Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration

Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses

Phases of a two dimensional large N gauge theory on a torus

We consider two-dimensional large N gauge theory with D adjoint scalars on a torus, which is obtained from a D+2 dimensional pure Yang-Mills theory on T^{D+2} with D small radii. The two dimensional model has various phases characterized by the holonomy of the gauge field around non-contractible cycles of the 2-torus. We determine the phase boundaries and derive the order of the phase transitions using a method, developed in an earlier work (arxiv:0910.4526), which is nonperturbative in the 'tHooft coupling and uses a 1/D expansion. We embed our phase diagram in the more extensive phase structure of the D+2 dimensional Yang-Mills theory and match with the picture of a cascade of phase transitions found earlier in lattice calculations (arxiv:0710.0098). We also propose a dual gravity system based on a Scherk-Schwarz compactification of a D2 brane wrapped on a 3-torus and find a phase structure which is similar to the phase diagram found in the gauge theory calculation.Comment: 28 pages (+ 17 pages of appendix + 6 pages of ref.); 8 figures; (v2) LaTeX Showkeys command deleted; (v3) refs and minor clarifications added; emphasized the new proposal for applying holography to nonsupersymmetric gauge theory; (v4) modified the arguments about holography; (v5) minor corrections, version appeared in PR

Unveiling the Online-Offline Divide: Predicting Retail Channel Membership for Luxury Jewelry Consumers Using Discriminant Analysis

The study explores the factors that influence consumers to choose between online and offline channels for purchasing products and services. Using a quantitative approach, data was collected from 352 respondents through a survey and analyzed using discriminant analysis. The study found that consumers tend to purchase products online for self- gratification, better offers, relative price, variety of products, product information, and better price comparison. On the other hand, consumers choose offline channels for quality, reliable information, quality of judgment, and better after-sales services. The papers implications extend to marketing practitioners, specifically in luxury product marketing for segmentation, targeting, and positioning

Functional Metagenomic Investigations of the Human Intestinal Microbiota

The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host

Habitat use pattern and conservation status of smooth–coated otters Lutrogale perspicillata in the Upper Ganges Basin, India

Modelo de uso del hábitat y estado de conservación de las nutrias lisas Lutrogale perspicillata en la zona alta de la cuenca del Ganges, India Las nutrias lisas habitan en varios sistemas fluviales importantes del Asia meridional y sus necesidades medioambientales las vinculan con problemas de seguridad alimentaria e hídrica, debido a la elevada densidad de humanos. La falta de datos de referencia sobre su distribución y ecología es otra limitación notable que la especie está afrontando en la India. El presente estudio se vio impulsado por el rápido descenso de la población de nutrias en el país y se centra en estimar el estado de conservación, el modelo de uso del hábitat y las amenazas asociadas en la zona alta de la cuenca del río Ganges (Asia septentrional). Nuestros resultados contribuyen a comprender mejor las complejas interacciones ecológicas y a elaborar medidas de conservación eficaces. Junto con las preferencias de hábitat, en el estudio también se informa sobre nuevas ubicaciones en la distribución de la especie. Asimismo se ponen de relieve las deficiencias existentes en la conservación de la especie y se sugieren las zonas cuya ordenación debería ser prioritaria.Smooth–coated otters inhabit several major river systems in southern Asia, and their environmental requirements link them to food and water security issues as the region is so densely populated by humans. The lack of baseline data on their distribution and ecology is another major constraint that the species is facing in India. The present study was stimulated by the rapid decline in the otter’s population in the country and focuses on estimating the conservation status, habitat use pattern, and associated threats in the upper Ganges River Basin (N India). Our findings contribute towards a better understanding of the complex ecological interactions and the design of effective conservation measures. Coupled with the habitat preferences, the study also provides new locations in the species distribution. This paper highlights the gap areas in the conservation of the species and suggests areas that should be prioritized for management.Modelo de uso del hábitat y estado de conservación de las nutrias lisas Lutrogale perspicillata en la zona alta de la cuenca del Ganges, India Las nutrias lisas habitan en varios sistemas fluviales importantes del Asia meridional y sus necesidades medioambientales las vinculan con problemas de seguridad alimentaria e hídrica, debido a la elevada densidad de humanos. La falta de datos de referencia sobre su distribución y ecología es otra limitación notable que la especie está afrontando en la India. El presente estudio se vio impulsado por el rápido descenso de la población de nutrias en el país y se centra en estimar el estado de conservación, el modelo de uso del hábitat y las amenazas asociadas en la zona alta de la cuenca del río Ganges (Asia septentrional). Nuestros resultados contribuyen a comprender mejor las complejas interacciones ecológicas y a elaborar medidas de conservación eficaces. Junto con las preferencias de hábitat, en el estudio también se informa sobre nuevas ubicaciones en la distribución de la especie. Asimismo se ponen de relieve las deficiencias existentes en la conservación de la especie y se sugieren las zonas cuya ordenación debería ser prioritaria

Chronic kidney disease is the major cause of death in Uddanam: a population-representative study using Smart Verbal Autopsy.

Introduction: Uddanam is an agricultural area with a high burden of chronic kidney disease of unknown aetiology (CKDu). Despite reports of many deaths due to CKD in the lay press, the exact contribution of CKD to deaths remains uncertain as most deaths occur outside medical care. Methods: We used SmartVA automated verbal autopsy (VA) tool to ascertain the cause-specific mortality fractions amongst a 2419 subject-strong general population cohort in Uddanam between 2018-2022. VA interviews were conducted twice with the family members of the deceased. Results: A total of 133 deaths were recorded, giving a crude death rate of 5.5%, 10 times higher than that recorded in national surveys. CKD was responsible for 45% of all deaths, followed by ischemic heart disease (15%) and respiratory disease (6%). Conclusion: This study confirms CKD as the leading cause of mortality in this high CKD burden area and provides crucial data for public health decision-making and resource allocation

Application of polarization ellipse technique for analysis of ULF magnetic fields from two distant stations in Koyna-Warna seismoactive region, West India

A new approach is developed to find the source azimuth of the ultra low frequency (ULF) electromagnetic (EM) signals believed to be emanating from well defined seismic zone. The method is test applied on magnetic data procured from the seismoactive region of Koyna-Warna, known for prolonged reservoir triggered seismicity. Extremely low-noise, high-sensitivity LEMI-30 search coil magnetometers were used to measure simultaneously the vector magnetic field in the frequency range 0.001–32 Hz at two stations, the one located within and another ~100 km away from the seismic active zone. During the observation campaign extending from 15 March to 30 June 2006 two earthquakes (EQs) of magnitude (M<sub><I>L</I></sub>>4) occurred, which are searched for the presence of precursory EM signals. <br><br> Comparison of polarization ellipses (PE) parameters formed by the magnetic field components at the measurement stations, in select frequency bands, allows discrimination of seismo-EM signals from the natural background ULF signals of magnetospheric/ionospheric origin. The magnetic field components corresponding to spectral bands dominated by seismo-EM fields define the PE plane which at any instant contains the source of the EM fields. Intersection lines of such defined PE planes for distant observation stations clutter in to the source region. Approximating the magnetic-dipole configuration for the source, the magnetic field components along the intersection lines suggest that azimuth of the EM source align in the NNW-SSE direction. This direction well coincides with the orientation of nodal plane of normal fault plane mechanism for the two largest EQs recorded during the campaign. More significantly the correspondence of this direction with the tectonic controlled trend in local seismicity, it has been surmised that high pressure fluid flow along the fault that facilitate EQs in the region may also be the source mechanism for EM fields by electrokinetic effect

A stochastic-Lagrangian particle system for the Navier-Stokes equations

This paper is based on a formulation of the Navier-Stokes equations developed by P. Constantin and the first author (\texttt{arxiv:math.PR/0511067}, to appear), where the velocity field of a viscous incompressible fluid is written as the expected value of a stochastic process. In this paper, we take $N$ copies of the above process (each based on independent Wiener processes), and replace the expected value with $\frac{1}{N}$ times the sum over these $N$ copies. (We remark that our formulation requires one to keep track of $N$ stochastic flows of diffeomorphisms, and not just the motion of $N$ particles.) We prove that in two dimensions, this system of interacting diffeomorphisms has (time) global solutions with initial data in the space \holderspace{1}{\alpha} which consists of differentiable functions whose first derivative is $\alpha$ H\"older continuous (see Section \ref{sGexist} for the precise definition). Further, we show that as $N \to \infty$ the system converges to the solution of Navier-Stokes equations on any finite interval $[0,T]$. However for fixed $N$, we prove that this system retains roughly $O(\frac{1}{N})$ times its original energy as $t \to \infty$. Hence the limit $N \to \infty$ and $T\to \infty$ do not commute. For general flows, we only provide a lower bound to this effect. In the special case of shear flows, we compute the behaviour as $t \to \infty$ explicitly.Comment: v3: Typo fixes, and a few stylistic changes. 17 pages, 2 figure

The systematic study of the influence of neutron excess on the fusion cross sections using different proximity-type potentials

Using different types of proximity potentials, we have examined the trend of variations of barrier characteristics (barrier height and its position) as well as fusion cross sections for 50 isotopic systems including various collisions of C, O, Mg, Si, S, Ca, Ar, Ti and Ni nuclei with $1\leq N/Z < 1.6$ condition for compound systems. The results of our studies reveal that the relationships between increase of barrier positions and decrease of barrier heights are both linear with increase of $N/Z$ ratio. Moreover, fusion cross sections also enhance linearly with increase of this ratio.Comment: 28 pages, 7 figures, 5 Table