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41.
Kuzoff RK; Sweere JA; Soltis DE; Soltis PS; Zimmer EA 《Molecular biology and evolution》1998,15(3):251-263
18S ribosomal RNA genes are the most widely used nuclear sequences for
phylogeny reconstruction at higher taxonomic levels in plants. However, due
to a conservative rate of evolution, 18S rDNA alone sometimes provides too
few phylogenetically informative characters to resolve relationships
adequately. Previous studies using partial sequences have suggested the
potential of 26S or large-subunit (LSU) rDNA for phylogeny retrieval at
taxonomic levels comparable to those investigated with 18S rDNA. Here we
explore the patterns of molecular evolution of entire 26S rDNA sequences
and their impact on phylogeny retrieval. We present a protocol for PCR
amplification and sequencing of entire (approximately 3.4 kb) 26S rDNA
sequences as single amplicons, as well as primers that can be used for
amplification and sequencing. These primers proved useful in angiosperms
and Gnetales and likely have broader applicability. With these protocols
and primers, entire 26S rDNA sequences were generated for a diverse array
of 15 seed plants, including basal eudicots, monocots, and higher eudicots,
plus two representatives of Gnetales. Comparisons of sequence dissimilarity
indicate that expansion segments (or divergence domains) evolve 6.4 to 10.2
times as fast as conserved core regions of 26S rDNA sequences in plants.
Additional comparisons indicate that 26S rDNA evolves 1.6 to 2.2 times as
fast as and provides 3.3 times as many phylogenetically informative
characters as 18S rDNA; compared to the chloroplast gene rbcL, 26S rDNA
evolves at 0.44 to 1.0 times its rate and provides 2.0 times as many
phylogenetically informative characters. Expansion segment sequences
analyzed here evolve 1.2 to 3.0 times faster than rbcL, providing 1.5 times
the number of informative characters. Plant expansion segments have a
pattern of evolution distinct from that found in animals, exhibiting less
cryptic sequence simplicity, a lower frequency of insertion and deletion,
and greater phylogenetic potential.
相似文献
42.
Background
Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies. 相似文献43.
44.
Swati Sharma Yamini Singh Rajat Sandhir Sayar Singh Lilly Ganju Bhuvnesh Kumar Rajeev Varshney 《BBA》2021,1862(8):148431
High altitude pulmonary edema (HAPE) is experienced by non-acclimatized sea level individuals on exposure to high altitude hypoxic conditions. Available evidence suggests that genetic factors and perturbed mitochondrial redox status may play an important role in HAPE pathophysiology. However, the precise mechanism has not been fully understood. In the present study, sequencing of mitochondrial DNA (mtDNA) from HAPE subjects and acclimatized controls was performed to identify pathogenic mutations and to determine their role in HAPE. Hypobaric hypoxia induced oxidative stress and metabolic alterations were also assessed in HAPE subjects. mtDNA copy number, mitochondrial oxidative phosphorylation (mtOXPHOS) activity, mitochondrial biogenesis were measured to determine mitochondrial functions. The data revealed that the mutations in Complex I genes affects the secondary structure of protein in HAPE subjects. Further, increased oxidative stress during hypobaric hypoxia, reduced mitochondrial biogenesis and mtOXPHOS activity induced metabolic reprogramming appears to contribute to mitochondrial dysfunctions in HAPE individuals. Haplogroup analysis suggests that mtDNA haplogroup H2a2a1 has potential contribution in the pathobiology of HAPE in lowlanders. This study also suggests contribution of altered mitochondrial functions in HAPE susceptibility. 相似文献
45.
Environmental stress at high altitude affects the myocardium at the physiological and molecular level. Characterized by hypobaric hypoxia and low temperatures, the cumulative impact of these stressors on the protein folding homeostasis in the heart is yet unexplored. The present study evaluates the collective effect of cold and hypoxia on the myocardial protein oxidation and activation of the endoplasmic reticulum (ER) stress response. Adult rats were exposed to either a singular acute stress of cold (10 °C; C), hypobaric hypoxia (7620 m; H) or simultaneously to both cold and hypobaric hypoxia (CH) for 6 h. Hypoxic stress amplified the free radical generation in H and CH groups, leading to enhanced HIF-1α expression. Coupled to cold stress, reduced oxygen availability caused substantial protein oxidative modifications, as well as cardiac tissue injury and matrix remodeling, evident in the histological staining. Presence of oxidized proteins caused a significant upregulation in expression of ER chaperones GRP78 and PDI in the cold hypoxia exposed animals. Enhanced proteolytic activity signaled the removal of misfolded proteins. Linked intricately to cellular stress response, cell survival kinases were expressed higher in CH group; however apoptotic CHOP (C/EBP homologous protein) expression remained unaltered. Administration of ER stress inducer, tunicamycin along with cold hypoxic stress, caused a discernible increase in protein oxidation and GRP78 expression, along with a significant elevation in proteasome and apoptotic activity. Highlighting the significance of a synergistic, rather than individual, effect of low oxygen and temperature on the protein folding machinery, our study provides evidence for the activation of ER stress response in the myocardium under acute high altitude stress. 相似文献
46.
Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion,
resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of
diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure
rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds
and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic
properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose
levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects
and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood
cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the
various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied
at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been
summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin
mimetic effects of Trigonella, manganese and vanadium. 相似文献
47.
Background
Cannabinoids bind to cannabinoid receptors CB1 and CB2 and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB2 may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis.Methodology/Principal Findings
We observed high expression of both CB2 and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB2-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231 (SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems.Conclusions/Significance
This study provides novel insights into the crosstalk between CB2 and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB2 receptors could be used for developing innovative therapeutic strategies against breast cancer. 相似文献48.
Marije Oosting Kathrin Buffen Subbarao RK Malireddi Patrick Sturm Ineke Verschueren Marije I Koenders Frank L van de Veerdonk Jos WM van der Meer Mihai G Netea Thirumala-Devi Kanneganti Leo AB Joosten 《Arthritis research & therapy》2012,14(6):R247
Introduction
The protein platform called the NOD-like-receptor -family member (NLRP)-3 inflammasome needs to be activated to process intracellular caspase-1. Active caspase-1 is able to cleave pro-Interleukin (IL)-1β, resulting in bioactive IL-1β. IL-1β is a potent proinflammatory cytokine, and thought to play a key role in the pathogenesis of Lyme arthritis, a common manifestation of Borrelia burgdorferi infection. The precise pathways through which B. burgdorferi recognition leads to inflammasome activation and processing of IL-1β in Lyme arthritis has not been elucidated. In the present study, we investigated the contribution of several pattern recognition receptors and inflammasome components in a novel murine model of Lyme arthritis.Methods
Lyme arthritis was elicited by live B. burgdorferi, injected intra-articularly in knee joints of mice. To identify the relevant pathway components, the model was applied to wild-type, NLRP3-/-, ASC-/-, caspase-1-/-, NOD1-/-, NOD2-/-, and RICK-/- mice. As a control, TLR2-/-, Myd88-/- and IL-1R-/- mice were used. Peritoneal macrophages and bone marrow-derived macrophages were used for in vitro cytokine production and inflammasome activation studies. Joint inflammation was analyzed in synovial specimens and whole knee joints. Mann-Whitney U tests were used to detect statistical differences.Results
We demonstrate that ASC/caspase-1-driven IL-1β is crucial for induction of B. burgdorferi-induced murine Lyme arthritis. In addition, we show that B. burgdorferi-induced murine Lyme arthritis is less dependent on NOD1/NOD2/RICK pathways while the TLR2-MyD88 pathway is crucial.Conclusions
Murine Lyme arthritis is strongly dependent on IL-1 production, and B. burgdorferi induces inflammasome-mediated caspase-1 activation. Next to that, murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and RICK independent. Also, caspase-1 activation by B. burgdorferi is dependent on TLR2 and MyD88. Based on present results indicating that IL-1 is one of the major mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL-1 activity may also have beneficial effects in chronic Lyme arthritis. 相似文献49.
Background
Previously it has been shown that insulin-mediated tyrosine phosphorylation of myosin heavy chain is concomitant with enhanced association of C-terminal SRC kinase during skeletal muscle differentiation. We sought to identify putative site(s) for this phosphorylation event. 相似文献50.