Mesothelioma is a rare form of cancer arising from a monolayer of mesothelial cells that form the lining of the internal body cavities and organs, with the vast majority of cases arising from the pleura (65-80%), less commonly from the peritoneum (10-30%), and rarely from the pericardium and tunica vaginalis testis (1-2%).
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary cutaneous T-cell lymphoma that shares significant clinical, histopathologic, and immunophenotypic overlap with lupus erythematosus panniculitis (LEP).
We performed immunohistochemistry for the MYC oncoprotein on 23 cases of SPTCL (one CD8 negative) and 12 cases of LEP to evaluate if there are quantitative or qualitative differences in protein expression of this marker in these entities.
In SPTCL cases, the percentage of all cells that were c-Myc positive ranged from 0.8% to 16%, with a mean of 5.0% and a median of 4.4%. In contrast, in the LEP cases, the percentage of c-Myc positive cells in the cases ranged from 0.34% to 3.7%, averaged 1.4%, and the median was 0.8%. The difference between the means of these two diagnostic categories was statistically significant. Fluorescence in situ hybridization performed on 4 cases of SPTCL with a relatively high level of MYC immunohistochemical staining, however, failed to demonstrate evidence of MYC rearrangement or amplification.
Our work demonstrates that MYC expression levels differ between these two histologic mimics and suggests that this important oncoprotein may play a role in the pathogenesis of SPTCL.
Publication date: July 2017
Source:Brain Research Bulletin, Volume 133
Author(s): Annadurai Anandhan, Maria S. Jacome, Shulei Lei, Pablo Hernandez-Franco, Aglaia Pappa, Mihalis I. Panayiotidis, Robert Powers, Rodrigo Franco
The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism.
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Publication date: July 2017
Source:Brain Research Bulletin, Volume 133
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Few studies have focused on the effects of long-term forest plantations on the soil profile of carbon (C) and nitrogen (N) stocks. In this study, we selected 78-year-old tree plantations that included three coniferous tree species (i.e., slash pine, hoop pine and kauri pine) and a Eucalyptus species in subtropical Australia. We measured soil extractable organic C (EOC) and N (EON) contents and total C and N stocks under different tree species on the forest floor and along a soil profile to 100 cm depth. The results showed that Eucalyptus had significantly higher soil EOC contents (3.3 Mg ha−1) than the other tree species (EOC of 1.9–2.3 Mg ha−1) and had significantly higher EON (156 kg ha−1) contents than slash pine (107 kg ha−1). Eucalyptus had significantly higher soil C (58.9 Mg ha−1) and N (2.03 Mg ha−1) stocks than the other tree species (22.3–27.6 Mg C ha−1 and 0.71–1.23 Mg N ha−1) at 0–100 cm depth. There were no differences in soil C stocks at the 0–100 cm depth among the coniferous tree species. Forest floor C stocks had stronger effects on mineral soil total N stocks than fine root biomass, whereas fine root biomass exerted stronger effects on soil total C stocks at the 0–100 cm depth than forest floor C and N stocks. Our results addressed large differences in soil C and N stocks under different tree species, which can provide useful information for local forest management practices in this region.
Publication date: Available online 10 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Henrik Petszulat, Oliver Seitz
Protein-templated reactions have been used for fragment-based drug discovery as well as for covalent labeling, detection and manipulation of proteins. In spite of the growing interest in protein-templated reactions, little is known about the design criteria. Herein we present a systematic study on the effects of proximity in peptide-templated reactions. To facilitate reaction monitoring at low concentrations we developed a fluorogenic native chemical ligation that is based on the integration of a fluorescence quencher in the thiol leaving group. The reaction system provided up to 39-fold increases of emission from a fluorescein unit. By using templates based on coiled coils as models we investigated the effect of misalignments. The distance-reactivity pattern for remotely aligned peptides was remarkably different to reaction scenarios that involved seamlessly annealed peptides with overhanging functional groups.
Publication date: Available online 10 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Rohit Singh, Vikas Kumar, Sonali S. Bharate, Ram A. Vishwakarma
Bergenin is a unique C-glycoside natural product possessing anti-inflammatory and anti-arthritic activity. It is hydrophilic molecule and stable under acidic conditions however is unstable at neutral-basic pH conditions. The rate of degradation is directly proportional to the increase in pH which might be one of the reasons for its low oral bioavailability. Thus, herein our objective was to improve its stability using prodrug strategy. Various ester and ether prodrugs were synthesized and studied for lipophilicity, chemical stability and enzymatic hydrolysis in plasma/ esterase. The stability of synthesized prodrugs was evaluated in buffers at different pH, in biorelevant media such as SGF, SIF, rat plasma and in esterase enzyme. All prodrugs displayed significantly improved lipophilicity compared with bergenin, which was in accordance with the criteria of drug-like compounds. Acetyl ester 4a2 appeared to be the most promising prodrug as it remained stable at gastric/intestinal pH and was completely transformed to the parent compound bergenin in plasma as desired for an ideal prodrug. The data presented herein, will help in designing stable prodrugs of unstable molecules with desired physicochemical properties in structurally similar chemotypes.
Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions.
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Diet and activity interventions in pregnancy reduce gestational weight gain, with no significant benefit for a composite of maternal and fetal outcomes, irrespective of maternal characteristics, and are not cost-effective
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One of the strategic objectives of the National Institute on Aging (NIA) is to "support the development of population-based data sets, especially from longitudinal studies, suitable for analysis of biological, behavioral, and social factors affecting health, well-being, and functional status through the life course." To contribute to that objective and to inform the development of a methodological research program for longitudinal studies, the Committee on National Statistics held a public workshop in June 2017. The discussion focused on challenges that are specific to the types of longitudinal studies supported by NIA and aimed to identify areas of methodological research that could be pursued in order to benefit from emerging methods, new techniques, or other opportunities to enhance the data and increase data collection efficiency. This publication summarizes the presentations and discussions from the workshop.
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Publication date: Available online 10 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Aya Mousa, Negar Naderpoor, Maximilian P.J. de Courten, Barbora de Courten
Recent evidence suggests that vitamin D deficiency may contribute to increased risk of depression. However, previous studies are limited by variability in participant characteristics including vitamin D deficiency status and presence of existing diseases, use of low doses of vitamin D supplementation for short durations, and use of co-interventions or psychotropic drugs. We examined whether 25-hydroxyvitamin D (25(OH)D) concentrations were associated with symptoms of depression, as well as whether vitamin D supplementation reduced symptoms of depression in overweight or obese and vitamin D-deficient, but otherwise healthy adults.Cross-sectional analyses were performed on baseline data from 63 (39M/24F) overweight or obese (body mass index (BMI) ≥25kg/m2) and vitamin D-deficient (25(OH)D ≤50 nmol/l) adults (mean age=31.3±8.5), without clinical depression. Participants were randomized to either a bolus oral dose of 100,000 IU followed by 4,000 IU daily of cholecalciferol, or matching placebo for 16 weeks. Interventional analyses were performed on data from 48 participants (30M/18F) who completed the trial. We measured serum 25(OH)D concentrations; anthropometry: BMI, waist-to-hip ratio (WHR), % body fat (dual X-ray absorptiometry); and depressive symptoms using the Beck Depression Inventory (BDI) before and after intervention. Data on dietary vitamin D intake (3-day food record), physical activity (international physical activity questionnaire), and sun exposure habits were collected using questionnaires.At baseline, mean 25(OH)D concentration was 32.9±11.3 nmol/l and total BDI score was 6.6±6.3 (range=0–33). There were no associations between 25(OH)D concentrations and total BDI scores or BDI subscales (all p>0.1). After the 16-week intervention, 25(OH)D concentrations increased in the vitamin D group compared to placebo (56.0±20.8 versus 2.7±13.9 nmol/L, respectively; p <0.0001). Change in total BDI scores did not differ between vitamin D and placebo groups (−2.0±4.5 versus −1.5±2.9, respectively; p=0.7). There were no differences in BDI subscales between groups (both p>0.1). Results remained non-significant after adjusting for multiple covariates including sun exposure, physical activity, and dietary vitamin D intake (all p>0.1).Our findings suggest that vitamin D deficiency may not be related to increased risk of depression in individuals without clinically significant depression and that the use of vitamin D supplementation may not be warranted for reducing depressive symptoms in this population. Further large-scale studies are needed to establish whether vitamin D supplementation may be beneficial for improving depressive symptoms in other population groups, including in those with existing depressive or psychiatric disorders.
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