The 2020 to 2021 California megafires and their impacts on wildlife habitat.

Fire activity during 2020 to 2021 in California, USA, was unprecedented in the modern record. More than 19,000 km2 of forest vegetation burned (10× more than the historical average), potentially affecting the habitat of 508 vertebrate species. Of the >9,000 km2 that burned at high severity, 89% occurred in large patches that exceeded historical estimates of maximum high-severity patch size. In this 2-y period, 100 vertebrate species experienced fire across >10% of their geographic range, 16 of which were species of conservation concern. These 100 species experienced high-severity fire across 5 to 14% of their ranges, underscoring potentially important changes to habitat structure. Species in this region are not adapted to high-severity megafires. Management actions, such as prescribed fires and mechanical thinning, can curb severe fire behavior and reduce the potential negative impacts of uncharacteristic fires on wildlife.

Epigenetic regulation of nuclear processes in fungal plant pathogens.

Through the association of protein complexes to DNA, the eukaryotic nuclear genome is broadly organized into open euchromatin that is accessible for enzymes acting on DNA and condensed heterochromatin that is inaccessible. Chemical and physical alterations to chromatin may impact its organization and functionality and are therefore important regulators of nuclear processes. Studies in various fungal plant pathogens have uncovered an association between chromatin organization and expression of in planta-induced genes that are important for pathogenicity. This review discusses chromatin-based regulation mechanisms as determined in the fungal plant pathogen Verticillium dahliae and relates the importance of epigenetic transcriptional regulation and other nuclear processes more broadly in fungal plant pathogens.

A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.

Rapid growth of the US wildland-urban interface raises wildfire risk.

The wildland-urban interface (WUI) is the area where houses and wildland vegetation meet or intermingle, and where wildfire problems are most pronounced. Here we report that the WUI in the United States grew rapidly from 1990 to 2010 in terms of both number of new houses (from 30.8 to 43.4 million; 41% growth) and land area (from 581,000 to 770,000 km2; 33% growth), making it the fastest-growing land use type in the conterminous United States. The vast majority of new WUI areas were the result of new housing (97%), not related to an increase in wildland vegetation. Within the perimeter of recent wildfires (1990-2015), there were 286,000 houses in 2010, compared with 177,000 in 1990. Furthermore, WUI growth often results in more wildfire ignitions, putting more lives and houses at risk. Wildfire problems will not abate if recent housing growth trends continue.

The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure.

GlaxoSmithKline and Astex Pharmaceuticals recently disclosed the discovery of the potent H-PGDS inhibitor GSK2894631A 1a (IC50 = 9.9 nM) as part of a fragment-based drug discovery collaboration with Astex Pharmaceuticals. This molecule exhibited good murine pharmacokinetics, allowing it to be utilized to explore H-PGDS pharmacology in vivo. Yet, with prolonged dosing at higher concentrations, 1a induced CNS toxicity. Looking to attenuate brain penetration in this series, aza-quinolines, were prepared with the intent of increasing polar surface area. Nitrogen substitutions at the 6- and 8-positions of the quinoline were discovered to be tolerated by the enzyme. Subsequent structure activity studies in these aza-quinoline scaffolds led to the identification of 1,8-naphthyridine 1y (IC50 = 9.4 nM) as a potent peripherally restricted H-PGDS inhibitor. Compound 1y is efficacious in four in vivo inflammatory models and exhibits no CNS toxicity.

The discovery of quinoline-3-carboxamides as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors.

With the goal of discovering more selective anti-inflammatory drugs, than COX inhibitors, to attenuate prostaglandin signaling, a fragment-based screen of hematopoietic prostaglandin D synthase was performed. The 76 crystallographic hits were sorted into similar groups, with the 3-cyano-quinoline 1a (FP IC50 = 220,000 nM, LE = 0.43) being a potent member of the 6,6-fused heterocyclic cluster. Employing SAR insights gained from structural comparisons of other H-PGDS fragment binding mode clusters, the initial hit 1a was converted into the 70-fold more potent quinoline 1d (IC50 = 3,100 nM, LE = 0.49). A systematic substitution of the amine moiety of 1d, utilizing structural information and array chemistry, with modifications to improve inhibitor stability, resulted in the identification of the 300-fold more active H-PGDS inhibitor tool compound 1bv (IC50 = 9.9 nM, LE = 0.42). This selective inhibitor exhibited good murine pharmacokinetics, dose-dependently attenuated PGD2 production in a mast cell degranulation assay and should be suitable to further explore H-PGDS biology.

Longitudinal Deformation of the Right Ventricle in Hypoplastic Left Heart Syndrome: A Comparative Study of 2D-Feature Tracking Magnetic Resonance Imaging and 2D-Speckle Tracking Echocardiography.

In hypoplastic left heart syndrome (HLHS), long-term outcome is closely related to right ventricular function. Echocardiography and magnetic resonance imaging (MRI) are routinely used for functional assessment. MRI 2D-tissue feature tracking (2D-FT) allows quantification of myocardial deformation but has not yet been applied to HLHS patients. We sought to investigate the feasibility of this technique and to compare the results to 2D-speckle tracking echocardiography (2D-STE). In routine MRI 2D anatomical four chamber view, cine images were recorded in 55 HLHS patients (median age 4.9 years [1.6, 17.0]). Regional and global peak systolic longitudinal strain (LS) and strain rate (LSR) were determined using 2D-FT software. Echocardiographic four chamber view was analyzed with 2D-STE. Visualization of all myocardial segments with MRI was excellent, regional, and global LS and LSR could be assessed in all data sets. In 2D-STE, 28% of apical segments could not be analyzed due to poor image quality. Agreement of 2D-FT MRI and 2D-STE was acceptable for global LS, but poor for global LSR. In MRI, regional LS was lower in the septal segments, while LSR was not different between the segments. GLS and GLSR correlated with ejection fraction (GLS: r = - 0.45 and r < 0.001, GLSR: r = - 0.34 and p = 0.01). With new post-processing options, the assessment of regional and global LS and LSR is feasible in routine MRI of HLHS patients. For LS, results were comparable with 2D-STE. The agreement was poor for LSR, which might relate to differences in temporal resolution between the two imaging modalities.

Tinea nigra: Report of three pediatrics cases. / Tiña negra: reporte de tres casos pediátricos.

INTRODUCTION: Tinea nigra is a superficial mycosis caused by Hortaea werneckii. Its clinical characte ristic is the appearance of a blackish brown macula of rapid growth, caused by the pigment produced by the fungus itself. The presence of a dark, fast growing, acral pigmentary lesion causes concern among patients and their treating physician about the possibility of a malignant pigmentary lesion. OBJECTIVE: To present a series of three clinical cases in pediatric patients with this pathology and to show the tools that help to make a differential diagnosis. CLINICAL CASES: Three patients between three and five years of age, which present a macular pigmented lesion on palms or soles, whose parents reported a rapid growth over a short period of time. Two of the patients reported previous trips to the Caribbean. Clinical and dermatoscopy suspicion of tinea nigra lead to a direct mycological exa mination, which confirmed the diagnosis. In all three cases, treatment with topical antifungals led to complete healing of the lesions. CONCLUSIONS: Although tinea nigra is rare in a dry climate, increasing travel of patients to tropical countries will increase the number of cases. Dermatoscopy and direct mycological examination are the tools that allow performing a correct diagnosis and avoiding unne cessary biopsies and/or surgeries.

[Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents]. / Onicomadesis secundaria a enfermedad pie-mano-boca: una manifestación frecuente y motivo de preocupación de los padres.

INTRODUCTION: Nail alterations in children are an important cause of parent anxiety and derive in multiple and unnecessary consultations. The onychomadesis corresponds to the complete and pain less detachment of the nail plate from the proximal fold. This self-resolving nail finding has been described as a late complication of hand-foot-mouth disease, a frequent viral exanthema in the pedia tric age. OBJECTIVE: To describe a classic pediatric case of hand-foot-mouth disease with subsequent onychomadesis. CLINICAL CASE: A 3-years-old male patient with an acute presentation of acute erythe matous perioral papulovesicles, which extend to upper extremities and hands, buttocks, thighs and feet, asymptomatic, and without compromising general condition. Skin lesions resolve completely, but after one month, he develops detachment of the nails, with subsequent complete recovery. Con clusions: The recognition of this association will allow primary care physicians to guide the parents about a benign and self-resolving process that may occur as part of the evolution of hand-foot-mouth disease, thus avoiding unnecessary anxiety, referral and treatments.

[German version of the de Morton mobility index. First clinical results from the process of the cross-cultural adaptation]. / Deutsche Version des De Morton Mobility Index. Erste klinische Ergebnisse aus dem Prozess der interkulturellen Adaptation.

BACKGROUND: The English version of the de Morton Mobility Index (DEMMI) enables allied health professions in an inpatient setting to assess the mobility of geriatric patients in a reliable, valid, easy and fast way, without showing any floor or ceiling effects. The aim of this study was the DEMMI's cross-cultural adaption into German language with further analysis of some of its psychometric properties based on this process. MATERIAL AND METHODS: Translation was done in a multistage procedure following international recommendations. Within clinical pilot testing the DEMMI was routinely applied over a period of 3 weeks in a geriatric hospital. User experiences were evaluated in a qualitative way and DEMMI test results were analyzed with the focus on practicability and responsiveness. RESULTS: A German DEMMI version has been translated and performed with 133 patients. The test takes approximately 10 min to administer, is save and easy to use and does not show any floor or ceiling effects. The DEMMI is valid for the whole mobility spectrum, that is why mobility changes can be realized sufficiently in contrast to the Timed Up And Go Test. CONCLUSION: The DEMMI is already applicable in the German-speaking world. However, further research on its validity and reproducibility are desirable.

Morphology, mineralogy, and solid-liquid phase separation characteristics of Cu and Zn precipitates produced with biogenic sulfide.

The morphology, mineralogy, and solid-liquid phase separation of the Cu and Zn precipitates formed with sulfide produced in a sulfate-reducing bioreactor were studied at pH 3, 5, and 7. The precipitates formed at pH 7 display faster settling rates, better dewaterability, and higher concentrations of settleable solids as compared to the precipitates formed at pH 3 and 5. These differences were linked to the agglomeration of the sulfidic precipitates and coprecipitation of the phosphate added to the bioreactor influent. The Cu and Zn quenched the intensity of the dissolved organic matter peaks identified by fluorescence-excitation emission matrix spectroscopy, suggesting a binding mechanism that decreases supersaturation, especially at pH 5. X-ray absorption fine structure spectroscopy analyses confirmed the precipitation of Zn-S as sphalerite and Cu-S as covellite in all samples, but also revealed the presence of Zn sorbed on hydroxyapatite. These analyses further showed that CuS structures remained amorphous regardless of the pH, whereas the ZnS structure was more organized at pH 5 as compared to the ZnS formed at pH 3 and 7, in agreement with the cubic sphalerite-type structures observed through scanning electron microscopy at pH 5.

[Innovative noninvasive gait-synchronized vibrotactile feedback system : "I can feel myself walking again"]. / Innovatives nichtinvasives gangsynchrones vibrotaktiles Feedbacksystem : "Ich fühle, wie ich gehe".

Despite intensive research and development of systems for restoration of sensory information, these have so far only been the subject of study protocols. A new noninvasive feedback system translates pressure loads on the forefoot and hindfoot into gait-synchronized vibrotactile stimulation of a defined skin area. To increase the authenticity, this treatment can be supplemented by a surgical procedure. Targeted sensory reinnervation (TSR) describes a microsurgical procedure in which a defined skin area on the amputated stump of the residual limb is first denervated and then reinnervated by a specific, transposed sensory nerve harvested from the amputated part of the limb. This creates a sensory interface at the residual stump. This article presents the clinical and orthopedic technical treatment pathway with this innovative vibrotactile feedback system and explains in detail the surgical procedure of TSR after amputation of the lower limb.

Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen.

The spatial organization of eukaryotic genomes is linked to their biological functions, although it is not clear how this impacts the overall evolution of a genome. Here, we uncover the three-dimensional (3D) genome organization of the phytopathogen Verticillium dahliae, known to possess distinct genomic regions, designated adaptive genomic regions (AGRs), enriched in transposable elements and genes that mediate host infection. Short-range DNA interactions form clear topologically associating domains (TADs) with gene-rich boundaries that show reduced levels of gene expression and reduced genomic variation. Intriguingly, TADs are less clearly insulated in AGRs than in the core genome. At a global scale, the genome contains bipartite long-range interactions, particularly enriched for AGRs and more generally containing segmental duplications. Notably, the patterns observed for V. dahliae are also present in other Verticillium species. Thus, our analysis links 3D genome organization to evolutionary features conserved throughout the Verticillium genus.

Rising wildfire risk to houses in the United States, especially in grasslands and shrublands.

Wildfire risks to homes are increasing, especially in the wildland-urban interface (WUI), where wildland vegetation and houses are in close proximity. Notably, we found that more houses are exposed to and destroyed by grassland and shrubland fires than by forest fires in the United States. Destruction was more likely in forest fires, but they burned less WUI. The number of houses within wildfire perimeters has doubled since the 1990s because of both housing growth (47% of additionally exposed houses) and more burned area (53%). Most exposed houses were in the WUI, which grew substantially during the 2010s (2.6 million new WUI houses), albeit not as rapidly as before. Any WUI growth increases wildfire risk to houses though, and more fires increase the risk to existing WUI houses.

Local Rather than Global H3K27me3 Dynamics Are Associated with Differential Gene Expression in Verticillium dahliae.

Differential growth conditions typically trigger global transcriptional responses in filamentous fungi. Such fungal responses to environmental cues involve epigenetic regulation, including chemical histone modifications. It has been proposed that conditionally expressed genes, such as those that encode secondary metabolites but also effectors in pathogenic species, are often associated with a specific histone modification, lysine27 methylation of H3 (H3K27me3). However, thus far, no analyses on the global H3K27me3 profiles have been reported under differential growth conditions in order to assess if H3K27me3 dynamics govern differential transcription. Using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing data from the plant-pathogenic fungus Verticillium dahliae grown in three in vitro cultivation media, we now show that a substantial number of the identified H3K27me3 domains globally display stable profiles among these growth conditions. However, we observe local quantitative differences in H3K27me3 ChIP-seq signals that are associated with a subset of differentially transcribed genes between media. Comparing the in vitro results to expression during plant infection suggests that in planta-induced genes may require chromatin remodeling to achieve expression. Overall, our results demonstrate that some loci display H3K27me3 dynamics associated with concomitant transcriptional variation, but many differentially expressed genes are associated with stable H3K27me3 domains. Thus, we conclude that while H3K27me3 is required for transcriptional repression, it does not appear that transcriptional activation requires the global erasure of H3K27me3. We propose that the H3K27me3 domains that do not undergo dynamic methylation may contribute to transcription through other mechanisms or may serve additional genomic regulatory functions. IMPORTANCE In many organisms, including filamentous fungi, epigenetic mechanisms that involve chemical and physical modifications of DNA without changing the genetic sequence have been implicated in transcriptional responses upon developmental or environmental cues. In fungi, facultative heterochromatin that can decondense to allow transcription in response to developmental changes or environmental stimuli is characterized by the trimethylation of lysine 27 on histone H3 (H3K27me3), and H3K27me3 has been implicated in transcriptional regulation, although the precise mechanisms and functions remain enigmatic. Based on ChIP and RNA sequencing data, we show for the soilborne broad-host-range vascular wilt plant-pathogenic fungus Verticillium dahliae that although some loci display H3K27me3 dynamics that can contribute to transcriptional variation, other loci do not show such a dependence. Thus, although we recognize that H3K27me3 is required for transcriptional repression, we also conclude that this mark is not a conditionally responsive global regulator of differential transcription upon responses to environmental cues.

Three putative DNA methyltransferases of Verticillium dahliae differentially contribute to DNA methylation that is dispensable for growth, development and virulence.

BACKGROUND: DNA methylation is an important epigenetic control mechanism that in many fungi is restricted to genomic regions containing transposable elements (TEs). Two DNA methyltransferases, Dim2 and Dnmt5, are known to perform methylation at cytosines in fungi. While most ascomycete fungi encode both Dim2 and Dnmt5, only few functional studies have been performed in species containing both. METHODS: In this study, we report functional analysis of both Dim2 and Dnmt5 in the plant pathogenic fungus Verticillium dahliae. RESULTS: Our results show that Dim2, but not Dnmt5 or the putative sexual-cycle-related DNA methyltransferase Rid, is responsible for the majority of DNA methylation under the tested conditions. Single or double DNA methyltransferase mutants did not show altered development, virulence, or transcription of genes or TEs. In contrast, Hp1 and Dim5 mutants that are impacted in chromatin-associated processes upstream of DNA methylation are severely affected in development and virulence and display transcriptional reprogramming in specific hypervariable genomic regions (so-called adaptive genomic regions) that contain genes associated with host colonization. As these adaptive genomic regions are largely devoid of DNA methylation and of Hp1- and Dim5-associated heterochromatin, the differential transcription is likely caused by pleiotropic effects rather than by differential DNA methylation. CONCLUSION: Overall, our study suggests that Dim2 is the main DNA methyltransferase in V. dahliae and, in conjunction with work on other fungi, is likely the main active DNMT in ascomycetes, irrespective of Dnmt5 presence. We speculate that Dnmt5 and Rid act under specific, presently enigmatic, conditions or, alternatively, act in DNA-associated processes other than DNA methylation.

The Interspecific Fungal Hybrid Verticillium longisporum Displays Subgenome-Specific Gene Expression.

Hybridization is an important evolutionary mechanism that can enable organisms to adapt to environmental challenges. It has previously been shown that the fungal allodiploid species Verticillium longisporum, the causal agent of verticillium stem striping in rapeseed, originated from at least three independent hybridization events between two haploid Verticillium species. To reveal the impact of genome duplication as a consequence of hybridization, we studied the genome and transcriptome dynamics upon two independent V. longisporum hybridization events, represented by the hybrid lineages "A1/D1" and "A1/D3." We show that V. longisporum genomes are characterized by extensive chromosomal rearrangements, including between parental chromosomal sets. V. longisporum hybrids display signs of evolutionary dynamics that are typically associated with the aftermath of allodiploidization, such as haploidization and more relaxed gene evolution. The expression patterns of the two subgenomes within the two hybrid lineages are more similar than those of the shared A1 parent between the two lineages, showing that the expression patterns of the parental genomes homogenized within a lineage. However, as genes that display differential parental expression in planta do not typically display the same pattern in vitro, we conclude that subgenome-specific responses occur in both lineages. Overall, our study uncovers genomic and transcriptomic plasticity during the evolution of the filamentous fungal hybrid V. longisporum and illustrates its adaptive potential. IMPORTANCEVerticillium is a genus of plant-associated fungi that includes a few plant pathogens that collectively affect a wide range of hosts. On several occasions, haploid Verticillium species hybridized into the stable allodiploid species Verticillium longisporum, which is, in contrast to haploid Verticillium species, a Brassicaceae specialist. Here, we studied the evolutionary genome and transcriptome dynamics of V. longisporum and the impact of the hybridization. V. longisporum genomes display a mosaic structure due to genomic rearrangements between the parental chromosome sets. Similar to other allopolyploid hybrids, V. longisporum displays an ongoing loss of heterozygosity and more relaxed gene evolution. Also, differential parental gene expression is observed, with enrichment for genes that encode secreted proteins. Intriguingly, the majority of these genes display subgenome-specific responses under differential growth conditions. In conclusion, hybridization has incited the genomic and transcriptomic plasticity that enables adaptation to environmental changes in a parental allele-specific fashion.

Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats.

The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.

Who uses sunbeds? A systematic literature review of risk groups in developed countries.

Skin cancer is caused by ultraviolet radiation (UVR). Indoor tanning is a totally avoidable risk behaviour. This review addresses the specific characteristics of sunbed users and the differences in motivation and risk perception compared with non-users. This review is based solely on empirical original articles. Based on literature searches with widely used reference databases ('PubMed', 'OVID', 'Social Citation Index', 'ERIC--Educational Resources Information Center', 'Web of Science' and the 'International Bibliography of the Social Sciences'), we included studies from developed nations with a publication date between 1 January 2000 and 12 August 2008. All studies were selected, classified and coded simultaneously by both authors on a blinded basis. All searches were performed on 13 and 14 August 2008. In accordance with the QUOROM and the MOOSE Statements, we identified 16 original studies. The typical sunbed user is female, between 17 and 30 years old, and tends to live a comparatively unhealthy lifestyle: Users smoke cigarettes and drink alcohol more frequently and eat less healthy food than non-users. Users are characterized by a lack of knowledge about health risks of UVR, and prompted by the frequent use of sunbeds by friends or family members and the experience of positive emotions and relaxation by indoor tanning. This review is the first systematic review on risk groups among sunbed users that has been published in a scientific journal. There is still a lack of information among users, particularly among young people regarding the safety of solariums.

[Cardiovascular magnetic resonance imaging in childhood - clinical indications and case studies]. / Kardiovaskuläre Magnetresonanztomografie im Kindesalter - klinische Indikationen und Beispiele.

In today's clinical practice cardiovascular magnetic resonance (CMR) imaging is increasingly used for assessment of congenital and acquired heart disease in children. CMR complements echocardiography and provides a noninvasive alternative to diagnostic cardiac catheterization. In contrast to echocardiography, CMR is not limited by acoustic windows, and unlike cardiac catheterization, CMR lacks ionizing radiation. Contiguous three and four dimensional data sets allow to display cardiac and thoracic vessel anatomy in any desired imaging plane. These characteristics provide unique images for the complete depiction of the pathological anatomy in particular in congenital heart disease. Furthermore CMR is also used for assessment of cardiac function, blood-flow measurements, tissue characterization, and, more recently, for evaluation of myocardial perfusion and viability. The following article reviews CMR indications in pediatric cardiology by means of clinical examples.