Irrigated agriculture alters near‐surface temperature and humidity, which may mask global climate change at the regional scale. However, observational studies of irrigation‐induced climate change are ...lacking in temperate, humid regions throughout North America and Europe. Despite unknown climate impacts, irrigated agriculture is expanding in the Midwest United States, where unconfined aquifers provide groundwater to support crop production on coarse soils. This is the first study in the Midwest United States to observe and quantify differences in regional climate associated with irrigated agricultural conversion from forests and rainfed agriculture. To this end, we established a 60 km transect consisting of 28 stations across varying land uses and monitored surface air temperature and relative humidity for 31 months in the Wisconsin Central Sands region. We used a novel approach to quantify irrigated land use in both space and time with a database containing monthly groundwater withdrawal estimates by parcel for the state of Wisconsin. Irrigated agriculture decreased maximum temperatures and increased minimum temperatures, thus shrinking the diurnal temperature range (DTR) by an average of 3°C. Irrigated agriculture also decreased the vapor pressure deficit (VPD) by an average of 0.10 kPa. Irrigated agriculture significantly decreased evaporative demand for 25% and 66% of study days compared to rainfed agriculture and forest, respectively. Differences in VPD across the land‐use gradient were highest (0.21 kPa) during the peak of the growing season, while differences in DTR were comparable year‐round. Interannual variability in temperature had greater impacts on differences in DTR and VPD across the land‐use gradient than interannual variability in precipitation. These regional climate changes must be considered together with increased greenhouse gas emissions, changes to groundwater quality, and surface water degradation when evaluating the costs and benefits of groundwater‐sourced irrigation expansion in the Midwest United States and similar regions around the world.
Irrigated agriculture alters near‐surface temperature and humidity, which may mask global climate change at the regional scale. This is the first study to quantify irrigation‐induced climate change in the Midwest United States using a 60 km transect consisting of 28 meteorological sensors across the Wisconsin Central Sands region. Irrigated agriculture decreased the diurnal temperature range and vapor pressure deficit compared to rainfed agriculture and forests. These regional climate impacts must be considered together with increased greenhouse gas emissions, groundwater quality concerns, and surface water degradation when evaluating irrigation expansion in the Midwest United States.
There are several plausible abiotic synthetic routes from prebiotic chemical materials to ribonucleotides and even short RNA oligomers. However, for refinement of the RNA World hypothesis to help ...explain the origins of life on the Earth, there needs to be a manner by which such oligomers can increase their length and expand their sequence diversity. Oligomers longer than at least 10-20 nucleotides would be needed for raw material for subsequent natural selection. Here, we explore spontaneous RNA-RNA recombination as a facile means by which such length and diversity enhancement could have been realized. Motivated by the discovery that RNA oligomers stored for long periods of time in the freezer expand their lengths, we systematically investigated RNA-RNA recombination processes. In addition to one known mechanism, we discovered at least three new mechanisms. In these, one RNA oligomer acts as a splint to catalyze the hybridization of two other oligomers and facilitates the attack of a 5'-OH, a 3'-OH, or a 2'-OH nucleophile of one oligomer onto a target atom of another. This leads to the displacement of one RNA fragment and the production of new recombinant oligomers. We show that this process can explain the spontaneous emergence of sequence complexity, both in vitro and in silico.
RNA expression and protein abundance are often at odds when measured in parallel, raising questions about the functional implications of transcriptomics data. Here, we present the concept of ...persistence, which attempts to address this challenge by combining protein half-life data with RNA expression into a single metric that approximates protein abundance. The longer a protein's half-life, the more influence it can have on its surroundings. This data offers a valuable opportunity to gain deeper insight into the functional meaning of transcriptome changes. We demonstrate the application of persistence using schizophrenia (SCZ) datasets, where it greatly improved our ability to predict protein abundance from RNA expression. Furthermore, this approach successfully identified persistent genes and pathways known to have impactful changes in SCZ. These results suggest that persistence is a valuable metric for improving the functional insight offered by transcriptomics data, and extended application of this concept could advance numerous research fields.
B vitamins are some of the most commonly required biochemical cofactors in living systems. Therefore, cellular metabolism of marine vitamin-requiring (auxotrophic) phytoplankton and bacteria would ...likely be significantly compromised if B vitamins (thiamin B ₁, riboflavin B ₂, pyridoxine B ₆, biotin B ₇, and cobalamin B ₁₂) were unavailable. However, the factors controlling the synthesis, ambient concentrations, and uptake of these key organic compounds in the marine environment are still not well understood. Here, we report vertical distributions of five B vitamins (and the amino acid methionine) measured simultaneously along a latitudinal gradient through the contrasting oceanographic regimes of the southern California-Baja California coast in the Northeast Pacific margin. Although vitamin concentrations ranged from below the detection limits of our technique to 30 pM for B ₂ and B ₁₂ and to ∼500 pM for B ₁, B ₆, and B ₇, each vitamin showed a different geographical and depth distribution. Vitamin concentrations were independent of each other and of inorganic nutrient levels, enriched primarily in the upper mesopelagic zone (depth of 100–300 m), and associated with water mass origin. Moreover, vitamin levels were below our detection limits (ranging from ≤0.18 pM for B ₁₂ to ≤0.81 pM for B ₁) in extensive areas (100s of kilometers) of the coastal ocean, and thus may exert important constraints on the taxonomic composition of phytoplankton communities, and potentially also on rates of primary production and carbon sequestration.
The common molecular mechanisms underlying psychiatric disorders are not well understood. Prior attempts to assess the pathological mechanisms responsible for psychiatric disorders have been limited ...by biased selection of comparable disorders, datasets/cohort availability, and challenges with data normalization. Here, using DisGeNET, a gene-disease associations database, we sought to expand such investigations in terms of number and types of diseases. In a top-down manner, we analyzed an unbiased cluster of 36 psychiatric disorders and comorbid conditions at biological pathway, cell-type, drug-target, and chromosome levels and deployed density index, a novel metric to quantify similarities (close to 1) and dissimilarities (close to 0) between these disorders at each level. At pathway level, we show that cognition and neurotransmission drive the similarity and are involved across all disorders, whereas immune-system and signal-response coupling (cell surface receptors, signal transduction, gene expression, and metabolic process) drives the dissimilarity and are involved with specific disorders. The analysis at the drug-target level supports the involvement of neurotransmission-related changes across these disorders. At cell-type level, dendrite-targeting interneurons, across all layers, are most involved. Finally, by matching the clustering pattern at each level of analysis, we showed that the similarity between the disorders is influenced most at the chromosomal level and to some extent at the cellular level. Together, these findings provide first insights into distinct cellular and molecular pathologies, druggable mechanisms associated with several psychiatric disorders and comorbid conditions and demonstrate that similarities between these disorders originate at the chromosome level and disperse in a bottom-up manner at cellular and pathway levels.
Objective
To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis ...(GCA).
Methods
In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age‐ and sex‐matched subjects were randomly selected from the general population and matched to patients at the time of diagnosis of GCA. Both groups were prospectively followed up over a 5‐year period.
Results
Severe infections were more frequent among patients with GCA during the first year after diagnosis, compared to general population controls (incidence rate ratio 2.1, 95% confidence interval 95% CI 1.2–3.4; incidence rate 11.1/100 patient‐years 95% CI 8.3–14.6 in patients with GCA versus 5.9/100 patient‐years 95% CI 4–8.4 in controls). Specifically, septic shock and infectious colitis were more frequent among the patients with GCA. Mortality caused by infections was higher in patients with GCA compared to controls (P < 0.0001 by log rank test). In analyses adjusted for age, among patients with GCA, a diagnosis of diabetes (hazard ratio HR 3.3, 95% CI 1.4–7.7) and a corticosteroid dosage that was >10 mg/day after 12 months of treatment (HR 4.61, 95% CI 1.38–15.36) were associated with death attributed to severe infection. The observed overall incidence of mortality was increased in patients with GCA during the early period of enrollment in the study (before 1997) (P = 0.0001 by log rank test), but thereafter was the same as that in the general population controls.
Conclusion
Frequencies of severe infections and rates of infection‐related mortality are increased during the first year after the diagnosis of GCA. The risk of infection increases in GCA patients with older age or in the presence of diabetes, or is greater when the dosage of corticosteroids has been increased to >10 mg/day after 12 months of treatment.
Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative ...insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE. A set of 119 genes with subtle-to-moderate impact predicted most forms of epilepsy with ~ 97% accuracy and characteristically mapped to upregulated homeostatic and downregulated synaptic pathways. The deconvolution of cellular proportions revealed opposing changes in diverse cell types. The proportion of nonneuronal cells increased whereas that of interneurons, except for those expressing vasoactive intestinal peptide (Vip), decreased, and pyramidal neurons of the cornu-ammonis (CA) subfields showed the highest variation in proportion. A probabilistic Bayesian-network demonstrated an aberrant and oscillating physiological interaction between nonneuronal cells involved in the blood-brain-barrier and Vip interneurons in driving seizures, and their role was evaluated insilico using transcriptomic changes induced by valproic-acid, which showed opposing effects in the two cell-types. Additionally, we revealed novel epileptic and antiepileptic mechanisms and predicted drugs using causal inference, outperforming the present drug repurposing approaches. These well-powered findings not only expand the understanding of TLE and seizure oscillation, but also provide predictive biomarkers of epilepsy, cellular and causal micro-circuitry changes associated with it, and a drug-discovery method focusing on these events.
Objective
Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in ...different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations.
Methods
We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded.
Results
To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug–drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute range 23–58 ml/minute) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml range 504–2,229 ng/ml versus 917 ng/ml range 208–3316 ng/ml) (P < 0.001).
Conclusion
We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
Introduction: Schnitzler syndrome is an auto-inflammatory disease defined by chronic urticarial eruption and monoclonal gammopathy.
18
F fluorodeoxyglucose positron emission tomography/computed ...tomography (PET/CT) is often performed, but its utility in Schnitzler syndrome has not been specifically investigated. The aim of this study was to determine whether PET/CT is informative in the diagnosis and follow-up of Schnitzler syndrome relative to other imaging techniques, including bone scans.
Patients and methods: Patients of this study were selected from the French cohort established by Néel et al. All patients with a diagnosis of Schnitzler syndrome (according to Strasbourg's and Lipsker's criteria) who had at least one PET/CT were included. Data were collected from medical records. PET/CT scans were all reviewed by a nuclear physician blinded to the clinical and imaging data.
Results: Ten patients underwent at least one PET/CT scan and all had at least one
99m
Technetium bone scan during their follow-up. The most frequent PET/CT abnormalities were diffuse bone-marrow and/or increased femoral fluorodeoxyglucose uptake, but they did not correlate with disease activity. Conversely, bone-scan abnormalities, including mainly increased radiotracer uptake in long bones, appeared to strongly correlate with Schnitzler syndrome activity.
Discussion: PET/CT does not appear to be useful for the diagnosis and follow-up of Schnitzler syndrome. However, bone scans appear to be more sensitive for diagnosis and may correlate with clinical activity. Bone scans may be well positioned to distinguish Schnitzler syndrome relapse from other aetiologies of bone, joint, or muscle pain.
Conclusion: Bone scans may be favoured over PET/CT in Schnitzler syndrome.
PDF
