Aerial and surface rivers: Downwind impacts on water availability from land use changes in Amazonia

The abundant evapotranspiration provided by the Amazon forests is an important component of the hydrological cycle, both regionally and globally. Since the last century, deforestation and expanding agricultural activities have been changing the ecosystem and its provision of moisture to the atmosphere. However, it remains uncertain how the ongoing land use change will influence rainfall, runoff, and water availability as findings from previous studies differ. Using moisture tracking experiments based on observational data, we provide a spatially detailed analysis recognizing potential teleconnection between source and sink regions of atmospheric moisture. We apply land use scenarios in upwind moisture sources and quantify the corresponding rainfall and runoff changes in downwind moisture sinks. We find spatially varying responses of water regimes to land use changes, which may explain the diverse results from previous studies. Parts of the Peruvian Amazon and western Bolivia are identified as the sink areas most sensitive to land use change in the Amazon and we highlight the current water stress by Amazonian land use change on these areas in terms of the water availability. Furthermore, we also identify the influential source areas where land use change may considerably reduce a given target sink's water reception (from our example of the Ucayali River basin outlet, rainfall by 5–12ĝ€% and runoff by 19–50ĝ€% according to scenarios). Sensitive sinks and influential sources are therefore suggested as hotspots for achieving sustainable land–water management

Aerial and surface rivers: downwind impacts on water availability from land use changes in Amazonia

The abundant evapotranspiration provided by the Amazon forests is an important component of the hydrological cycle, both regionally and globally. Since the last century, deforestation and expanding agricultural activities have been changing the ecosystem and its provision of moisture to the atmosphere. However, it remains uncertain how the ongoing land use change will influence rainfall, runoff, and water availability as findings from previous studies differ. Using moisture tracking experiments based on observational data, we provide a spatially detailed analysis recognizing potential teleconnection between source and sink regions of atmospheric moisture. We apply land use scenarios in upwind moisture sources and quantify the corresponding rainfall and runoff changes in downwind moisture sinks. We find spatially varying responses of water regimes to land use changes, which may explain the diverse results from previous studies. Parts of the Peruvian Amazon and western Bolivia are identified as the sink areas most sensitive to land use change in the Amazon and we highlight the current water stress by Amazonian land use change on these areas in terms of the water availability. Furthermore, we also identify the influential source areas where land use change may considerably reduce a given target sink's water reception (from our example of the Ucayali River basin outlet, rainfall by 5–12ĝ€% and runoff by 19–50ĝ€% according to scenarios). Sensitive sinks and influential sources are therefore suggested as hotspots for achieving sustainable land–water management

Prostate Cancer Risk Is not Altered by TP53AIP1 Germline Mutations in a German Case-Control Series

Prostate cancer susceptibility has previously been associated with truncating germline variants in the gene TP53AIP1 (tumor protein p53 regulated apoptosis inducing protein 1). For two apparently recurrent mutations (p.Q22fs and p.S32X) a remarkable OR of 5.1 was reported for prostate cancer risk. Since these findings have not been validated so far, we genotyped p.Q22fs and p.S32X in two German series with a total of 1,207 prostate cancer cases and 1,495 controls. The truncating variants were not significantly associated with prostate cancer in none of the two cohorts, nor in the combined analysis [odds ratio (OR) = 1.16; 95% confidence interval (CI 95%) = 0.62–2.15; p = 0.66]. Carriers showed no significant differences in family history of prostate cancer, age at diagnosis, Gleason score or PSA at diagnosis when compared to non-carrier prostate cancer cases. The large sample size of the combined cohort rejects a high-risk effect greater than 2.2 and indicates a limited role of TP53AIP1 in prostate cancer predisposition

Properties of slow-and fast-twitch skeletal muscle from mice with an inherited capacity for hypoxic exercise

Abstract Muscle fiber type, myosin heavy chain (MHC) isoform composition, capillary density (CD) and citrate synthase (CS) activity were investigated in predominantly slow-twitch (soleus or SOL) and fast-twitch (extensor digitorum longus or EDL) skeletal muscle from mice with inherited differences in hypoxic exercise tolerance. Striking differences in hypoxic exercise tolerance previously have been found in two inbred strains of mice, Balb/cByJ (C) and C57BL/6J (B6), and their F1 hybrid following exposure to hypobaric hypoxia. Mice from the three strains were exposed for 8 weeks to either normobaric normoxia or hypobaric hypoxia (1/2 atm). Hypoxia exposure led to a slightly higher 2b fiber composition and a lower fiber area of types 1 and 2a in SOL of all mice. In the EDL, muscle fiber and MHC isoform composition remained unaffected by chronic hypoxia. Chronic hypoxia did not significantly affect CD in either muscle from any of the three strains. There were relatively larger differences in CS activity among strains and treatment, and in SOL the highest CS activity was found in the F1 mice that had been acclimated to hypoxia. In general, however, neither differences among strains nor treatment in these properties of muscle vary in a way that clearly relates to inherited hypoxic exercise tolerance.

Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors

Background: About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We therefore investigated epigenome-wide DNA methylation profiles of PCa stratified by T2E status. Results: The study included 496 patients with clinically localized PCa who had a radical prostatectomy as primary treatment for PCa. Fluorescence in situ hybridization (FISH) "break-apart" assays were used to determine tumor T2E- fusion status, which showed that 266 patients (53.6 %) had T2E-positive PCa. The study showed global DNA methylation differences between tumor subtypes. A large number of differentially methylated CpG sites were identified (false-discovery rate [FDR] Q-value Conclusions: This study identified substantial differences in DNA methylation profiles of T2E-positive and T2E-negative tumors, thereby providing further evidence that different underlying oncogenic pathways characterize these molecular subtypes

The Delta Scuti star 38 Eri from the ground and from space

We present and discuss the pulsational characteristics of the Delta Scuti star 38 Eri from photometric data obtained at two widely spaced epochs, partly from the ground (1998) and partly from space (MOST, 2011). We found 18 frequencies resolving the discrepancy among the previously published frequencies. Some of the frequencies appeared with different relative amplitudes at two epochs, however, we carried out investigation for amplitude variability for only the MOST data. Amplitude variability was found for one of three frequencies that satisfy the necessary frequency criteria for linear-combination or resonant-mode coupling. Checking the criteria of beating and resonant-mode coupling we excluded them as possible reason for amplitude variability. The two recently developed methods of rotational-splitting and sequence-search were applied to find regular spacings based only on frequencies. Doublets or incomplete multiplets with l = 1, 2 and 3 were found in the rotational splitting search. In the sequence search method we identified four sequences. The averaged spacing, probably a combination of the large separation and the rotational frequency, is 1.724 ± 0.092 d-1. Using the spacing and the scaling relation \bar{ρ }= [0.0394, 0.0554] gcm-3 was derived. The shift of the sequences proved to be the integer multiple of the rotational splitting spacing. Using the precise MOST frequencies and multi-colour photometry in a hybrid way, we identified four modes with l = 1, two modes with l = 2, two modes with l = 3, and two modes as l = 0 radial modes

Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e−8) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e−11). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus

Prospective evaluation of NGS-based sequencing in epilepsy patients: results of seven NASGE-associated diagnostic laboratories

BackgroundEpilepsy is one of the most common and disabling neurological disorders. It is highly prevalent in children with neurodevelopmental delay and syndromic diseases. However, epilepsy can also be the only disease-determining symptom. The exact molecular diagnosis is essential to determine prognosis, comorbidity, and probability of recurrence, and to inform therapeutic decisions.Methods and materialsHere, we describe a prospective cohort study of patients with epilepsy evaluated in seven diagnostic outpatient centers in Germany. Over a period of 2 months, 07/2022 through 08/2022, 304 patients (317 returned result) with seizure-related human phenotype ontology (HPO) were analyzed. Evaluated data included molecular results, phenotype (syndromic and non-syndromic), and sequencing methods.ResultsSingle exome sequencing (SE) was applied in half of all patients, followed by panel (P) testing (36%) and trio exome sequencing (TE) (14%). Overall, a pathogenic variant (PV) (ACMG cl. 4/5) was identified in 22%; furthermore, a significant number of patients (12%) carried a reported clinically meaningful variant of unknown significance (VUS). The average diagnostic yield in patients ≤ 12 y was higher compared to patients &gt;12 y cf. Figure 2B vs. Figure 3B. This effect was more pronounced in cases, where TE was applied in patients ≤ 12 vs. &gt;12 y [PV (PV + VUS): patients ≤ 12 y: 35% (47%), patients &gt; 12 y: 20% (40%)]. The highest diagnostic yield was achieved by TE in syndromic patients within the age group ≤ 12 y (ACMG classes 4/5 40%). In addition, TE vs. SE had a tendency to result in less VUS in patients ≤ 12 y [SE: 19% (22/117) VUS; TE: 17% (6/36) VUS] but not in patients &gt;12 y [SE: 19% (8/42) VUS; TE: 20% (2/10) VUS]. Finally, diagnostic findings in patients with syndromic vs. non-syndromic symptoms revealed a significant overlap of frequent causes of monogenic epilepsies, including SCN1A, CACNA1A, and SETD1B, confirming the heterogeneity of the associated conditions.ConclusionIn patients with seizures—regardless of the detailed phenotype—a monogenic cause can be frequently identified, often implying a possible change in therapeutic action (36.7% (37/109) of PV/VUS variants); this justifies early and broad application of genetic testing. Our data suggest that the diagnostic yield is highest in exome or trio-exome-based testing, resulting in a molecular diagnosis within 3 weeks, with profound implications for therapeutic strategies and for counseling families and patients regarding prognosis and recurrence risk