Bridging DNA contacts allow Dps from E. coli to condense DNA.

The DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNA in vitro. However, the mechanism that allows these complexes to nucleate on DNA remains unclear. Here, we examine how DNA topology influences the formation of Dps-DNA complexes. We find that DNA supercoils offer the most preferred template for the nucleation of condensed Dps structures. More generally, bridging contacts between different regions of DNA can facilitate the nucleation of condensed Dps structures. In contrast, Dps shows little affinity for stretched linear DNA before it is relaxed. Once DNA is condensed, Dps forms a stable complex that can form inter-strand contacts with nearby DNA, even without free Dps present in solution. Taken together, our results establish the important role played by bridging contacts between DNA strands in nucleating and stabilizing Dps complexes.

Altered effective connectivity in sensorimotor cortices is a signature of severity and clinical course in depression.

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and dynamic causal modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with parametric empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory, whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex, an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross-validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (nonpharmacological) treatment, depression-associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

Influence of different drying techniques on quality parameters of mushroom and its utilization in development of ready to cook food formulation.

Three different drying methods: hot-air-drying (HAD), dehumidified drying (DD) and freeze drying (FD) were used to dry Indian white button mushrooms (Agaricus bisporus).  Dehumidified drying method has been proposed as an alternative technique  to improve the quality of dehydrated mushroom. Mushroom powder obtained by DD method had 33.29% protein, 17.21% uronic acid, and 10.93% ash content. It was  also a good source of ergosterol (422.18±5.80 mg/100 g dw), which is known as the precursor of Vitamin D2. Ethanolic extract of mushroom powder showed good antioxidant activity  with lower DPPH IC50 value (7.16±0.23 mg/mL) and also lower EC50 value of ABTS (4.36±0.04 mg/mL). Mushroom powder is added to ready to cook green gram based chilla mix (vegetable omelette mix) at 10%, 20% and 30% levels. The effect of incorporation of mushroom powder on quality characteristics of the formulation was studied. The results showed that the ready to cook mix containing 20% of mushroom powder had protein: 23.33 g; total dietary fiber: 10.75 g; ergosterol: 79.08 mg and also important minerals like calcium: 99.57 mg; potassium: 1203.49 mg; magnesium: 137.80 mg and zinc: 2.23 mg in 100 g of formulation. The formulated products were shelf-stable at ambient temperature for three months. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05680-9.

Studies on the partial characterization of extracted glycosaminoglycans from fish waste and its potentiality in modulating obesity through in-vitro and in-vivo.

Glycosaminoglycans (GAGs) are bioactive polysaccharides or glycoconjugates found in the fish waste having significant health impacts. In the present study it has been attempted to extract GAGs from mackerel fish waste through chemical and enzymatic methods. Further, the extracted GAGs (e-GAGs) were analyzed for their composition (uronic acid, total sugar & sulfate), chemical characterization was carried out through techniques of scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) & Proton NMR. Further, probable major GAGs present was identified by enzymatic digestion. The biological potential of the extracted glycoconjugate was assessed further through in-vitro and in-vivo studies. In-vitro biological activity showed good lipase inhibition (IC50, 2.6 mg/mL) and bile acid binding properties (dose-dependent). Lipid accumulation lowered in the e-GAGs differentiated 3T3L1 preadipocyte cells have also been observed. The high fat fed animal (in-vivo) study showed ameliorative effect via reducing blood sugar∼1.28↓, lipid profile↓, plasma insulin∼3.5↓, improved glucose tolerance, and homeostatic model assessment for insulin resistance (HOMA-IR, ∼3.0↓). Furthermore, elimination of bile acid (BA) due to GAG-BA binding properties resultant in removal of elevated fecal triglyceride and cholesterol suggesting its lipid lowering activity. Regulation of various proteins linked to carbohydrate and lipid metabolism including fatty acid synthase (FAS), low density lipoproteins receptor (LDL-R), 7α-hydroxylase, glucose transporter-4 (GLUT4) and Peroxisome proliferator- activated receptor gamma (PPAR-γ) were significant (p < 0.05) with e-GAGs treatment when compared to HFD group. Thus, the e-GAGs showed potential hypolipidemic activity through elimination of bile acid binding property together with regulating the specific protein related to obesity and its associated complications.

Sustained order-disorder transitions in a model colloidal system driven by rhythmic crosslinking.

Biological systems have the unique ability to self-organize and generate autonomous motion and work. Motivated by this, we investigate a 2D model colloidal network that can repeatedly transition between disordered states of low connectivity and ordered states of high connectivity via rhythmic binding and unbinding of biomimetic crosslinkers. We use Langevin dynamics to investigate the time-dependent changes in structure and collective properties of this system as a function of colloidal packing fractions and crosslinker oscillation periods and characterize the degree of order in the system by using network connectivity, bond length distributions, and collective motion. Our simulations suggest that we can achieve distinct states of this colloidal system with pronounced differences in microstructural order and large residence times in the ordered state when crosslinker kinetics and lifetimes depend directly on the oscillation period and this oscillation period is much larger than the colloidal diffusion time. Our results will provide insights into the rational design of smart active materials that can independently cycle between ordered and disordered states with desired material properties on a programmed schedule.

Rigidity and fracture of biopolymer double networks.

Tunable mechanics and fracture resistance are hallmarks of biological tissues whose properties arise from extracellular matrices comprised of double networks. To elucidate the origin of these desired properties, we study the shear modulus and fracture properties of a rigidly percolating double network model comprised of a primary network of stiff fibers and a secondary network of flexible fibers. We find that when the primary network density is just above its rigidity percolation threshold, the secondary network density can be tuned to facilitate stress relaxation via non-affine deformations and provide mechanical reinforcement. In contrast, when the primary network is far above its rigidity threshold, the double network is always stiff and brittle. These results highlight an important mechanism behind the tunability and resilience of biopolymer double networks: the secondary network can dramatically alter mechanical properties from compliant and ductile to stiff and brittle only when the primary network is marginally rigid.

Shape dependent multiferroic behavior in Bi2Fe4O9nanoparticles.

Ferroelectric and magnetic properties are investigated for Bi2Fe4O9nanoparticles with different shapes (cuboid and sphere-like) synthesized by hydrothermal and sol-gel method. The magnetic study reveals that coercivity, Neel temperature and remanent magnetization strongly depend on shape of the particle. The nanoparticle with sphere-like shape exhibits magnetization curve of antiferromagnetic (AFM) ordering with ferromagnetic (FM) component. As the particle shape changes from sphere-like to cuboid, the AFM component is dominating over the ferromagnetic component. A small exchange bias is also observed at low temperature in both the sphere-like and cuboid nanoparticle. The coercivity, remanent magnetization and Neel temperature of sphere-like nanoparticle is greater than cuboid nanoparticle. Ferroelectric measurement shows the remanent polarization of cuboid is greater than sphere-like nanoparticle but the coercivity is almost same. This Bi2Fe4O9nanoparticle shows a small change in polarization under magnetic field. The polarization value decreases with magnetic field increases. The magnetoelectric coupling-measured by change of remanent polarization under magnetic field are found to be greater in Bi2Fe4O9sphere-like nanoparticles. These shape dependent magnetic and ferroelectric properties are coming because of shape anisotropy.

Reconfiguration of Directed Functional Connectivity Among Neurocognitive Networks with Aging: Considering the Role of Thalamo-Cortical Interactions.

A complete picture of how subcortical nodes, such as the thalamus, exert directional influence on large-scale brain network interactions across age remains elusive. Using directed functional connectivity and weighted net causal outflow on resting-state fMRI data, we provide evidence of a comprehensive reorganization within and between neurocognitive networks (default mode: DMN, salience: SN, and central executive: CEN) associated with age and thalamocortical interactions. We hypothesize that thalamus subserves both modality-specific and integrative hub role in organizing causal weighted outflow among large-scale neurocognitive networks. To this end, we observe that within-network directed functional connectivity is driven by thalamus and progressively weakens with age. Secondly, we find that age-associated increase in between CEN- and DMN-directed functional connectivity is driven by both the SN and the thalamus. Furthermore, left and right thalami act as a causal integrative hub exhibiting substantial interactions with neurocognitive networks with aging and play a crucial role in reconfiguring network outflow. Notably, these results were largely replicated on an independent dataset of matched young and old individuals. Our findings strengthen the hypothesis that the thalamus is a key causal hub balancing both within- and between-network connectivity associated with age and maintenance of cognitive functioning with aging.

Differences in mechanical properties lead to anomalous phase separation in a model cell co-culture.

During the morphogenesis of tissues and tumors, cells often interact with neighbors with different mechanical properties, but the understanding of its role is lacking. We use active Brownian dynamics simulations to study a model co-culture consisting of two types of cells with the same size and self-propulsion speed, but different mechanical stiffness and cell-cell adhesion. As time evolves, the system phase separates out into clusters with distinct morphologies and transport properties for the two cell types. The density structure factors and the growth of cell clusters deviate from behavior characteristic of the phase separation in binary fluids. Our results capture emergent structure and motility previously observed in co-culture experiments and provide mechanistic insights into intercellular phase separation during development and disease.

Active cytoskeletal composites display emergent tunable contractility and restructuring.

The cytoskeleton is a model active matter system that controls processes as diverse as cell motility and mechanosensing. While both active actomyosin dynamics and actin-microtubule interactions are key to the cytoskeleton's versatility and adaptability, an understanding of their interplay is lacking. Here, we couple microscale experiments with mechanistic modeling to elucidate how connectivity, rigidity, and force-generation affect emergent material properties in composite networks of actin, tubulin, and myosin. We use multi-spectral imaging, time-resolved differential dynamic microscopy and spatial image autocorrelation to show that ballistic contraction occurs in composites with sufficient flexibility and motor density, but that a critical fraction of microtubules is necessary to sustain controlled dynamics. The active double-network models we develop, which recapitulate our experimental findings, reveal that while percolated actomyosin networks are essential for contraction, only composites with comparable actin and microtubule densities can simultaneously resist mechanical stresses while supporting substantial restructuring. The comprehensive phase map we present not only provides important insight into the different routes the cytoskeleton can use to alter its dynamics and structure, but also serves as a much-needed blueprint for designing cytoskeleton-inspired materials that couple tunability with resilience and adaptability for diverse applications ranging from wound healing to soft robotics.

Actin and microtubule crosslinkers tune mobility and control co-localization in a composite cytoskeletal network.

Actin and microtubule filaments, with their auxiliary proteins, enable the cytoskeleton to carry out vital processes in the cell by tuning the organizational and mechanical properties of the network. Despite their critical importance and interactions in cells, we are only beginning to uncover information about the composite network. The challenge is due to the high complexity of combining actin, microtubules, and their hundreds of known associated proteins. Here, we use fluorescence microscopy, fluctuation, and cross-correlation analysis to examine the role of actin and microtubules in the presence of an antiparallel microtubule crosslinker, MAP65, and a generic, strong actin crosslinker, biotin-NeutrAvidin. For a fixed ratio of actin and microtubule filaments, we vary the amount of each crosslinker and measure the organization and fluctuations of the filaments. We find that the microtubule crosslinker plays the principle role in the organization of the system, while, actin crosslinking dictates the mobility of the filaments. We have previously demonstrated that the fluctuations of filaments are related to the mechanics, implying that actin crosslinking controls the mechanical properties of the network, independent of the microtubule-driven re-organization.

Understanding self-construction of health among the slum dwellers of India: a culture-centred approach.

Disembarking from a traditional approach of narrow hazardous environmental and structural conditions in understanding urban slums' health problems and moving towards a new notion of what constitutes health for slum dwellers will open a new avenue to recognise whether and how health is being prioritised in disadvantaged settings. Drawing on in-depth semi-structured interviews with a total of 67 men and 68 women from Kolkata slums and 62 men and 48 women from Bangalore slums, this study explored how knowledge, social realities, material and symbolic drivers of a place interweave in shaping slum-dwellers' patterned way of understanding health, and the ways health and illnesses are managed. The current study adds to the growing evidence that ordinary members of the urban slums can articulate critical linkages between their everyday sociocultural realities and health conditions, which can support the design and delivery of interventions to promote wellbeing. The concept of health is not confined to an abstract idea but manifested in slum-dwellers' sporadic practices of preventive and curative care as well as everyday living arrangements, where a complex arrangement of physical, psychological, financial, sociocultural and environmental dimensions condition their body and wellbeing.

Non-monotonic dependence of stiffness on actin crosslinking in cytoskeleton composites.

The cytoskeleton is able to precisely tune its structure and mechanics through interactions between semiflexible actin filaments, rigid microtubules and a suite of crosslinker proteins. However, the role that each of these components, as well as the interactions between them, plays in the dynamics of the composite cytoskeleton remains an open question. Here, we use optical tweezers microrheology and fluorescence confocal microscopy to reveal the surprising ways in which actin crosslinking tunes the viscoelasticity and mobility of actin-microtubule composites from steady-state to the highly nonlinear regime. While previous studies have shown that increasing crosslinking in actin networks increases elasticity and stiffness, we instead find that composite stiffness displays a striking non-monotonic dependence on actin crosslinking - first increasing then decreasing to a response similar to or even lower than un-linked composites. We further show that actin crosslinking has an unexpectedly strong impact on the mobility of microtubules; and it is in fact the microtubule mobility - dictated by crosslinker-driven rearrangements of actin filaments - that controls composite stiffness. This result is at odds with conventional thought that actin mobility drives cytoskeleton mechanics. More generally, our results demonstrate that - when crosslinking composite materials to confer strength and resilience - more is not always better.

Triggered disassembly and reassembly of actin networks induces rigidity phase transitions.

Non-equilibrium soft materials, such as networks of actin proteins, have been intensely investigated over the past decade due to their promise for designing smart materials and understanding cell mechanics. However, current methods are unable to measure the time-dependent mechanics of such systems or map mechanics to the corresponding dynamic macromolecular properties. Here, we present an experimental approach that combines time-resolved optical tweezers microrheology with diffusion-controlled microfluidics to measure the time-evolution of microscale mechanical properties of dynamic systems during triggered activity. We use these methods to measure the viscoelastic moduli of entangled and crosslinked actin networks during chemically-triggered depolymerization and repolymerization of actin filaments. During disassembly, we find that the moduli exhibit two distinct exponential decays, with experimental time constants of ∼169 min and ∼47 min. Conversely, during reassembly, measured moduli initially exhibit power-law increase with time, after which steady-state values are achieved. We develop toy mathematical models that couple the time-evolution of filament lengths with rigidity percolation theory to shed light onto the molecular mechanisms underlying the observed mechanical transitions. The models suggest that these two distinct behaviors both arise from phase transitions between a rigidly percolated network and a non-rigid regime. Our approach and collective results can inform the general principles underlying the mechanics of a large class of dynamic, non-equilibrium systems and materials of current interest.

The gendered experience with respect to health-seeking behaviour in an urban slum of Kolkata, India.

BACKGROUND: Empirical evidence shows that the relationship between health-seeking behaviour and diverse gender elements, such as gendered social status, social control, ideology, gender process, marital status and procreative status, changes across settings. Given the high relevance of social settings, this paper intends to explore how gender elements interact with health-seeking practices among men and women residing in an Indian urban slum, in consideration of the unique socio-cultural context that characterises India's slums. METHODS: The study was conducted in Sahid Smriti Colony, a peri-urban slum of Kolkata, India. The referral technique was used for selecting participants, as people in the study area were not very comfortable in discussing their health issues and health-seeking behaviours. The final sample included 66 participants, 34 men and 32 women. Data was collected through individual face-to-face in-depth interviews with a semi-structured questionnaire. RESULTS: The data analysis shows six categories of reasons underlying women's preferences for informal healers, which are presented in the form of the following themes: cultural competency of care, easy communication, gender-induced affordability, avoidance of social stigma and labelling, living with the burden of cultural expectations and geographical and cognitive distance of formal health care. In case of men ease of access, quality of treatment and expected outcome of therapies are the three themes that emerged as the reasons behind their preferences for formal care. CONCLUSION: Our results suggest that both men and women utilise formal and informal care, but with different motives and expectations, leading to contrasting health-seeking outcomes. These gender-induced contrasts relate to a preference for socio-cultural (women) versus technological (men) therapies and long (women) versus fast (men) treatment, and are linked to their different societal and familial roles. The role of women in following and maintaining socio-cultural norms leads them to focus on care that involves long discussions mixed with socio-cultural traits that help avoid economic and social sanctions, while the role of men as bread earners requires them to look for care that ensures a fast and complete recovery so as to avoid financial pressures.

Active and passive transport of cargo in a corrugated channel: A lattice model study.

Inside cells, cargos such as vesicles and organelles are transported by molecular motors to their correct locations via active motion on cytoskeletal tracks and passive, Brownian diffusion. During the transportation of cargos, motor-cargo complexes (MCCs) navigate the confining and crowded environment of the cytoskeletal network and other macromolecules. Motivated by this, we study a minimal two-state model of motor-driven cargo transport in confinement and predict transport properties that can be tested in experiments. We assume that the motion of the MCC is directly affected by the entropic barrier due to confinement if it is in the passive, unbound state but not in the active, bound state where it moves with a constant bound velocity. We construct a lattice model based on a Fokker Planck description of the two-state system, study it using a kinetic Monte Carlo method and compare our numerical results with analytical expressions for a mean field limit. We find that the effect of confinement strongly depends on the bound velocity and the binding kinetics of the MCC. Confinement effectively reduces the effective diffusivity and average velocity, except when it results in an enhanced average binding rate and thereby leads to a larger average velocity than when unconfined.

Patterns of illness disclosure among Indian slum dwellers: a qualitative study.

BACKGROUND: Slum dwellers display specific traits when it comes to disclosing their illnesses to professionals. The resulting actions lead to poor health-seeking behaviour and underutilisation of existing formal health facilities. The ways that slum people use to communicate their feelings about illness, the type of confidants that they choose, and the supportive and unsupportive social and cultural interactions to which they are exposed have not yet been studied in the Indian context, which constitutes an important knowledge gap for Indian policymakers and practitioners alike. To that end, this study examines the patterns of illness disclosure in Indian slums and the underpinning factors which shape the slum dwellers' disclosing attitude. METHODS: In-depth, semi-structured interviews were conducted among 105 men and 113 women who experienced illness in the year prior to the study period. Respondents were selected from four urban slums in two Indian cities, Bangalore and Kolkata. RESULTS: Findings indicate that women have more confidants at different social levels, while men have a limited network of disclosures which is culturally and socially mediated. Gender role limitations, exclusion from peer groups and unsupportive local situations are the major cause of disclosure delay or non-disclosure among men, while the main concerns for women are a lack of proper knowledge about illness, unsupportive responses received from other people on certain occasions, the fear of social stigma, material loss and the burden of the local situation. Prompt sharing of illness among men is linked with prevention intention and coping with biological problems, whereas factors determining disclosure for women relate to ensuring emotional and instrumental safety, preventing collateral damage of illness, and preventing and managing biological complications. CONCLUSIONS: The findings reveal that patterns of disclosure are not determined by the acknowledgment of illness but largely depend on the interplay between individual agency, disclosure consequences and the socio cultural environment. The results of this study can contribute significantly to mitigating the pivotal knowledge gap between health policymakers, practitioners and patients, leading to the formulation of policies that maximise the utilisation of health facilities in slums.

Dynamic self-organization of microwell-aggregated cellular mixtures.

Cells with different cohesive properties self-assemble in a spatiotemporal and context-dependent manner. Previous studies on cell self-organization mainly focused on the spontaneous structural development within a short period of time during which the cell numbers remained constant. However the effect of cell proliferation over time on the self-organization of cells is largely unexplored. Here, we studied the spatiotemporal dynamics of self-organization of a co-culture of MDA-MB-231 and MCF10A cells seeded in a well defined space (i.e. non-adherent microfabricated wells). When cell-growth was chemically inhibited, high cohesive MCF10A cells formed a core surrounded by low cohesive MDA-MB-231 cells on the periphery, consistent with the differential adhesion hypothesis (DAH). Interestingly, this aggregate morphology was completely inverted when the cells were free to grow. At an initial seeding ratio of 1 : 1 (MDA-MB-231 : MCF10A), the fast growing MCF10A cells segregated in the periphery while the slow growing MDA-MB-231 cells stayed in the core. Another morphology developed at an inequal seeding ratio (4 : 1), that is, the cell mixtures developed a side-by-side aggregate morphology. We conclude that the cell self-organization depends not only on the cell cohesive properties but also on the cell seeding ratio and proliferation. Furthermore, by taking advantage of the cell self-organization, we purified human embryonic stem cells-derived pancreatic progenitors (hESCs-PPs) from co-cultured feeder cells without using any additional tools or labels.

Structure-function relations and rigidity percolation in the shear properties of articular cartilage.

Among mammalian soft tissues, articular cartilage is particularly interesting because it can endure a lifetime of daily mechanical loading despite having minimal regenerative capacity. This remarkable resilience may be due to the depth-dependent mechanical properties, which have been shown to localize strain and energy dissipation. This paradigm proposes that these properties arise from the depth-dependent collagen fiber orientation. Nevertheless, this structure-function relationship has not yet been quantified. Here, we use confocal elastography, quantitative polarized light microscopy, and Fourier-transform infrared imaging to make same-sample measurements of the depth-dependent shear modulus, collagen fiber organization, and extracellular matrix concentration in neonatal bovine articular cartilage. We find weak correlations between the shear modulus |G(∗)| and both the collagen fiber orientation and polarization. We find a much stronger correlation between |G(∗)| and the concentration of collagen fibers. Interestingly, very small changes in collagen volume fraction vc lead to orders-of-magnitude changes in the modulus with |G(∗)| scaling as (vc - v0)(ξ). Such dependencies are observed in the rheology of other biopolymer networks whose structure exhibits rigidity percolation phase transitions. Along these lines, we propose that the collagen network in articular cartilage is near a percolation threshold that gives rise to these large mechanical variations and localization of strain at the tissue's surface.