Skeletal Muscle Health and Cognitive Function: A Narrative Review

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.     

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model

We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.     

New natural 2-acetoxy fatty acids using chemical ionization and electron impact mass spectrometry

The phospholipids of the spongePolymastia gleneni contain saturated long chain (C_22–30)-acetoxy fatty acids. Their structures were assigned based on chromatographic and spectrometric data as well as comparison with a synthetic sample. The use of capillary gas chromatography combined with chemical ionization and electron impact mass spectrometry was instrumental in the eludication of structures, since only a very small amount of crude lipids was available. Part 10 of “Phospholipids in Marine Organisms.” For Part 9 in this series, see reference 12.     

Bovine ovarian non-genomic progesterone binding sites: presence in follicular and luteal cell membranes

We have shown recently that the bovine corpus luteum (CL) possesses specific luteal cell surface membrane binding sites for progesterone. We have now confirmed and extended these observations to compare the subcellular distribution of these binding sites in developing, mature and regressing CL. The median buoyant densities of luteal progesterone binding sites from early-, mid- and late-luteal phase CL were similar (though three of five density profiles for late-luteal phase CL showed association of steroid binding with a fraction with a lower density), and clearly resolved from nuclear, mitochondrial, lysosomal, peroxisomal, Golgi-endoplasmic reticulum-lysosomal and smooth endoplasmic reticulum markers. Specific binding of [3H]progesterone overlapped with the distributions of 5'-nucleotidase and luteinizing hormone receptor (luteal cell surface membrane markers) in both control and digitonin-treated gradients at all stages of the luteal phase. Since steroidogenic 'large luteal' and 'small luteal' cells of the CL are derived from the granulosa cells (GC) and theca of the preovulatory follicle, we also investigated whether similar receptors were present in the follicle, and describe for the first time specific membrane binding sites for progesterone in purified GC and thecal membranes from healthy bovine follicles of different sizes. Specific binding increased linearly with GC and thecal membrane protein concentration; however, it was detectable only when digitonin was included in the binding incubation. Binding sites were specific for progesterone; unlabelled progesterone competed for [3H]progesterone binding at low concentrations (IC50, 35 and 31 nmol/l) compared with testosterone (IC50, 905 and 870 nmol/l) and delta4-androstenedione (IC50, 1050 and 660 nmol/l) for GC and thecal receptors respectively. In contrast, oestradiol, oestrone, pregnenolone, cortisol, cholesterol, and a genomic progesterone receptor antagonist, RU486, competed poorly. Steroid binding was present in GC and thecal membranes of follicles of all sizes, but [3H]progesterone binding to GC membranes decreased significantly with increasing follicle size (P<0.02), perhaps indicating developmental regulation of GC membrane non-genomic progesterone receptors in the preovulatory bovine follicle. We suggest that these membrane steroid receptors may be involved in the autocrine/paracrine regulation of follicular function by progesterone.     

Hazardous waste management problem: The case for incineration

We define the hazardous waste management problem as the combined decisions of selecting the disposal method, siting the disposal plants and deciding on the waste flow structure. The hazardous waste management problem has additional requirements depending on the selected disposal method. In this paper we focus on incineration, for which the main additional requirement is to satisfy the air pollution standards imposed by the governmental restrictions. We propose a cost-based mathematical model in which the satisfaction of air pollution standards is also incorporated. We used the Gaussian Plume equation in measuring the air pollution concentrations at population centers. A large-scale implementation of the proposed model within Turkey is provided.     

Tobacco craving predicts lapse to smoking among adolescent smokers in cessation treatment.

Previous research indicates that tobacco craving predicts relapse to smoking among adult smokers attempting to quit. We hypothesized a similar relationship between craving and lapse (any smoking following a period of abstinence) among adolescent smokers during the treatment phase of a clinical trial. A visit was considered a lapse visit if the participant reported smoking or had a carbon monoxide level of 7 ppm or greater subsequent to an abstinent visit. A total of 34 participants (mean age = 14.9 years [SD = 1.3]; mean cigarettes/day = 18.0 [SD = 7.6]; mean Fagerstr?m Test for Nicotine Dependence score = 6.8 [SD = 1.34]; 65% female), were included in the present analysis of 167 treatment visits. Logistic regression analyses showed a positive relationship between degree of craving, measured by the Questionnaire on Smoking Urges, and lapse during smoking cessation treatment (p = .013). Additionally, linear regression analyses demonstrated a strong positive association between cigarettes smoked per day and craving scores (p<.001). Taken together with other data, these findings suggest that degree of craving might influence tobacco abstinence for adolescent smokers. Thus monitoring and addressing craving appears useful to increase the success of adolescent smoking cessation.