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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.
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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4.
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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5.
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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6.
QTLian breeding for climate resilience in cereals: progress and prospects.
Choudhary, M, Wani, SH, Kumar, P, Bagaria, PK, Rakshit, S, Roorkiwal, M, Varshney, RK
Functional & integrative genomics. 2019;(5):685-701
Abstract
The ever-rising population of the twenty-first century together with the prevailing challenges, such as deteriorating quality of arable land and water, has placed a big challenge for plant breeders to satisfy human needs for food under erratic weather patterns. Rice, wheat, and maize are the major staple crops consumed globally. Drought, waterlogging, heat, salinity, and mineral toxicity are the key abiotic stresses drastically affecting crop yield. Conventional plant breeding approaches towards abiotic stress tolerance have gained success to limited extent, due to the complex (multigenic) nature of these stresses. Progress in breeding climate-resilient crop plants has gained momentum in the last decade, due to improved understanding of the physiochemical and molecular basis of various stresses. A good number of genes have been characterized for adaptation to various stresses. In the era of novel molecular markers, mapping of QTLs has emerged as viable solution for breeding crops tolerant to abiotic stresses. Therefore, molecular breeding-based development and deployment of high-yielding climate-resilient crop cultivars together with climate-smart agricultural practices can pave the path to enhanced crop yields for smallholder farmers in areas vulnerable to the climate change. Advances in fine mapping and expression studies integrated with cheaper prices offer new avenues for the plant breeders engaged in climate-resilient plant breeding, and thereby, hope persists to ensure food security in the era of climate change.
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7.
Peer pressure: evolutionary responses to biotic pressures in wine yeasts.
Conacher, CG, Rossouw, D, Bauer, FFB
FEMS yeast research. 2019;(7)
Abstract
In the macroscopic world, ecological interactions between multiple species of fauna and flora are recognised as major role-players in the evolution of any particular species. By comparison, research on ecological interactions as a driver of evolutionary adaptation in microbial ecosystems has been neglected. The evolutionary history of the budding yeast Saccharomyces cerevisiae has been extensively researched, providing an unmatched foundation for exploring adaptive evolution of microorganisms. However, in most studies, the habitat is only defined by physical and chemical parameters, and little attention is paid to the impact of cohabiting species. Such ecological interactions arguably provide a more relevant evolutionary framework. Within the genomic phylogenetic tree of S. cerevisiae strains, wine associated isolates form a distinct clade, also matched by phenotypic evidence. This domestication signature in genomes and phenomes suggests that the wine fermentation environment is of significant evolutionary relevance. Data also show that the microbiological composition of wine fermentation ecosystems is dominated by the same species globally, suggesting that these species have co-evolved within this ecosystem. This system therefore presents an excellent model for investigating the origins and mechanisms of interspecific yeast interactions. This review explores the role of biotic stress in the adaptive evolution of wine yeast.
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8.
Protein kinase-mediated signalling in priming: Immune signal initiation, propagation, and establishment of long-term pathogen resistance in plants.
Hake, K, Romeis, T
Plant, cell & environment. 2019;(3):904-917
Abstract
"Priming" in plant phytopathology describes a phenomenon where the "experience" of primary infection by microbial pathogens leads to enhanced and beneficial protection of the plant against secondary infection. The plant is able to establish an immune memory, a state of systemic acquired resistance (SAR), in which the information of "having been attacked" is integrated with the action of "being prepared to defend when it happens again." Accordingly, primed plants are often characterized by faster and stronger activation of immune reactions that ultimately result in a reduction of pathogen spread and growth. Prerequisites for SAR are (a) the initiation of immune signalling subsequent to pathogen recognition, (b) a rapid defence signal propagation from a primary infected local site to uninfected distal parts of the plant, and (c) a switch into an immune signal-dependent establishment and subsequent long-lasting maintenance of phytohormone salicylic acid-based systemic immunity. Here, we provide a summary on protein kinases that contribute to these three conceptual aspects of "priming" in plant phytopathology, complemented by data addressing the role of protein kinases crucial for immune signal initiation also for signal propagation and SAR.
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9.
DEAD box helicases as promising molecular tools for engineering abiotic stress tolerance in plants.
Nidumukkala, S, Tayi, L, Chittela, RK, Vudem, DR, Khareedu, VR
Critical reviews in biotechnology. 2019;(3):395-407
Abstract
Diverse abiotic stresses constitute one of the major factors which adversely affect the normal plant growth and development which results worldwide in decreased agricultural productivity. At present, utilization of new molecular tools to achieve improved stress tolerance and increased crop productivity is highly desirable. Abiotic stress in plants induces expression of a wide range of genes like transcription factors, defense related genes and so on, and the products of these genes are important in combating stress conditions. Helicases are one such category of proteins that play a key role in maintaining the genomic integrity of the cell by participating in nucleic acid mediated processes such as recombination, replication, and repair of DNA as well as the unwinding of misfolded RNA structures that are formed during stress conditions. The DEAD box helicases are a subgroup of helicases which contain the amino acids Asp-Glu-Ala-Asp (DEAD) and are involved in the above molecular functions that mediate adaptation to stress. Overexpression of DEAD box helicases is known to provide stress tolerance in various plants and thus their use in developing stress tolerant plants is gaining importance. The plausible physiological mechanisms of helicases in bestowing abiotic stress tolerance of plants include ROS scavenging, enhanced photosynthesis, ion homeostasis and regulation of various stress responsive genes. In this review, the characteristics of plant DEAD box helicases and the stress conditions under which they express are discussed. We have provided a detailed description on the transgenic plants overexpressing DEAD box helicases with an emphasis on their stress tolerance abilities.
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10.
Sugar as a therapeutic target for the cognitive restoration following traumatic brain injury.
Kumar, A
Current opinion in neurology. 2019;(6):815-821
Abstract
PURPOSE OF REVIEW This review aims to discuss examples of changes in glucose (sugar) metabolism after traumatic brain injury (TBI). It will attempt to provide an understanding of what changes in glucose metabolism mean for the injured brain. It will further identify potential therapeutic target(s) emanating from our growing understanding of glucose pathways and their roles in TBI. RECENT FINDINGS Although a significant fraction of glucose is utilized for the energy production in the brain, a small fraction is utilized in other, often ignored pathways. Recent studies have unraveled unexpected biological effects of glucose through these pathways, including redox regulation, genetic and epigenetic regulation, glycation of proteins, nucleotide synthesis and amino acid synthesis. SUMMARY A number of regulatory players in minor glucose metabolic pathways, such as folate and chondroitin sulfate proteoglycans, have recently been identified as potential targets to restore cognitive functions. Targeting of these players should be combined with the supplementation of alternative energy substrates to achieve the maximal cognitive restoration after TBI. This multimodal therapeutic strategy deserves testing in various models of TBI. VIDEO ABSTRACT Supplemental digital video content 1: Video that demonstrates an effective therapeutic strategy for the cognitive restoration after TBI. http://links.lww.com/CONR/A46.