Computational Approaches to Investigate and Design Lipid-binding Domains for Membrane Biosensing

Association of proteins with cellular membranes is critical for signaling and membrane trafficking processes. Many peripheral lipid-binding domains have been identified in the last few decades and have been investigated for their specific lipid-sensing properties using traditional in vivo and in vitro studies.  However, several knowledge-gaps remain owing to intrinsic limitations of these methodologies. Thus, novel approaches are necessary to further our understanding in lipid-protein biology. This review briefly discusses lipid binding domains that act as specific lipid biosensors and provides a broad perspective on the computational approaches such as molecular dynamics (MD) simulations and machine learning (ML)-based techniques that can be used to study protein-membrane interactions. We also highlight the need for de novo design of proteins that elicit specific lipid binding properties

Petrologic and minerochemical trends of acapulcoites, winonaites and lodranites: New evidence from image analysis and EMPA investigations

A comprehensive classification of primitive achondrites is difficult due to the high compositional and textural variability and the low number of samples available. Besides oxygen isotopic analysis, other minerochemical and textural parameters may provide a useful tool to solve taxonomic and genetic problems related to these achondrites. The results of a detailed modal, textural and minerochemical analysis of a set of primitive achondrites are presented and compared with literature data. All the samples show an extremely variable modal composition among both silicate and opaque phases. A general trend of troilite depletion vs. silicate fraction enrichment has been observed, with differences among coarse-grained and fine-grained meteorites. In regard to the mineral chemistry, olivine shows marked differences between the acapulcoite-lodranite and winonaite groups, while a compositional equilibrium between matrix and chondrules for both groups, probably due to the scarce influence of metamorphic grade on this phase, was observed. The analysis of Cr and Mn in clinopyroxene revealed two separate clusters for the acapulcoite/lodranite and winonaite groups, while the analysis of the reduction state highlighted three separate clusters. An estimate of equilibrium temperatures for the acapulcoite-lodranite and winonaite groups is provided. Finally, proposals regarding the genetic processes of these groups are discussed

New eastern limit of the geographic distribution of Orsinigobius punctatissimus (Canestrini, 1864) (Teleostei: Gobiiformes: Gobiidae) in northeastern Italy, with biological notes on the species

A record of the gobiid Orsinigobius punctatissimus (Canestrini, 1864) from the springs of the Gorizia Karst (Italy, Friuli-Venezia Giulia) is reported, extending the eastern limit of the geographic distribution of the species. This goby lives in threatened spring habitats, and has recently become rarer. However, although O. punctatissimus is listed in the Italian Red List of threatened species as “Critically Endangered” (CR), the International Union for Conservation of Nature Red List of threatened species classifies it as “Near Threatened” (NT). Despite its risk of extinction, the species is not included in the annexes of the Habitat Directive (EU Directive 92/43/EEC) or other international wildlife protection conventions. Information is given on the taxonomy, distribution, biology and conservation of the species

Development of n-DoF preloaded structures for impact mitigation in cobots

A core issue in collaborative robotics is that of impact mitigation, especially when collisions happen with operators. Passively compliant structures can be used as the frame of the cobot, although usually they are implemented by means of a single DoF. However, n-DoF preloaded structures offer a number of advantages, in terms of flexibility in designing their behavior. In this work we propose a comprehensive framework for classifying n-DoF preloaded structures, including 1-, 2-, and 3-dimensional arrays. Also, we study the implications of the peculiar behavior of these structures - which present sharp stiff-to-compliant transitions at design-determined load thresholds - on impact mitigation. To this regard, an analytical n-DoF dynamic model was developed and numerically implemented. A prototype of a 10-DoF structure was tested under static and impact loads, showing a very good agreement with the model. Future developments will see the application of n-DoF preloaded structures to impact-mitigation on cobots and in the field of mobile robots, as well as to the field of novel architected materials

Toward chemically resolved computer simulations of dynamics and remodeling of biological membranes

Cellular membranes are fundamental constituents of living organisms. Apart from defining the boundaries of the cells, they are involved in a wide range of biological functions, associated with both their structural and the dynamical properties. Biomembranes can undergo large-scale transformations when subject to specific environmental changes, including gel–liquid phase transitions, change of aggregation structure, formation of microtubules, or rupture into vesicles. All of these processes are dependent on a delicate interplay between intermolecular forces, molecular crowding, and entropy, and their understanding requires approaches that are able to capture and rationalize the details of all of the involved interactions. Molecular dynamics-based computational models at atom-level resolution are, in principle, the best way to perform such investigations. Unfortunately, the relevant spatial and time dimensionalities involved in membrane remodeling phenomena would require computational costs that are today unaffordable on a routinely basis. Such hurdles can be removed by coarse-graining the representations of the individual molecular components of the systems. This procedure anyway reduces the possibility of describing the chemical variations in the lipid mixtures composing biological membranes. New hybrid particle field multiscale approaches offer today a promising alternative to the more traditional particle-based simulations methods. By combining chemically distinguishable molecular representations with mesoscale-based computationally affordable potentials, they appear as one of the most promising ways to keep an accurate description of the chemical complexity of biological membranes and, at the same time, cover the required scales to describe remodeling events

A detailed mineralogical, petrographic, and geochemical study of the highly reduced chondrite, Acfer 370

Among the many ungrouped meteorites, Acfer 370, NWA 7135, and El Médano 301—probably along with the chondritic inclusion in Cumberland Falls and ALHA 78113—represent a homogeneous grouplet of strongly reduced forsterite‐rich chondrites characterized by common textural, chemical, mineralogical, and isotopic features. All of these meteorites are much more reduced than OCs, with a low iron content in olivine and low‐Ca pyroxene. In particular, Acfer 370 is a type 4 chondrite that has olivine and low‐Ca pyroxene compositional ranges of Fa 5.2–5.8 and Fs 9.4–33.4, respectively. The dominant phase is low‐Ca pyroxene (36.3 vol%), followed by Fe‐Ni metal (16.3 vol%) and olivine (15.5 vol%); nevertheless, considering the Fe‐oxyhydroxide (due to terrestrial weathering), the original metal content was around 29.6 vol%. Finally, the mean oxygen isotopic composition Δ17O = +0.68‰ along with the occurrence of a silica phase, troilite, Ni‐rich phosphides, chromite, and oldhamite confirms that these ungrouped meteorites have been affected by strong reduction and are different from any other group recognized so far

Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity

Diacylglycerols (DAGs) are bioactive lipids that are ubiquitously present at low concentrations in cellular membranes. Upon the activation of lipid remodeling enzymes such as phospholipase C and phosphatidic acid phosphatase, DAG concentration increases, leading to a disruption of the lamellar phase of lipid membranes. To investigate the structural origin of these phenomena, here we develop a coarse-grained model for DAGs that is able to correctly reproduce its physicochemical properties, including interfacial tension and flip-flop rate. We find that even at low concentrations a nonnegligible percentage of DAG molecules occupies the interleaflet space. At high concentrations, DAG molecules undergo a phase- separation process from lamellar lipids, segregating in DAG-only blisters and effectively reducing the DAG surface pool available to peripheral enzymes. Our results allow for a better understanding of the role of DAGs in cellular membranes and provide a new tool for the quantitative estimation of low-abundance lipids on membrane properties