Biochemical and biophysical changes in plasma and erythrocyte membranes of alcohol consuming type 2 diabetics: A clinical study

Background and aims: Effects of alcohol consumption on blood glucose levels is unpredictable and more so with a known type 2 diabetic. Since type 2 diabetes is a chronic condition with impairment of glucose metabolism, influence of excess alcohol consumption in such a derailed metabolism is ought to be investigated. Our aim was to understand the interpolating relationship between the metabolisms of glucose and alcohol, by investigating the biochemical and biophysical changes in plasma and erythrocytes respectively. Methods We performed a clinical study with 20 human subjects wherein non-alcoholics, non-diabetics were considered as controls and the test subjects were categorized as alcoholics, diabetics and alcoholic diabetics. Findings were analysed against the control group. Results Increased plasma AST, ALT, ALP, and LDH enzyme activity; higher levels of nitric oxide, thiobarbituric acid reactive species (TBARS) both in plasma and erythrocyte lysate; higher fasting and postprandial glucose, glycated haemoglobin levels (Hb1Ac) levels; elevated levels of erythrocyte membrane total cholesterol / phospholipids (C/P) ratio and altered erythrocyte membrane fluidity in the alcoholic diabetics was noted. Conclusion Alcohol induced oxidative and nitrosative stress during its metabolism and its worsening effects in type II diabetics leading to a failure in the overall metabolic homeostasis is evident from the study.

Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons

The inhibition of voltage-gated sodium (NaV) channels in somatosensory neurons presents a promising novel modality for the treatment of pain. However, the precise contribution of these channels to neuronal excitability, the cellular correlate of pain, is unknown; previous studies using genetic knockout models or pharmacologic block of NaV channels have identified general roles for distinct sodium channel isoforms, but have never quantified their exact contributions to these processes. To address this deficit, we have utilized dynamic clamp electrophysiology to precisely tune in varying levels of NaV1.8 and NaV1.9 currents into induced pluripotent stem cell-derived sensory neurons (iPSC-SNs), allowing us to quantify how graded changes in these currents affect different parameters of neuronal excitability and electrogenesis. We quantify and report direct relationships between NaV1.8 current density and action potential half-width, overshoot, and repetitive firing. We additionally quantify the effect varying NaV1.9 current densities have on neuronal membrane potential and rheobase. Furthermore, we examined the simultaneous interplay between NaV1.8 and NaV1.9 on neuronal excitability. Finally, we show that minor biophysical changes in the gating of NaV1.8 can render human iPSC-SNs hyperexcitable, in a first-of-its-kind investigation of a gain-of-function NaV1.8 mutation in a human neuronal background.

Garlic Extract: Inhibition of Biochemical and Biophysical Changes in Glycated HSA

Glycation of various biomolecules contributes to structural changes and formation of several high molecular weight fluorescent and non-fluorescent, advanced glycation end products (AGEs). AGEs and glycation are involved in various health complications. Synthetic medicines, including metformin, have several adverse effects. Natural products and their derivatives are used in the treatment of various diseases due to their significant therapeutic qualities. Allium sativum (garlic) is used in traditional medicines because of its antioxidant, anti-inflammatory, and anti-diabetic properties. This study aimed to determine the anti-glycating and AGEs inhibitory activities of garlic. Biochemical and biophysical analyses were performed for in vitro incubated human serum albumin (HSA) with 0.05 M of glucose for 1, 5, and 10 weeks. Anti-glycating and AGEs inhibitory effect of garlic was investigated in glycated samples. Increased biochemical and biophysical changes were observed in glycated HSA incubated for 10 weeks (G-HSA-10W) as compared to native HSA (N-HSA) as well as glycated HSA incubated for 1 (G-HSA-1W) and 5 weeks (G-HSA-5W). Garlic extract with a concentration of ≥6.25 µg/mL exhibited significant inhibition in biophysical and biochemical changes of G-HSA-10W. Our findings demonstrated that garlic extract has the ability to inhibit biochemical and biophysical changes in HSA that occurred due to glycation. Thus, garlic extract can be used against glycation and AGE-related health complications linked with chronic diseases in diabetic patients due to its broad therapeutic potential.

Dynamic Allostery Highlights the Evolutionary Differences between the CoV-1 and CoV-2 Main Proteases

ABSTRACTThe SARS-CoV-2 coronavirus has become one of the most immediate and widely-studied systems since its identification and subsequent global outbreak from 2019-2020. In an effort to understand the biophysical changes as a result of mutations, the mechanics of multiple different proteins within the SARS-CoV-2 virus have been studied and compared with SARS-CoV-1. Focusing on the main protease (mPro), we first explored the long range dynamic-relationship, particularly in cross-chain dynamics, using the Dynamic Coupling Index (DCI) to investigate the dynamic coupling between the catalytic site residues and the rest of the protein, both inter and intra chain for the CoV-1 and CoV-2 mPro. We found that there is significant cross-chain coupling between these active sites and distal residues in the CoV-2 mPro but it was missing in CoV-1. The enhanced long distance interactions, particularly between the two chains, suggest subsequently enhanced cooperativity for CoV-2. A further comparative analysis of the dynamic flexibility using the Dynamic Flexibility Index (DFI) between the CoV-1 and CoV-2 mPros shows that the inhibitor binding near active sites induces change in flexibility to a distal region of the protein, opposite in behavior between the two systems; this region becomes more flexible upon inhibitor binding in CoV-1 while it becomes less flexible in the CoV-2 mPro. Upon inspection, we show that, on average, the dynamic flexibility of the sites substituted from CoV-1 to CoV-2 changes significantly less than the average calculated across all residues within the structure, indicating that the differences in behaviors between the two systems is likely the result of allosteric influence, where the new substitutions in COV-2 induce flexibility and dynamical changes elsewhere in the structure.SIGNIFICANCEHere we have conducted a comparative analysis between the SARS-CoV-1 and SARS-CoV-2 mPro systems to shed mechanistic insight on the biophysical changes associated with the mutations between these two enzymes. Our work shows that the CoV-2 mPro system exhibits enhanced cross-chain communication between catalytic site residues and the rest of the structure. Further, both dynamic coupling and dynamic flexibility analyses indicates that, largely, the dynamic changes as evaluated by DCI and DFI occur at sites other than the mutation sites themselves, indicating that the functional differences between these two proteins are a result of dynamic allostery

Use of Selected Spectral Ratios to Assess the Response of Pineapple to Potassium Nutrition

Potassium (K) nutrition in pineapple grown on tropical peat can be problematic due to high precipitation which encourages leaching losses. Non-destructive tools that can assess K deficiency and the accompanying changes in biophysical and biochemical properties within pineapple is a good strategy to employ. In this study, we assessed the biophysical changes in pineapple (var. MD2) in response to different K rates by using a hyperspectral approach. K deficiency was detected at 171 days after planting. Shortage of K also exhibited a shift in red edge towards shorter wavelengths between 500-700 nm. In addition, spectral ranges of 430-680 nm, as well as 680-752 nm were found to be most effective in differentiating spectral response to varying K rates. Three vegetation indices, i.e. Normalized Pigment Chlorophyll Index (NPCI), Plant Senescence Index (PSRI) and Red-edge Vegetation Index (RVSI) were found to best describe K treatment effects on pineapple canopy reflectance. This study could be extended further to include pineapple varieties other than MD2, and also key nutrients, such as N and P, for better fertilizer management in peat-grown pineapple.

Analysis of Nanotoxicity with Integrated Omics and Mechanobiology

Nanoparticles (NPs) in biomedical applications have benefits owing to their small size. However, their intricate and sensitive nature makes an evaluation of the adverse effects of NPs on health necessary and challenging. Since there are limitations to conventional toxicological methods and omics analyses provide a more comprehensive molecular profiling of multifactorial biological systems, omics approaches are necessary to evaluate nanotoxicity. Compared to a single omics layer, integrated omics across multiple omics layers provides more sensitive and comprehensive details on NP-induced toxicity based on network integration analysis. As multi-omics data are heterogeneous and massive, computational methods such as machine learning (ML) have been applied for investigating correlation among each omics. This integration of omics and ML approaches will be helpful for analyzing nanotoxicity. To that end, mechanobiology has been applied for evaluating the biophysical changes in NPs by measuring the traction force and rigidity sensing in NP-treated cells using a sub-elastomeric pillar. Therefore, integrated omics approaches are suitable for elucidating mechanobiological effects exerted by NPs. These technologies will be valuable for expanding the safety evaluations of NPs. Here, we review the integration of omics, ML, and mechanobiology for evaluating nanotoxicity.

Transformation of coffee-growing landscapes across Latin America. A review

In Latin America, the cultivation of Arabica coffee (Coffea arabica) plays a critical role in rural livelihoods, biodiversity conservation, and sustainable development. Over the last 20 years, coffee farms and landscapes across the region have undergone rapid and profound biophysical changes in response to low coffee prices, changing climatic conditions, severe plant pathogen outbreaks, and other drivers. Although these biophysical transformations are pervasive and affect millions of rural livelihoods, there is limited information on the types, location, and extent of landscape changes and their socioeconomic and ecological consequences. Here we review the state of knowledge on the ongoing biophysical changes in coffee-growing regions, explore the potential socioeconomic and ecological impacts of these changes, and highlight key research gaps. We identify seven major land-use trends which are affecting the sustainability of coffee-growing regions across Latin America in different ways. These trends include (1) the widespread shift to disease-resistant cultivars, (2) the conventional intensification of coffee management with greater planting densities, greater use of agrochemicals and less shade, (3) the conversion of coffee to other agricultural land uses, (4) the introduction of Robusta coffee (Coffea canephora) into areas not previously cultivated with coffee, (5) the expansion of coffee into forested areas, (6) the urbanization of coffee landscapes, and (7) the increase in the area of coffee produced under voluntary sustainability standards. Our review highlights the incomplete and scattered information on the drivers, patterns, and outcomes of biophysical changes in coffee landscapes, and lays out a detailed research agenda to address these research gaps and elucidate the effects of different landscape trajectories on rural livelihoods, biodiversity conservation, and other aspects of sustainable development. A better understanding of the drivers, patterns, and consequences of changes in coffee landscapes is vital for informing the design of policies, programs, and incentives for sustainable coffee production.

Identification and Characterization of Antimicrobial Peptides From Butterflies: An Integrated Bioinformatics and Experimental Study

Butterflies represent one of the largest animal groups on Earth, yet antimicrobial peptides (AMPs) of this group are less studied in comparison with their moth counterparts. This study employed an integrated bioinformatics approach to survey natural AMPs from publicly available genomic datasets. Numerous AMPs, including cecropins, defensins, and moricins, were identified and subsequently used as templates for the design of a series of synthetic AMPs that mimicked the naturally occurring sequences. Despite differing biological effects among the various sequences, the synthetic AMPs exhibited potent antibacterial and antifungal activities in vitro and in vivo, without inducing hemolysis, which implied their therapeutic potential in infectious diseases. Electron and confocal fluorescence microscopies revealed that the AMPs induced distinct morphological and biophysical changes on microbial cell membranes and nuclei, suggesting that the antimicrobial effects were related to a mechanism of membrane penetration and nucleic acid binding by the peptides. In conclusion, this study not only offers insights into butterfly AMPs but also provides a practical strategy for high-throughput natural AMP discoveries that will have implications for future research in this area.

TRPV Protein Family—From Mechanosensing to Cancer Invasion

Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical stimuli and drive intracellular signaling pathways through spatio-temporally controlled Ca2+-influx. Mechanosensitive Ca2+-channels, therefore, act as critical components in the rapid transmission of physical signals into biologically compatible information to impact crucial processes during development, morphogenesis and regeneration. Given the mechanosensitive nature of many of the TRP family channels, they must also respond to the biophysical changes along the development of several pathophysiological conditions and have also been linked to cancer progression. In this review, we will focus on the TRPV, vanilloid family of TRP proteins, and their connection to cancer progression through their mechanosensitive nature.