Role of KASH domain lengths in the regulation of LINC complexes.

The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN-KASH complex. We show that longer KASH domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH domains. In agreement with our models, our in vivo results show that swapping the KASH domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans

Combined Effects of Nanoroughness and Ions Produced by Electrodeposition of Mesoporous Bioglass Nanoparticle for Bone Regeneration

Providing appropriate biophysical and biochemical cues to the interface is a facile strategy to enhance the osteogenic ability of metallic implants. Here we exploited this through the incorporation of mesoporous bioactive glass nanoparticles (MBGN) at a high content (1:1 by weight) to a biopolymer chitosan in the electrodeposition process of titanium. The MGBN/chitosan layer thickness, tunable by electrodeposition parameters, exhibited an accelerated ability of apatite mineral induction in a body simulating medium. Of note, the involvement of MBGN could generate nanoscale roughness in a unique range of 10-25 nm. Moreover, the layer showed a slowly releasing profile of ions (calcium and silicate) over weeks at therapeutically relevant doses. The ion-releasing nanotopological surface was demonstrated to alter the preosteoblasts responses in a way favorable for osteogenic differentiation. The combinatory cues of nanotopology (25 nm roughness) and ion release enabled highly accelerated cellular anchorage with somewhat limited spreading area at initial periods. The subsequent osteoblastic differentiation behaviors on the engineered surface, as examined up to 21 days, showed significantly enhanced alkaline phosphate activity and up-regulated expression of bone-associated genes (ALP, Col I, OPN, and OCN). These results indicate that the combinatory cues provided by nanotopology (25 nm roughness) and ions released from MBGN are highly effective in stimulating osteoblastic differentiation and suggest that the MBGN/chitosan may serve as a potential composition for bone implant coatings

Statistically derived contributions of diverse human influences to twentieth-century temperature changes

The warming of the climate system is unequivocal as evidenced by an increase in global temperatures by 0.8 °C over the past century. However, the attribution of the observed warming to human activities remains less clear, particularly because of the apparent slow-down in warming since the late 1990s. Here we analyse radiative forcing and temperature time series with state-of-the-art statistical methods to address this question without climate model simulations. We show that long-term trends in total radiative forcing and temperatures have largely been determined by atmospheric greenhouse gas concentrations, and modulated by other radiative factors. We identify a pronounced increase in the growth rates of both temperatures and radiative forcing around 1960, which marks the onset of sustained global warming. Our analyses also reveal a contribution of human interventions to two periods when global warming slowed down. Our statistical analysis suggests that the reduction in the emissions of ozone-depleting substances under the Montreal Protocol, as well as a reduction in methane emissions, contributed to the lower rate of warming since the 1990s. Furthermore, we identify a contribution from the two world wars and the Great Depression to the documented cooling in the mid-twentieth century, through lower carbon dioxide emissions. We conclude that reductions in greenhouse gas emissions are effective in slowing the rate of warming in the short term.F.E. acknowledges financial support from the Consejo Nacional de Ciencia y Tecnologia (http://www.conacyt.gob.mx) under grant CONACYT-310026, as well as from PASPA DGAPA of the Universidad Nacional Autonoma de Mexico. (CONACYT-310026 - Consejo Nacional de Ciencia y Tecnologia; PASPA DGAPA of the Universidad Nacional Autonoma de Mexico

Sol-gel based materials for biomedical applications

Sol-gel chemistry offers a flexible approach to obtaining a diverse range of materials. It allows differing chemistries to be achieved as well as offering the ability to produce a wide range of nano-/micro-structures. The paper commences with a generalized description of the various sol-gel methods available and how these chemistries control the bulk properties of the end products. Following this, a more detailed description of the biomedical areas where sol-gel materials have been explored and found to hold significant potential. One of the interesting fields that has been developed recently relates to hybrid materials that utilize sol-gel chemistry to achieve unusual composite properties. Another intriguing feature of sol-gels is the unusual morphologies that are achievable at the micro- and nano-scale. Subsequently the ability to control pore chemistry at a number of different length scales and geometries has proven to be a fruitful area of exploitation, that provides excellent bioactivity and attracts cellular responses as well as enables the entrapment of biologically active molecules and their controllable release for therapeutic action. The approaches of fine-tuning surface chemistry and the combination with other nanomaterials have also enabled targeting of specific cell and tissue types for drug delivery with imaging capacity

Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings

Demystifying Data Science Projects: A Look on the People and Process of Data Science Today

Peer reviewe

Most vital segment barriers

We study continuous analogues of "vitality" for discrete network flows/paths, and consider problems related to placing segment barriers that have highest impact on a flow/path in a polygonal domain. This extends the graph-theoretic notion of "most vital arcs" for flows/paths to geometric environments. We give hardness results and efficient algorithms for various versions of the problem, (almost) completely separating hard and polynomially-solvable cases

Algebraic charge liquids

High temperature superconductivity emerges in the cuprate compounds upon changing the electron density of an insulator in which the electron spins are antiferromagnetically ordered. A key characteristic of the superconductor is that electrons can be extracted from them at zero energy only if their momenta take one of four specific values (the `nodal points'). A central enigma has been the evolution of the zero energy electrons in the metallic state between the antiferromagnet and the superconductor, and recent experiments yield apparently contradictory results. The oscillation of the resistance in this metal as a function of magnetic field indicate that the zero energy electrons carry momenta which lie on elliptical `Fermi pockets', while ejection of electrons by high intensity light indicates that the zero energy electrons have momenta only along arc-like regions. We present a theory of new states of matter, which we call `algebraic charge liquids', which arise naturally between the antiferromagnet and the superconductor, and reconcile these observations. Our theory also explains a puzzling dependence of the density of superconducting electrons on the total electron density, and makes a number of unique predictions for future experiments.Comment: 6+8 pages, 2 figures; (v2) Rewritten for broader accessibility; (v3) corrected numerical error in Eq. (5