Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy

Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17β‐estradiol has been suggested as a contributing factor to aging‐related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre‐ and postmenopausal women to establish proteome‐wide profiles, associated with the difference in age (30–34 years old vs. 54–62 years old), menopausal status (premenopausal vs. postmenopausal), and use of hormone replacement therapy (HRT; user vs. nonuser). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic (MZ) cotwin pairs of whom the other sister was current HRT user or the other had never used HRT. Label‐free proteomic analyses resulted in the quantification of 797 muscle proteins of which 145 proteins were for the first time associated with female aging using proteomics. Furthermore, we identified 17β‐estradiol as a potential upstream regulator of the observed differences in muscle energy pathways. These findings pinpoint the underlying molecular mechanisms of the metabolic dysfunction accruing upon menopause, thus having implications for understanding the complex functional interactions between female reproductive hormones and health.     

Predictive Factors of Late Venous Aortocoronary Graft Failure: Ultrastructural Studies

Background

Venous aortocoronary graft arterialization may precede a preterm occlusion in some coronary artery bypass grafting (CABG) patients. The aim of the present study was to identify ultrastructural variations in the saphenous vein wall that may have an impact on the development of venous graft disease in CABG patients.

Methods

The study involved 365 consecutive patients with a mean age of 62.9±9.4 years who underwent isolated CABG. The thickness and area of the whole venous wall, the tunica intima, the tunica media and the adventitia and the number and shape (length, thickness and length/thickness ratio) of the nuclei in the medial smooth muscle cells nuclei in the distal saphenous vein segments were evaluated by ultrastructural studies. Patients were followed up for 41 to 50 months (mean 45.1±5.1). Saphenous vein graft patency was assessed by follow-up coronary angiography. Logistic regression models were used to identify independent risk factors for late graft failure.

Results

In 71 patients significant lesions in the saphenous vein grafts were observed. The whole venous wall thickness (437.5 µm vs. 405.5 µm), tunica media thickness (257.2 µm vs. 211.5 µm), whole venous wall area (2.23 mm² vs. 2.02 mm²) and tunica media area (1.09 mm² vs. 0.93 mm²) were significantly larger for this group of patients than for those without graft disease. In the latter group more elongated smooth muscle cell nuclei (higher length/thickness ratio) were found in the tunica media of the saphenous vein segments. Thickening of the saphenous vein tunica media and chunky smooth muscle cell nuclei were identified as independent risk factors for graft disease development.

Conclusions

Saphenous vein tunica media hypertrophy (resulting in wall thickening) and chunky smooth muscle cell nuclei might predict the development of venous graft disease.     

Skeletal Lesions in Human Tuberculosis May Sometimes Heal: An Aid to Palaeopathological Diagnoses

In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses.     

Large-scale candidate gene analysis of HDL particle features

Background

HDL cholesterol (HDL-C) is an established marker of cardiovascular risk with significant genetic determination. However, HDL particles are not homogenous, and refined HDL phenotyping may improve insight into regulation of HDL metabolism. We therefore assessed HDL particles by NMR spectroscopy and conducted a large-scale candidate gene association analysis.

Methodology/Principal Findings

We measured plasma HDL-C and determined mean HDL particle size and particle number by NMR spectroscopy in 2024 individuals from 512 British Caucasian families. Genotypes were 49,094 SNPs in >2,100 cardiometabolic candidate genes/loci as represented on the HumanCVD BeadChip version 2. False discovery rates (FDR) were calculated to account for multiple testing. Analyses on classical HDL-C revealed significant associations (FDR<0.05) only for CETP (cholesteryl ester transfer protein; lead SNP rs3764261: p = 5.6*10⁻¹⁵) and SGCD (sarcoglycan delta; rs6877118: p = 8.6*10⁻⁶). In contrast, analysis with HDL mean particle size yielded additional associations in LIPC (hepatic lipase; rs261332: p = 6.1*10⁻⁹), PLTP (phospholipid transfer protein, rs4810479: p = 1.7*10⁻⁸) and FBLN5 (fibulin-5; rs2246416: p = 6.2*10⁻⁶). The associations of SGCD and Fibulin-5 with HDL particle size could not be replicated in PROCARDIS (n = 3,078) and/or the Women''s Genome Health Study (n = 23,170).

Conclusions

We show that refined HDL phenotyping by NMR spectroscopy can detect known genes of HDL metabolism better than analyses on HDL-C.     

Specificity of Formation of Complexes Between Coat Protein and Bacteriophage f2 RNA

The specificity of formation of phage f2 RNA-protein complexes was studied. Complex I contains up to 8 mol of coat protein per 1 mol of RNA. Its formation proceeds equally well in medium (i) without magnesium ions, (ii) containing magnesium ions, (iii) containing 4 mM EDTA, and (iv) at temperatures from 0 to 45 C. Complex II contains up to 200 mol of coat protein per 1 mol of RNA. Its formation is inhibited by the presence of magnesium ions in medium. Formaldehyde- or methoxyamine-treated f2 RNA in which only exposed bases were modified showed a normal pattern of complex II formation, whereas formation of complex I was inhibited or abolished. We conclude that complex I formation involves the interaction between coat protein and specific region of exposed bases in RNA. A possible site of attachment of coat protein is discussed.     

The Yin and Yang of carbon nanomaterials in atherosclerosis

With unique characteristics such as high surface area, capacity of various functionalization, low weight, high conductivity, thermal and chemical stability, and free radical scavenging, carbon nanomaterials (CNMs) such as carbon nanotubes (CNTs), fullerene, graphene (oxide), carbon nanohorns (CNHs), and their derivatives have increasingly been utilized in nanomedicine and biomedicine. On the one hand, owing to ever-increasing applications of CNMs in technological and industrial fields as well as presence of combustion-derived CNMs in the ambient air, the skepticism has risen over the adverse effects of CNMs on human being. The influences of CNMs on cardiovascular system and cardiovascular diseases (CVDs) such as atherosclerosis, of which consequences are ischemic heart disease and ischemic stroke, as the main causes of death, is of paramount importance. In this regard, several studies have been devoted to specify the biomedical applications and cardiovascular toxicity of CNMs. Therefore, the aim of this review is to specify the roles and applications of various CNMs in atherosclerosis, and also identify the key role playing parameters in cardiovascular toxicity of CNMs so as to be a clue for prospective deployment of CNMs.     

Current and future potential distributions of three Dracaena Vand. ex L. species under two contrasting climate change scenarios in Africa

Forest undergrowth plants are tightly connected with the shady and humid conditions that occur under the canopy of tropical forests. However, projected climatic changes, such as decreasing precipitation and increasing temperature, negatively affect understory environments by promoting light‐demanding and drought‐tolerant species. Therefore, we aimed to quantify the influence of climate change on the spatial distribution of three selected forest undergrowth plants, Dracaena Vand. ex L. species, D. afromontana Mildbr., D. camerooniana Baker, and D. surculosa Lindl., simultaneously creating the most comprehensive location database for these species to date. A total of 1,223 herbarium records originating from tropical Africa and derived from 93 herbarium collections worldwide have been gathered, validated, and entered into a database. Species‐specific Maxent species distribution models (SDMs) based on 11 bioclimatic variables from the WorldClim database were developed for the species. HadGEM2‐ES projections of bioclimatic variables in two contrasting representative concentration pathways (RCPs), RCP2.6 and RCP8.5, were used to quantify the changes in future potential species distribution. D. afromontana is mostly sensitive to temperature in the wettest month, and its potential geographical range is predicted to decrease (up to ?63.7% at RCP8.5). Optimum conditions for D. camerooniana are low diurnal temperature range (6–8°C) and precipitation in the wettest season exceeding 750 mm. The extent of this species will also decrease, but not as drastically as that of D. afromontana. D. surculosa prefers high precipitation in the coldest months. Its potential habitat area is predicted to increase in the future and to expand toward the east. This study developed SDMs and estimated current and future (year 2050) potential distributions of the forest undergrowth Dracaena species. D. afromontana, naturally associated with mountainous plant communities, was the most sensitive to predicted climate warming. In contrast, D. surculosa was predicted to extend its geographical range, regardless of the climate change scenario.