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81.
Simms TM Wright MR Hernandez M Perez OA Ramirez EC Martinez E Herrera RJ 《American journal of physical anthropology》2012,148(4):618-631
Although previous studies have characterized the genetic structure of populations from Haiti and Jamaica using classical and autosomal STR polymorphisms, the patrilineal influences that are present in these countries have yet to be explored. To address this lacuna, the current study aims to investigate, for the first time, the potential impact of different ancestral sources, unique colonial histories, and distinct family structures on the paternal profile of both groups. According to previous reports examining populations from the Americas, island-specific demographic histories can greatly impact population structure, including various patterns of sex-biased gene flow. Also, given the contrasting autosomal profiles provided in our earlier study (Simms et al.: Am J Phys Anthropol 142 (2010) 49-66), we hypothesize that the degree and directionality of gene flow from Europeans, Africans, Amerindians, and East Asians are dissimilar in the two countries. To test this premise, 177 high-resolution Y-chromosome binary markers and 17 Y-STR loci were typed in Haiti (n = 123) and Jamaica (n = 159) and subsequently utilized for phylogenetic comparisons to available reference collections encompassing Africa, Europe, Asia (East and South), and the New World. Our results reveal that both studied populations exhibit a predominantly South-Saharan paternal component, with haplogroups A1b-V152, A3-M32, B2-M182, E1a-M33, E1b1a-M2, E2b-M98, and R1b2-V88 comprising 77.2% and 66.7% of the Haitian and Jamaican paternal gene pools, respectively. Yet, European derived chromosomes (i.e., haplogroups G2a*-P15, I-M258, R1b1b-M269, and T-M184) were detected at commensurate levels in Haiti (20.3%) and Jamaica (18.9%), whereas Y-haplogroups indicative of Chinese [O-M175 (3.8%)] and Indian [H-M69 (0.6%) and L-M20 (0.6%)] ancestry were restricted to Jamaica. 相似文献
82.
Lonardo E Hermann PC Mueller MT Huber S Balic A Miranda-Lorenzo I Zagorac S Alcala S Rodriguez-Arabaolaza I Ramirez JC Torres-Ruíz R Garcia E Hidalgo M Cebrián DÁ Heuchel R Löhr M Berger F Bartenstein P Aicher A Heeschen C 《Cell Stem Cell》2011,9(5):433-446
Nodal and Activin belong to the TGF-β superfamily and are important regulators of embryonic stem cell fate. Here we investigated whether Nodal and Activin regulate self-renewal of pancreatic cancer stem cells. Nodal and Activin were hardly detectable in more differentiated pancreatic cancer cells, while cancer stem cells and stroma-derived pancreatic stellate cells markedly overexpressed Nodal and Activin, but not TGF-β. Knockdown or pharmacological inhibition of the Nodal/Activin receptor Alk4/7 in cancer stem cells virtually abrogated their self-renewal capacity and in vivo tumorigenicity, and reversed the resistance of orthotopically engrafted cancer stem cells to gemcitabine. However, engrafted primary human pancreatic cancer tissue with a substantial stroma showed no response due to limited drug delivery. The addition of a stroma-targeting hedgehog pathway inhibitor enhanced delivery of the Nodal/Activin inhibitor and translated into long-term, progression-free survival. Therefore, inhibition of the Alk4/7 pathway, if combined with hedgehog pathway inhibition and gemcitabine, provides a therapeutic strategy for targeting cancer stem cells. 相似文献
83.
84.
Jessica Voisin Francesca Farina Swati Naphade Morgane Fontaine Kizito‐Tshitoko Tshilenge Carlos Galicia Aguirre Alejandro Lopez‐Ramirez Julia Dancourt Aurélie Ginisty Satish Sasidharan Nair Kuruwitage Lakshika Madushani Ningzhe Zhang Fran?ois‐Xavier Lejeune Marc Verny Judith Campisi Lisa M. Ellerby Christian Neri 《Aging cell》2020,19(11)
85.
Mayara Caldas Ramos Cunha Fabiana da Silva Lima Marco Aurélio Ramirez Vinolo Araceli Hastreiter Rui Curi Primavera Borelli Ricardo Ambrósio Fock 《PloS one》2013,8(3)
Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states. 相似文献
86.
The anomeric specificity of D-glucose phosphorylation by hepatic glucose-6-phosphatase was examined in rat liver microsomes incubated in the presence of carbamoyl phosphate. At 10 degrees C, the Km for the equilibrated hexose and phosphate donor was close to 56 mM and 11 mM, respectively. The enzymic activity, which was increased in diabetic rats, was about 40% lower in untreated than in sonicated microsomes. No anomeric difference in affinity was found in sonicated microsomes. In untreated microsomes, however, the Km for beta-D-glucose was slightly lower than that for alpha-D-glucose. The maximal velocity was higher with beta- than alpha-D-glucose in both untreated and sonicated microsomes. These data indicate that the phosphotransferase activity of glucose-6-phosphatase cannot account for the higher rate of glycolysis and glycogen synthesis found in hepatocytes exposed to alpha- rather than beta-D-glucose. 相似文献
87.
Ramirez DM Leppla SH Schneerson R Shiloach J 《Journal of industrial microbiology & biotechnology》2002,28(4):232-238
The protective antigen (PA) is one of the three components of the anthrax toxin. It is a secreted nontoxic protein with a
molecular weight of 83 kDa and is the major component of the currently licensed human vaccine for anthrax. Due to limitations
found in the existing vaccine formulation, it has been proposed that genetically modified PA may be more effective as a vaccine.
The expression and the stability of two recombinant PA (rPA) variants, PA-SNKE-ΔFF-E308D and PA-N657A, were studied. These
proteins were expressed in the nonsporogenic avirulent strain BH445. Initial results indicated that PA-SNKE-ΔFF-E308D, which
lacks two proteolysis-sensitive sites, is more stable than PA-N657A. Process development was conducted to establish an efficient
production and purification process for PA-SNKE-ΔFF-E308D. pH, media composition, growth strategy and protease inhibitors
composition were analyzed. The production process chosen was based on batch growth of B. anthracis using tryptone and yeast extract as the only source of carbon, pH control at 7.5, and antifoam 289. Optimal harvest time
was 14–18 h after inoculation, and EDTA (5 mM) was added upon harvest for proteolysis control. Recovery of the rPA was performed
by expanded-bed adsorption (EBA) on a hydrophobic interaction chromatography (HIC) resin, eliminating the need for centrifugation,
microfiltration and diafiltration. The EBA step was followed by ion exchange and gel filtration. rPA yields before and after
purification were 130 and 90 mg/l, respectively. The purified rPA, without further treatment, treated with small amounts of
formalin or adsorbed on alum, induced, high levels of IgG anti-PA with neutralization activities. Journal of Industrial Microbiology & Biotechnology (2002) 28, 232–238 DOI: 10.1038/sj/jim/7000239
Received 28 August 2001/ Accepted in revised form 20 December 2001 相似文献
88.
T1alpha, a differentiation gene of lung alveolar epithelial type I cells, is developmentally regulated and encodes an apical membrane protein of unknown function. Morphological differentiation of type I cells to form the air-blood barrier starts in the last few days of gestation and continues postnatally. Although T1alpha is expressed in the foregut endoderm before the lung buds, T1alpha mRNA and protein levels increase substantially in late fetuses when expression is restricted to alveolar type I cells. We generated T1alpha null mutant mice to study the role of T1alpha in lung development and differentiation and to gain insight into its potential function. Homozygous null mice die at birth of respiratory failure, and their lungs cannot be inflated to normal volumes. Distal lung morphology is altered. In the absence of T1alpha protein, type I cell differentiation is blocked, as indicated by smaller airspaces, many fewer attenuated type I cells, and reduced levels of aquaporin-5 mRNA and protein, a type I cell water channel. Abundant secreted surfactant in the narrowed airspaces, normal levels of surfactant protein mRNAs, and normal patterns and numbers of cells expressing surfactant protein-B suggest that differentiation of type II cells, also alveolar epithelial cells, is normal. Anomalous proliferation of the mesenchyme and epithelium at birth with unchanged numbers of apoptotic cells suggests that loss of T1alpha and/or abnormal morphogenesis of type I cells alter the proliferation rate of distal lung cells, probably by disruption of epithelial-mesenchymal signaling. 相似文献
89.
H Yoshioka H Zhang F Ramirez M G Mattei M Moradi-Ameli M van der Rest M K Gordon 《Genomics》1992,13(3):884-886
A 1.8-kb cDNA encoding portion of a novel collagenous chain was isolated from a human rhabdomyosarcoma cell line by cross-hybridization using a chicken type V collagen probe. Sequence analysis suggests that this chain belongs to the recently discovered group of collagens, termed the FACIT class of macromolecules. This cDNA was used to locate the corresponding gene (D6S228E) to chromosome 6, notably at position 6q12-q14. Interestingly, within this region of human chromosome 6 residues the alpha 1 (IX) collagen gene (COL9A1), a member of the FACIT group. 相似文献
90.
Francesco Ramirez J. Gregory Mears Arthur Bank 《Molecular and cellular biochemistry》1980,31(1):133-145
Summary The structure and organization of the human globin genes at the nucleotide level has been established by restriction endonuclease digestion of cellular DNA, and by the isolation and purification of these. genes in phage vectors. With this approach it has been possible to define alterations at the DNA level resulting in a group of inherited diseases of man known as the thalassemia syndromes, and related disorders. Combined with other known genetic and biochemical data, these studies provide a framework for understanding the pathogenesis of these disorders at the molecular level. 相似文献