Dxr is essential in Mycobacterium tuberculosis and fosmidomycin resistance is due to a lack of uptake

Fosmidomycin is a phosphonic antibiotic which inhibits 1-deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr), the first committed step of the non-mevalonate pathway of isoprenoid biosynthesis. In Mycobacterium tuberculosis Dxr is encoded by Rv2870c, and although the antibiotic has been shown to inhibit the recombinant enzyme [1], mycobacteria are intrinsically resistant to fosmidomycin at the whole cell level. Fosmidomycin is a hydrophilic molecule and in many bacteria its uptake is an active process involving a cAMP dependent glycerol-3-phosphate transporter (GlpT). The fact that there is no glpT homologue in the M. tuberculosis genome and the highly impervious nature of the hydrophobic mycobacterial cell wall suggests that resistance may be due to a lack of cellular penetration

Anywhere Out of this World

This essay discusses my paintings alongside Merleau-Ponty\u27s theories of perception and the history of form and color in painting. The relationship between perception and color is examined in the work of Paul Cézanne, Hans Hofmann, and Luis Barragán, along with Henri Matisse\u27s Chapel of the Rosary

Managing Uncertainty in Chronic Illness From Patient Perspectives

Chronic illness is an increasing concern in the United States as the Centers for Disease Control and Prevention reports that 50% of adults have at least one chronic illness. When individuals must adjust to chronic illness, they may experience uncertainty regarding the illness, prognosis, and symptoms. The purpose of this qualitative, phenomenological study was to explore the management strategies of uncertainty in chronic illness from patients’ perspectives. Merle Mishel’s uncertainty in illness theory was the framework used to explore the lives of individuals diagnosed and living with chronic illness. In-depth interviews were conducted with eight individuals who have chronic disease. Results revealed themes that individuals with chronic illness do experience uncertainty and that it impacts almost all aspects of their lives. Some of the themes identified were chronic illness, uncertainty, impact of uncertainty on daily living, coping or managing uncertainty, and communication from the healthcare team about uncertainty. The individuals expressed changes in daily activities and retraining their minds to accept their new normal. This study offers coping and management strategies that healthcare professionals can implement into treatment plans to improve the quality of life for individuals with uncertainty in chronic illness. The information produced from this study will aid healthcare providers in understanding the need to address the uncertainty at diagnoses and offer ways to assist patients in coping and managing uncertaint

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Soil organic carbon development and turnover in natural and disturbed salt marsh environments

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 48(2), (2021): e2020GL090287, https://doi.org/10.1029/2020GL090287.Salt marsh survival with sea‐level rise (SLR) increasingly relies on soil organic carbon (SOC) accumulation and preservation. Using a novel combination of geochemical approaches, we characterized fine SOC (≤1 mm) supporting marsh elevation maintenance. Overlaying thermal reactivity, source (δ13C), and age (F14C) information demonstrates several processes contributing to soil development: marsh grass production, redeposition of eroded material, and microbial reworking. Redeposition of old carbon, likely from creekbanks, represented ∼9%–17% of shallow SOC (≤26 cm). Soils stored marsh grass‐derived compounds with a range of reactivities that were reworked over centuries‐to‐millennia. Decomposition decreases SOC thermal reactivity throughout the soil column while the decades‐long disturbance of ponding accelerated this shift in surface horizons. Empirically derived estimates of SOC turnover based on geochemical composition spanned a wide range (640–9,951 years) and have the potential to inform predictions of marsh ecosystem evolution.This work was supported by NSF (OCE1233678) and NOAA (NA14OAR4170104 and NA14NOS4190145) grants to ACS, USGS Coastal & Marine Geology Program, and PIE‐LTER (NSF OCE1238212 and OCE1637630).2021-06-1

Playlists and time perspective

Research on playlists has focused on how usage is related to technological and music industry variables, and the demographic characteristics of users. However, it also seems reasonable to suspect a psychological component to playlist usage. The present research considered an individual’s propensity to devise and make use of playlists in terms of time perspective. Significant results indicate an emphasis on the time at hand while listening, so that playlist use has a present-orientated time perspective, rather than a future-oriented time perspective. The findings support other recent research illustrating that exercising control over everyday listening is an important aspect of musical behavior in present-day music listening

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Entropy and Action of Dilaton Black Holes

We present a detailed calculation of the entropy and action of $U(1)~2$ dilaton black holes, and show that both quantities coincide with one quarter of the area of the event horizon. Our methods of calculation make it possible to find an explanation of the rule $S = A/4$ for all static, spherically symmetric black holes studied so far. We show that the only contribution to the entropy comes from the extrinsic curvature term at the horizon, which gives $S = A/4$ independently of the charge(s) of the black hole, presence of scalar fields, etc. Previously, this result did not have a general explanation, but was established on a case-by-case basis. The on-shell Lagrangian for maximally supersymmetric extreme dilaton black holes is also calculated and shown to vanish, in agreement with the result obtained by taking the limit of the expression obtained for black holes with regular horizon.The physical meaning of the entropy is discussed in relation to the issue of splitting of extreme black holes.Comment: 15 p., SU-ITP-92-2