The M2 splice isoform of pyruvate kinase (PKM2) is a key enzyme for generating pyruvate and ATP in the glycolytic pathway, whereas the role of PKM2 in tumorigenesis remains a subject of debate. In this study, we found PKM2 is highly expressed in melanoma patients and the malignance is positively corelated with high PKM2 activity and glycolytic capability in melanoma cells. Suppression of PKM2 expression by knocking down markedly attenuated malignant phenotype both in vitro and in vivo, and restoration...
ABSTRACT Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of estimated BMR with incidence of 13 obesity‐related cancers in the European Prospective Investigation into Cancer and Nutrition. Estimated BMR...
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Abstract Background Our goal was to elucidate the differences in degree of technical difficulty of thyroidectomy in patients with autoimmune thyroid diseases. Methods Charts of adult patients who had undergone thyroidectomy were reviewed. Patients with Hashimoto's Thyroiditis (HT) or Graves' Disease (GD) were individually compared to a control group of patients with early stage malignancy or goiter. Results The HT (n = 65) group was significantly more likely to have friable (P = .001)...
Abstract Background Balancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC. Methods We presented a retrospective review of patients with T3‐4 NPC treated by intensity‐modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow‐up data for survival and late toxicities were analyzed....
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Abstract Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress. PACAP knockout (KO) mice...
Abstract Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4′,5-trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based...
Abstract The accumulation of senescent cells in tissues is causally linked to the development of several age-related diseases; the removal of senescent glial cells in animal models prevents Tau accumulation and cognitive decline. Senescent cells can arise through several distinct mechanisms; one such mechanism is dysregulation of alternative splicing. In this study, we characterised the senescent cell phenotype in primary human astrocytes in terms of SA-β-Gal staining and SASP...
Abstract Intestinal barrier dysfunction is hypothesized to be a contributing determinant of two prominent characteristics of aging: inflammation and decline in physical function. A relationship between microbial translocation (MT), or their biomarkers (lipopolysaccharide binding protein-1 [LBP-1], soluble cluster of differentiation [sCD]-14), and physical function has been reported in healthy older adults, rats, and invertebrates. However, it is not known whether the existence...
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The CDK1 kinase is required for most eukaryotic cell cycles. The active site is generated by essential, structural elements, among which the PSTAIRE motif in the critical C-helix, is universally conserved in metazoans. The CDK2 kinase, sharing the PSTAIRE, arose early in metazoan evolution and permitted subdivision of tasks along the S-M-phase axis. The marine planktonic chordate, Oikopleura dioica, is the only metazoan known to possess more than a single CDK1 ortholog, and all of its 5 paralogs...
The tropical and subtropical Andes have among the highest levels of biodiversity in the world. Understanding the forces that underlie speciation and diversification in the Andes is a major focus of research. Here we tested two hypotheses of species origins in the Andes: 1. Vicariance mediated by orogenesis or shifting habitat distribution. 2. Parapatric diversification along elevational environmental gradients. We also sought insights on the factors that impacted the phylogeography of co-distributed...
Are first-generation (F1) hybrids typically intermediate for all traits that differentiate their parents? Or are they similar to one parent for most traits, or even mismatched for divergent traits? Although the phenotype of otherwise viable and fertile hybrids determines their fate, little is known about the general patterns, predictors, and consequences of phenotype expression in hybrids. To address this empirical gap, we compiled data from nearly 200 studies where traits were measured in a common...
The diversity and biology of unicellular relatives of animals has strongly informed our understanding of the transition from single-celled organisms to the multicellular Metazoa. Here we analyse the cellular structures and complex life cycles of the novel unicellular holozoans Pigoraptor and Syssomonas (Opisthokonta). Both lineages are characterized by complex life cycles with a variety of cell types, the formation of multicellular aggregations and syncytium-like structures, and an unusual diet for...
Antagonistic interactions between the sexes are important drivers of evolutionary divergence. Interlocus sexual conflict is generally theorised as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary. Here we build on previous theory and suggest that when these two loci are located on the X and Y (or Z and W) chromosomes, it can lead to cycles of antagonistic coevolution between the sex chromosomes and the two sexes. To test this hypothesis, we performed...
Maize landraces are well adapted to their local environments and present valuable sources of genetic diversity for breeding and conservation. But the maintenance of open-pollinated landraces in ex-situ programs is challenging, as regeneration of seed can often lead to inbreeding depression and the loss of diversity due to genetic drift. Recent reports suggest that the production of doubled-haploid (DH) lines from landraces may serve as a convenient means to preserve genetic diversity in a homozygous...
In social insects, cuticular hydrocarbons function in nestmate recognition and also provide a waxy barrier against desiccation, but basic evolutionary genetic features, including the heritability of hydrocarbon profiles and how they are shaped by natural selection are largely unknown. We used a new pharaoh ant (Monomorium pharaonis) laboratory mapping population to estimate the heritability of individual cuticular hydrocarbons, genetic correlations between hydrocarbons, and fitness consequences of...
Recent analyses of genomic sequence data suggest cross-species gene flow is common in both plants and animals, posing challenges to species tree inference. We examine the levels of gene flow needed to mislead species tree estimation with three species and either episodic introgressive hybridization or continuous migration between an outgroup and one ingroup species. Several species tree estimation methods are examined, including the majority-vote method based on the most common gene tree topology...
Insect-bacterial symbioses are ubiquitous, but there is still much to uncover about how these relationships establish, persist and evolve. The tsetse endosymbiont Sodalis glossinidius displays intriguing metabolic adaptations to its microenvironment, but the process by which this relationship evolved remains to be elucidated. The recent chance discovery of the free-living species of the Sodalis genus, S. praecaptivus, provides a serendipitous starting point from which to investigate the evolution...
The wild maize, commonly known as teosinte, has a wide distribution and is abundant in Mexico. Previous reports indicate that the environmental conditions are determinant in the distribution and amount of genetic diversity. In this work, we used a set of neutral markers in a large number of samples and localities to explore the influence on genetic diversity of historical environmental shifts. We genotyped 527 individuals from 29 localities using a set of 22 microsatellites. We found high levels...
The Kingman coalescent process is a classical model of gene genealogies in population genetics. It generates Yule-distributed, binary ranked tree topologies -- also called histories -- with a finite number of n leaves, together with n - 1 exponentially distributed time lengths: one for each each layer of the history. Using a discrete approach, we study the lengths of the external branches of Yule distributed histories, where the length of an external branch is defined as the rank of its parent node....
The CDK1 kinase is required for most eukaryotic cell cycles. The active site is generated by essential, structural elements, among which the PSTAIRE motif in the critical C-helix, is universally conserved in metazoans. The CDK2 kinase, sharing the PSTAIRE, arose early in metazoan evolution and permitted subdivision of tasks along the S-M-phase axis. The marine planktonic chordate, Oikopleura dioica, is the only metazoan known to possess more than a single CDK1 ortholog, and all of its 5 paralogs...
Because of their replication mode and segmented dsRNA genome, homologous recombination is assumed to be rare in the rotaviruses. We analyzed 23,627 complete rotavirus genome sequences available in the NCBI Virus Variation database, and found 109 instances of homologous recombination, at least 11 of which prevailed across multiple sequenced isolates. In one case, recombination may have generated a novel rotavirus VP1 lineage. We also found strong evidence for intergenotypic recombination in which...
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