Lack of Evidence from Studies of Soluble Protein Fragments that Knops Blood Group Polymorphisms in Complement Receptor-Type 1 Are Driven by Malaria

Complement receptor-type 1 (CR1, CD35) is the immune-adherence receptor, a complement regulator, and an erythroid receptor for Plasmodium falciparum during merozoite invasion and subsequent rosette formation involving parasitized and non-infected erythrocytes. The non-uniform geographical distribution of Knops blood group CR1 alleles Sl1/2 and McCa/b may result from selective pressures exerted by differential exposure to infectious hazards. Here, four variant short recombinant versions of CR1 were produced and analyzed, focusing on complement control protein modules (CCPs) 15–25 of its ectodomain. These eleven modules encompass a region (CCPs 15–17) key to rosetting, opsonin recognition and complement regulation, as well as the Knops blood group polymorphisms in CCPs 24–25. All four CR1 15–25 variants were monomeric and had similar axial ratios. Modules 21 and 22, despite their double-length inter-modular linker, did not lie side-by-side so as to stabilize a bent-back architecture that would facilitate cooperation between key functional modules and Knops blood group antigens. Indeed, the four CR1 15–25 variants had virtually indistinguishable affinities for immobilized complement fragments C3b (KD = 0.8–1.1 µM) and C4b (KD = 5.0–5.3 µM). They were all equally good co-factors for factor I-catalysed cleavage of C3b and C4b, and they bound equally within a narrow affinity range, to immobilized C1q. No differences between the variants were observed in assays for inhibition of erythrocyte invasion by P. falciparum or for rosette disruption. Neither differences in complement-regulatory functionality, nor interactions with P. falciparum proteins tested here, appear to have driven the non-uniform geographic distribution of these alleles

Application of novel analytical ultracentrifuge analysis to solutions of fungal mannans

Polysaccharides, the most abundant biopolymers, are required for a host of activities in lower organisms, animals, and plants. Their solution characterization is challenging due to their complex shape, heterogeneity, and size. Here, recently developed data analysis approaches were applied for traditional sedimentation equilibrium and velocity methods in order to investigate the molar mass distribution(s) of a subtype of polysaccharide, namely, mannans from four Candida spp. The molecular weight distributions of these mannans were studied using two recently developed equilibrium approaches: SEDFIT-MSTAR and MULTISIG, resulting in corroboratory distribution profiles. Additionally, sedimentation velocity data for all four mannans, analyzed using ls-g*(s) and Extended Fujita approaches, suggest that two of the fungal mannans (FM-1 and FM-3) have a unimodal distribution of molecular species whereas two others (FM-2 and FM-4) displayed bi-modal and broad distributions, respectively: this demonstrates considerable molecular heterogeneity in these polysaccharides, consistent with previous observations of mannans and polysaccharides in general. These methods not only have applications for the characterization of mannans but for other biopolymers such as polysaccharides, DNA, and proteins (including intrinsically disordered proteins)

A review of modern approaches to the hydrodynamic characterisation of polydisperse macromolecular systems in biotechnology

This short review considers the range of modern techniques for the hydrodynamic characterisation of macromolecules – particularly large glycosylated systems used in the food, biopharma and healthcare industries. The range or polydispersity of molecular weights and conformations presents special challenges compared to proteins. The review is aimed, without going into any great theoretical or methodological depth, to help the Industrial Biotechnologist choose the appropriate methodology or combination of methodologies for providing the detail he/she needs for particular applications

MultiSig: a new high-precision approach to the analysis of complex biomolecular systems

MultiSig is a newly developed mode of analysis of sedimentation equilibrium (SE) experiments in the analytical ultracentrifuge, having the capability of taking advantage of the remarkable precision (~0.1 % of signal) of the principal optical (fringe) system employed, thus supplanting existing methods of analysis through reducing the ‘noise’ level of certain important parameter estimates by up to orders of magnitude. Long-known limitations of the SE method, arising from lack of knowledge of the true fringe number in fringe optics and from the use of unstable numerical algorithms such as numerical differentiation, have been transcended. An approach to data analysis, akin to ‘spatial filtering’, has been developed, and shown by both simulation and practical application to be a powerful aid to the precision with which near-monodisperse systems can be analysed, potentially yielding information on protein-solvent interaction. For oligo- and poly-disperse systems the information returned includes precise average mass distributions over both cell radial and concentration ranges and mass-frequency histograms at fixed radial positions. The application of MultiSig analysis to various complex heterogenous systems and potentially multiply-interacting carbohydrate oligomers is described

Biomorpher: interactive evolution for parametric design

Combining graph-based parametric design with metaheuristic solvers has to date focussed solely on performance based criteria and solving clearly defined objectives. In this paper, we outline a new method for combining a parametric modelling environment with an interactive Cluster-Orientated Genetic Algorithm (COGA). In addition to performance criteria, evolutionary design exploration can be guided through choice alone, with user motivation that cannot be easily defined. As well as numeric parameters forming a genotype, the evolution of whole parametric definitions is discussed through the use of genetic programming. Visualisation techniques that enable mixing small populations for interactive evolution with large populations for performance-based optimisation are discussed, with examples from both academia and industry showing a wide range of applications

The Changing Face of Winter: Lessons and Questions From the Laurentian Great Lakes

Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter-period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world\u27s seasonally freezing lakes and seas

Structure and lithology of the Japan Trench subduction plate boundary fault

The 2011 Mw9.0 Tohoku-oki earthquake ruptured to the trench with maximum coseismic slip located on the shallow portion of the plate boundary fault. To investigate the conditions and physical processes that promoted slip to the trench, Integrated Ocean Drilling Program Expedition 343/343T sailed 1 year after the earthquake and drilled into the plate boundary ∼7 km landward of the trench, in the region of maximum slip. Core analyses show that the plate boundary décollement is localized onto an interval of smectite-rich, pelagic clay. Subsidiary structures are present in both the upper and lower plates, which define a fault zone ∼5–15m thick. Fault rocks recovered from within the clay-rich interval contain a pervasive scaly fabric defined by anastomosing, polished, and lineated surfaces with two predominant orientations. The scaly fabric is crosscut in several places by discrete contacts across which the scaly fabric is truncated and rotated, or different rocks are juxtaposed. These contacts are inferred to be faults. The plate boundary décollement therefore contains structures resulting from both distributed and localized deformation. We infer that the formation of both of these types of structures is controlled by the frictional properties of the clay: the distributed scaly fabric formed at low strain rates associated with velocity-strengthening frictional behavior, and the localized faults formed at high strain rates characterized by velocity-weakening behavior. The presence of multiple discrete faults resulting from seismic slip within the décollement suggests that rupture to the trench may be characteristic of this margin

Winter Targeted Observing Periods during the Year of Polar Prediction in the Southern Hemisphere (YOPP-SH)

The Year of Polar Prediction in the Southern Hemisphere (YOPP-SH) held seven targeted observing periods (TOPs) during the 2022 austral winter to enhance atmospheric predictability over the Southern Ocean and Antarctica. The TOPs of 5–10-day duration each featured the release of additional radiosonde balloons, more than doubling the routine sounding program at the 24 participating stations run by 14 nations, together with process-oriented observations at selected sites. These extra sounding data are evaluated for their impact on forecast skill via data denial experiments with the goal of refining the observing system to improve numerical weather prediction for winter conditions. Extensive observations focusing on clouds and precipitation primarily during atmospheric river (AR) events are being applied to refine model microphysical parameterizations for the ubiquitous mixed-phase clouds that frequently impact coastal Antarctica. Process studies are being facilitated by high-time-resolution series of observations and forecast model output via the YOPP Model Intercomparison and Improvement Project (YOPPsiteMIIP). Parallel investigations are broadening the scope and impact of the YOPP-SH winter TOPs. Studies of the Antarctic tourist industry’s use of weather services show the scope for much greater awareness of the availability of forecast products and the skill they exhibit. The Sea Ice Prediction Network South (SIPN South) analysis of predictions of the sea ice growth period reveals that the forecast skill is superior to the sea ice retreat phase

Malunion after midshaft clavicle fractures in adults: The current view on clavicular malunion in the literature

This is an overview of the current literature on malunion after midshaft clavicle fracture. Anatomy, trauma mechanism, classification, incidence, symptoms, prevention, and treatment options are all discussed. The conclusion is that clavicle malunion is a distinct clinical entity that can be treated successfully