Modeling Denitrification : Can We Report What We Don't Know?

Funding Information: This study is the products of a workshop funded by the Deutsche Forschungsgemeinschaft through the research unit DFG‐FOR 2337: Denitrification in Agricultural Soils: Integrated Control and Modelling at Various Scales (DASIM), and by the German Federal Ministry of Education and Research (BMBF) under the “Make our Planet Great Again—German Research Initiative”, Grant 306060, implemented by the German Academic Exchange Service (DAAD). This work was supported by the European Union's Horizon 2020 research and innovation programme project VERIFY (grant agreement no. 776810). We would like to thank the contribution of all workshop participants of the II. DASIM Modeler Workshop. Publisher Copyright: © 2023. The Authors.Peer reviewedPublisher PD

A case report of vibration-induced hand comorbidities in a postwoman

<p>Abstract</p> <p>Background</p> <p>Prolonged exposure to hand-transmitted vibration is associated with an increased occurrence of symptoms and signs of disorders in the vascular, neurological and osteoarticular systems of the upper limbs. However, the available epidemiological evidence is derived from studies on high vibration levels caused by vibratory tools, whereas little is known about possible upper limb disorders caused by chronic exposure to low vibration levels emitted by fixed sources.</p> <p>Case presentation</p> <p>We present the case of a postwoman who delivered mail for 15 years using a low-powered motorcycle. The woman was in good health until 2002, when she was diagnosed with bilateral Raynaud's phenomenon. In March 2003 a bilateral carpal tunnel syndrome was electromyographically diagnosed; surgical treatment was ineffective. Further examinations in 2005 highlighted the presence of chronic tendonitis (right middle finger flexor).</p> <p>Risk assessment</p> <p>From 1987, for 15 years, our patient rode her motorcycle for 4 h/day, carrying a load of 20-30 kg. For about a quarter of the time she drove over country roads. Using the information collected about the tasks carried out every day by the postwoman and some measurements performed on both handles of the motorcycle, as well as on both iron parts of the handlebars, we reconstructed the woman's previous exposure to hand-arm vibration. 8-hour energy-equivalent frequency weighted acceleration was about 2.4 m/s². The lifetime dose was 1.5 × 10⁹(m²/s⁴)hd.</p> <p>Conclusions</p> <p>The particular set of comorbidities presented by our patient suggests a common pathophysiological basis for all the diseases. Considering the level of exposure to vibrations and the lack of specific knowledge on the effects of vibration in women, we hypothesize an association between the work exposure and the onset of the diseases.</p

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

MicroRNAs (miRNAs) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression. Since their initial discovery, they have been shown to be involved in many cellular processes, and their misexpression is associated with disease etiology. Currently, nearly 2,800 human miRNAs are annotated in public repositories. A key question in miRNA research is how many miRNAs are harbored by the human genome. To answer this question, we examined 1,323 short RNA sequence samples and identified 3,707 novel miRNAs, many of which are human-specific and tissue-specific. Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology

DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2).

Recent studies show that the region of DNA brought into close proximity to the fetal gamma-globin genes in deletional forms of hereditary persistence of fetal hemoglobin (HPFH) is selectively hypomethylated (and presumably active) in normal erythroid tissue. This region is normally located approximately 100 kilobases (kb) 3' to the fetal genes. The continued expression of fetal hemoglobin in adult life in these forms of HPFH has been ascribed to the effect of this erythroid-specific region in altering local chromosomal structure and allowing transcription. Because transcriptional activity is often associated with hypomethylation, we have examined the methylation status of the gamma-globin genes and the truncated psi beta gene on the HPFH chromosome to determine whether juxtaposition of this erythroid-specific region results in a generalized hypomethylation of the globin gene region upstream of the deletion breakpoint. Genomic DNA purified from nucleated red blood cells (nRBC) from a patient with HPFH-2/beta O thalassemia was digested with Msp I or Hpa II, and the methylation pattern determined on the HPFH chromosome by using secondary cleavage with restriction enzymes which span the deletion breakpoint. These studies show that in nRBC the HPFH-2 chromosome is hypomethylated in the 3'-juxtaposed region (3'JR) and in the region of the gamma-globin genes. In contrast, Msp I sites near the truncated psi beta-globin gene remain methylated, suggesting that only a subset of CpG sites upstream from the 3'JR become hypomethylated in HPFH-2. This subset of sites corresponds to those which are normally hypomethylated when fetal genes are active. The continued high level of fetal globin expression is, therefore, not associated with a generalized hypomethylation upstream from the deletion junction

A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction.

We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-like globin gene cluster. The 3' breakpoint of this deletion maps beyond the 3'-HVR, a region implicated as a hot spot for the generation of other large deletional events within the alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases

A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction.

We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-like globin gene cluster. The 3' breakpoint of this deletion maps beyond the 3'-HVR, a region implicated as a hot spot for the generation of other large deletional events within the alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases

A greater than 200 kb deletion removing the entire beta-like globin gene cluster in a family of Irish descent.

We describe a new deletional form of gamma delta beta-thalassemia segregating in two generations of a family of Irish descent. Affected family members present with a beta-thalassemia minor phenotype, normal Hb A2 and Hb F levels. Genomic blotting analyses on DNA from affected family members show heterozygosity for a large deletion beginning at least 15 kb upstream of the 5' endpoint of the gamma delta beta-thalassemia-1 deletion, extending through the entire beta-like globin gene cluster, and continuing for at least 10 kb beyond the 3' endpoint of the deletion associated with the Spanish form of delta beta 0-thalassemia. This deletion is among the largest described so far, and removes at least 205 kb encompassing the entire beta-like globin gene cluster on chromosome 11

Genotyping beta-globin gene mutations on copolymer-coated glass slides with the ligation detection reaction.

BACKGROUND: Methods are needed to analyze small amounts of samples for variation in disease causing genes. One means is to couple the sensitivity and multiplexing capability of the ligation detection reaction (LDR) with the use of simple glass slides specifically functionalized with a novel polymer coating to enhance sensitivity. METHODS: Wedeveloped an array-based genotyping assay based on glass slides coated with copolymer (N,Ndimethylacrylamide, N,N-acryloyloxysuccinimide, and 3-(trimethoxysilyl)propyl methacrylate). The assay consists of an LDR with genomic DNA followed by a universal PCR (U-PCR) of genomic DNA–templated LDR product. The LDR occurs in the presence of 3 primers for each sequence variant under investigation: 2 distinguishing primers (allele specific and perfectly complementary to wild-type and mutant alleles) and 1 common locus-specific primer. The 2 allele-specific primers have different capture sequences for binding different complementary probes on a tag array. The LDR product templated from genomic DNA is made fluorescent during the U-PCR via incorporation of a Cy5-labeled universal primer into all LDR products; detection occurs on the coated glass slides. RESULTS: The assay was designed to detect 7 prevalent mutations in the -globin gene (HBB, hemoglobin, beta) in amultiplex format, and signals for the different alleles are detected by their fluorescence. The assay was applied to 40 genomicDNAsamples from both control individuals and patients with known -thalassemia mutations. Results show good correspondence between the patients’ genotypes as assessed by DNA sequence analysis and those generated from the LDR assays. CONCLUSIONS: The developed technology allows accurate identification of sequence variants in a simple, cost-effective way and offers good flexibility for scaling to other applications with different numbers of single nucleotide polymorphisms or mutations to be detected