Measurement of distances and locations of thoracic and lumbar vertebral bodies from CT scans in cases of spinal deformation.

BACKGROUND: Spinal deformations, except for acute injuries, are among the most frequent reasons for visiting an orthopaedic specialist and musculoskeletal treatment in adults and adolescents. Data on the morphology and anatomical structures of the spine are therefore of interest to orthopaedics, physicians, and medical scientists alike, in the broad field from diagnosis to therapy and in research. METHODS: Along the course of developing supplementary methods that do not require the use of ionizing radiation in the assessment of scoliosis, twenty CT scans from females and males with various severity of spinal deformations and body shape have been analysed with respect to the transverse distances between the vertebral body and the spinous process end tip and the skin, respectively, at thoracic and lumbar vertebral levels. Further, the locations of the vertebral bodies have been analysed in relation to the patient's individual body shape and shown together with those from other patients by normalization to the area encompassed by the transverse body contour. RESULTS: While the transverse distance from the vertebral body to the skin varies between patients, the distances from the vertebral body to the spinous processes end tips tend to be rather similar across different patients of the same gender. Tables list the arithmetic mean distances for all thoracic and lumbar vertebral levels and for different regions upon grouping into mild, medium, and strong spinal deformation and according to the range of spinal deformation. CONCLUSIONS: The distances, the clustering of the locations of the vertebral bodies as a function of the vertebral level, and the trends therein could in the future be used in context with biomechanical modeling of a patient's individual spinal deformation in scoliosis assessment using 3D body scanner images during follow-up examinations.

Influence of ion and hydration atmospheres on RNA structure and dynamics: insights from advanced theoretical and computational methods.

RNA, a highly charged biopolymer composed of negatively charged phosphate groups, defies electrostatic repulsion to adopt well-defined, compact structures. Hence, the presence of positively charged metal ions is crucial not only for RNA's charge neutralization, but they also coherently decorate the ion atmosphere of RNA to stabilize its compact fold. This feature article elucidates various modes of close RNA-ion interactions, with a special emphasis on Mg2+ as an outer-sphere and inner-sphere ion. Through examples, we highlight how inner-sphere chelated Mg2+ stabilizes RNA pseudoknots, while outer-sphere ions can also exert long-range electrostatic interactions, inducing groove narrowing, coaxial helical stacking, and RNA ring formation. In addition to investigating the RNA's ion environment, we note that the RNA's hydration environment is relatively underexplored. Our study delves into its profound interplay with the structural dynamics of RNA, employing state-of-the-art atomistic simulation techniques. Through examples, we illustrate how specific ions and water molecules are associated with RNA functions, leveraging atomistic simulations to identify preferential ion binding and hydration sites. However, understanding their impact(s) on the RNA structure remains challenging due to the involvement of large length and long time scales associated with RNA's dynamic nature. Nevertheless, our contributions and recent advances in coarse-grained simulation techniques offer insights into large-scale structural changes dynamically linked to the RNA ion atmosphere. In this connection, we also review how different cutting-edge computational simulation methods provide a microscopic lens into the influence of ions and hydration on RNA structure and dynamics, elucidating distinct ion atmospheric components and specific hydration layers and their individual and collective impacts.

Dynamic Counterion Condensation Model Decodes Functional Dynamics of RNA Pseudoknot in SARS-CoV-2: Control of Ion-Mediated Pierced Lasso Topology.

The programmed frameshifting stimulatory element, a promising drug target for COVID-19 treatment, involves a RNA pseudoknot (PK) structure. This RNA PK facilitates frameshifting, enabling RNA viruses to translate multiple proteins from a single mRNA, which is a key strategy for their rapid evolution. Overcoming the challenges of capturing large-scale structural changes of RNA under the influence of a dynamic counterion environment (K+ and Mg2+), the study extended the applications of a newly developed dynamic counterion condensation (DCC) model. DCC simulations reveal potential folding pathways of this RNA PK, supported by the experimental findings obtained using optical tweezers. The study elucidates the pivotal role of Mg2+ ions in crafting a lasso-like RNA topology, a novel RNA motif that governs dynamic transitions between the ring-opened and ring-closed states of the RNA. The pierced lasso component guided by Mg2+-mediated interactions orchestrates inward and outward motion fine-tuning tension on the slippery segment, a critical factor for optimizing frameshifting efficiency.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin ß4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling. Chronic treatment with sotorasib induced WNT expression and activated the WNT/ß-catenin signaling pathway. Thus, silencing both ITGB4 and ß-catenin significantly improved sotorasib sensitivity in tolerant, acquired, and inherently resistant cells. In addition, the proteasome inhibitor carfilzomib (CFZ) exhibited synergism with sotorasib by down-regulating ITGB4 and ß-catenin expression. Furthermore, adagrasib phenocopies the combination effect of sotorasib and CFZ by suppressing KRAS activity and inhibiting cell cycle progression in inherently resistant cells. Overall, our findings unveil previously unrecognized nongenetic mechanisms underlying resistance to sotorasib and propose a promising treatment strategy to overcome resistance.

Intrinsically Disordered Regions Function as a Cervical Collar to Remotely Regulate the Nodding Dynamics of SARS-CoV-2 Prefusion Spike Heads.

The SARS-CoV-2 prefusion spike heads (receptor binding domains, RBDs) frequently nod down and up to interact with host cell receptors. As the spike protein is a trimeric unit of significant size, to understand its large-scale structural dynamics associated with the nodding mechanism and the mutational impact on the same, we develop a topological symmetry-information-loaded coarse-grained structure-based model of a spike trimer using recent cryo-EM structural data. Our study reveals the control of two distant intrinsically disordered regions (IDRs), namely, 630 and FPPR loops, over the nodding dynamics of spike heads. We find that the order-disorder transition of IDRs becomes more evident in the variants of concern (VOCs) that are associated with the characteristic mutation, D614G, in the proximity of these IDRs. In some VOCs, the two other mutations A570D and S982A also show an integral effect. The driver mutation D614G instigates a salt-bridge disruption, altering the order-disorder dynamics of both 630 and FPPR loops and their interaction with the C-terminal domains (CTD1/CTD2). This altered connectivity in these mutants allows the two IDRs to act collectively as a "cervical collar" for the RBD, supporting various spike head postures, consistent with cryo-EM results available for specific cases. The IDRs' control over the spike structure and dynamics presents an exciting opportunity where they can be targeted as remote operational switches to artificially maneuver the nod for effective therapeutic interventions.

Reversible Electrochromic/Electrofluorochromic Dual Switching in Zn(II)-Based Metallo-Supramolecular Polymer Films.

The introduction of novel materials with multifunctional chromogenic properties, such as electrochromic/electrofluorochromic (EC/EFC) properties, has recently attracted prospective interest in the development of various optoelectronic devices and smart windows. In this study, a novel Zn(II)-based metallo-supramolecular polymer (polyZn) has been developed as an ON/OFF switchable EFC application with prominent EC behavior. In this regard, the polymeric chain of polyZn was first synthesized by 1:1 complexation in a zigzag manner with Zn(II) ions at the metal center and 4,4'-[bis(2,2':6',2″-terpyridinyl)benzene]triphenylamine (LTPY-TPA) as the redox-active ditopic ligand. The polyZn exhibits excellent solubility in organic solvents and can form a very good uniform thin film on an indium tin oxide/glass substrate by spin-coating. In a neutral state, transparent polyZn exhibits a bright yellow color to the naked eye (absorption at ∼325 nm). The electroactive triphenylamine (TPA) core of LTPA-TPY, however, undergoes reversible single-electron oxidation when a positive bias of +1.6 V vs Ag/Ag+ is applied, generating radical cations (TPA ↔ TPA•+) with a significant drop in transparency (77%). A noticeable chromic shift in the hue of the film from brilliant yellow to green was observed with the appearance of a near-infrared absorption band at ∼897 nm with a tail of 1300-1600 nm. Interestingly, in addition to this EC phenomenon, the fabricated solid-state polyZn film exhibits intense, high-contrast reddish-orange photoluminescence with λem = 650 nm, which is significantly desired as a molecular probe for bioimaging. Both the TPA core and the redox-inactive Zn(II)-terpyridine core emit orange-red photoluminescence in polyZn, which is significantly quenched upon the oxidation of the film and is re-emitted at 0.0 V vs Ag/Ag+. This ON/OFF EFC transition was sustained for several cycles. This study should motivate to design and create distinctive new unique materials with combined EC/EFC behavior for the fabrication of optoelectronic devices by combining a metal-fluorescent core with a redox-active spacer.

Evolution of Sequence and Structure of SARS-CoV-2 Spike Protein: A Dynamic Perspective.

Novel coronavirus (SARS-CoV-2) enters its host cell through a surface spike protein. The viral spike protein has undergone several modifications/mutations at the genomic level, through which it modulated its structure-function and passed through several variants of concern. Recent advances in high-resolution structure determination and multiscale imaging techniques, cost-effective next-generation sequencing, and development of new computational methods (including information theory, statistical methods, machine learning, and many other artificial intelligence-based techniques) have hugely contributed to the characterization of sequence, structure, function of spike proteins, and its different variants to understand viral pathogenesis, evolutions, and transmission. Laying on the foundation of the sequence-structure-function paradigm, this review summarizes not only the important findings on structure/function but also the structural dynamics of different spike components, highlighting the effects of mutations on them. As dynamic fluctuations of three-dimensional spike structure often provide important clues for functional modulation, quantifying time-dependent fluctuations of mutational events over spike structure and its genetic/amino acidic sequence helps identify alarming functional transitions having implications for enhanced fusogenicity and pathogenicity of the virus. Although these dynamic events are more difficult to capture than quantifying a static, average property, this review encompasses those challenging aspects of characterizing the evolutionary dynamics of spike sequence and structure and their implications for functions.

Hierarchical Hydration Dynamics of RNA with Nano-Water-Pool at Its Core.

Many functional RNAs fold into a compact, roughly globular shape by minimizing the electrostatic repulsion between their negatively charged phosphodiester backbone. The fold of such close, compact RNA architecture is often so designed that its outer surface and complex core both are predominately populated by phosphate groups loosely sequestering bases in the intermediate layers. A number of helical junctions maintain the RNA core and its nano-water-pool. While the folding of RNA is manifested by its counterion environment composed of mixed mono- and divalent salts, the concerted role of ion and water in maintaining an RNA fold is yet to be explored. In this work, detailed atomistic simulations of SAM-I and Add Adenine riboswitch aptamers, and subgenomic flavivirus RNA (sfRNA) have been performed in a physiological mixed mono- and divalent salt environment. All three RNA systems have compact folds with a core diameter of range 1-1.7 nm. The spatiotemporal heterogeneity of RNA hydration was probed in a layer-wise manner by distinguishing the core, the intermediate, and the outer layers. The layer-wise decomposition of hydrogen bonds and collective single-particle reorientational dynamics reveal a nonmonotonic relaxation pattern with the slowest relaxation observed at the intermediate layers that involves functionally important tertiary motifs. The slowness of this intermediate layer is attributed to two types of long-resident water molecules: (i) water from ion-hydration layers and (ii) structurally trapped water (distant from ions). The relaxation kinetics of the core and the surface water essentially exposed to the phosphate groups show well-separated time scales from the intermediate layers. In the slow intermediate layers, site-specific ions and water control the functional dynamics of important RNA motifs like kink-turn, observed in different structure-probing experiments. Most interestingly, we find that as the size of the RNA core increases (SAM1 core < sfRNAcore < Add adenine core), its hydration tends to show faster relaxation. The hierarchical hydration and the layer-wise base-phosphate composition uniquely portray the globular RNA to act like a soft vesicle with a quasi-dynamic nano-water-pool at its core.

Biomimetic Stratum Corneum Liposome Models: Lamellar Organization and Permeability Studies.

The stratum corneum (SC), the outer layer of the skin, plays a crucial role as a barrier protecting the underlying cells from external stress. The SC comprises three key components: ceramide (CER), free fatty acid (FFA), and cholesterol, along with small fractions of cholesterol sulfate and cholesterol ester. In order to gain a deeper understanding about the interdependence of the two major components, CER and FFA, on the organizational, structural, and functional properties of the SC layer, a library of SC lipid liposome (SCLL) models was developed by mixing CER (phytosphingosine or sphingosine), FFA (oleic acid, palmitic acid, or stearic acid), cholesterol, and cholesterol sulfate. Self-assembly of the SC lipids into lamellar phases was first confirmed by small-angle X-ray scattering. Short periodicity and long periodicity phases were identified for SCLLs containing phytosphingosines and sphingosine CERs, respectively. Furthermore, unsaturation in the CER acyl and FFA chains reduced the lipid conformational ordering and packing density of the liposomal bilayer, which were measured by differential scanning calorimetry and Fourier transform infrared spectroscopy. The introduction of unsaturation in the CER and/or FFA chains also impacted the lamellar integrity and permeability. This extensive library of SCLL models exhibiting physiologically relevant lamellar phases with defined structural and functional properties may potentially be used as a model system for screening pharmaceuticals or cosmetic agents.

Scoliosis assessment tools to reduce follow-up X-rays.

Purpose: Clinical examinations of scoliosis often includes X-rays. Regular clinical monitoring is recommended in particular at young age, because of the high risk of progression during periods of rapid growth. Supplementary methods free of ionizing radiation thus could help to reduce the potential risk of ionizing radiation related health problems. Methods: Twelve 3D scan images from female and male patients with different types and severities of spinal deformations were analysed using body scanner image analysis tools. The scan images were captured with a 3D body scanner, which used an infrared sensor and a video camera. To calculate and compare with the patient's specific spinal deformations, simulations based on finite elements methods were performed on biomechanical models of ribcage and spinal column. Results: The methods and parameters presented here are in good agreement with corresponding X-rays, used for comparison. High correlation coefficients of ‖ρ s ‖ ≥ 0.87 between Cobb angle and lateral deviation, as well as between Cobb angle and rotation of the vertebrae, indicate that the parameters could provide supplementary informations in the assessment of spinal deformations. So-called apex angles, in addition introduced to relate the results of the present method with Cobb angles, show strong correlations of ‖ρ s ‖ ≥ 0.68 and thus could be used for comparison in later follow-up examinations. Conclusion: The user-friendly 3D body scanner image analysis tools enable orthopaedic specialists to simulate, visualize and inspect patient's specific spinal deformations. The method is intended to provide supplementary information in complement to the Cobb angle for the assessment of spinal deformations in clinical daily routine and might have the potential to reduce X-rays in follow-up examinations. The Translational Potential of this article: The study presents a new method, based on 3D body scanner images and biomechanical modelling, that has the potential to reduce X-rays when monitoring scoliosis especially in young patients.

Editorial: Topical Collection on Emergent Dynamics of Biological Networks.

This special issue 'Emergent properties of biological networks' celebrates the growing and vibrant international community of researchers working on questions in the area of cellular and tissue-level biological physics. Networks are a common way to represent biological systems ranging from sub-cellular protein signaling to the entire ecosystem, elucidating the crosstalk among different interacting entities. Recent advances in highthroughput cellular measurement technologies, cost-effective next-generation sequencing, and development of new computational methods (including algorithmic, statistical, graph theoretical concepts, machine learning, and many artificial intelligence-based techniques) have truly revolutionized the investigation of biological networks by uncovering and predicting emergent phenomena that have great implications in both biology and medicine.

Effects of immunosuppressants on T-cell dynamics: Understanding from a generic coarse-grained immune network model.

Long-term immunosuppressive therapy is a drug regimen often used to lower aggressive immune responses in various chronic inflammatory diseases. However, such long-term therapy leading to immune suppression may trigger other adverse reactions in the immune system. The rising concern regarding the optimal dose and duration of such treatment has motivated us to understand non-classical immunomodulatory responses induced by various immunosuppressive steroid and secosteroid drugs such as glucocorticoid and vitamin D supplements. The immunomodulatory actions of such immunosuppressants (that govern the adaptive immune response) are often mediated through their characteristic control over CD4+ T-cells involving pro- and antiinflammatory T-cells. Several early studies attempted to decode temporal and dose-dependent behaviors of such pro- and anti-inflammatory T-cells using the chemical dynamics approach. We first summarize these early works. Then, we develop a minimal coarse-grained kinetic network model to capture the commonality in their immunomodulatory functions. This generic model successfully reproduces the characteristic dynamical features, including the clinical latency period in long-term T-cell dynamics. The temporal behavior of T-cells is found to be sensitive to specific rate parameters and doses of immunosuppressants. The steady-state analysis reflects the transition from an early classified weakly regulated (autoimmune-prone) immune state to a strongly regulated state (immunocompromised state), separated by an intervening state of moderate/balanced regulation. An optimal dose and duration are essential in rescuing balanced immune regulation. This review elucidates how developing a simple generic coarse-grained immune network model may provide immense information that helps diagnose inefficacy in adaptive immune function before and after administering immunosuppressants such as glucocorticoid or vitamin D.

Dynamic effects of the spine of hydrated magnesium on viral RNA pseudoknot structure.

In the cellular environment, a viral RNA Pseudoknot (PK) structure is responsive to its prevailing ion atmosphere created by a mixture of monovalent and divalent cations. We investigate the influence of such a mixed-salt environment on RNA-PK structure at an atomic resolution through three sets of 1.5 µs explicit solvent molecular dynamics (MD) simulations and also by building a dynamic counterion-condensation (DCC) model at varying divalent Mg2+ concentrations. The DCC model includes explicit interaction of the ligand and adjacent chelated Mg2+ by extending the recently developed generalized Manning condensation model. Its implementation within an all-atom structure-based molecular dynamics framework bolsters its opportunity to explore large-length scale and long-timescale phenomena associated with complex RNA systems immersed in its dynamic ion environment. In the present case of RNA-PK, both explicit MD and DCC simulations reveal a spine of hydrated-Mg2+ to induce stem-I and stem-II closure where the minor groove between these stems is akin to breathing. Mg2+ mediated minor-groove narrowing is coupled with local base-flipping dynamics of a base triple and quadruple, changing the stem structure of such RNA. Contrary to the conversational view of the indispensable need for Mg2+ for the tertiary structure of RNA, the study warns about the plausible detrimental effect of specific Mg2+-phosphate interactions on the RNA-PK structure beyond a certain concentration of Mg2+.

Quantifying Mutational Response to Track the Evolution of SARS-CoV-2 Spike Variants: Introducing a Statistical-Mechanics-Guided Machine Learning Method.

The emergence of SARS-CoV-2 and its variants that critically affect global public health requires characterization of mutations and their evolutionary pattern from specific Variants of Interest (VOIs) to Variants of Concern (VOCs). Leveraging the concept of equilibrium statistical mechanics, we introduce a new responsive quantity defined as "Mutational Response Function (MRF)" aptly quantifying domain-wise average entropy-fluctuation in the spike glycoprotein sequence of SARS-CoV-2 based on its evolutionary database. As the evolution transits from a specific variant to VOC, we find that the evolutionary crossover is accompanied by a dramatic change in MRF, upholding the characteristic of a dynamic phase transition. With this entropic information, we have developed an ancestral-based machine learning method that helps predict future domain-specific mutations. The feedforward binary classification model pinpoints possible residues prone to future mutations that have implications for enhanced fusogenicity and pathogenicity of the virus. We believe such MRF analyses followed by a statistical mechanics augmented ML approach could help track different evolutionary stages of such species and identify a critical evolutionary transition that is alarming.

A non-invasive method for scoliosis assessment-A new mathematical concept using polar angle.

Scoliosis is one of the most common pediatric spinal diseases that leads to a three-dimensional deformity of the spine and has a high risk of progression during growth. Regular clinical monitoring and follow-up X-rays are needed to providing proper treatment at that time. Repetitive X-rays can results in an increased risk of radiation related health problems. We present a non-invasive, ionizing radiation-free method for assessing scoliosis and its progression from the 3D images of the body torso, captured by a body scanner. A new concept is introduced based on a mathematical method in polar coordinate system to quantify and characterize the deformities in the torso from 2D transverse cross-sections of the 3D torso images at example cases for a healthy individual and for two patients with scoliosis. To capture quantitatively the characteristics of scoliosis, and to verify them at the example cases two asymmetry parameters and a linear fitting parameter are calculated: a) back side area asymmetry, b) left right area asymmetry, and c) coefficient of determination (R2). Within the analyzed patients, both the area asymmetries are maximum at the apex of scoliosis, and increase with the severity of scoliosis. R2 values are smaller in the case of patients compared with the healthy. Furthermore, the parameters show a trend when compared with the Cobb angle from the X-ray and the findings match with clinical examination. Therefore, the quantities are able to capture, certain characteristics associated with scoliosis. These quantities can be compared as a measure of deformities of torso, during the follow-up examinations in the future, without ionizing radiations.

A terpyridine based hydrogel system for reversible transmissive-to-dark electrochromism and bright-to-quenched electrofluorochromism.

A carboxylic acid-containing terpyridine-based hydrogelator (TPPCA) is synthesized to afford a self-assembly induced TPPCA hydrogel, which was used as an all-in-one electrochrome in electrochromic devices (ECDs) to demonstrate reversible transparent-to-black electrochromism with fast darkening and bleaching time of 8.3 s and 9.5 s, respectively, high photopic coloration efficiency of 65.8 cm2 C-1 and high optical memory. The ECD also revealed bluish-white to quenched emission simultaneously under the -3.5 V to 0 V voltage range.

Miniature ß-Hairpin Mimetic by Intramolecular Hydrogen Bond and C-H···π Interactions.

Canonically, protein ß-hairpin motifs are stabilized by intramolecular hydrogen bonds. Here, we attempt to develop a rational design recipe for a miniature hairpin structure stabilized by hydrogen bonding as well as C-H···π interaction and try to understand how such a stabilization effect varies with different functional groups at each terminus. Database analysis shows that the α-amino acids with an aromatic side chain will not favor that kind of C-H···π stabilized hairpin structure. However, hybrid tripeptides with an N-terminal Boc-Trp-Aib corner residue and C-terminal aromatic ω-amino acids fold into the hairpin conformation with a central ß-turn/open-turn that is reinforced by a C-H···π interaction. The CCDC database analysis further confirms that this C-H···π stabilized hairpin motif is general for Boc-protected tripeptides containing Aib in the middle and aromatic functionality at the C-terminus. The different α-amino acids like Leu/Ala/Phe/Pro/Ser at the N-terminus have a minor influence on the C-H···π interaction and stabilities of the folded structures in solid-state. However, the hybrid peptides exhibit different degrees of conformational heterogeneity both in the solid and solution phase, which is common for this kind of flexible small molecule. Conformational heterogeneity in the solution phase including the C-H···π stabilized ß-hairpin structures are characterized by the molecular dynamics (MD) simulations explaining their plausible origin at an atomistic level.

Electrochromic and photochromic behaviour in a single metal-organic framework containing a redox-active linker.

A Zr-based metal organic framework with naphthalene diimide teracarboxylate linkers is reported for its dual electrochromic and photochromic behavior. MOF crystals display reversible yellow to green photochromism upon exposure to visible light and colourless to dark-brown reversible electrochromism on applying a potential of 0 to -2.5 V. The MOF thin film shows good colouration efficiency at 550 nm, which is the highest sensitivity of the human eye.

A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics.

Mitochondrial inner NEET (MiNT) and the outer mitochondrial membrane (OMM) mitoNEET (mNT) proteins belong to the NEET protein family. This family plays a key role in mitochondrial labile iron and reactive oxygen species (ROS) homeostasis. NEET proteins contain labile [2Fe-2S] clusters which can be transferred to apo-acceptor proteins. In eukaryotes, the biogenesis of [2Fe-2S] clusters occurs within the mitochondria by the iron-sulfur cluster (ISC) system; the clusters are then transferred to [2Fe-2S] proteins within the mitochondria or exported to cytosolic proteins and the cytosolic iron-sulfur cluster assembly (CIA) system. The last step of export of the [2Fe-2S] is not yet fully characterized. Here we show that MiNT interacts with voltage-dependent anion channel 1 (VDAC1), a major OMM protein that connects the intermembrane space with the cytosol and participates in regulating the levels of different ions including mitochondrial labile iron (mLI). We further show that VDAC1 is mediating the interaction between MiNT and mNT, in which MiNT transfers its [2Fe-2S] clusters from inside the mitochondria to mNT that is facing the cytosol. This MiNT-VDAC1-mNT interaction is shown both experimentally and by computational calculations. Additionally, we show that modifying MiNT expression in breast cancer cells affects the dynamics of mitochondrial structure and morphology, mitochondrial function, and breast cancer tumor growth. Our findings reveal a pathway for the transfer of [2Fe-2S] clusters, which are assembled inside the mitochondria, to the cytosol.

Role of Glycogen Synthase Kinase-3 in the Etiology of Type 2 Diabetes Mellitus: A Review.

The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.