3,5-Dinitro­benzyl methane­sulfonate

The title compound, C8H8N2O7S, an inter­mediate in the synthesis of N,N-bis­(2-hydroxy­ethyl)-3,5-dinitro­aniline, exists as a discrete mol­ecule; the nitro groups are twisted with respect to the aromatic system [dihedral angles = 17.0 (1) and 26.3 (1)°]

N-[3-(tert-Butyl­dimethyl­siloxymeth­yl)-5-nitro­phen­yl]acetamide

The title compound, C15H24N2O4Si, was prepared by the reaction of (3-acetamido-5-nitro­benz­yl)methanol with tert-butyl­dimethyl­silyl chloride and is a key inter­mediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent mol­ecules in the structure, which differ primarily in the rotation about the C—O bond next to the Si atom. Two strong N—H⋯O hydrogen bonds align the mol­ecules into a wide ribbon extending approximately parallel to the b axis

N-{3-[Bis(2-hydroxy­ethyl)amino­meth­yl]-5-nitro­phen­yl}benzamide

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitro­benzyl methane­sulfonate with diethano­lamine and is an inter­mediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent mol­ecules, which differ only in the orientations of the hydroxy­ethyl groups. In the crystal structure, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link mol­ecules into one-dimensional chains

Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.

UnlabelledCoccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region.ImportanceCoccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii

Cortical and trabecular bone benefits of mechanical loading are maintained long term in mice independent of ovariectomy.

Skeletal loading enhances cortical and trabecular bone properties. How long these benefits last after loading cessation remains an unresolved, clinically relevant question. This study investigated long-term maintenance of loading-induced cortical and trabecular bone benefits in female C57BL/6 mice and the influence of a surgically induced menopause on the maintenance. Sixteen-week-old animals had their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse tibial axial compression loading model. Left tibias were not loaded and served as internal controls. Animals were subsequently detrained (restricted to cage activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX surgery being performed at 0 weeks detraining. Loading increased midshaft tibia cortical bone mass, size, and strength, and proximal tibia bone volume fraction. The cortical bone mass, area, and thickness benefits of loading were lost by 26 weeks of detraining because of heightened medullary expansion. However, loading-induced benefits on bone total area and strength were maintained at each detraining time point. Similarly, the benefits of loading on bone volume fraction persisted at all detraining time points. The long-term benefits of loading on both cortical and trabecular bone were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone properties at early (4 and 8 weeks) detraining time points and trabecular bone properties at all detraining time points. These cumulative data indicate loading has long-term benefits on cortical bone size and strength (but not mass) and trabecular bone morphology, which are not influenced by a surgically induced menopause. This suggests skeletal loading associated with physical activity may provide long-term benefits by preparing the skeleton to offset both the cortical and trabecular bone changes associated with aging and menopause

A judgement bias test to assess affective state and potential therapeutics in a rat model of chemotherapy-induced mucositis

Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40–60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.Rebecca P. George, Timothy H. Barker, Kerry A. Lymn, Dylan A. Bigatton, Gordon S. Howarth and Alexandra L. Whittake

PoLAR-FIT: Pliocene Landscapes and Arctic Remains—Frozen in Time

This short summary presents selected results of an ongoing investigation into the feedbacks that contribute to amplified Arctic warming. The consequences of warming for Arctic biodiversity and landscape response to global warmth are currently being interpreted. Arctic North American records of large-scale landscape and paleoenvironmental change during the Pliocene are exquisitely preserved and locked in permafrost, providing an opportunity for paleoenvironmental and faunal reconstruction with unprecedented quality and resolution. During a period of mean global temperatures only ~2.5°C above modern, the Pliocene molecular, isotopic, tree-ring, paleofaunal, and paleofloral records indicate that the high Arctic mean annual temperature was 11°C–19°C above modern values, pointing to a much shallower latitudinal temperature gradient than exists today. It appears that the intense Neogene warming caused thawing and weathering to liberate sediment and create a continuous and thick (>2.5 km in places) clastic wedge from at least Banks Island to Meighen Island to form a coastal plain that provided a highway for camels and other mammals to migrate and evolve in the high Arctic. In this summary we highlight the opportunities that exist for research on these and related topics with the PoLAR-FIT community.RÉSUMÉCe bref résumé présente les résultats choisis d'une enquête en cours sur les déclencheurs qui contribuent à l’amplification du réchauffement de l'Arctique. Les conséquences du réchauffement sur la biodiversité arctique et de la réponse du paysage au réchauffement climatique sont en cours d’être interprété. Des dossiers nord-américains de paysage à grande échelle et le changement paléoenvironnementales durant le Pliocène sont exceptionnellement préservés et scellées dans un état de congélation qui fournissant une occasion pour la reconstruction paléoenvironnementale et faunistique avec une qualité et une résolution sans précédent. Pendent une période de réchauffement global seulement ~2,5°C au-dessus de moderne les dossiers, moléculaire, isotopique, annaux de croissance, paléofaunistique et paléovégétation indiquent que l'Arctique a connu une augmentation de la température annuelle moyenne de 11°C–19°C au-dessus de moderne, en montrant un inferieur gradient de température latitudinal qu'aujourd'hui. Il semble que le réchauffement intense pendent le Néogène a provoqué la décongélation et erosion pour libérer les sédiments et créer une plaine côtière continuel et épaisse (> 2,5 km dans lieux) qui a fourni une route pour les chameaux et autres mammifères pour migrer et évoluer dans l’Haut-Arctique. Dans ce résumé, nous soulignons les opportunités qui existent pour la recherche sur ces sujets et les sujets connexes avec la communauté PoLAR-FIT

Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions

Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations.NIH/NIAIDUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R21AI28536]; NIH/NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM121750]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]