Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.

The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Zasp52 strengthens whole embryo tissue integrity through supracellular actomyosin networks.

During morphogenesis, large-scale changes of tissue primordia are coordinated across an embryo. In Drosophila, several tissue primordia and embryonic regions are bordered or encircled by supracellular actomyosin cables, junctional actomyosin enrichments networked between many neighbouring cells. We show that the single Drosophila Alp/Enigma-family protein Zasp52, which is most prominently found in Z-discs of muscles, is a component of many supracellular actomyosin structures during embryogenesis, including the ventral midline and the boundary of the salivary gland placode. We reveal that Zasp52 contains within its central coiled-coil region a type of actin-binding motif usually found in CapZbeta proteins, and this domain displays actin-binding activity. Using endogenously-tagged lines, we identify that Zasp52 interacts with junctional components, including APC2, Polychaetoid and Sidekick, and actomyosin regulators. Analysis of zasp52 mutant embryos reveals that the severity of the embryonic defects observed scales inversely with the amount of functional protein left. Large tissue deformations occur where actomyosin cables are found during embryogenesis, and in vivo and in silico analyses suggest a model whereby supracellular Zasp52-containing cables aid to insulate morphogenetic changes from one another.

Cryo-EM structure of metazoan TRAPPIII, the multi-subunit complex that activates the GTPase Rab1.

The TRAPP complexes are nucleotide exchange factors that play essential roles in membrane traffic and autophagy. TRAPPII activates Rab11, and TRAPPIII activates Rab1, with the two complexes sharing a core of small subunits that affect nucleotide exchange but being distinguished by specific large subunits that are essential for activity in vivo. Crystal structures of core subunits have revealed the mechanism of Rab activation, but how the core and the large subunits assemble to form the complexes is unknown. We report a cryo-EM structure of the entire Drosophila TRAPPIII complex. The TRAPPIII-specific subunits TRAPPC8 and TRAPPC11 hold the catalytic core like a pair of tongs, with TRAPPC12 and TRAPPC13 positioned at the joint between them. TRAPPC2 and TRAPPC2L link the core to the two large arms, with the interfaces containing residues affected by disease-causing mutations. The TRAPPC8 arm is positioned such that it would contact Rab1 that is bound to the core, indicating how the arm could determine the specificity of the complex. A lower resolution structure of TRAPPII shows a similar architecture and suggests that the TRAPP complexes evolved from a single ur-TRAPP.

Individual- and community-level social determinants of health are associated with cognition in older adults with focal epilepsy.

OBJECTIVE: Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. MATERIALS AND METHODS: We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. RESULTS: After controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother's education, lower father's and mother's occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father's education, and higher ADI values compared to those who were cognitively intact. CONCLUSION: We provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities.

Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats.

Osteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

Colonization-persistence trade-offs in natural bacterial communities.

Fitness equalizing mechanisms, such as trade-offs, are recognized as one of the main factors promoting species coexistence in community ecology. However, they have rarely been explored in microbial communities. Although microbial communities are highly diverse, the coexistence of their multiple taxa is largely attributed to niche differences and high dispersal rates, following the principle 'everything is everywhere, but the environment selects'. We use a dynamical stochastic model based on the theory of island biogeography to study highly diverse bacterial communities over time across three different systems (soils, alpine lakes and shallow saline lakes). Assuming fitness equalization mechanisms, here we newly analytically derive colonization-persistence trade-offs, and report a signal of such trade-offs in natural bacterial communities. Moreover, we show that different subsets of species in the community drive this trade-off. Rare taxa, which are occasional and more likely to follow independent colonization/extinction dynamics, drive this trade-off in the aquatic communities, while the core sub-community did it in the soils. We conclude that equalizing mechanisms may be more important than previously recognized in bacterial communities. Our work also emphasizes the fundamental value of dynamical models for understanding temporal patterns and processes in highly diverse communities.

Understanding stochastic and deterministic assembly processes in microbial communities along temporal, spatial and environmental scales.

Identifying the main drivers of community assembly remains an open fundamental question in ecology. Dispersal processes introduce randomness in community composition while selection for particular environments creates predictable assemblages. However, the interaction between selection and dispersal processes is still poorly understood. Here, we address this question in bacterial and microeukaryotic communities inhabiting a highly dynamic system of ephemeral (hyper)saline lakes. We show that the combination of beta-diversity decomposition methods and a temporal approach based on colonization and extinction dynamics yields new insights into the relative effect of selection and dispersal along environmental gradients. Selective pressure and dispersal-related processes simultaneously shape each local community with variable strength and effect. The dominance of selection vs. dispersal shifted from stochastic to deterministic assembly as salinity increased along the gradient. This transition also had an impact on the temporal dynamics of the lakes as community turnover decreased at high salinities because both colonization and extinction rates slowed down. Only microeukaryotic richness decreased along the gradient due to lower effective colonization at higher salinities, suggesting that the net effect of selection and dispersal is determined by both environmental conditions and the idiosyncrasy of the different microbial ecologies. Our results emphasize the use of temporal approaches in combination with standard statistical methods for a better understanding of the dynamic processes underlying community assembly.

The ergogenic effects of acute carbohydrate feeding on endurance performance: a systematic review, meta-analysis and meta-regression.

A systematic review with meta-analysis was conducted to analyze the effect of carbohydrate (CHO) intake during exercise and some variables that could moderate this effect on endurance performance. We included 136 studies examining the effect of CHO ingestion during endurance exercise in the meta-analysis. The overall effect on performance showed a significant increase after CHO intake compared to the placebo/control groups. A larger effect of CHO consumption is observed in time to exhaustion than in time trials performance test. Moreover, the effectiveness of CHO supplementation was greater the longer the duration of the events. Also, there seems to be a higher effect of CHO intake in lower trained than in higher trained participants. In contrast, the magnitude of performance change of CHO intake is not affected by the dosage, ergometer used, the type of intake of the CHO ingestion and the type of CHO. In addition, a lower rate of perceived exertion and higher power and heart rate are significantly associated with the ingestion of CHO during endurance exercise. These results reinforce that acute CHO feeding is an effective strategy for improving endurance performance, especially, in less trained subjects participating in time to exhaustion tests of longer durations.

A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

The Accuracy and Absolute Reliability of a Knee Surgery Assistance System Based on ArUco-Type Sensors.

Recent advances allow the use of Augmented Reality (AR) for many medical procedures. AR via optical navigators to aid various knee surgery techniques (e.g., femoral and tibial osteotomies, ligament reconstructions or menisci transplants) is becoming increasingly frequent. Accuracy in these procedures is essential, but evaluations of this technology still need to be made. Our study aimed to evaluate the system's accuracy using an in vitro protocol. We hypothesised that the system's accuracy was equal to or less than 1 mm and 1° for distance and angular measurements, respectively. Our research was an in vitro laboratory with a 316 L steel model. Absolute reliability was assessed according to the Hopkins criteria by seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. The system's accuracy in assessing distances had a mean error of 1.203 mm and an uncertainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observers, almost perfect or perfect. The mean error for the distance's determination was statistically larger than 1 mm (1.203 mm) but with a trivial effect size. The mean error assessing angular values was statistically less than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

"You Measure Us and You Depress Us": Healthism and the Subjective Impact of Body Measurements on Secondary School Students.

This study explores adolescents' subjective experiences when facing body measurements at school, performed to evaluate the effects of a school-based intervention to promote physical activity. Three semi-structured interviews (n = 3) and two focus groups (n = 7 and 3) were conducted with adolescents after measuring some variables related to their weight and adiposity. Observational data (n = 88) collected by the two researchers in charge of the measurements were also obtained. Findings derived from our thematic analysis question the suitability of body measurements as social contexts where the core ideas of healthism emerge. Some adolescents lived body measurements as negative social experiences, promoting body dissatisfaction, social comparison, embarrassment, and simplistic associations between health and body shape, which could hinder their adherence to healthy habits. We emphasize the role of qualitative research when evaluating pre/posttests of school-based intervention studies, not just the interventions themselves, to generate knowledge to improve research protocols and prevent unwanted psychological outcomes in participants.

The tangled evolutionary history of a long-debated Mesoamerican taxon: The Velazquez Woodpecker (Melanerpes santacruzi, Aves: Picidae).

The Velazquez Woodpecker Melanerpes santacruzi is a highly polytypic species distributed from east-central Mexico to northern Nicaragua. The ample variation in body size, barring of the plumage, and the coloration of nasal tufts, neck, and belly have fueled debates about the taxonomy and evolutionary history of the species; however, the processes generating these patterns of variation and the underlying population dynamics throughout the species' distribution remain poorly understood. Here, we employed reduced representation genome sequencing (NextRAD) and Ecological Niche Modeling methods to test the distinctiveness of the Velazquez Woodpecker based on this new set of genomic data and analyze the correspondence of the genetic structure and ecological differentiation with phenotypic variation and geographic distribution. From phylogenetic and demographic analyses including the Golden-Fronted (M. aurifrons) and Red-bellied Woodpecker (M. carolinus), we obtained results congruent with previous molecular phylogenies. The clades of M. santacruzi and M. carolinus-M. aurifrons are reciprocally monophyletic, although the sister group relationship of M. aurifrons is ambiguous. Using genetic and ecological analyses, we found that the species is structured into three genetically and ecologically differentiated groups comprising the subspecies (1) M. s. santacruzi, (2) M. s. dubius and (3) M. s. grateloupensis-polygrammus-veraecrucis. These groups diverged recently, with two splits between 250,000 and 150,000 years ago, and show a significant genetic admixture among them, especially in their current contact zones. Ecological and demographic models suggest the existence of intermittent areas of sympatry and connectivity among populations of M. santacruzi since the Last Interglacial period. We also found evidence of bi-directional gene flow between the species M. aurifrons and the nearby populations of M. santacruzi (M. s. grateloupensis), along the Sierra Madre Oriental in northeastern Mexico. Gene flow seems to be uneven, with prevalence of movement in the direction from M. aurifrons to M. s. grateloupensis.

Autonomic stress response of physiotherapy student in the different scenarios of an objective structured clinical examination.

The aim of the present research was to analyse modifications in the autonomic stress response of Physiotherapy students undergoing a 12-scenario Objective Structured Clinical Evaluation (OSCE). A total of 86 last year students of the Physiotherapy bachelor's degree (27.29 years (SD = 6.66); 36 females and 50 males) randomly assigned were monitored during the complete OSCE to measure heart rate variability (HRV) in temporal, frequency, and non-linear domains. The HRV analysed showed a large anticipatory stress response of students maintained during the entire evaluation. The stress response varied regarding OSCE station complexity and demands and the highest sympathetic response was not found in higher emotional scenarios.The autonomic modulation monitoring allows teachers to design OSCE scenarios more adapted to the students, limiting the effect of the stress response to allow a better performance.

Ready for Combat, Psychophysiological Modifications in a Close-Quarter Combat Intervention After an Experimental Operative High-Intensity Interval Training.

ABSTRACT: Tornero-Aguilera, JF, Fernandez-Elias, VE, and Clemente-Suárez, VJ. Ready for combat, psychophysiological modifications in a close-quarter combat intervention after an experimental operative HIIT. J Strength Cond Res 36(3): 732-737, 2022-This study aimed to analyze the effect of an experimental operative high-intensity interval training (HIIT) program on the psychophysiological response of soldiers in a close-quarter combat (CQC) intervention. The psychophysiological response of 22 professional soldiers in a CQC before and after an experimental 2-week operative HIIT was analyzed. Training intervention produced a significant increase in blood lactate, isometric hand-grip strength, perceived stress, rates of perceived exertion, anxiety response, heart rate, and autonomic sympathetic modulation and a significant decrease in cortical arousal requirements. An experimental operative high-intensity interval training produced an increase on the psychophysiological operativity for CQC scenarios, increasing the sympathetic and physiological response and decreasing the cortical arousal requirement of soldiers.

Fungal Planet description sheets: 1383-1435.

Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum lauri-silvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes. Citation: Crous PW, Boers J, Holdom D, et al. 2022. Fungal Planet description sheets: 1383-1435. Persoonia 48: 261-371. https://doi.org/10.3767/persoonia.2022.48.08.

Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Fabrication of strong magnetic micron-sized supraparticles with anisotropic magnetic properties for magnetorheology.

We propose three different techniques to synthesize anisotropic magnetic supraparticles for their incorporation in the formulation of magnetorheological fluids with novel potential applications. The techniques include microtransfer molding, electrodeposition and microfluidic flow-focusing devices. Although the yield of these methods is not large, with their use, it is possible to synthesize supraparticles with anisotropy in both their magnetic content and shape. The magnetorheological characteristics (yield stress) of the resulting field-induced structures were computed using finite element method simulations and demonstrated to be strongly dependent on the microstructural anisotropy of the supraparticles. In anisotropic particles, the simulated yield stress is always larger than that of the isotropic ones consisting of magnetically homogeneous spherical particles.

Matching methods to quantify wildfire effects on forest carbon mass in the U.S. Pacific Northwest.

Forest wildfires consume and redistribute carbon within forest carbon pools. Because the incidence of wildfires is unpredictable, quantifying wildfire effects is challenging due to the lack of prefire data or controls from experiments over a large landscape. We explored a quasi-experimental method, propensity score matching, to estimate wildfire effects on aboveground forest woody carbon mass in Washington and Oregon, United States. Observational data, including national forest inventory plot measurements and satellite imagery metrics, were utilized to obtain a control set of unburned plots that are comparable to burned plots in terms of environmental conditions as well as spatial locations. Three matching methods were implemented: propensity score matching (PSM), spatial matching (SM), and distance-adjusted propensity score matching (DAPSM). We investigated if propensity score matching with and without spatial adjustment led to different outcomes in terms of (1) balance in covariate distributions between burned and control plots, (2) mean carbon mass obtained from the selected control plots compared to burned and all unburned plots, and (3) estimates of wildfire effects by burn severity. We found that PSM and SM, which use only the environmental covariate set or the spatial distance for estimating propensity scores, respectively, did not appear to produce a comparable set of control plots in terms of the estimated propensity scores and the outcomes of mean carbon mass. DAPSM was the preferred method both in balancing the observed covariates and in dealing with unobservable confounding variables through spatial adjustment. The average wildfire effects estimated by DAPSM showed clear evidence of redistribution of carbon among aboveground woody pools, from live to dead trees, but the consumption of total woody carbon by wildfire was not substantial. Only moderate burn severity led to significant reduction of total woody carbon mass across Washington and Oregon forests (64% of control plots remained on average). This study provides an applied example of a quasi-experimental approach to quantify the effects of a natural disturbance for which experimental settings are unavailable. The study results suggest that incorporating spatial information in addition to environmental covariates would yield a comparable set of control plots for wildfire effects quantification.

Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles.

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated.