Biomarker Response to Galactic Cosmic Ray-Induced NOx and the Methane Greenhouse Effect in the Atmosphere of an Earthlike Planet Orbiting an M-Dwarf Star

Planets orbiting in the habitable zone (HZ) of M-Dwarf stars are subject to high levels of galactic cosmic rays (GCRs) which produce nitrogen oxides in earthlike atmospheres. We investigate to what extent this NOx may modify biomarker compounds such as ozone (O3) and nitrous oxide (N2O), as well as related compounds such as water (H2O) (essential for life) and methane (CH4) (which has both abiotic and biotic sources) . Our model results suggest that such signals are robust, changing in the M-star world atmospheric column by up to 20% due to the GCR NOx effects compared to an M-star run without GCR effects and can therefore survive at least the effects of galactic cosmic rays. We have not however investigated stellar cosmic rays here. CH4 levels are about 10 times higher than on the Earth related to a lowering in hydroxyl (OH) in response to changes in UV. The increase is less than reported in previous studies. This difference arose partly because we used different biogenic input. For example, we employed 23% lower CH4 fluxes compared to those studies. Unlike on the Earth, relatively modest changes in these fluxes can lead to larger changes in the concentrations of biomarker and related species on the M-star world. We calculate a CH4 greenhouse heating effect of up to 4K. O3 photochemistry in terms of the smog mechanism and the catalytic loss cycles on the M-star world differs considerably compared with the Earth

Benefit of Problem-Based Learning for Psychosocial Medicine: first experiences at the medical faculty of berne

Aim: Presentation of skills and knowledge of medical students in psychiatry or psychosocial medicine in basic study (year 1 to 3) after the introduction of a problem oriented learning curriculum at the Medical Faculty of Berne.Method: Description of the curriculum with the different teaching units, and the evaluation by means of formative tools used by students and tutors.Results: With reference to qualitative comparison students of the problem based learning track showed a better preparation of the different teaching units than did traditional students. Moreover, compared to classical teaching, students in problem based learning rated the commitment of the teachers higher. The formative results showed a better adherence to the teaching modules, a higher effort in self learning and a higher interest in psychological or psychiatric learning items.Discussion: The higher commitment of teachers and the explicit structuring of the teaching contents in psychiatry and psychosocial medicine showed positive effects in the learning strategy of students. Beside the fact that exams have been adapted to the new curriculum one can assume that the learning style has changed. This might be a result of the better learning environment in the new curriculum. However, there is not clear how and to what extent these changes will remain active until the final exams of the medical curriculum when psychosocial contents will be reexamined.Conclusions: The intense commitment of the teachers and the better structuring of the subject matter may lead to a better integration of psychosocial and psychiatric issues into the medical curriculum

The C-terminus of glycosylphosphatidylinositol-specific phospholipase D is essential for biological activity

AbstractGlycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) (EC 3.1.4.50) from mammalian serum is a 115 kDa glycoprotein consisting of 816 amino acids. We found that C-terminal deletions of only two to five amino acids reduced GPI-PLD enzymatic activity by roughly 70% as compared to wild-type protein. C-terminal deletions of more than five amino acids resulted in a complete loss of GPI-PLD enzymatic activity. Point mutations at position 811 indicate that Tyr-811 may play a major role in maintaining the biological activity of GPI-PLD

Repression of nuclear lamin A and C gene expression in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells

The lamins A, B and C which are differentially expressed during ontogenesis and differentiation are karyoskeletal proteins forming a polymeric meshwork at the inner nuclear membrane. Using Northern blot analyses we investigated the steady state levels of the three lamin specific RNA transcripts in neoplastic cells derived from 16 untreated patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) and in ALL and NHL established cell lines. Whereas lamin B mRNA was present in all, lamin A and C transcripts were observed in none of the malignant cell samples except one of a common-ALL patient (precursor B-ALL, cytoplasmic μ chain negative). All three lamin mRNAs were detected in normal peripheral blood lymphocytes, however, only after mitogenic stimulation with concanavalin A. Our results provide evidence that expression of lamin A and C is repressed in neoplastic blast cells derived from patients with ALL or NHL and suggest that lamin A and C gene repression is not related to cell proliferation but might be relevant to the differentiated stages of the lymphoid cells in vivo

Immunogenotyping with antigen receptor gene probes as a diagnostic tool in childhood acute lymphoblastic leukaemia

13 cases of childhood acute lymphoblastic leukaemia (ALL) were studied combining cell surface marker analysis with immunogenotyping by Southern blot hybridisation with a panel of antigen receptor gene probes. The immunophenotypes were unequivocal: 7 patients had B-phenotype and 6 patients T-phenotype ALL. In several patients immunogenotypes were not fully consistent with the respective phenotypes. For example, 2 B-cell precursor ALL had rearranged TCR beta chain genes and 2 T-ALL rearrangement of Ig heavy-chain genes. All cases showed clonal rearrangement or deletions within the TCR delta gene locus. TCR delta gene rearrangements might, therefore, serve as markers of clonality but not of B- or T-lineage in immature lymphoid neoplasms. We conclude that in current diagnostic practice immunogenotyping is a supplement rather than an alternative to immunophenotyping by surface marker analysis

Valproic Acid-Associated Acute Pancreatitis: Systematic Literature Review

Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0–24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate