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1.
An Intricate Connection between Alternative Splicing and Phenotypic Plasticity in Development and Cancer.
Biamonti, G, Infantino, L, Gaglio, D, Amato, A
Cells. 2019;(1)
Abstract
During tumor progression, hypoxia, nutrient deprivation or changes in the extracellular environment (i.e., induced by anti-cancer drugs) elicit adaptive responses in cancer cells. Cellular plasticity increases the chance that tumor cells may survive in a challenging microenvironment, acquire new mechanisms of resistance to conventional drugs, and spread to distant sites. Re-activation of stem pathways appears as a significant cause of cellular plasticity because it promotes the acquisition of stem-like properties through a profound phenotypic reprogramming of cancer cells. In addition, it is a major contributor to tumor heterogeneity, depending on the coexistence of phenotypically distinct subpopulations in the same tumor bulk. Several cellular mechanisms may drive this fundamental change, in particular, high-throughput sequencing technologies revealed a key role for alternative splicing (AS). Effectively, AS is one of the most important pre-mRNA processes that increases the diversity of transcriptome and proteome in a tissue- and development-dependent manner. Moreover, defective AS has been associated with several human diseases. However, its role in cancer cell plasticity and tumor heterogeneity remains unclear. Therefore, unravelling the intricate relationship between AS and the maintenance of a stem-like phenotype may explain molecular mechanisms underlying cancer cell plasticity and improve cancer diagnosis and treatment.
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2.
Predictors of Intestinal Adaptation in Children.
Venick, RS
Gastroenterology clinics of North America. 2019;(4):499-511
Abstract
In children, short-bowel syndrome (SBS) accounts for two-thirds of the cases of intestinal failure, and motility disorders and congenital mucosal diarrheal disorders account for the remaining one-third. Children with SBS are supported primarily by parenteral nutrition, which is the single-most important therapy contributing to their improved prognosis. More than 90% of children with SBS who are cared for at experienced intestinal rehabilitation programs survive, and roughly 60% to 70% undergo intestinal adaptation and achieve full enteral autonomy. This article focuses on the predictors of pediatric intestinal adaptation and discusses the pathophysiology and clinical management of children with SBS.
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3.
Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle.
Fritzen, AM, Thøgersen, FB, Thybo, K, Vissing, CR, Krag, TO, Ruiz-Ruiz, C, Risom, L, Wibrand, F, Høeg, LD, Kiens, B, et al
Cells. 2019;(3)
Abstract
Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I⁻IV activities were increased by 51% and 46⁻61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I⁻IV activities by 29⁻36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.
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4.
Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: A focus on "secondary" physiological determinants.
Cholewa, J, Trexler, E, Lima-Soares, F, de Araújo Pessôa, K, Sousa-Silva, R, Santos, AM, Zhi, X, Nicastro, H, Cabido, CET, de Freitas, MC, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:241-251
Abstract
Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperemia and cellular swelling experienced during resistance training. It has been suggested that these effects play a role in hypertrophic adaptations. Over the past 2 decades, sport supplement products have been marketed to promote exercise hyperemia and intracellular fluid storage, thereby enhancing hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperemia include vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as β-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting "secondary" physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation, and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and might guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. The aim of this review was to bring into focus new perspectives associated with secondary physiological effects induced by supplementation and to determine their relevance.
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5.
Do invasive alien plants differ from non-invasives in dominance and nitrogen uptake in response to variation of abiotic and biotic environments under global anthropogenic change?
Liu, YY, Sun, Y, Müller-Schärer, H, Yan, R, Zhou, ZX, Wang, YJ, Yu, FH
The Science of the total environment. 2019;:634-642
Abstract
Plant invasion is the outcome of complicated interactions of both biotic and abiotic environments (i.e. eutrophication and human-induced propagules) under global anthropogenic change. Here, we want to know why some alien clonal plant species become invasive and others do not in the introduced range with variations of both abiotic and biotic environments under global anthropogenic change. We selected three invasive alien and three co-occurring, non-invasive alien clonal plant species in China, and grew them under the constant or variable soil nutrient environments in a native community with low or high vegetative propagule pressure (i.e. simulating pressure of anthropogenic alien propagules). Invasive alien species produced more biomass than non-invasives. Interestingly, invasive species benefited significantly greater from high propagule pressure than non-invasives. Biomass and evenness of native communities were greater with non-invasive than with invasive target species. Invasive plants showed a greater increase of leaf N and decrease of leaf C: N ratio when subject to variable nutrients in comparison to constant nutrients than non-invasives. The negative effects of variable nutrients on evenness of native communities were significantly greater under invasive than non-invasive target species. Moreover, biomass of native communities was significantly negatively related to biomass of invasive species. Variable nutrients significantly promoted the negative biomass relationship between non-invasive species and native communities under high propagule pressure and the negative biomass-evenness relationship between invasive species and native communities. Our study suggests that soil nutrient variability and vegetative propagule pressure influence the growth and leaf C and N uptake of alien clonal plant species in native experimental communities, especially under the high propagule pressure and nutrient variability. Invasive alien clonal species have higher performance and advantages over non-invasives. Future studies should also test the mechanisms that invasive and non-invasive or native plants differ in native communities of native or introduced ranges in the field.
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6.
Low skeletal muscle capillarization limits muscle adaptation to resistance exercise training in older adults.
Moro, T, Brightwell, CR, Phalen, DE, McKenna, CF, Lane, SJ, Porter, C, Volpi, E, Rasmussen, BB, Fry, CS
Experimental gerontology. 2019;:110723
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Abstract
OBJECTIVES Adequate muscle perfusion supports the transport of nutrients, oxygen and hormones into muscle fibers. Aging is associated with a substantial decrease in skeletal muscle capillarization, fiber size and oxidative capacity, which may be improved with regular physical activity. The aim of this study was to investigate the relationship between muscle capillarization and indices of muscle hypertrophy (i.e. lean mass; fiber cross sectional area (CSA)) in older adults before and after 12 weeks of progressive resistance exercise training (RET). DESIGN Interventional study SETTING AND PARTICIPANTS 19 subjects (10 male and 9 female; 71.1 ± 4.3 years; 27.6 ± 3.2 BMI) were enrolled in the study and performed a whole body RET program for 12 weeks. Subjects where then retrospectively divided into a LOW or HIGH group, based on their pre-RET capillary-to-fiber perimeter exchange index (CFPE). Physical activity level, indices of capillarization (capillaries-to-fiber ratio, C:Fi; CFPE index and capillary-to-fiber interface, LC-PF index), muscle hypertrophy, muscle protein turnover and mitochondrial function were assessed before and after RET. RESULTS Basal capillarization (C:Fi; CFPE and LP-CF index) correlates with daily physical activity level (C:Fi, r = 0.57, p = 0.019; CFPE index, r = 0.55, p = 0.024; LC-PF index, r = 0.56, p = 0.022) and CFPE and LC-PF indices were also positively associated with oxidative capacity (respectively r = 0.45, p = 0.06; r = 0.67, p = 0.004). Following RET, subjects in the HIGH group underwent hypertrophy with significant improvements in muscle protein synthesis and muscle fiber CSA (p < 0.05). However, RET did not promote muscle hypertrophy in the LOW group, but RET significantly increased muscle capillary density (p < 0.05). CONCLUSION/IMPLICATIONS Muscle fiber capillarization before starting an exercise training program may be predictive of the muscle hypertrophic response to RET in older adults. Increases in muscle fiber size following RET appear to be blunted when muscle capillarization is low, suggesting that an adequate initial capillarization is critical to achieve a meaningful degree of muscle adaptation to RET.
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The cAMP/Protein Kinase a Pathway Regulates Virulence and Adaptation to Host Conditions in Cryptococcus neoformans.
Caza, M, Kronstad, JW
Frontiers in cellular and infection microbiology. 2019;:212
Abstract
Nutrient sensing is critical for adaptation of fungi to environmental and host conditions. The conserved cAMP/PKA signaling pathway contributes to adaptation by sensing the availability of key nutrients such as glucose and directing changes in gene expression and metabolism. Interestingly, the cAMP/PKA pathway in fungal pathogens also influences the expression of virulence determinants in response to nutritional and host signals. For instance, protein kinase A (PKA) in the human pathogen Cryptococcus neoformans plays a central role in orchestrating phenotypic changes, such as capsule elaboration and melanin production, that directly impact disease development. In this review, we focus first on insights into the role of the cAMP/PKA pathway in nutrient sensing for the model yeast Saccharomyces cerevisiae to provide a foundation for understanding the pathway in C. neoformans. We then discuss key features of cAMP/PKA signaling in C. neoformans including new insights emerging from the analysis of transcriptional and proteomic changes in strains with altered PKA activity and expression. Finally, we highlight recent studies that connect the cAMP/PKA pathway to cell surface remodeling and the formation of titan cells.
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Controversy in Nutrition Recommendations for Short Bowel Syndrome: How Type of SBS Impacts Response.
Austin, K, Bonnes, S, Daniel, H
Current gastroenterology reports. 2019;(12):64
Abstract
PURPOSE OF REVIEW This review examines the current recommendations for dietary management of patients living with short bowel syndrome (SBS) and outlines the need for future research to provide optimal care for this unique group of patients. RECENT FINDINGS Providers caring for patients with SBS lack sufficient data to help guide recommendations regarding diet. The majority of studies are conducted at a single medical institution on a small number of anatomically diverse patients. Multi-center studies would allow for inclusion of a larger number of patients and may lead to more individualized dietary recommendations. Patients with short bowel syndrome should be evaluated on an individual basis by a multidisciplinary team including physicians, dieticians, pharmacists, and nurses specializing in the care of these complex patients. Tailoring both medical and nutritional therapy will help realize the overarching goal for these patients of maintaining adequate nutrition with diet and medications, and achieving independence from parenteral support.
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Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes.
Serebrovska, TV, Grib, ON, Portnichenko, VI, Serebrovska, ZO, Egorov, E, Shatylo, VB
High altitude medicine & biology. 2019;(4):383-391
Abstract
Background: Intermittent hypoxia/normoxia training (IHT) is considered a possible means to alleviate chronic diseases such as diabetes. In the last decade, another method of intermittent hypoxia/hyperoxia training (IHHT) began to enter the clinical practice, when the periods of breathing with atmospheric air are replaced by breathing a hyperoxic mixture. The present study compared the impact of adaptation to IHHT versus IHT on some metabolic variables in prediabetic patients. Methods: A placebo-controlled trial included 55 patients with prediabetes, sea level residents, ages 51-74 years. Control Group (16 patients) took sham 3-week course, and the IHHT Group (17 patients) and IHT Group (22 patients) received similar actual sessions of IHHT or IHT five times a week for 3 weeks, each session consisting four cycles of 5 minutes of hypoxia (12% O2) followed by 3 minutes of hyperoxia (IHHT, 33% O2) or 5 minutes of normoxia (IHT, breathing room air). Fasting glucose, oral glucose tolerance test (OGTT), blood lipids, and the level of blood oxygen saturation (SpO2) were investigated at baseline, as well as 1 day and 1 month after IHHT/IHT termination. Results: The study showed the same positive effect of two types of training: equal reduction of serum glucose concentrations, both fasting and 2 hours of OGTT; decreased total blood cholesterol and low-density lipoproteins; and an equally smaller drop in SpO2 during acute hypoxic test (breathing with 12% O2 for 20 minutes). Improved parameters persisted 1 month after training termination in both groups. Conclusion: One of the advantages of IHHT over IHT observed in this study could be some reduction in the duration of the sessions due to shortening reoxygenation periods. Further studies are required to search for additional beneficial effects of IHHT when using other training modes or other pathologies.
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Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training.
Newman, AA, Grimm, NC, Wilburn, JR, Schoenberg, HM, Trikha, SRJ, Luckasen, GJ, Biela, LM, Melby, CL, Bell, C
The Journal of clinical endocrinology and metabolism. 2019;(6):1953-1966
Abstract
CONTEXT The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.