Protracted shearing at mid‐crustal conditions during large‐scale thrusting in the Scandinavian Caledonides

During continental collision, large tracts of crust are mobilised along major shear zones. The metamorphic conditions at which these zones operate, the duration of thrusting, and the deformation processes that facilitated hundreds of km of tectonic transport are still unclear. In the Scandinavian Caledonides, the Lower Seve Nappe displays a main mylonitic foliation with thickness of ~1 km. This foliation is overprinted by a brittle‐to‐ductile deformation pattern localized in C and C’‐type shear bands proximal to the tectonic contact with the underlying Särv Nappe. Thermobarometry of amphibolites and micaschists suggest a first high‐pressure stage at 400‐500°C and 1‐1.3 GPa recorded in mineral relics. The main mylonitic foliation developed under epidote amphibolite facies conditions along the retrograde path from 600°C and 1 GPa to 500°C and 0.5 GPa. Age dating of synkinematic titanite grains in the amphibolites indicates that this mylonitic fabric formed at around 417 ± 9 Ma, but older ages spanning 460‐430 Ma could represent earlier stages of mylonitization. The shear bands developed at lower metamorphic conditions of 300‐400°C and ~0.3 GPa. In the micaschists, the recrystallized grain size of quartz decreases towards the shear bands. Monomineralic quartz layers are eventually dismembered to form polyphase aggregates deforming by dominant grain size sensitive creep accompanied by slip in muscovite and chlorite. Plagioclase zoning truncations suggest that the shear bands originated by fracturing followed by ductile deformation. The results suggest protracted and long‐lasting shearing under amphibolite to greenschist facies conditions during the juxtaposition, stacking and exhumation of the Lower Seve Nappe

Body mass index is not a predictor of biochemical recurrence after radical prostatectomy in Dutch men diagnosed with prostate cancer

Contains fulltext : 95677.pdf (publisher's version ) (Closed access)PURPOSE: To determine the effect of body mass index (BMI) on clinical and pathological characteristics at time of diagnosis and on risk of biochemical recurrence after radical prostatectomy among Dutch men diagnosed with prostate cancer. METHODS: In total, 1,116 prostate cancer patients with known BMI, diagnosed between 2003 and 2006, were identified from the population-based cancer registry held by the Comprehensive Cancer Centre East, The Netherlands. Of these, 504 patients underwent a radical prostatectomy. Patients were categorized as normal weight (BMI /= 30 kg/m(2)). Multivariable proportional hazards regression models, adjusted for age, prediagnostic PSA levels, and pathological characteristics were used to evaluate BMI as a prognostic factor for biochemical recurrence after radical prostatectomy. RESULTS: Overall, clinical and biopsy characteristics did not significantly differ among BMI groups. Pathological characteristics after radical prostatectomy did not significantly differ among BMI groups, except for tumor stage, which was highest in obese patients (P = 0.017). For patients treated with radical prostatectomy, 5-year risk (95% Confidence Intervals) of biochemical recurrence was 30% (23-37%) for normal weight, 32% (25-39%) for overweight, and 25% (9-41%) for obese patients (log rank P = 0.810). BMI was not an independent prognostic factor for biochemical recurrence in multivariable proportional hazards regression analyses (HR 0.99 per kg/m(2), 95% CI: 0.93-1.06). CONCLUSIONS: Compared with non-obese men, pathological tumor stage tended to be higher in obese men. Clinical relevance of this finding is unclear, because BMI was not an independent predictor of biochemical recurrence after radical prostatectomy

For Psyche

In the present study we investigated peroxisomal functions in cultured human muscle cells from control subjects and from a patient with the Zellweger syndrome, a genetic disease characterized by the absence of morphologically distinguishable peroxisomes in liver and kidney. In homogenates of cultured muscle cells from control subjects, catalase is contained within subcellular particles, acyl-CoA:dihydroxyacetonephosphate acyltransferase activity is present and palmitoyl-CoA can be oxidized by a peroxisomal beta-oxidative pathway; these findings are indicative of the presence of peroxisomes in the cells. In homogenates of cultured muscle cells from the patient with the Zellweger syndrome, acyl-CoA:dihydroxyacetonephosphate acyltransferase activity was deficient, peroxisomal beta-oxidation of palmitoyl-CoA was impaired and catalase was not particle-bound. These findings indicate that functional peroxisomes are absent in muscle from patients with the Zellweger syndrome. We conclude that cultured human muscle cells can be used as a model system to study peroxisomal functions in muscle and the consequences for this tissue of a generalized dysfunction of peroxisome

Validation of Claims Data for Absorbing Pads as a Measure for Urinary Incontinence after Radical Prostatectomy, a National Cross-Sectional Analysis

The use of healthcare insurance claims data for urinary incontinence (UI) pads has the potential to serve as an objective measure for assessing post-radical prostatectomy UI rates, but its validity for this purpose has not been established. The aim of this study is to correlate claims data with Patient Reported Outcome Measures (PROMs) for UI pad use. Patients who underwent RP in the Netherlands between September 2019 and February 2020 were included. Incontinence was defined as the daily use of ≥1 pad(s). Claims data for UI pads at 12-15 months after RP were extracted from a nationwide healthcare insurance database in the Netherlands. Participating hospitals provided PROMS data. In total, 1624 patients underwent RP. Corresponding data of 845 patients was provided by nine participating hospitals, of which 416 patients were matched with complete PROMs data. Claims data and PROMs showed 31% and 45% post-RP UI (≥1 pads). UI according to claims data compared with PROMs had a sensitivity of 62%, specificity of 96%, PPV of 92%, NPV of 75% and accuracy of 81%. The agreement between both methods was moderate (κ = 0.60). Claims data for pads moderately align with PROMs in assessing post-prostatectomy urinary incontinence and could be considered as a conservative quality indicator.</p

Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces cerevisiae CEN.PK113-1A

<p>Abstract</p> <p>Background</p> <p>The yeast <it>Saccharomyces cerevisiae </it>is able to adjust to external oxygen availability by utilizing both respirative and fermentative metabolic modes. Adjusting the metabolic mode involves alteration of the intracellular metabolic fluxes that are determined by the cell's multilevel regulatory network. Oxygen is a major determinant of the physiology of <it>S. cerevisiae </it>but understanding of the oxygen dependence of intracellular flux distributions is still scarce.</p> <p>Results</p> <p>Metabolic flux distributions of <it>S. cerevisiae </it>CEN.PK113-1A growing in glucose-limited chemostat cultures at a dilution rate of 0.1 h^-1with 20.9%, 2.8%, 1.0%, 0.5% or 0.0% O₂in the inlet gas were quantified by ¹³C-MFA. Metabolic flux ratios from fractional [U-¹³C]glucose labelling experiments were used to solve the underdetermined MFA system of central carbon metabolism of <it>S. cerevisiae</it>.</p> <p>While ethanol production was observed already in 2.8% oxygen, only minor differences in the flux distribution were observed, compared to fully aerobic conditions. However, in 1.0% and 0.5% oxygen the respiratory rate was severely restricted, resulting in progressively reduced fluxes through the TCA cycle and the direction of major fluxes to the fermentative pathway. A redistribution of fluxes was observed in all branching points of central carbon metabolism. Yet only when oxygen provision was reduced to 0.5%, was the biomass yield exceeded by the yields of ethanol and CO₂. Respirative ATP generation provided 59% of the ATP demand in fully aerobic conditions and still a substantial 25% in 0.5% oxygenation. An extensive redistribution of fluxes was observed in anaerobic conditions compared to all the aerobic conditions. Positive correlation between the transcriptional levels of metabolic enzymes and the corresponding fluxes in the different oxygenation conditions was found only in the respirative pathway.</p> <p>Conclusion</p> <p>¹³C-constrained MFA enabled quantitative determination of intracellular fluxes in conditions of different redox challenges without including redox cofactors in metabolite mass balances. A redistribution of fluxes was observed not only for respirative, respiro-fermentative and fermentative metabolisms, but also for cells grown with 2.8%, 1.0% and 0.5% oxygen. Although the cellular metabolism was respiro-fermentative in each of these low oxygen conditions, the actual amount of oxygen available resulted in different contributions through respirative and fermentative pathways.</p

Risk of poultry compartments for transmission of Highly Pathogenic Avian Influenza.

When outbreaks of Highly Pathogenic Avian Influenza (HPAI) occur in OIE member countries with until then disease-free status, member countries can use 'compartmentalisation'. A compartment may be defined as a subset of farms under a common management system, complying with certain stringent surveillance, control and biosecurity measures, and based on that may receive a disease-free status. Based on this disease-free status the compartment is exempted from certain transport restrictions coming into force in case of outbreaks occurring in the country. For deciding whether a candidate compartment is granted official compartment status, it is relevant to assess the additional HPAI transmission risks that would arise due to the exemptions granted. These risks consist of both additional local transmission risks as well as the additional risk of a 'jump' of HPAI infection from one poultry area, via the compartment, to another area. Here such risk assessment is carried out using a spatial mathematical model for between-farm transmission in the Netherlands, yielding insight in the roles of compartment composition and contact structure and identify relevant evaluation criteria for granting HPAI compartment status. At the core of this model are transmission probabilities associated with indirect between-farm contacts, e.g. through feed delivery, egg collection and professional visitors. These probabilities were estimated from Dutch epidemic outbreak data in earlier work. The additional risk of a jump of HPAI from one area, via the compartment, to another area is calculated relative to the direct jump risk. The results show that additional transmission risks caused by a compartment to other farms are mainly dependent on the distance of densely populated poultry areas (DPPAs) to the nearest compartment farm. Apart from conditions on these distances, we also recommend specific routing requirements for transport and other movements within the compartment

Peroxisomal and mitochondrial carnitine acetyltransferases of Saccharomyces cerevisiae are encoded by a single gene.

Carnitine acetyltransferase (CAT) is present in mitochondria and peroxisomes of oleate-grown Saccharomyces cerevisiae. Both proteins are encoded by the same gene, YCAT, which encodes a protein with a mitochondrial targeting signal (MTS) at the N-terminus, and a peroxisomal targeting signal type 1 (PTS-1) at the C-terminus. Deletion of both motifs revealed the presence of an additional internal targeting sequence. Import of CAT via this internal signal was shown to be dependent on PAS10, a protein which is required for the import of PTS-1 containing proteins. An interaction of PAS10 with this internal targeting signal was demonstrated using the yeast two-hybrid technique. Expression of the YCAT gene behind a heterologous promoter resulted in loss of peroxisomal targeting, indicating that differential targeting is controlled at transcriptional or translational level. Determination of the 5'-ends of YCAT mRNAs revealed that YCAT transcripts initiating after the first AUG were present in oleate-grown cells. These transcripts were virtually absent in acetate- or glycerol-grown cells. We propose that in response to oleate, shorter transcripts are produced from which the peroxisomal form of CAT is translated, resulting in a CAT protein without a MTS, which can be targeted to peroxisomes