Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, β-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that β-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and β-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving β-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin

Global impacts of Covid-19 on lifestyles and health and preparation preferences: an international survey of 30 countries

Background: The health area being greatest impacted by coronavirus disease 2019 (COVID-19) and residents' perspective to better prepare for future pandemic remain unknown. We aimed to assess and make cross-country and cross-region comparisons of the global impacts of COVID-19 and preparation preferences of pandemic. Methods: We recruited adults in 30 countries covering all World Health Organization (WHO) regions from July 2020 to August 2021. 5 Likert-point scales were used to measure their perceived change in 32 aspects due to COVID-19 (-2 = substantially reduced to 2 = substantially increased) and perceived importance of 13 preparations (1 = not important to 5 = extremely important). Samples were stratified by age and gender in the corresponding countries. Multidimensional preference analysis displays disparities between 30 countries, WHO regions, economic development levels, and COVID-19 severity levels. Results: 16 512 adults participated, with 10 351 females. Among 32 aspects of impact, the most affected were having a meal at home (mean (m) = 0.84, standard error (SE) = 0.01), cooking at home (m = 0.78, SE = 0.01), social activities (m = -0.68, SE = 0.01), duration of screen time (m = 0.67, SE = 0.01), and duration of sitting (m = 0.59, SE = 0.01). Alcohol (m = -0.36, SE = 0.01) and tobacco (m = -0.38, SE = 0.01) consumption declined moderately. Among 13 preparations, respondents rated medicine delivery (m = 3.50, SE = 0.01), getting prescribed medicine in a hospital visit / follow-up in a community pharmacy (m = 3.37, SE = 0.01), and online shopping (m = 3.33, SE = 0.02) as the most important. The multidimensional preference analysis showed the European Region, Region of the Americas, Western Pacific Region and countries with a high-income level or medium to high COVID-19 severity were more adversely impacted on sitting and screen time duration and social activities, whereas other regions and countries experienced more cooking and eating at home. Countries with a high-income level or medium to high COVID-19 severity reported higher perceived mental burden and emotional distress. Except for low- and lower-middle-income countries, medicine delivery was always prioritised. Conclusions: Global increasing sitting and screen time and limiting social activities deserve as much attention as mental health. Besides, the pandemic has ushered in a notable enhancement in lifestyle of home cooking and eating, while simultaneously reducing the consumption of tobacco and alcohol. A health care system and technological infrastructure that facilitate medicine delivery, medicine prescription, and online shopping are priorities for coping with future pandemics

Sequence stratigraphy, sandstone architecture, and depositional systems of the Lower Miocene succession in the Carancahua Bay Area, Texas Gulf Coast

textThis study defines depositional environments and constructs the sequence stratigraphic framework of the lower Miocene Oakville Formation and the basal part of the middle Miocene Lagarto Formation in the Carancahua Bay area. The Early Miocene of the northwestern Gulf of Mexico represents a tectonically stable period with a high sediment influx. The analysis is based on a data set composed of 45 well logs and 200 mile2 area 3D seismic volume. The study interval was divided into five depositional sequences 1-5 that encompass 0.6-2.5 My. LST, TST, and HST systems tracts were recognized by stacking patterns and bounding surfaces. Sequence thickness increases from sequence 1 to 3 and displays reverse thickness trends from sequence 3 to 5, implying changes in accommodation space relative to sediment supply, beginning with high rates of accommodation and evolving into low accommodation rates relative. Besides type-1 depositional sequence which forms during relative sea-level fall below the shoreline break, regressive units of T-R sequence model were also defined and delineated. The interval contains four regressive units, R-Unit1-4. The R-Unit net sandstone maps exhibit the same characteristic of a dip-oriented source of delta-plain origin and a delta-front depocenter basinward. Integration of well log patterns, sandstone dispersal trends from net sandstone maps and seismic stratal slices led to interpretation of depositional environments in each sequence. LST deposits are represented mainly by incised-valley fill facies. TSTs are composed predominantly of retrogradational barrier/tidal-inlet facies, whereas other TSTs contain lagoonal and reworked deltaic systems. HST1 is composed mainly of fluvial-dominated deltaic systems, whereas deltaic systems in other HSTs exhibit wave-influenced deltaic and strandplain depositional systems. The integrated methodology reveals depositional facies variations in contrast to previous work that interpreted these deposits as shorezone systems. During LSTs coarse-grained sediments bypassed shelf through incised valley systems to a downdip depocenter. More sandy sediments were stored on shelf as deltaic and strandplain deposits during HSTs. In contrast to the others, destructive process occurred in TSTs and reworked sandy sediments, for example from delta fronts to barrier bar and lagoonal facies. Submarine fans form by sediments transported through incised-valley systems and delta fronts are commonly good reservoirs. Hence, presence of such depositional facies in the study area might be genetically linked to exploration targets.Geological Science

Deep lacustrine clinoforms : formation, architectures, and deposits

This dissertation is a study of the occurrence, geometry, stratigraphy and sedimentological characteristics of shelf-margin clinoforms in a deep lake setting. Because of their formation in a hydrologically closed environment, and reduced salinity water, lake clinoforms’ characteristics can differ from their well-studied marine counterparts. An investigation on lake clinoforms can lead to a better understanding of lake depositional processes, particularly those that provide a linkage between the co-genetic shallow-deepwater depositional environments, and consequent sediment dispersals in a deep lake setting. Even though similar processes also operate in a deep-marine setting, their interaction within the reduced salinity water of a lake can build deposits and stratigraphy that differ from marine basin fill. Hence, this study provides a good example of lake clinoforms and their deposits, which can be used for comparison with those of marine environment. For the most part, this study is performed on the western Dacian Basin datasets, which comprise subsurface and outcrop data. The subsurface dataset includes three overlapping 3D seismic volumes that cover 1,700 square-kilometer area and well data. The entire basin fill succession is exposed and allows up to 1000 m thick sedimentological data to be collected. The seismic data analysis suggests that a closed nature and isolation from the effects of eustatic sea-level changes contributed to limited aggradation of the Dacian clinoform topsets and significant sediment partition to the deep-lacustrine environments, which led to rapid foreset progradation and high bottomset aggradation. Integration between the subsurface and outcrop datasets shows that direct sediment transport from the shelf to the basin-floor environments is common and carried through hyperpycnal-flow channels and mass-wasting of the shelf edge. Based on the Dacian Basin clinoforms’ distinctive bottomset geometry, a special attention was given to the base-of-slope as a crucial point to scrutinize basin-floor sedimentation and sediment partitioning between the deepwater slope and basin floor settings. From the Dacian Basin seismic dataset, a base-of-slope trajectory analytical concept is developed and proposed as a complimentary predictive tool to the shelf-edge trajectory concept. The base-of-slope trajectory analysis was also applied to other published clinoform data to test its applicabilityGeological Science

High Calcium Enhances Calcium Oxalate Crystal Binding Capacity of Renal Tubular Cells via Increased Surface Annexin A1 but Impairs Their Proliferation and Healing

Hypercalciuria is associated with kidney stone formation and impaired renal function. However, responses of renal tubular cells upon exposure to high-calcium environment remain largely unknown. We thus performed a proteomic analysis of altered proteins in renal tubular cells induced by high-calcium and evaluated functional significance of these changes. MDCK cells were maintained with or without 20 mM CaCl2 for 72 h. Cellular proteins were then analyzed by two-dimensional electrophoresis (2-DE) (n = 5 gels derived from 5 independent culture flasks per group). Spot matching and quantitative intensity analysis revealed 20 protein spots (from a total of 700) that were differentially expressed between the two groups. These altered proteins were then identified by Q-TOF-MS and MS/MS analyses, including those involved in calcium binding, protein synthesis, carbohydrate metabolism, lipid metabolism, cell proliferation, mitosis regulation, apoptosis, cell migration, oxidative stress, and ion transport. Protein network analysis and functional validation revealed that high-calcium-exposed cells had 36.5% increase in calcium oxalate monohydrate (COM) crystal-binding capacity. This functional change was consistent to the expression data in which annexin A1 (ANXA1), a membrane-associated calcium-binding protein, was markedly increased on the apical surface of high-calcium-exposed cells. Pretreatment with anti-ANXA1 antibody could neutralize this increasing crystal-binding capacity. Moreover, high-calcium exposure caused defects in cell proliferation and wound healing. These expression and functional data demonstrate the enhanced crystal-binding capacity but impaired cell proliferation and wound healing in renal tubular cells induced by high-calcium. Taken together, these phenomena may contribute, at least in part, to the pathogenic mechanisms of hypercalciuria-induced nephrolithiasis and impaired renal function. Our in vitro study offers several candidates for further targeted functional studies to confirm their relevance in hypercalciuria and kidney stone disease in vivo