Tillage modifies soil structure and crop residue distribution and in turn affects the ability of soil micro-organisms to degrade soil organic matter and release nutrients for crop growth. In organic ...farming, soil microbiological activity is of primary importance as nutrient supply is mainly dependent on the degradation of soil organic matter by soil micro-organisms. The aim of this work was therefore to study, in organic farming, the effects of four tillage systems mouldboard ploughing (MP), shallow mouldboard ploughing (SMP), reduced tillage (RT) and shallow soil tillage (ST) on soil structure, soil microbial biomass (SMB) and its potential activity (Cmin) during the first year following the treatments. To study simultaneously the effects of soil structure modifications and crop residue distribution on SMB and Cmin, we adopted a sampling scheme based on a morphological description of soil profiles. We distinguished and sampled compacted and non-compacted clods (Δ and Γ clods) at three depths (0-5, 5-15 and 15-30 cm). This method enabled us to have a precise estimation of the effects of tillage treatments on SMB and Cmin. MP reduced compacted zones and limited unfavourable conditions for microbial growth and enabled a homogenous distribution of SMB in the soil profile. At the opposite, the ST increased compacted zones in the soil profile and limited SMB development below the top few centimetres. The SMP and the RT systems appeared as intermediate techniques. RT seemed to be a conservation tillage technique which could be used in organic farming.
1
S 16257 is a new bradycardic agent. Its electropharmacological profile has been compared to that of the known bradycardic compound UL‐FS 49 (Zatebradine). Intracellular recordings of action ...potentials (APs) were performed with conventional glass microelectrodes.
2
In the rabbit isolated sino‐atrial node (SAN) tissue, S 16257 and UL‐FS 49 (1 μm, 3 μm and 10 μm) were equipotent in slowing spontaneous APs firing predominantly by decreasing the rate of diastolic depolarization (at 3 μm, – 23.8 ± 3.9% and – 27.9 ± 2.6%, respectively). For the two compounds a maximal effect was obtained at 3 μm. In these preparations, action potential duration at 50% of total repolarization (APD50) was more affected by UL‐FS 49 than S 16257 at any concentration tested (at 3 μm, + 8.9 ± 2.9% and + 29.1 ± 3.7% for S 16257 and UL‐FS 49, respectively; P ≤ 0.01).
3
To estimate the direct effects on AP duration, driven cardiac preparations were exposed to these agents. In guinea‐pig papillary muscles, paced at a frequency of 1 Hz, increasing concentrations of S 16257 or UL‐FS 49 (0.1 to 10 μm, 30 min exposure for each concentration) slightly prolonged AP repolarization. This prolongation was more marked for UL‐FS 49 (at 1 μm, + 6.1 ± 0.6% and + 11.2 ± 1.3% elevation of APD50, for S 16257 and UL‐FS 49, respectively).
4
Application of UL‐FS 49 (3 μm) to rabbit Purkinje fibres, triggered at a frequency of 0.25 Hz, induced a marked prolongation of APD50 and APD90 (+ 149.4 ± 51.2% and + 86.0 ± 15.4%, respectively). S 16257 (3 μm) induced only a weak prolongation of AP (+ 14.1 ± 5.0% and + 14.8 ± 3.3% for APD50 and APD90, respectively) significantly smaller than in the case of UL‐FS 49.
5
These results show that S 16257 slows the rate of spontaneous AP firing in isolated SAN mainly by a reduction of the diastolic depolarization of the cells, which suggests an inhibition of the pace‐maker current (If). S 16257 and UL‐FS 49 are equipotent in their bradycardic effect but S 16257 is more specific as it induces less increase in myocardial repolarization time.
We show that the conformational features of the molecular complexes of E. coli beta-galactosidase and O-glycosides may differ from those formed with closely related compounds in their chemical ...nature, such as C- and S-glycosyl analogues. In the particular case presented here, NMR and ab initio quantum mechanical results show that the 3D-shapes of the ligand/inhibitor within the enzyme binding site depend on the chemical nature of the compounds. In fact, they depend on the relative size of the stereoelectronic barriers for chair deformation or for rotation around Phi glycosidic linkage.
Boris Vian is a rare phenomenon. Nothing short of a national treasure in France, he is hardly known overseas. In his lifetime, he divided literary opinion with masterpieces that failed to sell and ...best sellers that caused outrage, trials and even deaths, including his own. As an impresario, he became the figurehead of the jazz scene that marked the French left bank at the end of the Second World War and was responsible for bringing Duke Ellington and Miles Davis to France. As a musician, he played his trumpet against the advice of cardiologists, sang pacifist songs before audiences of outraged patriots and, in passing, created French rock ‘n’ roll. Posthumously, he became known for his theatre, film scripts and poetry as well as for his novels. And in May ’68 he became a revolutionary icon.
Boris Vian is a rare phenomenon. Nothing short of a national treasure in France, he is hardly known overseas. In his lifetime, he divided literary opinion with masterpieces that failed to sell and ...best sellers that caused outrage, trials and even deaths, including his own. As an impresario, he became the figurehead of the jazz scene that marked the French left bank at the end of the Second World War and was responsible for bringing Duke Ellington and Miles Davis to France. As a musician, he played his trumpet against the advice of cardiologists, sang pacifist songs before audiences of outraged patriots and, in passing, created French rock ‘n’ roll. Posthumously, he became known for his theatre, film scripts and poetry as well as for his novels. And in May ’68 he became a revolutionary icon.
Summary
Background
The malignant mechanisms that control the development of cutaneous T‐cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific ...intracellular signalling pathways, such as RAS–mitogen‐activated protein kinase, T‐cell receptor (TCR)–phospholipase C gamma 1 (PLCG1)–nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)–signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL.
Objectives
To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL.
Methods
We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin‐fixed paraffin‐embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR–PLCG1–NFAT, JAK–STAT and NF‐κB pathways. Folliculotropism and large‐cell transformation were also examined.
Results
NFAT and nuclear factor kappa B (NF‐κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large‐cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF‐negative cases. A significant association of NFAT with NF‐κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T‐cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell‐survival pathways. A higher mutational allele frequency was detected in advanced stages.
Conclusions
Our results show that STAT3 is activated in advanced cases and is associated with large‐cell transformation, while the activation of NFAT and NF‐κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications.
What's already known about this topic?
Mycosis fungoides is characterized by a clonal expansion of T cells in the skin.
The mechanisms controlling disease development and progression are not fully understood.
What does this study add?
An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level.
Signal transducer and activator of transcription 3 activation was associated with large‐cell transformation and was more frequent in advanced stages.
A genomic analysis of cutaneous T‐cell lymphoma‐associated genes was performed. Nine mutations were detected.
What is the translational message?
These results could have important implications for the treatment of MF in the near future.
Linked Comment: Ødum. Br J Dermatol 2020; 182:16–17.
The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are ...susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. Unexpectedly, in these domains, AID deaminates active promoters and eRNA+ enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing, we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment.
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•AID targets are interconnected in 3D nuclear space•Targeted networks overlap predominantly with super-enhancer domains•Both promoters and transcriptionally active cognate enhancers are damaged by AID•Tethered regulatory elements cooperate to recruit AID activity
AID targets in the genome are interconnected in 3D networks that overlap with super-enhancer domains, revealing the role of the nuclear architecture and the B cell regulome in recruiting AID activity.
Bacterial meningitis, frequently caused by Streptococcus pneumoniae (pneumococcus), represents a substantial global health threat leading to long-term neurological disorders. This study focused on ...the cholesterol-binding toxin pneumolysin (PLY) released by pneumococci, specifically examining clinical isolates from patients with meningitis and comparing them to the PLY-reference S. pneumoniae strain D39. Clinical isolates exhibit enhanced PLY release, likely due to a significantly higher expression of the autolysin LytA. Notably, the same single amino acid (aa) D380 substitution in the PLY D4 domain present in all clinical isolates significantly enhances cholesterol binding, pore-forming activity, and cytotoxicity toward SH-SY5Y-derived neuronal cells. Scanning electron microscopy of human neuronal cells and patch clamp electrophysiological recordings on mouse brain slices confirm the enhanced neurotoxicity of the PLY variant carrying the single aa substitution. This study highlights how a single aa modification enormously alters PLY cytotoxic potential, emphasizing the importance of PLY as a major cause of the neurological sequelae associated with pneumococcal meningitis.
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•Pneumococcal meningitis isolates release more PLY than the reference strain D39•The PLY of the clinical isolates has a single aa substitution compared to the D39 PLY•This single aa substitution significantly enhances PLY pore-forming activity•Higher pore-forming activity leads to higher cytotoxicity toward neurons
Natural sciences; Biological sciences; Biochemistry; Neuroscience; Molecular neuroscience; Microbiology; Medical Microbiology
Introduction
Psychiatrists should be aware of the new challenges and needs that globalization poses.
Objectives
To highlight the need for a culturally sensitive approach to mental health.
Methods
...Non-systematic review of “cultural consultation” on PubMed.
Results
Most people assume a direct connection between pathophysiology and clinical symptoms. However, evidence shows that the translation of pathophysiology and psychopathology into specific symptoms is mediated by cognitive processes and social interactions, which reflect models/practices specific to our culture. Patients focus on specific aspects of being sick, reinforced by cultural narratives or to fit expectations. Thus, people from different cultural backgrounds might have trouble communicating; cultural idioms of distress can be misinterpreted. The role of structural violence bestowed upon cultural minorities, which leads to discrimination and social exclusion, has extensively been studied as a risk factor for mental illness. Furthermore, ignoring cultural differences and diversity has been shown to contribute to healthcare disparities, hampering access to care and diminishing the quality of care received. In Canada, the Cultural Consultation Model provides cultural expertise, either by evaluating patients (preferably accompanied by the referring doctor, a translator and cultural mediator) for 1-3 sessions, providing recommendations to the referring doctor; or providing consulting to a referring doctor or organisation, through general guidance or discussion of specific cases.
Conclusions
In an evergrowing globalization process, we will inevitably have more contact with patients from culturally distinct backgrounds. To provide the best care, we must be aware of the ways in which culture can shape symptom expression, and take into account cultural explanations and preferences.
Disclosure
No significant relationships.
Introduction
Research has shown that ethnic/racial minorities have a higher risk of homelessness, involvement with the criminal system, psychiatric misdiagnosis, treatment delay, and being prescribed ...first (versus second) generation antipsychotics.
Objectives
To investigate if the disparities found in the community are replicated in incarcerated patients.
Methods
Systematic review on PubMed for articles that fulfilled criteria for 4 domains: prison, psychosis, race/ethnic, and treatment.
Results
Forty-one articles matched the search criteria. Of those, 24 were irrelevant; 2 were inaccessible. Fifteen articles were considered; most highlighted the interplay between the criminal system, homelessness, mental disorders, and ethnic/racial minorities. Five articles highlighted differences in treatment. One stated that African-Americans and Asians were less likely than Whites to have access to mental health services. Concerning treatment for substance use disorders, one study found Hispanic inmates were more often engaged in treatment, followed by Caucasians and lastly, African-Americans; a different study reported the percentage of Whites and Blacks receiving treatment was similar, while Latinos were under-represented. Whites were most likely to have mental health counseling/substance use treatment as part of their sentence. A study from New-Zealand stated that treatment for mental disorders was less common for Maoris, in whom suicidal thoughts were often unrecognized. The last study reported a higher risk of self-harm for foreign patients, coupled with non-recognition/misinterpretation of symptoms.
Conclusions
Racial/ethnic inequalities show that disparities in healthcare are pervasive in all settings. More studies are needed to better understand the complex nature of this problem.
Disclosure
No significant relationships.
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