Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations.

BACKGROUND: A large number of challenging medically relevant genes (CMRGs) are situated in complex or highly repetitive regions of the human genome, hindering comprehensive characterization of genetic variants using next-generation sequencing technologies. In this study, we employed long-read sequencing technology, extensively utilized in studying complex genomic regions, to characterize genetic alterations, including short variants (single nucleotide variants and short insertions and deletions) and copy number variations, in 370 CMRGs across 41 individuals from 19 global populations. RESULTS: Our analysis revealed high levels of genetic variants in CMRGs, with 68.73% exhibiting copy number variations and 65.20% containing short variants that may disrupt protein function across individuals. Such variants can influence pharmacogenomics, genetic disease susceptibility, and other clinical outcomes. We observed significant differences in CMRG variation across populations, with individuals of African ancestry harboring the highest number of copy number variants and short variants compared to samples from other continents. Notably, 15.79% to 33.96% of short variants were exclusively detectable through long-read sequencing. While the T2T-CHM13 reference genome significantly improved the assembly of CMRG regions, thereby facilitating variant detection in these regions, some regions still lacked resolution. CONCLUSION: Our results provide an important reference for future clinical and pharmacogenetic studies, highlighting the need for a comprehensive representation of global genetic diversity in the reference genome and improved variant calling techniques to fully resolve medically relevant genes.

Mechanistic Insights into a Novel Controllable Phase-Transition Polymer for Enhanced Oil Recovery in Mature Waterflooding Reservoirs.

Expanding swept volume technology via continuous-phase polymer solution and dispersed-phase particle gel is an important technique to increase oil production and control water production in mature waterflooding reservoirs. However, problems such as the low viscosity retention rate, deep migration, and weak mobility control of conventional polymers, and the contradiction between migration distance of particle gel and plugging strength, restrict the long-term effectiveness of oil displacement agents and the in-depth sweep efficiency expanding capability in reservoirs. Combined with the technical advantages of polymer and particle gel, a novel controllable phase-transition polymer was developed and systematically studied to gain mechanistic insights into enhanced oil recovery for mature waterflooding reservoirs. To reveal the phase-transition mechanism, the molecular structure, morphology, and rheological properties of the controllable phase-transition polymer were characterized before and after phase transition. The propagation behavior of the controllable phase-transition polymer in porous media was studied by conducting long core flow experiments. Two-dimensional micro visualization and parallel core flooding experiments were performed to investigate the EOR mechanism from porous media to pore level. Results show that the controllable phase-transition polymer could change phase from dispersed-phase particle gel to continuous-phase solution with the prolongation of ageing time. The controllable phase-transition polymer exhibited phase-transition behavior and good propagation capability in porous media. The results of micro visualization flooding experiments showed that the incremental oil recovery of the controllable phase-transition polymer was highest when a particle gel and polymer solution coexisted, followed by a pure continuous-phase polymer solution and pure dispersed-phase particle gel suspension. The recovery rate of the novel controllable phase-transition polymer was 27.2% after waterflooding, which was 8.9% higher than that of conventional polymer, providing a promising candidate for oilfield application.

Triazole phenotypes and genotypic characterization of clinical Aspergillus fumigatus isolates in China.

This study investigated the triazole phenotype and genotypic of clinical Aspergillus fumigatus isolates from China. We determined the triazole susceptibility profiles of 159 A. fumigatus isolates collected between 2011 and 2015 from four different areas in China tested against 10 antifungal drugs using the Clinical Laboratory Standard Institute M38-A2 method. For the seven itraconazole-resistant A. fumigatus isolates identified in the study, the cyp51A gene, including its promoter region, was sequenced and the mutation patterns were characterized. The resistant isolates were genotyped by microsatellite typing to determine the genetic relatedness to isolates from China and other countries. The frequency of itraconazole resistance in A. fumigatus isolates in our study was 4.4% (7/159). Six of the seven triazole-resistant isolates were recovered from the east and southeast of China, and one from was recovered from the west of China. No resistant isolates were found in the north. Three triazole-resistant isolates exhibited the TR34/L98H mutation, two carried the TR34/L98H/S297T/F495I mutation and one harbored a G54V mutation in the cyp51A gene. Analysis of the microsatellite markers from seven non-wild-type isolates indicated the presence of five unique genotypes, which clustered into two major genetic groups. The cyp51A gene mutations TR34/L98H and TR34/L98H/S297T were the most frequently found mutations, and the G54V mutation was reported for the first time in China. The geographic origin of the triazole-resistant isolates appeared to concentrate in eastern and south-eastern areas, which suggests that routine antifungal susceptibility testing in these areas should be performed for all clinically relevant A. fumigatus isolates to guide antifungal therapy and for epidemiological purposes.

Characterization of the photocurrents generated by the laser of atomic force microscopes.

The conductive atomic force microscope (CAFM) has become an essential tool for the nanoscale electronic characterization of many materials and devices. When studying photoactive samples, the laser used by the CAFM to detect the deflection of the cantilever can generate photocurrents that perturb the current signals collected, leading to unreliable characterization. In metal-coated semiconductor samples, this problem is further aggravated, and large currents above the nanometer range can be observed even without the application of any bias. Here we present the first characterization of the photocurrents introduced by the laser of the CAFM, and we quantify the amount of light arriving to the surface of the sample. The mechanisms for current collection when placing the CAFM tip on metal-coated photoactive samples are also analyzed in-depth. Finally, we successfully avoided the laser-induced perturbations using a two pass technique: the first scan collects the topography (laser ON) and the second collects the current (laser OFF). We also demonstrate that CAFMs without a laser (using a tuning fork for detecting the deflection of the tip) do not have this problem.

Moving graphene devices from lab to market: advanced graphene-coated nanoprobes.

After more than a decade working with graphene there is still a preoccupying lack of commercial devices based on this wonder material. Here we report the use of high-quality solution-processed graphene sheets to fabricate ultra-sharp probes with superior performance. Nanoprobes are versatile tools used in many fields of science, but they can wear fast after some experiments, reducing the quality and increasing the cost of the research. As the market of nanoprobes is huge, providing a solution for this problem should be a priority for the nanotechnology industry. Our graphene-coated nanoprobes not only show enhanced lifetime, but also additional unique properties of graphene, such as hydrophobicity. Moreover, we have functionalized the surface of graphene to provide piezoelectric capability, and have fabricated a nano relay. The simplicity and low cost of this method, which can be used to coat any kind of sharp tip, make it suitable for the industry, allowing production on demand.

Note: Fabrication of a fast-response and user-friendly environmental chamber for atomic force microscopes.

The atomic force microscope is one of the most widespread tools in science, but many suppliers do not provide a competitive solution to make experiments in controlled atmospheres. Here, we provide a solution to this problem by fabricating a fast-response and user-friendly environmental chamber. We corroborate the correct functioning of the chamber by studying the formation of local anodic oxidation on a silicon sample (biased under opposite polarities), an effect that can be suppressed by measuring in a dry nitrogen atmosphere. The usefulness of this chamber goes beyond the example here presented, and it could be used in many other fields of science, including physics, mechanics, microelectronics, nanotechnology, medicine, and biology.

Nanoscale characterization of PM2.5 airborne pollutants reveals high adhesiveness and aggregation capability of soot particles.

In 2012 air pollutants were responsible of seven million human death worldwide, and among them particulate matter with an aerodynamic diameter of 2.5 micrometers or less (PM2.5) are the most hazardous because they are small enough to invade even the smallest airways and penetrate to the lungs. During the last decade the size, shape, composition, sources and effect of these particles on human health have been studied. However, the noxiousness of these particles not only relies on their chemical toxicity, but particle morphology and mechanical properties affect their thermodynamic behavior, which has notable impact on their biological activity. Therefore, correlating the physical, mechanical and chemical properties of PM2.5 airborne pollutants should be the first step to characterize their interaction with other bodies but, unfortunately, such analysis has never been reported before. In this work, we present the first nanomechanical characterization of the most abundant and universal groups of PM2.5 airborne pollutants and, by means of atomic force microscope (AFM) combined with other characterization tools, we observe that fluffy soot aggregates are the most sticky and unstable. Our experiments demonstrate that such particles show strong adhesiveness and aggregation, leading to a more diverse composition and compiling all possible toxic chemicals.