Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

Background: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors.

Methods: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden.

Rotational phase transitions in antifluorite-type osmate and iridate compounds.

We present temperature-dependent single-crystal diffraction results on seven antifluorite-typeA2MeX6compounds with= Os or Ir: KOsCl,OsBrwith= K, Rb, Cs and NH, and KIrwith= Cl and Br. The structural transitions in this family arise fromoctahedron rotations that generate a rich variety of symmetries depending on the rotation axis and stacking schemes. In order to search for local distortions in the high-symmetry phase we perform refinements of anharmonic atomic displacement parameters with comprehensive data sets.

On the role of nucleotides and lipids in the polymerization of the actin homolog MreB from a Gram-positive bacterium.

bacterial actin MreB assembles into dynamic membrane-associated filamentous structures that exhibit circumferential motion around the cell. Current knowledge of MreB biochemical and polymerization properties remains limited and is mostly based on MreB proteins from Gram-negative species. In this study, we report the first observation of organized protofilaments by electron microscopy and the first 3D-structure of MreB from a Gram-positive bacterium.

Reconstituted in vitro systems to reveal the roles and functions of septins.

Septins are essential cytoskeletal proteins involved in key cellular processes and have also been implicated in diseases from cancers to neurodegenerative pathologies. However, they have not been as thoroughly studied as other cytoskeletal proteins. In vivo, septins interact with other cytoskeletal proteins and with the inner plasma membrane.

A human septin octamer complex sensitive to membrane curvature drives membrane deformation with a specific mesh-like organization.

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane and decouple their role from other partners, we used a combination of bottom-up in vitro methods.

EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells.

The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP).

Pesticide exposure affects DNA methylation patterns in natural populations of a mayfly.

Chemical pollutants derived from agricultural activities represent a major threat to freshwater biota. Despite growing evidence involving epigenetic processes, such as DNA methylation, in response to pesticide contamination in agroecosystems, research on wild populations of non-model species remains scarce, particularly for endemic freshwater arthropods. Using the MethylRAD method, this study investigates whether exposure to pesticide contamination in natural populations of the endemic mayfly A.

Direct observation of the conformational states of formin mDia1 at actin filament barbed ends and along the filament.

The fine regulation of actin polymerization is essential to control cell motility and architecture and to perform essential cellular functions. Formins are key regulators of actin filament assembly, known to processively elongate filament barbed ends and increase their polymerization rate. Different models have been extrapolated to describe the molecular mechanism governing the processive motion of formin FH2 domains at polymerizing barbed ends.

Bottom-Up In Vitro Methods to Assay the Ultrastructural Organization, Membrane Reshaping, and Curvature Sensitivity Behavior of Septins.

Membrane remodeling occurs constantly at the plasma membrane and within cellular organelles. To fully dissect the role of the environment (ionic conditions, protein and lipid compositions, membrane curvature) and the different partners associated with specific membrane reshaping processes, we undertake in vitro bottom-up approaches. In recent years, there has been keen interest in revealing the role of septin proteins associated with major diseases.

Spatial autocorrelation signatures of ecological determinants on plant community characteristics in high Andean wetlands.

Understanding how biological communities are shaped is a central tenet of community ecology. Recent evidence highlights the potential of decoupling diversity spatial autocorrelation into its positive and negative components to reveal community assembly processes that would otherwise remain undetected, as well as to improve understanding of their impacts on different facets of diversity. Yet, such approaches have only been implemented to investigate the effects of a few assembly drivers on a small number of diversity components.

Purification and Quality Control of Recombinant Septin Complexes for Cell-Free Reconstitution.

Septins are a family of conserved eukaryotic GTP-binding proteins that can form cytoskeletal filaments and higher-order structures from hetero-oligomeric complexes. They interact with other cytoskeletal components and the cell membrane to participate in important cellular functions such as migration and cell division. Due to the complexity of septins' many interactions, the large number of septin genes (13 in humans), and the ability of septins to form hetero-oligomeric complexes with different subunit compositions, cell-free reconstitution is a vital strategy to understand the basics of septin biology.

Impact of natural and artificial prenatal stimulation on the behavioural profile of Japanese quail.

As the sensory systems of vertebrates develop prenatally, embryos perceive many environmental stimuli that can influence the ontogeny of their behaviour. Whether the nature and intensity of prenatal stimuli affect this ontogeny differently remains to be investigated. In this context, this study aimed to analyse the effects of prenatal auditory stimulation (natural stimulation, NS; predator vocalisations or artificial stimulation, AS; metallic sounds) on the subsequent behaviour of young Japanese quail (Coturnix coturnix japonica).

skin anisotropy dataset from annular suction test.

To characterize the anisotropic and viscoelastic behaviors of the skin, we conducted an experimental campaign of suction tests using the CutiScan®CS100 device from Courage and Khazaka electronics. In this data paper, we present the raw acquired data of the tests and their respective treated data. The tests were performed 30 times on the anterior forearm of a 28-year-old Caucasian male at different pressure set-points, ranging from 100 to 500 mbar with an increment of 20 mbar, at ambient temperature in a windowless room.

Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms.

Septin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9 subunit (also known as SEPTIN9). Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9, thus not recapitulating its native assembly into hetero-octameric complexes.

Treatment of gaseous emissions from tire manufacturing industry using lab-scale biofiltration pilot units.

Continuously seeking the improvement of environmental protection, the limitation of exhaust emissions is of significance for the tire manufacturing industry. The aim of this study is to assess the potential of biofiltration for the treatment of such gaseous emissions. This work highlights that biofiltration is able to remove both hydrophilic and hydrophobic compounds within a single pilot unit of biofiltration.

Correlative AFM and fluorescence imaging demonstrate nanoscale membrane remodeling and ring-like and tubular structure formation by septins.

Septins are ubiquitous cytoskeletal filaments that interact with the inner plasma membrane and are essential for cell division in eukaryotes. In cellular contexts, septins are often localized at micrometric Gaussian curvatures, where they assemble onto ring-like structures. The behavior of budding yeast septins depends on their specific interaction with inositol phospholipids, enriched at the inner leaflet of the plasma membrane.

Persistence of Coxsackievirus B4 in Pancreatic β Cells Disturbs Insulin Maturation, Pattern of Cellular Proteins, and DNA Methylation.

Coxsackievirus-B4 (CV-B4) can persist in pancreatic cell lines and impair the phenoytpe and/or gene expressions in these cells; however, the models used to study this phenomenon did not produce insulin. Therefore, we investigated CV-B4 persistence and its consequences in insulin-producing pancreatic β cells. The insulin-secreting rat β cell line, INS-1, was infected with CV-B4.

[Cryo-electron microcopy for a new vision of the cell and its components].

Cryo-electron microscopy (cryo-EM) is a technique for imaging biological samples that plays a central role in structural biology, with high impact on research fields such as cell and developmental biology, bioinformatics, cell physics and applied mathematics. It allows the determination of structures of purified proteins within cells. This review describes the main recent advances in cryo-EM, illustrated by examples of proteins of biomedical interest, and the avenues for future development.