Search

This article discusses the importance of implementing emergency vitrification protocols in IVF laboratories to manage crises and ensure the safety of patients and reproductive material. The article highlights the vulnerability of medical-assisted reproduction due to its dependence on technology, transportation, and a substantial workforce. It also presents a case study from a laboratory in China that successfully implemented emergency vitrification during a flood. The article emphasizes the need for comprehensive emergency disaster management plans, adequate resources, and the skills and adaptability of embryologists in navigating emergencies. It also raises ethical considerations and the importance of proactive planning and collaboration to mitigate risks and uphold the highest standards of care in reproductive medicine. [Extracted from the article]

Complex multiphase reaction rims that form during garnet breakdown are known as kelyphite coronae and are common amongst exhumed mantle xenoliths. It has long been established that a reaction of garnet and olivine produces kelyphite corona consisting of spinel and pyroxenes, and that preservation of high-pressure garnet cores requires sufficiently rapid uplift of material through the spinel lherzolite stability field from depths of at least 60 km. We present new high-pressure, high-temperature experiments of garnet breakdown in the spinel–lherzolite stability field demonstrating that a series of cascading reactions can reproduce the multilayer, multiphase kelyphites seen in nature. In all experiments where breakdown occurred, a melt appears to have moderated the reactions towards equilibrium; we believe this to be the first experimental confirmation of the importance of such melts in garnet breakdown reactions. In our experiments at least three distinct zones of concentric kelyphite growth can occur at a single pressure, temperature condition; we suggest, therefore, that such kelyphites seen in natural samples do not have to be caused by a multistage uplift path as is often assumed. Kelyphitic coronae surrounding garnet have previously been used to estimate uplift rates; however, the lack of kinetic data for relevant exhumation reactions has limited their use for PTt pathway estimations and the understanding of emplacement mechanisms. In order to constrain accurate PTt pathways we use reaction rim thickness as a proxy for reaction progress and present preliminary results for the kinetics of garnet breakdown. [ABSTRACT FROM AUTHOR]

Motivation To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analyzing this resource. Here, we use tools from graph theory to define an Atlas classification scheme for automatically categorizing certain protein substructures. Results Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein–protein interaction motifs, we present a suite of computational resources designed for analyzing these assemblies. iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control. Applying a graph theory-based Atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils. The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels. Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the 'dark matter' of coiled-coil structures; i.e. those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design. Availability and implementation iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket). This repository also contains all the data generated when classifying the protein graphs. The Atlas of Coiled Coils is available at: http://coiledcoils.chm.bris.ac.uk/atlas/app. [ABSTRACT FROM AUTHOR]

Motivation: The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. Results: Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. [ABSTRACT FROM AUTHOR]

This article examines how civilian defense militias shape violence during civil war. We define civilian defense forces as a sedentary and defensive form of pro-government militia that incumbents often use to harness the participation of civilians during a counterinsurgency campaign. We argue that civilian defense forces reduce the problem of insurgent identification. This leads to a reduction in state violence against civilians. However, we also claim that these actors undermine civilian support for insurgents, which leads to an increase in rebel violence against civilians and overall intensification of conflict. A statistical analysis of government and rebel violence against civilians from 1981 to 2005 and a qualitative assessment of a civilian defense force operating in Iraq from 2005 to 2009 offer strong support for our theoretical claims. These findings provide further insight into pro-government militias and their effects on violence. They also have wider ethical implications for the use of civilian collaborators during civil war. [ABSTRACT FROM AUTHOR]

Motivation: The ability to accurately model protein structures at the atomistic level underpins efforts to understand protein folding, to engineer natural proteins predictably and to design proteins de novo. Homology-based methods are well established and produce impressive results. However, these are limited to structures presented by and resolved for natural proteins. Addressing this problem more widely and deriving truly ab initio models requires mathematical descriptions for protein folds; the means to decorate these with natural, engineered or de novo sequences; and methods to score the resulting models.Results: We present CCBuilder, a web-based application that tackles the problem for a defined but large class of protein structure, the α-helical coiled coils. CCBuilder generates coiled-coil backbones, builds side chains onto these frameworks and provides a range of metrics to measure the quality of the models. Its straightforward graphical user interface provides broad functionality that allows users to build and assess models, in which helix geometry, coiled-coil architecture and topology and protein sequence can be varied rapidly. We demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil structures from the PDB, which cover >96% of the known coiled-coil types, and by generating models for rarer and de novo coiled-coil structures.Availability and implementation: CCBuilder is freely available, without registration, at http://coiledcoils.chm.bris.ac.uk/app/cc_builder/Contact: D.N.Woolfson@bristol.ac.uk or Chris.Wood@bristol.ac.uk [ABSTRACT FROM AUTHOR]

A number of recent studies have used the compositional relationship between magmatic crystals and their carrier liquids to understand processes within volcanic plumbing systems. Here, an extensive compilation of electron microprobe data for Icelandic olivine and glass compositions is used to examine the distribution of the forsterite content of olivine macrocrysts within single lava flows, and the relationship of these olivines to their carrier basaltic liquids. A dataset of 7836 olivine and 233 glass point analyses was examined and 11 eruptions were identified where glass data and over 60 crystal core compositions were available. In common with many basaltic suites, single olivine crystals typically have uniform core compositions with narrow normally zoned rims. Accordingly, in 10 of the 11 Icelandic eruptions over 90% of the olivines are too forsteritic to be in equilibrium with their carrier basaltic liquids. The sampling density of the dataset permitted statistical investigation of the distribution of olivine compositions that contain information that can be used to provide new constraints on magmatic processes. The results of both kernel density estimates and Gaussian mixture modelling indicate that each of the 11 eruptions contained at least one robust peak in olivine compositions. Out of these 11 eruptions, eight show unimodal distributions of macrocryst olivine forsterite content, two are bimodal and one is polymodal. An important feature of the relationship between the carrier glass compositions and the distribution of olivine forsterite contents is that, for 10 of the 11 flows, a strong peak in the olivine compositional distribution occurs at forsterite contents that are 2–3 mol % higher than those expected for olivines in equilibrium with the carrier liquid. This offset peak is not predicted for olivines generated by simple equilibrium or fractional crystallization models. Instead, the distribution of olivine compositions and its relationship with the carrier liquids can be accounted for using a three-stage model. In the first stage, fractional crystallization and crystal settling generate a mush pile on the floor of a magma chamber. Compositional stratification is present in this mush, with the olivines at its base being more forsteritic than those at its top, reflecting the evolution of liquid compositions during fractional crystallization. The olivines in the uppermost part of the mush are close to equilibrium with basaltic liquid in the interior of the chamber. In the second stage local diffusion acts to homogenize single crystals in the mush, creating the uniform cores observed upon eruption. Concurrently the chemical gradient across the full thickness of the mush pile is altered by diffusion through the interstitial melt phase, reducing the variance of olivine core compositions in the mush. This process never reaches completion in the Icelandic flows but does generate a single peak in olivine compositions close to the mean forsterite content of the olivines in the crystal pile. Finally, the mush is disaggregated into the carrier liquid of the chamber interior shortly before eruption, creating the diffusional rim overprints. Quantitative models of this process indicate that the observed offset peak in olivine compositions can be generated after 42–8000 years of diffusion in a mush pile, depending on the mush thickness. Key features of the compositional distribution of olivines in basalts can therefore be accounted for using a simple model of mush generation and disaggregation. [ABSTRACT FROM PUBLISHER]

Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. However, the role of miRNAs in the regulation of stem cell growth and differentiation is not well understood. We show herein that microRNA (miR)-134 levels are maximally elevated at day 4 after retinoic acid-induced differentiation or day 2 after N2B27-induced differentiation of mouse embryonic stem cells (mESCs), but this change is not observed during embryoid body differentiation. The elevation of miR-134 levels alone in mESCs enhances differentiation toward ectodermal lineages, an effect that is blocked by a miR-134 antagonist. The promotion of mESC differentiation by miR-134 is due, in part, to its direct translational attenuation of Nanog and LRH1, both of which are known positive regulators of Oct4/POU5F1 and mESC growth. Together, the data demonstrate that miR-134 alone can enhance the differentiation of mESCs to ectodermal lineages and establish a functional role for miR-134 in modulating mESC differentiation through its potential to target and regulate multiple mRNAs. [ABSTRACT FROM AUTHOR]

Few studies have assessed the accuracy of patient recall of doctor-diagnosed heart attack and stroke on postal questionnaire, yet such data are widely used in epidemiologic studies. In the national prospective British Regional Heart Study of 7,735 men aged 40–59 years, based in general practice and followed up for a mean 13.8 years, a mailed questionnaire was sent to all available survivors in 1992. Patient recall of doctor-diagnosed heart attack and stroke was compared with the 316 new general practice-reported heart attacks and 102 new general practice-reported strokes from the medical record reviews. Both study and general practice records were checked for all discordant findings, and corrections were made to the study database. Patients tended to overrecall major cardiovascular events more than they underrecalled them, 33% versus 6% for heart attacks and 25% versus 11% for strokes. Among overrecalled heart attacks, other circulatory problems were present in 78% of the subjects; transient ischemic attacks accounted for 57% of overrecalled strokes. In contrast, the general practice record review system tended to underreport events rather than to overreport them, 3% versus 0.3% for heart attacks and 23% versus 5% for strokes. Patient recall of doctor-diagnosed heart attack and stroke provides a useful method for estimating prevalence rates and resource needs, but the tendency to overestimation needs to be recognized. In etiologic studies when strict diagnostic case criteria are essential, patient recall should be used to complement rather than to supplant medical record data. Am J Epidemiol 1998; 148:355–61. [ABSTRACT FROM AUTHOR]

Examines the localization and expression of nitric oxide synthase (NOS) enzymes in the human uterine cervix during pregnancy and parturition. Presence of the three NOS isoforms in non-pregnant and pregnant states; Increase in NOS isoform expression in pregnancy; Involvement of NO in cervical ripening during pregnancy.