Reduced synaptic activity and dysregulated extracellular matrix pathways are common phenotypes in midbrain neurons derived from sporadic and mutation-associated Parkinson's disease patients

Several mutations that cause Parkinson's disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: Neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, shows pathways and mechanisms that are central and convergent to PD and suggests a strong involvement of the tetra-partite synapse in PD pathology.

Should Routine Pulmonary Function Tests be Performed in Patients with Left Ventricular Dysfunction and/or Congestive Heart Failure undergoing Cardiac Surgery?

Background It is controversial whether pulmonary function testing should be performed routinely in cardiac surgery patients. The aim of our study was to focus on patients who have congestive heart failure, caused by left ventricular dysfunction or left-sided heart valve disease, and study the prognostic value of performing preoperative pulmonary function testing on their postoperative outcomes Methods: This is a retrospective propensity score matched study that included 366 patients with congestive heart failure who underwent cardiac surgery and had preoperative pulmonary function test. The patients were divided into two groups: Group 1; who had a normal or mild reduction in pulmonary function tests and group 2; who had moderate to severe reduction in pulmonary function tests. The postoperative outcomes, including pulmonary complications, were compared between the two groups. Results Pulmonary function tests were normal or mildly reduced in 190 patients (group 1) and moderately to severely reduced in 176 patients (group 2). Propensity matching identified 111 matched pairs in each group with balanced preoperative and operative characteristics. Compared to group 1, Group 2 had longer duration of mechanical ventilation [12 (7.5- 16) vs. 9 (6.5- 13) hours, p<0.001], higher postoperative Creatinine [111 (90- 142) vs. 105 (81- 128) µmol/dl, p=0.02] and higher hospital mortality (6.31% vs 0%, p=0.02). Conclusion In congestive heart failure patients undergoing cardiac surgery, moderate to severe reduction of pulmonary function test was associated with longer duration of mechanical ventilation and higher hospital mortality.

Species monitoring through space and time — combining microfluidic SNP genotyping and environmental niche modelling on herbarium specimens of the rare Northern dragonhead, Dracocephalum ruyschiana (Lamiaceae)

Aim: We have studied population genetic change through time in the Northern dragonhead, Dracocephalum ruyschiana (Lamiaceae); a plant species that has experienced a drastic population decline and habitat loss in Europe. We aimed at adding a historic level to the monitoring of dragonhead by testing a microfluidic SNP array approach on herbarium specimens up to 200 years old and comparing the genomic results with that of modern populations in Norway. We also aimed to gain a more holistic species knowledge to guide monitoring efforts by combining herbarium genomics with ecological niche modelling (ENM). Location: Europe (mainly Norway) Methods: We have applied a microfluidic array consisting of 96 SNP markers on 130 herbarium specimens collected from 1820 to 2008. Obtained genotype data were compared with SNP data from modern samples using various population genetic analyses. We used sample metadata and observational records to model the species’ environmental niche. Results: The SNP array successfully genotyped all included herbarium specimens but was less capable of capturing diversity outside of Norway, which was genetically highly divergent from the Norwegian dragonheads. The historic-modern comparison revealed similar genetic structure in space and limited change through time in Norway. The ENM suggests that dragonhead has not fully achieved its potential distribution in Norway, which is anchored in warmer and drier regions, including areas where it does not occur today. Main conclusions: With the appropriate design procedures, the SNP array technology is promising for genotyping old herbarium specimens; an invaluable source of information from the past. We found no signs of the severe reduction in population size in our temporal genomic data of Norwegian dragonhead. Regardless, the regional populations in Norway are genetically divergent, both from each other and more so from populations outside of Norway, rendering continued protection of all existing populations of the species relevant.

Post-COVID19 Lung Fibrosis: An Worrying Experience of COVID19 Survivors

Patients recovering from confirmed COVID19 particularly moderate to severe disease, those treated in HDU / ICU support with high flow nasal cannula & Mechanical ventilation ,experienced different symptoms ranging from tiredness, fatigue to severe exertional dyspnea. High resolution CT scan of Chest of these such patients showed persistent radiological abnormalities simulating progressive fibrotic lung disease. Lung function including CO transfer factor revealed moderate to severe reduction. In case of patients recovered from moderate to severe COVID19 pneumonia, lung fibrosis is a big problem and it is one of the most worrying long-term complications. Lung fibrosis was documented in previous Severe Acute Respiratory Syndrome & Middle east Respiratory Syndrome pathology, and current observational studies suggests that pulmonary fibrosis could also complicate infection by SARSCOV2. The objective of our study was to set up a criteria of patients who are at risk to develop such serious complication, thus giving a chance for early detection of post-COVID19 lung fibrosis and thus preventing such disabling complication by proper andearly intervention . Bangladesh J Medicine July 2022; 33(1) : 114-119

Time is of the essence: the molecular mechanisms of primary microcephaly

Primary microcephaly is a brain growth disorder characterized by a severe reduction of brain size and thinning of the cerebral cortex. Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development. Centrosomes are microtubule organizing centers that participate in several processes, including controlling polarity, catalyzing spindle assembly in mitosis, and building primary cilia. Understanding which of these processes are altered and how these disruptions contribute to microcephaly pathogenesis is a central unresolved question. In this review, we revisit the different models that have been proposed to explain how centrosome dysfunction impairs cortical development. We review the evidence supporting a unified model in which centrosome defects reduce cell proliferation in the developing cortex by prolonging mitosis and activating a mitotic surveillance pathway. Finally, we also extend our discussion to centrosome-independent microcephaly mutations, such as those involved in DNA replication and repair.

Diacylglycerol kinase A is essential for polymyxin resistance provided by EptA, MCR-1 and other lipid A phosphoethanolamine transferases.

Gram-negative bacteria utilize glycerophospholipids (GPLs) as phospho-form donors to modify various surface structures. These modifications play important roles in bacterial fitness in diverse environments influencing cell motility, recognition by the host during infection, and antimicrobial resistance. A well-known example is the modification of the lipid A component of lipopolysaccharide by the phosphoethanolamine (pEtN) transferase EptA that utilizes phosphatidyethanoalmine (PE) as the phospho-form donor. Addition of pEtN to lipid A promotes resistance to cationic antimicrobial peptides (CAMPs), including the polymyxin antibiotics like colistin. A consequence of pEtN modification is the production of diacylglycerol (DAG) that must be recycled back into GPL synthesis via the diacylglycerol kinase A (DgkA). DgkA phosphorylates DAG forming phosphatidic acid, the precursor for GPL synthesis. Here we report that deletion of dgkA in polymyxin-resistant E. coli results in a severe reduction of pEtN modification and loss of antibiotic resistance. We demonstrate that inhibition of EptA is regulated post-transcriptionally and is not due to EptA degradation during DAG accumulation. We also show that the inhibition of lipid A modification by DAG is a conserved feature of different Gram-negative pEtN transferases. Altogether, our data suggests that inhibition of EptA activity during DAG accumulation likely prevents disruption of GPL synthesis helping to maintain cell envelope homeostasis.

Ozone Variation during the Development of a Tropical Cyclone: Case Study

The aim of this work was to study the variation in the total ozone column amount (TOC) during the life cycle of the tropical cyclone (TC) that occurred over the northwest Indian Ocean from 14 to 25 October 2008. This goal was achieved through examining the behavior of the tropical cyclone tilt under vertically varying background flows in association with the cyclone development. Thus, the vertical wind shear (VWS) was estimated as one of the most important dynamical parameters related to TC formation and intensity changes. Moreover, we estimated the variations in the daily values of TOC during the period of cyclone activity. We found that the magnitude of VWS increased during the growth period, and VWS weakened during the decay period. Anomalies of daily TOC were found to reduce steadily before and during the cyclone formation, followed by an increasing trend after the dissipation of cyclone. It was also found that during the development of the tropical cyclone, an outflow developed in the upper levels, having high velocities that extended beyond the tropopause up to the lower stratosphere. As a result, the lowest value of TOC during the tropical cyclone was due to a large amount of injected water vapor from the troposphere into the stratosphere through the convection processes. This was mostly photo-dissociated into OH and atomic O by deep solar radiation in the upper and lower stratosphere, leading to a severe reduction in stratospheric ozone.

Integrative transcription start site analysis and physiological phenotyping reveal torpor-specific expression program in mouse skeletal muscle

Mice enter an active hypometabolic state, called daily torpor when they experience a lowered caloric intake under cold ambient temperature. During torpor, the oxygen consumption rate in some animals drops to less than 30% of the normal rate without harming the body. This safe but severe reduction in metabolism is attractive for various clinical applications; however, the mechanism and molecules involved are unclear. Therefore, here we systematically analyzed the gene expression landscape on the level of the RNA transcription start sites in mouse skeletal muscles under various metabolic states to identify torpor-specific transcribed regulatory patterns. We analyzed the soleus muscles from 38 mice in torpid and non-torpid conditions and identified 287 torpor-specific promoters out of 12,862 detected promoters. Furthermore, we found that the transcription factor ATF3 is highly expressed during torpor deprivation and its binding motif is enriched in torpor-specific promoters. Atf3 was also highly expressed in the heart and brown adipose tissue during torpor and systemically knocking out Atf3 affected the torpor phenotype. Our results demonstrate that mouse torpor combined with powerful genetic tools is useful for studying active hypometabolism.

Production Efficiency of Animal-Feed Obtained From Food Waste in Japan

Converting food waste into animal-feed is highly useful for tackling the problem of food waste, which is particularly severe in developed countries. This study quantified inefficiencies in converting food waste into animal-feed and identified their causes through a data envelopment analysis (DEA) of the monthly input–output data of two producers of animal-feed obtained from food waste in Japan. Our empirical analysis revealed that the producers of animal-feed obtained from food waste (especially those treating food waste from retail and service industries) demonstrated inefficiencies in production technology and scale; moreover, expanding the production scale and improving the quality of food waste could enhance production efficiency. Based on the empirical results, specific policy implications were provided for the widespread use of animal-feed obtained from food waste in Japan and elsewhere, globally. Furthermore, it was found that the COVID-19 pandemic contributed to a severe reduction in the production efficiency of animal-feed producers treating food waste obtained from retail and service industries.

AN ETHNOBOTANICAL SURVEY OF WILD EDIBLE MUSHROOMS - A POTENTIAL RESOURCE OF FOOD AND INCOME GENERATION IN PABBAR VALLEY, HIMACHAL PRADESH, INDIA

The Western Himalayan region is rich in wild mushrooms. The people living in this area have extensive traditional mycological knowledge. The wild edible mushrooms have been consumed from the earliest history and also possess medicinal properties. The seasonal collections of wild edible mushrooms constitute a food with nutritional value and a source of income for the rural local inhabitants. In the present day, mushrooms are valued as popular food because of low in fat, carbohydrate, and cholesterol-free, and rich in vitamins. The lifestyle change is now responsible for a severe reduction in the collection of these mushrooms. The knowledge in the local environment gets lost when it is not gathered. The study aimed to investigate the knowledge and use of wild edible mushrooms in Pabbar Valley, Himachal Pradesh. A total of 13 species of mushrooms belonging to 11 families were identified as edible from the area. Morchella spp. are collected mainly for trade purposes.