Genetic architecture of plasma Alzheimer disease biomarkers.

Genome-wide association studies (GWAS) of cerebrospinal fluid (CSF) Alzheimer's Disease (AD) biomarker levels have identified novel genes implicated in disease risk, onset and progression. However, lumbar punctures have limited availability and may be perceived as invasive. Blood collection is readily available and well accepted, but it is not clear whether plasma biomarkers will be informative for genetic studies. Here we perform genetic analyses on concentrations of plasma amyloid-ß peptides Aß40 (n = 1,467) and Aß42 (n = 1,484), Aß42/40 (n = 1467) total tau (n = 504), tau phosphorylated (p-tau181; n = 1079) and neurofilament light (NfL; n = 2,058). GWAS and gene-based analysis was used to identify single variant and genes associated with plasma levels. Finally, polygenic risk score and summary statistics were used to investigate overlapping genetic architecture between plasma biomarkers, CSF biomarkers and AD risk. We found a total of six genome-wide significant signals. APOE was associated with plasma Aß42, Aß42/40, tau, p-tau181 and NfL. We proposed 10 candidate functional genes on the basis of 12 single nucleotide polymorphism-biomarker pairs and brain differential gene expression analysis. We found a significant genetic overlap between CSF and plasma biomarkers. We also demonstrate that it is possible to improve the specificity and sensitivity of these biomarkers, when genetic variants regulating protein levels are included in the model. This current study using plasma biomarker levels as quantitative traits can be critical to identification of novel genes that impact AD and more accurate interpretation of plasma biomarker levels.

Morphological and molecular characterization of brown-banded broodsacs and metacercariae of Leucochloridium (Trematoda: Leucochloridiidae) parasitizing the semi-slug Omalonyx unguis (Succineidae) in Argentina.

Trematodes of the genus Leucochloridium exhibit an unusual transmission strategy among mollusks (intermediate host). The fully developed sporocyst, housing encysted metacercariae, displays vivid coloration and rhythmic activity in the snail's tentacle, mimicking insect larvae. These strategies attract insectivorous birds, their final hosts, thereby increasing the chances of completing their life cycle. In South America, the reports of adults and larval stages of Leucochloridium are scarce. Brown-banded broodsac of Leucochloridium sp. were obtained from Omalonyx unguis collected in a shallow lake from Corrientes Province, Argentina. Here, we morphologically characterized the larval stages (broodsac and metacercaria), identified the parasite through DNA sequences from nuclear 28S-rRNA (28S) and the mitochondrial cytochrome c oxidase I (COI) genes, and explored its evolutionary affinities with the Leucochloridium species available in GenBank. The present broodsac displays brown bands, with a yellowish background in the first two-thirds and yellowish-white in the last third. Based on morphological comparisons, the broodsac and metacercaria described in this study could not be conclusively categorized under any known South American species of Leucochloridium. In relation to the phylogenetic reconstructions, Leucochloridium sp. consistently clustered with L. perturbatum, and species delimitation analyses resulted in recognized Leucochloridium sp. from Argentina as a distinct species. The DNA sequences obtained in this study constitute the first genetic data generated for sporocyst broodsacs in South America. Future studies, incorporating morphology, genetic, and biological data, will be essential for both species identification and the elucidation of leucochloridiid diversity in the region.

Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome.

INTRODUCTION: This study aimed to investigate the influence of the overall Alzheimer's disease (AD) genetic architecture on Down syndrome (DS) status, cognitive measures, and cerebrospinal fluid (CSF) biomarkers. METHODS: AD polygenic risk scores (PRS) were tested for association with DS-related traits. RESULTS: The AD risk PRS was associated with disease status in several cohorts of sporadic late- and early-onset and familial late-onset AD, but not in familial early-onset AD or DS. On the other hand, lower DS Mental Status Examination memory scores were associated with higher PRS, independent of intellectual disability and APOE (PRS including APOE, PRSAPOE , p = 2.84 × 10-4 ; PRS excluding APOE, PRSnonAPOE , p = 1.60 × 10-2 ). PRSAPOE exhibited significant associations with Aß42, tTau, pTau, and Aß42/40 ratio in DS. DISCUSSION: These data indicate that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits. HIGHLIGHTS: Examination of the polygenic risk of AD in DS presented here is the first of its kind. AD PRS influences memory aspects in DS individuals, independently of APOE genotype. These results point to an overlap between the genes and pathways that leads to AD and those that influence dementia and memory decline in the DS population. APOE ε4 is linked to DS cognitive decline, expanding cognitive insights in adults.

Development of an aqueous ultrasound-assisted extraction process of bioactive compounds from beet leaves: a proposal for reducing losses and increasing biomass utilization.

BACKGROUND: Red beet plants are cultivated worldwide for the consumption of their roots, generating large amounts of unexploited by-products. In particular, beet leaves (BLs) represent about 50% of the whole plant and are usually discarded as waste. This constitutes not only an economic issue, since multiple resources invested in the production will be wasted, but also an environmental problem because of the pollution associated with their disposal. However, BLs comprise an important source of functional compounds (polyphenols and betalains) that could be recovered from the raw material, representing a sustainable solution for the underutilization of this by-product. This study proposes the recovery of polyphenols and betalains using an aqueous ultrasound-assisted extraction (UAE) process at different powers (35, 50, and 100 W) that was characterized and optimized. RESULTS: UAE significantly enhanced the recovery of bioactive compounds and shortened the time required for extraction in comparison with traditional macerations (35 < 50 < 100 W). During UAE, the temperature of the systems increased as a function of the power applied, favouring the recovery of these phytochemicals. Additionally, a Box-Behnken design and response surface methodology were employed to optimize UAE conditions (90 W ultrasound power, 1:20 solid:liquid ratio, 16 min extraction time), under which the yields were 14.9 mg g-1 (polyphenols), 949.1 µg g-1 (betaxanthins), and 562.2 µg g-1 (betacyanins), consistent with the values predicted by the models. CONCLUSION: This study enabled the development of a green-solvent UAE process that constitutes an effective post-harvest by-products strategy to minimize losses and increase biomass utilization through the recovery of bioactive compounds from BLs, promoting sustainability in the agri-food chain. © 2020 Society of Chemical Industry.

Landscape factors modulating patterns of salmonid distribution during summer in north Patagonian rivers.

Understanding how ecosystem processes influencing fish distribution operate across spatial scales is important to understand biological invasions. Salmonids, originally from the Northern Hemisphere, have been repeatedly introduced throughout the world, making them an ideal group to test hypotheses about factors driving invasions. We assessed the influence of environmental variables at the watershed scale on the abundance and structure of salmonid assemblages in the breeding streams of the Upper Limay river basin, Rio Negro, Argentina. We combined field captures with digital map data and geographic information systems to examine landscape-level patterns of salmonid abundance in 35 representative sub-basins of the environmental gradient. We employed a hierarchical cluster analysis and classification and regression tree models to relate the abundance of salmonids and types of species assemblages with environmental characteristics at watershed level. We found stream localization, precipitation regime, altitude and air temperature to be important predictors of the abundance and assemblage structure of salmonids. Total catches showed an increasing gradient of catch-per-unit-effort from west to east and from north to south, with Oncorhynchus mykiss being the most abundant species. O. mykiss relative abundance was westward skewed, where smaller catchments with steeper and shaded valleys are drained by less productive streams with more irregular hydrological regimes, like those found in this species' North American native range. In contrast, the abundance of Salmo trutta abundance was eastward skewed, where larger, sunnier and more gently sloped catchments result in more productive streams with stable hydrological regimes, like those found in that species' European native range. Thus, differential salmonid abundance could result from the interplay between the evolutionary fingerprint left by each species' native environment (especially flow and temperature regimes) and the availability of those conditions in new environments to which they have been translocated. By furthering our understanding of how landscape conditioned invasion success, these findings can help guide the management of economically important introduced fish.

Secukinumab versus ustekinumab for skin clearance in patients with moderate to severe psoriasis after a year of treatment: Real-world practice.

A descriptive retrospective, study comparing the first 29 patients who received ustekinumab at our unit following its approval in September 2009 with 30 patients who received secukinumab after its marketing in Spain in November 2015 was conducted. The secukinumab treatment group showed higher whitening rates and a higher percentage of patients reached a psoriasis area and severity index (PASI) 75 response (89.65 vs. 73.33%, p = .108) than those in the ustekinumab treatment group at Week 52. The number of patients achieving a PASI 90 response was particularly remarkable and statistically significant (82.75 vs. 43.33%, p = .002). Better PASI 75 response rates were also observed in the secukinumab group than in the ustekinumab group after 52 weeks in biologic-naïve patients (89 vs. 72%, p = .586) and among those previously treated with one line (92 vs. 100%, p = 1.00) or with two or more previous biologic lines (88 vs. 62%, p = .336). These differences were greater in the number of patients reaching a PASI 90 response in the secukinumab group than in the ustekinumab group in biologic-naïve patients (78 vs. 63%, p = .642) and in those previously treated with one (92 vs. 50%, p = .083) or with two or more treatment lines (75 vs. 31%, p = .080). These regular-practice results overlap or surpass those obtained in the CLEAR clinical trial.

Metacercariae of Strigeidae Parasitizing Amphibians of the Chaco Region in Argentina.

The goal of the present study was to analyze the metacercariae found in adult amphibians collected in the Argentinean Chaco region. A total of 194 frogs, Leptodactylus chaquensis, Leptodactylus latinasus, and Lepidobatrachus laevis was examined for digeneans. Three different larval trematodes of the genus Strigea (Digenea, Strigeidae) were found infecting the liver, mesentery, body cavity, and muscle of frogs. These metacercariae are described and illustrated for the first time and provide new information on the composition of metacercariae in amphibians, thus contributing to the knowledge of larval trematodes biodiversity in the Neotropical region. We also present new information on the morphology and morphometry of strigeid metacercariae.

Larval digenean communities in Biomphalaria species in two contrasting wetlands from South America.

A key factor in the colonization probabilities of parasites is the host's characteristic habitat. Considering that rice fields are simple habitats compared with natural wetlands, we comparatively analyzed the composition of the cercariae communities in Biomphalaria snails in an agricultural and a nonagricultural habitat of Corrientes Province, Argentina. We collected 2998 Biomphalaria snails from November 2011 to May 2012: B. tenagophila, B. occidentalis, B. peregrina, and B. orbignyi in the nonagricultural habitat and B. straminea in the agricultural habitat. Nine cercaria species were found in the nonagricultural habitat and 12 in the agricultural habitat, with overall parasite prevalence of 9.27 and 7.69%, respectively. The overall prevalence and mean species richness of cercariae showed no significant differences between habitats. The cercariae communities of the 2 habitats showed low similarity (38%), sharing 4 species. The mean species diversity of cercariae was higher in the nonagricultural habitat. Our results suggest that rice fields provide conditions for the hosts and cercariae that are somewhat similar to those of nonagricultural wetlands, although the contrasting characteristics of habitats can influence the presence of different intermediate and definitive hosts and consequently impact parasite diversity.

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

Prevalence of Functional Alterations and the Effects of Thyroid Autoimmunity on the Levels of TSH in an Urban Population of Colombia: A Population-Based Study.

BACKGROUND: The population prevalence of functional alterations and thyroid autoimmunity is high, and numerous genetic and environmental aspects have been described as triggering factors. OBJECTIVES: The objective of this study was to determine the prevalence of functional alterations and thyroid autoimmunity in an urban population of Colombia. MATERIALS AND METHODS: It is a cross-sectional, population-based study (n = 9,638) conducted on an urban population of Popayán-Cauca-Colombia between February 5th, 2018, to December 11th, 2021. The variables evaluated were thyrotropin (TSH), free T4 (FT4), and anti-thyroid antibodies (thyroid peroxidase antibodies: TPOAb, and thyroglobulin antibodies: TgAb). RESULTS: TSH in men was significantly higher than in women. No differences were observed in the values of FT4, TPOAb, and TgAb (according to sex). The prevalence of normal thyroid function and subclinical hypothyroidism was significantly higher in men. The positivity of TPOAb and TgAb was 22.3% and 19.2%, respectively. TSH levels increased with age (both in men and in women). In participants with normal FT4 and negative TPOAb, the TSH was significantly higher. TSH was significantly higher in TPOAb-positive individuals and among those with TPOAb and TgAb positives, as well as in women with positive TPOAb and men with positive TPOAb and TgAb. CONCLUSION: In an urban population of Colombia, TSH was found to be higher than in populations of other geographical areas, especially in older individuals and in the presence of positive anti-thyroid antibodies, a high prevalence of functional alterations and thyroid autoimmunity was also found. These findings can be explained by excess iodine consumption and some environmental factors.

Population Status of Vitamin B12 Values in the General Population and in Individuals with Type 2 Diabetes, in Southwestern Colombia.

Vitamin B12 (B12) is necessary for the proper functioning of the central and peripheral nervous systems. Although there is no exact definition for B12 levels, a value of 200 pg/mL is compatible with deficiency, 200-299 pg/mL is considered borderline, and 300 pg/mL is considered normal. In population studies, the prevalence of B12 deficiency ranges between 2.9% and 35%. Furthermore, many medications, such as metformin [for type 2 diabetes mellitus (T2DM)], can cause B12 deficiency. The objectives of this study were to determine the population status of B12 in southwestern Colombia (and the status of B12 in subjects with T2DM). In the total population (participants with and without T2DM), the prevalence of B12 deficiency was 17.8%; that of borderline was 19.3%; and that of normal levels was 62.9%. The prevalence of deficiency increased with age and was significantly higher in those aged ≥60 years (p = 0.000). In T2DM subjects, the prevalence of deficiency was significantly higher concerning those without T2DM (p = 0.002) and was significantly higher in those who received >1 gm/day of metformin (p = 0.001). Thus, the prevalence of deficiency and borderline levels of B12 in our population was high, particularly in those >60 years of age. B12 deficiency was significantly higher in individuals with T2DM than in individuals without T2DM, especially among those receiving high doses of metformin.

Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aß) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; ß = 0.35, SE = 0.01, P = 6.2 × 10-311, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; ß = 0.07, SE = 0.01, P = 9.2 × 10-09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; ß = 0.1, SE = 0.02, P = 2.4 × 10-10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; ß = 0.16, SE = 0.03, P = 1.1 × 10-09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, ß = 0.79, SE = 0.14, P = 1.4 × 10-08, MAF = 0.006, sex-interaction P = 9.8 × 10-07) and chr11p.15.2 (rs192346166, ß = 0.94, SE = 0.17, P = 3.7 × 10-08, MAF = 0.004, sex-interaction P = 1.3 × 10-03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.

First record of Cotylurus metacercariae (Trematoda:Strigeidae) in Biomphalaria straminea (Planorbidae) from Argentina: morphological and molecular identification.

In the study of the biology of trematode species, the knowledge of the larval stages in snail hosts is important to elucidate their complete life cycle. The goal of the present study was to describe a new tetracotyle-type metacercaria found in the freshwater mollusk Biomphalaria straminea sampled in a rice field from Corrientes province, Argentina. To this end, 1,768 snails were collected from the cultivated plots and irrigated channels during the flooding periods (from the time of sowing to soon after rice harvesting) between December 2016 and May 2017. We used morphological and molecular analysis to characterize the tetracotyle-type metacercariae. Its morphological traits and the internal transcribed spacers (ITS1 and ITS2 plus 5.8S; ~1200 pb) from nuclear ribosomal DNA (rDNA) were amplified and sequenced. From 1,768 specimens of B. straminea screened, 52 were found infected with metacercariae of tetracotyle type (2.9%) that were identified as Cotylurus genus. A total of 218 metacercariae were found encysted in the ovotestis or between the mantle and viscera of B. straminea. Bioinformatic analysis showed that the metacercarial rDNA sequences shared 94% identity with those of Cotylurus gallinulae from Mexico and 100% identity with those of Cotylurus sp. from Brazil. In this study, the morphological descriptions are supplemented with the first molecular identification of a metacercaria related to Cotylurus parasitizing planorbids from Argentina. Also, our study provides a new morphological description in B. straminea, thus broadening the geographical distribution. The life cycle of this Cotylurus metacercariae is unknown and there are no reports of adult stages parasitizing waterfowl in Argentina.

Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.

Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aß42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aß positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], ß = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], ß = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], ß = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aß and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.

Burnout syndrome in athletes and their association with body image dissatisfaction at a private university.

BACKGROUND: Burnout syndrome, from the sporting point of view, is the integration of both physical and emotional signs, caused by the high demands in competition. According to several studies, the prevalence of burnout syndrome is influenced by several factors that would lead to athlete's body image dissatisfaction. METHODS: The study design is cross-sectional analysis. The study sample was 352 athletes selected from the Universidad Peruana de Ciencias Aplicadas (UPC). The main variables of this study are the burnout syndrome; which was measured by Athlete Burnout Questionnaire (ABQ) and body image dissatisfaction, through thirteen Scale drawings contour figure Gardner. To find the association between body image dissatisfaction and burnout syndrome Poisson regression was used. RESULTS: Athletes with burnout syndrome have 1.08 times more likely having body image dissatisfaction with a value P=0.011 (95% CI: 1.02-1.15). It was also found that a sport collectively practiced is a protective factor for Burnout Syndrome with P=0.015 (95% CI: 0.4-0.9). CONCLUSIONS: Relation between burnout syndrome and body image dissatisfaction in athletes was found. In addition, a relationship between practicing an individual sport and burnout syndrome was also found. More studies are necessary to confirm these relationships.

A new genus of Cystidicolid nematode from the stomach of Galaxias maculatus (Osmeriformes: Galaxiidae) in Patagonia (Argentina).

During a parasitological survey of Galaxias maculatus (Jenyns) from Patagonian Andean Lakes, specimens of a new species of nematode were collected from the stomach of fish and studied by light and scanning electron microscopy. This species is described as the only member of a newly proposed genus of Cystidicolidae by having oral opening dorsoventrally elongated, 2 lateral pseudolabia, 4 cephalic papillae, stoma (vestibule) elongated, esophagus divided into anterior muscular and posterior glandular sections, and caudal alae in males. Placonema n. gen. (Habronematoidea, Cystidicolidae) is characterized by the combination of the following features: oral opening dorsoventrally elongated demarcated by 4 sclerotized plates and 2 well-developed pseudolabia projected to the buccal cavity, each pseudolabium with conspicuous, conical, anterior protuberances. Four cephalic papillae and deirids simple. Male with caudal alae, area rugosa absent, 4 pairs of preanal papillae, unpaired papilla present on anterior cloacal lip, and 6 pairs of postanal papillae. Larvigerous eggs without filaments. Placonema pataguense n. gen. n. sp. infects the stomach of G. maculatus from Lake Patagua (Patagonia, Argentina) and is the first species of Cystidicolidae described from G. maculatus.

Gender-Bashing in Adolescents: Structural Relations with Heterosexual Matrix, Racism/Xenophobia and Attitudes Toward Bullying.

BACKGROUND: This study examined the combined influence of gender variables (specifically gender stereotypes, sexism, and genderism/transphobia) as well as racism/xenophobia and attitudes toward bullying roles on gender-bashing. METHODS: A trans-cultural sample of 2410 Spanish and Portuguese students participated in the study (mean age = 15.13). Structural equation modeling and multiple group analyses were used to examine the relationships among variables. RESULTS: The model revealed a good fit with the data for the whole sample. Results showed that instrumentality, hostile sexism, genderism/transphobia, racism/xenophobia, and positive attitudes toward the bully were positively correlated with gender-bashing. An inverse pattern was also observed: expressiveness, benevolent sexism, and positive attitudes toward the defender were negatively correlated with gender-bashing. Overall, the eight variables explained 48% of the variance of gender-bashing. Structural relationships among the assessed constructs were equivalent for girls and boys, and for Spain and Portugal. CONCLUSIONS: These results reveal the need to implement inclusive educational policies to improve school health, which promote expressiveness, egalitarian attitudes, and sexual and cultural diversity.

Fish thermal habitat current use and simulation of thermal habitat availability in lakes of the Argentine Patagonian Andes under climate change scenarios RCP 4.5 and RCP 8.5.

Habitat use in relation to the thermal habitat availability and food source as a forcing factor on habitat selection and use of Percichthys trucha (Creole perch), Oncorhynchus mykiss (rainbow trout), Salmo trutta (brown trout) and Salvelinus fontinalis (brook trout) were determined as well as future potential thermal habitat availability for these species under climate change scenarios Representative Concentration Pathways 4.5 and 8.5. This study was conducted in three interconnected lakes of Northern Patagonia (Moreno Lake system). Data on fish abundance was obtained through gill netting and hydroacoustics, and thermal profiles and fish thermal habitat suitability index curves were used to identify current species-specific thermal habitat use. Surface air temperatures from the (NEX GDDP) database for RCP scenarios 4.5 and 8.5 were used to model monthly average temperatures of the water column up to the year 2099 for all three lakes, and to determine potential future habitat availability. In addition, data on fish diet were used to determine whether food could act as a forcing factor in current habitat selection. The four species examined do not use all the thermally suitable habitats currently available to them in the three lakes, and higher fish densities are not necessarily constrained to their "fundamental thermal niches" sensu Magnuson et al. (1979), as extensive use is made of less suitable habitats. This is apparently brought about by food availability acting as a major forcing factor in habitat selection and use. Uncertainties related to the multidimensionality inherent to habitat selection and climate change imply that fish resource management in Patagonia will not be feasible through traditional incremental policies and strategic adjustments based on short-term predictions, but will have to become highly opportunistic and adaptive.

Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP.

Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. To identify the genes and pathways that are dysregulated in FTLD-tau, we performed transcriptomic analyses in induced pluripotent stem cell (iPSC)-derived neurons carrying MAPT p.R406W and CRISPR/Cas9-corrected isogenic controls. We found that the expression of the MAPT p.R406W mutation was sufficient to create a significantly different transcriptomic profile compared with that of the isogeneic controls and to cause the differential expression of 328 genes. Sixty-one of these genes were also differentially expressed in the same direction between MAPT p.R406W carriers and pathology-free human control brains. We found that genes differentially expressed in the stem cell models and human brains were enriched for pathways involving gamma-aminobutyric acid (GABA) receptors and pre-synaptic function. The expression of GABA receptor genes, including GABRB2 and GABRG2, were consistently reduced in iPSC-derived neurons and brains from MAPT p.R406W carriers. Interestingly, we found that GABA receptor genes, including GABRB2 and GABRG2, are significantly lower in symptomatic mouse models of tauopathy, as well as in brains with progressive supranuclear palsy. Genome wide association analyses reveal that common variants within GABRB2 are associated with increased risk for frontotemporal dementia (P < 1 × 10-3). Thus, our systems biology approach, which leverages molecular data from stem cells, animal models, and human brain tissue can reveal novel disease mechanisms. Here, we demonstrate that MAPT p.R406W is sufficient to induce changes in GABA-mediated signaling and synaptic function, which may contribute to the pathogenesis of FTLD-tau and other primary tauopathies.