertion sequences is a large but coherent group which was originally named to avoid confusion between a number of identical or nearly identical IS that were identified at about the same time and given different names (IS15D, IS26, IS46, IS140, IS160, IS176). The underlying common mechanistic feature of all IS6 family members which have been investigated is that they appear to transpose by replicative transposition and form pseudo compound transposons with the flanking IS in direct repeat and in which associated genes are simply transferred to the target replicon and lost from the donor.In the accompanying letter Hall raises a number of very serious and wide-ranging criticisms of our recent review article concerning the IS6 family of insertion sequences. She clearly feels that we have undervalued her work and that we question or ignore certain of her in vivo results. This impression is almost certainly the result of the standard of proof we generally apply to mechanistic aspects of transposition where we think it important to identify transposition intermediates including the types of synaptic, strand cleavage and strand transfer complexes involved.

Re: Concept and application of relaxing radial retinectomy for retinal detachment with advanced proliferative vitreoretinopathy

The following is a response to the recent review article by Girsang and colleagues (Int J Retina Vitreous. 2020;6:46), who describe concept and application of relaxing radial retinectomy for retinal detachment with advanced proliferative vitreoretinopathy. We discuss the distribution of the retinal nerve fiber layer, an aspect not touched on by the authors, and the importance of its consideration in determining visual field outcomes when performing retinectomy. Moreover, we share our clinical experience with both radial and circumferential retinectomy and discuss scenarios where the combination of both is more effective.

What’s Past Is Prologue: History of Nonalcoholic Fatty Liver Disease

Since the initial descriptions in the early 1980s by Dr. Ludwig et al. and Drs. Schaffner and Thaler, who firstly coined the terms nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), this liver disease has become a global health problem worldwide, causing considerable liver-related and extra-hepatic morbidity and mortality. Based on pathophysiological insights gained from the past decades, it has been clearly established that NAFLD is a metabolic liver disease whose etiology and pathogenesis extends beyond the liver and that NAFLD has important clinical implications, especially in terms of an increased risk of developing both cardiovascular disease (which represents the leading cause of death in this patient population) and other extra-hepatic manifestations, such as type 2 diabetes mellitus, chronic kidney disease, and some extra-hepatic cancers. The aim of this brief commentary is to discuss a recent review article written by Dr. Lonardo and colleagues, who raised awareness of the history of NAFLD. Since “What’s past is prologue”, I believe that this review article focusing on the history of NAFLD may contribute to better understanding the disease itself, as well as to anticipating the lines of the future clinical and pharmacological research of this common and burdensome liver disease.

Climate Change: A New Challenge for the Winemaking Sector

Viticulture and winemaking have a strong socio-economic importance worldwide. Weather and climate represent key forcing factors for grapevine development, yields, and quality. Hence, climate change is expected to pose a strong impact on this crop, threatening the sustainability of the winemaking sector. Recent-past trends show noticeable warming in the grapevine growing season, as well as changes in the precipitation patterns in many renowned winemaking regions worldwide. Furthermore, climate projections point to enhanced stress conditions for grapevine growth under future scenarios. The strong evidence for a significant warming and drying in the upcoming decades urges adaptation measures to be taken by the winemaking sector. The aim of this editorial is to provide an updated overview of the adaptation measures that can be used by sector stakeholders to mitigate the negative impacts of climate change. A recent review article, which highlights several adaptation strategies to ensure the future sustainability of this important sector, is hereby analyzed.

HSP90 inhibitors for IPF/COVID-19

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from preclinical studies on its inhibition and the intracellular signaling pathways involved, in a recent review article (Review). In this Article entry, we will introduce the main findings discussed in the review and focus on its translation and possible significance in the era of the SARS-CoV-2 pandemic.

Toward a transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects: challenges, opportunities, and next steps

Cognitive impairment has emerged as a key treatment priority in neuropsychiatric disorders. However, there is a lack of treatments with solid and lasting efficacy on cognition. A neurocircuitry-based biomarker model of pro-cognitive effects is critically needed to select among new candidate treatments. In a recent review of functional magnetic resonance imaging (fMRI) studies in mood disorders, we found that cognitive impairments are consistently accompanied by aberrant (hypo- and hyper-) activity in the dorsal prefrontal cortex (PFC) and the default mode network (DMN), and that activity change in these regions commonly occurs with cognitive improvements. Here, we (i) review the putative model from our recent review article, which explains the discrepant findings regarding the direction of aberrant dorsal PFC activity and treatment-related activity change in mood disorders. Inspired by the Research Domain Criteria project, we do this in order to (ii) examine whether a similar pattern of activity change occurs across distinct neuropsychiatric disorders and thereby provides a common biomarker for pro-cognitive effects. Lastly, we (iii) discuss whether dorsal PFC and DMN target engagement is a putative transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects, and (iv) outline the necessary next steps to address this question.