Molecular annotation of G protein variants in a neurological disorder.

Heterotrimeric G proteins transduce extracellular chemical messages to generate appropriate intracellular responses. Point mutations in GNAO1, encoding the G protein αo subunit, have been implicated in a pathogenic condition characterized by seizures, movement disorders, intellectual disability, and developmental delay (GNAO1 disorder). However, the effects of these mutations on G protein structure and function are unclear. Here, we report the effects of 55 mutations on Gαo conformation, thermostability, nucleotide binding, and hydrolysis, as well as interaction with Gßγ subunits, receptors, and effectors. Our effort reveals four functionally distinct groups of mutants, including one group that sequesters receptors and another that sequesters Gßγ, both acting in a genetically dominant manner. These findings provide a more comprehensive understanding of disease-relevant mutations and reveal that GNAO1 disorder is likely composed of multiple mechanistically distinct disorders that will likely require multiple therapeutic strategies.

Multisystem inflammatory syndrome in children and SARS-CoV-2 variants: a two-year ambispective multicentric cohort study in Catalonia, Spain.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe disease temporarily related to SARS-CoV-2. We aimed to describe the epidemiological, clinical, and laboratory findings of all MIS-C cases diagnosed in children < 18 years old in Catalonia (Spain) to study their trend throughout the pandemic. This was a multicenter ambispective observational cohort study (April 2020-April 2022). Data were obtained from the COVID-19 Catalan surveillance system and from all hospitals in Catalonia. We analyzed MIS-C cases regarding SARS-CoV-2 variants for demographics, symptoms, severity, monthly MIS-C incidence, ratio between MIS-C and accumulated COVID-19 cases, and associated rate ratios (RR). Among 555,848 SARS-CoV-2 infections, 152 children were diagnosed with MIS-C. The monthly MIS-C incidence was 4.1 (95% CI: 3.4-4.8) per 1,000,000 people, and 273 (95% CI: 230-316) per 1,000,000 SARS-CoV-2 infections (i.e., one case per 3,700 SARS-CoV-2 infections). During the Omicron period, the MIS-C RR was 8.2 (95% CI: 5.7-11.7) per 1,000,000 SARS-CoV-2 infections, which was significantly lower (p < 0.001) than that for previous variant periods in all age groups. The median [IQR] age of MIS-C was 8 [4-11] years, 62.5% male, and 80.2% without comorbidities. Common symptoms were gastrointestinal findings (88.2%) and fever > 39 °C (81.6%); nearly 40% had an abnormal echocardiography, and 7% had coronary aneurysm. Clinical manifestations and laboratory data were not different throughout the variant periods (p > 0.05).  Conclusion: The RR between MIS-C cases and SARS-CoV-2 infections was significantly lower in the Omicron period for all age groups, including those not vaccinated, suggesting that the variant could be the main factor for this shift in the MISC trend. Regardless of variant type, the patients had similar phenotypes and severity throughout the pandemic. What is Known: • Before our study, only two publications investigated the incidence of MIS-C regarding SARS-CoV-2 variants in Europe, one from Southeast England and another from Denmark. What is New: • To our knowledge, this is the first study investigating MIS-C incidence in Southern Europe, with the ability to recruit all MIS-C cases in a determined area and analyze the rate ratio for MIS-C among SARS-CoV-2 infections throughout variant periods. • We found a lower rate ratio of MISC/infections with SARS-CoV-2 in the Omicron period for all age groups, including those not eligible for vaccination, suggesting that the variant could be the main factor for this shift in the MISC trend.

Infecció per SARS-CoV-2 I escolarització / No disponible

No disponible

Tracing source and mobility of arsenic and trace elements in a hydrosystem impacted by past mining activities (Morelos state, Mexico).

The Sierra Huautla (Morelos State, Mexico) is a biological reserve with historical mines of Ag and Pb. In this area, waters used by inhabitants are contaminated by arsenic (As). An integrated environmental survey was realized both in waters and sediments to better constrain the source and the mobility of As and other trace elements. Two areas of interest were selected: (1) the Nexpa River ecosystem to determine the local geochemical background, and (2) the Huautla area, affected by past mining activities. This study allowed the definition of the local geochemical baseline in sediments or in waters, demonstrated uncontaminated by TE in the Nexpa area, except for As in the dissolved phase or for Cd in Suspended Particulate Matters (SPM). In the Huautla area, TE contents in water were higher than the World Health Organization (WHO) limits for Al, As and Mn in unfiltered waters, and only for As in the dissolved phase. Speciation analyses revealed arsenic to be present only as the toxic-inorganic arsenate species, As(+V). In SPM, Ag, As, Cd and Zn concentrations were higher than Sediment Quality Guidelines (SQG). The different geochemical indice (EF: 5, PLI: 3, EF: Igeo: 5-3) demonstrated that SPM were significantly contaminated and consistute an health risk for Huautla inhabitants exposed to As-contaminated waters and TE-rich SPM. The combination of mineralogy, chemistry, C and S stable isotopes with thermodynamic modeling indicate dissolutions of minerals from local geological formations, sorption-desorption phenomena from clays and oxy-hydroxides, and the weathering responsible for the transport of the TE-rich SPM (1.8 wt% for 17% of the total TE concentration). Moreover, the past mining activity would be a source of the contamination only for As in waters from flooded mines.

Groundwater Flow Processes and Human Impact along the Arid US-Mexican Border, Evidenced by Environmental Tracers: The Case of Tecate, Baja California.

With the increasing population, urbanization and industry in the arid area of Tecate, there is a concomitant increase in contaminants being introduced into the Tecate River and its aquifer. This contamination is damaging the usable groundwater supply and making local residents and commercial enterprises increasingly dependent on imported water from the Colorado River basin. In this study we apply a suite of chemical and isotopic tracers in order to evaluate groundwater flow and assess contamination trends. Groundwater recharge occurs through mountain-block and mountain-front recharge at higher elevations of the ranges. Groundwater from the unconfined, alluvial aquifer indicates recent recharge and little evolution. The increase in salinity along the flow path is due to interaction with weathering rock-forming silicate minerals and anthropogenic sources such as urban wastewater, residual solids and agricultural runoff from fertilizers, livestock manure and/or septic tanks and latrines. A spatial analysis shows local differences and the impact of the infiltration of imported waters from the Colorado River basin. The general trend of impaired water quality has scarcely been documented in the last decades, but it is expected to continue. Since the groundwater system is highly vulnerable, it is necessary to protect groundwater sources.

Nena de 5 anys amb lesions cutànies simètriques de tres dies d'evolució / No disponible

No disponible

Territorial approach to increased energy consumption of water extraction from depletion of a highlands Mexican aquifer.

This work proposes a method to estimate increased energy consumption of pumping caused by a drawdown of groundwater level and the equivalent energy consumption of the motor-pump system in an aquifer under intensive exploitation. This method has been applied to the Valley of Toluca aquifer, located in the Mexican highlands, whose intensive exploitation is reflected in a decline in the groundwater level of between 0.10 and 1.6 m/year. Results provide a summary of energy consumption and a map of energy consumption isopleths showing the areas that are most susceptible to increases in energy consumption due to pumping. The proposed method can be used to estimate the effect of the intensive exploitation of the Valley of Toluca aquifer on the energy consumption of groundwater extraction. Finding reveals that, for the year 2006, groundwater extraction in the urban zone required 2.39 times more energy than the conditions observed 38 years earlier. In monetary terms, this reflects an increase of USD$ 3 million annually, according to 2005 energy production costs.

Adolescent amb dolor abdominal recurrent i manifestacions neuropsiquiàtriques / No disponible

No disponible

Invaginación colocólica del adulto secundaria a tumor miofibroblástico inflamatorio / Adult colocolic intussusception secondary to inflammatory myofibroblastic tumor

No disponible

Environmental effects of aquifer overexploitation: a case study in the highlands of Mexico.

There are several environmental processes occurring under aquifer overexploitation conditions. These processes include groundwater table decline, subsidence, attenuation and drying of springs, decrease of river flow, and increased pollution vulnerability, among others processes. Some of these effects have been observed on the Upper Basin of the Lerma River. The Lerma River begins in the SE of the Valley of Toluca at 2,600 m asl, in the wetland known as Lagoons of Almoloya del Río. This wetland is made up of a group of lagoons, which are an important aquatic system from an environmental point of view. The water inflow of this wetland is a discharge of springs, which occur between the fractured volcanic material of the mountain range and granular volcanic-continental deposits of the Valley of Toluca aquifer. The intensive exploitation of the Valley of Toluca aquifer to supply urban and industrial water to Mexico City and Toluca began in 1950 and is responsible for a steady decline of piezometric levels of 1-3.5 m/yr. Other effects of this exploitation--the drying of the wetland, the decrease of river flow and the land subsidence--caused serious ecological and social impacts. The authorities declared this aquifer as overexploited in order to reduce the exploitation and preserve the availability of water resources in this important region.