Search

​​​​​​​To meet the global goal of net-zero CO2 emissions by 2050, many governments are turning to Carbon Capture and Storage (CCS) as a critical technology. Brazil is the largest CO2 emitter in South America and the 7th largest globally, yet it is in the early stages of CCS development. Using publicly available geological and infrastructure data, this study evaluates the feasibility and suitability of saline aquifers for CO2 storage in onshore intracratonic basins in southern Brazil. Saline aquifers deemed suitable for CO2 sequestration are those below 800 m deep, with a thickness greater than 20 m, and in areas with regionally extensive caprock at least 10 m thick. Using these criteria, we classify areas within the Rio Bonito Formation of the Paraná Basin and the Mucuri Member in the onshore extent of the Espírito Santo Basin into potential and exclusion areas for CO2 storage. The Rio Bonito Formation is present in the central-southern Paraná Basin and ranges from outcrop exposures to over 3900 m depth. The formation ranges in thickness from 25–350 m, and sandstone intervals within the formation have a cumulative thickness between 13 and 150 m. Caprocks consist mainly of shale and siltstone. Based on the criteria used, CO2 sequestration in the Rio Bonito Formation is optimal in two zones of the Paraná Basin that extend over ca. 27 700 km2 (northern zone) and ca. 38 100 km2 (southern zone). The Mucuri Member is present in almost the entire onshore extent of the Espírito Santo Basin and ranges in depth from 500 to 2650 m. The unit reaches 400 m thick with a cumulative thickness of sandstone layers ranging from 0 to 320 m. Caprocks consist mainly of evaporites, but shale and sandstone intervals are also present. CO2 sequestration in the Mucuri Member is optimal in one zone of the onshore Espírito Santo Basin, which extends over ca. 630 km2. Together, these zones have the capacity to store > 6.1 Gt CO2 providing Brazil with suitable capacity for reducing its CO2 emissions over the short- to medium-term.

Efficiency indices for inverters have been developed with the increasing adoption of photovoltaic (PV) systems. The European and Californian efficiencies are widely recognized, focusing on static inverter operation. Standards such as EN50530 and IEC 62891 introduced dynamic efficiency tests considering irradiance variations, but without a methodology to weigh the efficiencies within a single index. To address this gap, our study proposes a methodology to define an overall efficiency considering both static and dynamic inverter operation. Irradiance data with sub-minute sampling is classified into irradiance and irradiance derivative ranges. Then, weights for static and dynamic efficiency tests are obtained, and less significant ones are discarded. The results were applied to three PV inverters tested in the laboratory. By eliminating the less significant tests, the number of dynamic tests was reduced from 30 to 10. In two of the inverters, the inclusion of dynamic tests resulted in a 2\% reduction in overall efficiency compared to the static. An overall efficiency index is relevant for better comparing different PV inverters, especially when considering dynamic behaviors. This index may be significant for the PV market, governmental energy efficiency programs, and inverter manufacturers, providing guidelines to enhance the efficiency of their products.

Uma versão analítica do método de ordenadas discretas (ADO) é usada para determinar uma solução precisa e consistente para o problema do Reverso de Temperatura em misturas binárias de gases rarefeitos. As equações cinéticas usadas são baseadas no modelo cinético McCormack. Apresenta-se o desenvolvimento completo de uma solução analítica na variável espacial, além de resultados numéricos para os valores críticos do calor latente para a inversão de sentido do gradiente de temperatura e do fluxo de calor de cada gás nas misturas Neônio-Argônio e Hélio-Xenônio. O algoritmo é considerado simples de ser elaborado e o código desenvolvido (em FORTRAN) requer em torno de um segundo para ser executado em um computador com processador Intel Core i3 - 2.30 GHz.

Rationale & Objective: Itching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes. Study Design: This was a longitudinal cohort study. Setting & Participants: Patients from Brazil, France, and the United States enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013 to 2021, an international prospective cohort study of adults with nondialysis dependent CKD, and an estimated glomerular filtration rate (eGFR) of

Rationale & Objective: Conservative kidney management (CKM) is a viable treatment option for many patients with chronic kidney disease. However, CKM practices and resources in the United States are not well described. We undertook this study to gain a better understanding of factors influencing uptake of CKM by describing: (1) characteristics of patients who choose CKM, (2) provider practice patterns relevant to CKM, and (3) CKM resources available to providers. Study Design: Cross-sectional study. Setting & Participants: This study is a cross-sectional analysis of data from US nephrology clinics enrolled in the chronic kidney disease Outcomes and Practice Patterns Study (CKDopps) collected between 2014 and 2020. Data for this study includes chart-abstracted characteristics of patients with an estimated glomerular filtration rate ≤30mL/min/1.73m2 (n=1018) and available information on whether a decision had been made to pursue CKM at the time of kidney failure, patient (n=407) reports of discussions about forgoing dialysis, and provider (n=26) responses about CKM delivery and available resources in their health systems. Analytical Approach: Descriptive statistics were used to report patient demographics, clinical information, provider demographics, and clinic characteristics. Results: Among data from 1018 patients, 68 (7%) were recorded as planning for CKM. These patients were older, had more comorbidities, and were more likely to require assistance with transfers. Of the 407 patient surveys, 18% reported a conversation about forgoing dialysis with their nephrologist. A majority of providers felt comfortable discussing CKM; however, no clinics had a dedicated clinic or protocol for CKM. Limitations: Inconsistent survey terminology and unlinked patient and provider responses. Conclusions: Few patients reported discussion of forgoing dialysis with their providers and even fewer anticipated a choice of CKM on reaching kidney failure. Most providers were comfortable discussing CKM, but practiced in clinics that lacked dedicated resources. Further research is needed to improve the implementation of a CKM pathway. Plain-Language Summary: For older comorbid adults with kidney failure, conservative kidney management (CKM) can be an appropriate treatment choice. CKM is a holistic approach with treatment goals of maximizing quality of life and preventing progression of chronic kidney disease (CKD) without initiation of dialysis. We investigated US CKM practices and found that among 1018 people with CKD, only 7% were planning for CKM. Of 407 surveyed patients, 18% reported a conversation with their provider about forgoing dialysis. In contrast, most providers felt comfortable discussing CKM; however, none reported working in an environment with a dedicated CKM clinic or protocol. Our data show the need for further CKM education in the United States as well as dedicated resources for its delivery.

Abstract Background Recessive loss-of-function variations in HINT1 cause a peculiar subtype of Charcot-Marie-Tooth disease: neuromyotonia and axonal neuropathy (NMAN; OMIM[#137200]). With 25 causal variants identified worldwide, HINT1 mutations are among the most common causes of recessive neuropathy. The majority of patients are compound heterozygous or homozygous for a Slavic founder variant (c.110G>C, p.Arg37Pro) that has spread throughout Eurasia and America. Results In a cohort of 46 genetically unresolved Lithuanian patients with suspected inherited neuropathy, we identified eight families with HINT1 biallelic variations. Most patients displayed sensorimotor or motor-predominant axonal polyneuropathy and were homozygous for the p.Arg37Pro variant. However, in three families we identified a novel variant (c.299A>G, p.Glu100Gly). The same variant was also found in an American patient with distal hereditary motor neuropathy in compound heterozygous state (p.Arg37Pro/p.Glu100Gly). Haplotype analysis demonstrated a shared chromosomal region of 1.9 Mb between all p.Glu100Gly carriers, suggesting a founder effect. Functional characterization showed that the p.Glu100Gly variant renders a catalytically active enzyme, yet highly unstable in patient cells, thus supporting a loss-of-function mechanism. Conclusion Our findings broaden NMAN’s genetic epidemiology and have implications for the molecular diagnostics of inherited neuropathies in the Baltic region and beyond. Moreover, we provide mechanistic insights allowing patient stratification for future treatment strategies.

Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.

The archetype of a cycle has played an essential role in explaining observations of nature over thousands of years. At present, this perception significantly influences the worldview of modern societies, including several areas of science. In the Earth sciences, the concept of cyclicity offers simple analytical solutions in the face of complex events and their respective products, in both time and space. Current stratigraphic research integrates several methods to identify repetitive patterns in the stratigraphic record and to interpret oscillatory geological processes. This essay proposes a historical review of the cyclic conceptions from the earliest phases in the Earth sciences to their subsequent evolution into current stratigraphic principles and practices, contributing to identifying opportunities in integrating methodologies and developing future research mainly associated with quantitative approaches.

This paper aims to reconstruct Middle Bronze Age (MBA; 1600–1250 BCE) land use practices in the northwestern Alpine foreland (SW Germany, Hegau). We used a multi-proxy approach including the analysis of biogeochemical proxies from colluvial deposits and buried topsoils in the surroundings of the well-documented settlement site of Anselfingen and off-site pollen data from two peat bogs. This approach allowed for in-depth insights into the MBA subsistence economy and shows that the MBA in the northwestern Alpine foreland was a period of establishing settlements with sophisticated land management and land use practices. The reconstruction of phases of colluvial deposition was based on ages from optically stimulated luminescence (OSL) and radiocarbon (AMS14C) dating from multi-layered colluvial deposits and supports the local archaeological record with the first phase of major colluvial deposition occurring during the MBA followed by phases of colluvial deposition during the Iron Age, the Medieval period and modern times. The on-site deposition of charred archaeobotanical remains and animal bones from archaeological features, as well as polycyclic aromatic hydrocarbons (PAHs), charcoal spectra, phytoliths, soil microstructure, urease enzymatic activity, microbial biomass carbon (Cmic) and heavy metal contents from colluvial deposits, were used as proxies for on-site and near-site land use practices. The charcoal spectra indicate MBA forest management which favored the dominance of Quercus in the woodland vegetation in the surrounding area north of the settlement site. Increased levels of 5β stanols (up to 40 %) and the occurrence of pig bones (up to 14 %) support the presence of a forest pasture mainly used for pig farming. In the surrounding area south of the settlement, an arable field with a buried MBA plow horizon (2Apb) could be verified by soil micromorphological investigations and high concentrations of grass phytoliths from leaves and stems. Agricultural practices (e.g., plowing) focussed on five staple crops (Hordeum distichon/vulgare, Triticum dicoccum, Triticum monococcum, Triticum spelta, Triticum aestivum/turgidum), while the presence of stilted pantries as storage facilities and of heat stones indicate post-harvest processing of cereal crops and other agrarian products within the settlement. In the area surrounding the settlement, increased levels of urease activity, compared to microbial biomass carbon (up to 2.1 µg N µg Cmic-1), and input of herbivorous and omnivorous animal faeces indicate livestock husbandry on fallow land. The PAH suites and their spatial distribution support the use of fire for various purposes, e.g., for opening and maintaining the landscape, for domestic burning and for technical applications. The off-site palynological data support the observed change in on-site and near-site vegetation as well as the occurrence of related land use practices. During the Early and Middle Bronze Age, fire played a major role in shaping the landscape (peak of micro-charcoal during the MBA), and anthropogenic activities promoted Quercus-dominated forest ecosystems at the expense of natural beech forests. This indicates a broader regional human influence in the northwestern Alpine foreland at low- and mid-altitude inland sites during the Middle Bronze Age.

Bioluminescence imaging tends to rely on transgenic luciferase-expressing cells and animals. Here the authors report a portable bioluminescent system to non-invasively measure intra- and extracellular enzymes in vivo in non-transgenic animals which do not express luciferase.

Abstract CLEC16A has been shown to play a role in autophagy/mitophagy processes. Additionally, genetic variants in CLEC16A have been implicated in multiple autoimmune diseases. We generated an inducible whole-body knockout, Clec16a ΔUBC mice, to investigate the loss of function of CLEC16A. The mice exhibited a neuronal phenotype including tremors and impaired gait that rapidly progressed to dystonic postures. Nerve conduction studies and pathological analysis revealed loss of sensory axons that are associated with this phenotype. Activated microglia and astrocytes were found in regions of the CNS. Several mitochondrial-related proteins were up- or down-regulated. Upregulation of interferon stimulated gene 15 (IGS15) were observed in neuronal tissues. CLEC16A expression inversely related to IGS15 expression. ISG15 may be the link between CLEC16A and downstream autoimmune, inflammatory processes. Our results demonstrate that a whole-body, inducible knockout of Clec16a in mice results in an inflammatory neurodegenerative phenotype resembling spinocerebellar ataxia.

With therapeutic trials on the horizon for Charcot-Marie-Tooth type 1A (CMT1A), reliable, valid, and responsive clinical outcome assessments and biomarkers are essential. Accelerate Clinical Trials in CMT (ACT-CMT) is an international study designed to address important gaps in CMT1A clinical trial readiness including the lack of a validated, responsive functional outcome measure for adults, and a lack of validated biomarkers for multicenter application in clinical trials in CMT1A. The primary aims of ACT-CMT include validation of the Charcot-Marie-Tooth Functional Outcome Measure, magnetic resonance imaging of intramuscular fat accumulation as a lower limb motor biomarker, and in-vivo reflectance confocal microscopy of Meissner corpuscle sensory receptor density, a sensory biomarker. Initial studies have indicated that these measures are feasible, reliable and valid. A large prospective, multi-site study is necessary to fully validate and examine the responsiveness of these outcome measures in relation to existing outcomes for use in future clinical trials involving individuals with CMT1A. Two hundred 15 adults with CMT1A are being recruited to participate in this prospective, international, multi-center study. Serial assessments, up to 3 years, are performed and include the CMT-FOM, CMT Exam Score-Rasch, Overall Neuropathy Limitations Scale, CMT-Health Index, as well as nerve conduction studies, and magnetic resonance imaging and Meissner corpuscle biomarkers. Correlations using baseline data will be examined for validity. Longitudinal analyses will document the changes in function, intramuscular fat accumulation, Meissner corpuscle sensory receptor density. Lastly, we will use anchor-based and other statistical methods to determine the minimally clinically important change for these clinical outcome assessments and biomarkers in CMT1A. Reliable, and responsive clinical outcome assessments of function and disease progression biomarkers are urgently needed for application in early and late phase clinical trials in CMT1A. The ACT-CMT study protocol will address this need through the prospective, longitudinal, multicenter examination in unprecedented detail of novel and existing clinical outcome assessments and motor and sensory biomarkers, and enhance international clinical trial infrastructure, training and preparedness for future therapeutic trials in CMT and related neuropathies.

In this work we solve the nonlinear strong evaporation problem in rarefied gas dynamics. The analysis is based on the BGK model, with three dimensional velocity vector, derived from the Boltzmann equation. We present the complete development of a closed form solution for evaluating density, velocity, temperature perturbations and the heat flux of a gas. Numerical results are presented and discussed.

We analyzed Trim2A/A mice, generated by CRISPR-Cas9, which have a recessive, null mutation of Trim2. Trim2A/A mice develop ataxia that is associated with a severe loss of cerebellar Purkinje cells and a peripheral neuropathy. Myelinated axons in the CNS, including those in the deep cerebellar nuclei, have focal enlargements that contain mitochondria and neurofilaments. In the PNS, there is a loss of myelinated axons, particularly in the most distal nerves. The pathologically affected neuronal populations – primary sensory and motor neurons as well as cerebellar Purkinje cells – express TRIM2, suggesting that loss of TRIM2 in these neurons results in cell autonomous effects on their axons. In contrast, these pathological findings were not found in a second strain of Trim2 mutant mice (Trim2C/C), which has a partial deletion in the RING domain that is needed for ubiquitin ligase activity. Both the Trim2A and the Trim2C alleles encode mutant TRIM2 proteins with reduced ubiquitination activity. In sum, Trim2A/A mice are a genetically authentic animal model of a recessive axonal neuropathy of humans, apparently for a function that does not depend on the ubiquitin ligase activity.

Mutations in TUBB4A result in a spectrum of leukodystrophy including Hypomyelination with Atrophy of Basal Ganglia and Cerebellum (H-ABC), a rare hypomyelinating leukodystrophy, often associated with a recurring variant p.Asp249Asn (D249N). We have developed a novel knock-in mouse model harboring heterozygous (Tubb4aD249N/+) and the homozygous (Tubb4aD249N/D249N) mutation that recapitulate the progressive motor dysfunction with tremor, dystonia and ataxia seen in H-ABC. Tubb4aD249N/D249N mice have myelination deficits along with dramatic decrease in mature oligodendrocytes and their progenitor cells. Additionally, a significant loss occurs in the cerebellar granular neurons and striatal neurons in Tubb4aD249N/D249N mice. In vitro studies show decreased survival and dysfunction in microtubule dynamics in neurons from Tubb4aD249N/D249N mice. Thus Tubb4aD249N/D249N mice demonstrate the complex cellular physiology of H-ABC, likely due to independent effects on oligodendrocytes, striatal neurons, and cerebellar granule cells in the context of altered microtubule dynamics, with profound neurodevelopmental deficits.

BAG3 is a Hsp70 co-chaperone that is highly expressed in muscles. Here the authors show that several myofibrillar myopathy causing BAG3 mutations are not impaired in Hsp70 binding, but rather impair the ADP-ATP exchange step of the Hsp70 cycle, causing the aggregation of BAG3, Hsp70 and Hsp70 clients and leading to a collapse of protein homeostasis.

Oligodendrocyte:oligodendrocyte (O:O) gap junction (GJ) coupling is a widespread and essential feature of the CNS, and is mediated by connexin47 (Cx47) and Cx32. Loss of function mutations affecting Cx47 results in a severe leukodystrophy, Pelizeus-Merzbacher-like disease (also known as Hypomyelinating Leukodystrophy 2), which can be reproduced in mice lacking both Cx47 and Cx32. Here we report the gene expression profile of the cerebellum – an affected brain region – in mice lacking both Cx47 and Cx32. Of the 43,174 mRNA probes examined, we find decreased expression of 23 probes (corresponding to 23 genes) and increased expression of 545 probes (corresponding to 348 genes). Many of the genes with reduced expression map to oligodendrocytes, and two of them (Fa2h and Ugt8a) are involved in the synthesis of myelin lipids. Many of the genes with increased expression map to lymphocytes and microglia, and involved in leukotrienes/prostaglandins synthesis and chemokines/cytokines interactions and signaling pathways. In accord, immunostaining showed T- and B-cells in the cerebella of mutant mice as well as activated microglia and astrocytes. Thus, in addition to the loss of GJ coupling, there is a prominent immune response in mice lacking both Cx47 and Cx32.

Introduction: The importance of local references values has been well described in the literature; this is because the characteristics of the population may influence the laboratory tests. Objective: To establish the reference range for traditional and extended red blood cell parameters and reticulocyte indices in order to investigate its application in patients with chronic kidney disease (CKD). Materials and methods: 249 blood donors (125 males and 124 females) were selected to establish the reference values. The hemodialysis sample consisted of 62 patients with terminal CKD (48 male and 14 female). All analyzes were performed using the Sysmex XE-5000 automated hematology analyzer. Results: Differences between reference values was observed in relation to gender: red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), percentage of hyperchromic red blood cells (%HYPER), percentage of microcytosis (%MICRO), percentage of macrocytosis (%MACRO), absolute reticulocyte count (RET), reticulocyte hemoglobin content (RET-He), immature reticulocyte fraction (IFR), low fluorescence reticulocytes (LFR), medium fluorescence reticulocytes (MFR), and high fluorescence reticulocytes (HFR). Individuals with CKD presented RBC, HGB, HCT, MCHC, red cell distribution width expressed as coefficient of variation (RDW-CV), percentage of hypochromic red blood cells (%HYPO), percentage of reticulocytes (RET%), RET (female group), IFR, LFR, MFR, and HFR results compatible with the anemic state, which can be observed in 91.8% of patients. All studied parameters were in the area under the curve (AUC) > 0.4. In male group, %HYPO (AUC: 0.806) and IFR (AUC: 0.762) presented higher AUC values, while female group presented %HYPO (AUC: 0.806), %HYPER (AUC: 0.815), and IFR (AUC: 0.660). Conclusion: The medical advancement, the development of new techniques and hematological parameters have revealed important information about functional integrity of bone marrow, diagnosis of anemia and recombinant human erythropoietin monitoring therapy used in hemodialysis patients.

The vector form factor of the pion is calculated in the framework of chiral effective field theory with vector mesons included as dynamical degrees of freedom. To construct an effective field theory with a consistent power counting, the complex-mass scheme is applied.

Cats with orthopedic conditions are a prominent part of the clinical work of veterinary. Conditions such as comminuted fractures, bone tumors and non-unions are often difficult to repair and may require the use of bone grafts for treatment. This study evaluated cortical bone allografts preserved in honey, frozen or lyophilized for correcting long bone defects created in the diaphysis of the right femur of domestic cats (n=24). In the control group (n=6), the defect was repaired using autogenous cortical bone graft. In the remaining animals (n=6/group), the defect was repaired with cortical bone allografts preserved in honey, frozen or lyophilized. Success of graft incorporation and length of time for consolidation were assessed through clinical, radiographic and histological evaluations performed up to 180 days. In the control, frozen, honey and lyophylized groups, respectively, success of graft incorporation was 91.6%, 83.3%, 75%, and 25%, with corresponding mean length of time for consolidation of 83.1, 78, 105 and 120 days. Incorporation percentage in the lyophilized group was significantly lower than in the frozen and control groups. In conclusion, bone grafts preserved in honey or frozen were effective for repairing cortical defects in the femurs of cats as compared to autogenous cortical bone grafts.

In addition to the extensive gap junction coupling between astrocytes themselves, oligodendrocytes are thought to be exclusively coupled to astrocytes (O:A coupling) via heterotypic gap junctions composed of Cx47:Cx43 and Cx32:Cx30. We used fluorescent dyes to examine functional coupling in acute slices from the cerebra of mice lacking Cx32 and/or Cx47. In the corpus callosum, unexpectedly, oligodendrocytes appeared to be directly and exclusively coupled to other oligodendrocytes (O:O coupling), and electron microscopy revealed gap junctions between adjacent oligodendrocytes. O:O coupling was more affected in mice lacking Cx32 than in mice lacking Cx47. In the neocortex, oligodendrocytes appeared to be directly and exclusively coupled to astrocytes; Cx47, but not Cx32, was required for O:A coupling.

Dominant mutations in GJB2, the gene encoding the human gap junction protein connexin26 (Cx26), cause hearing loss. We investigated whether dominant Cx26 mutants interact directly with Cx30. HeLa cells stably expressing nine dominant Cx26 mutants, six associated with non-syndromic hearing loss (W44C, W44S, R143Q, D179N, R184Q and C202F) and three associated with hearing loss and palmoplantar keratoderma (G59A, R75Q and R75W), individually or together with Cx30, were analyzed by immunocytochemistry, co-immunoprecipitation, and functional assays (scrape-loading and/or fluorescence recovery after photobleaching). When expressed alone, all mutants formed gap junction plaques, but with impaired intercellular dye transfer. When expressed with Cx30, all mutants co-localized and co-immunoprecipitated with Cx30, indicating they likely co-assembled into heteromers. Furthermore, 8/9 Cx26 mutants inhibited the transfer of neurobiotin or calcein, indicating that these Cx26 mutants have trans-dominant effects on Cx30, an effect that may contribute to the pathogenesis of hearing loss.