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1.
J Dairy Sci ; 103(11): 10161-10174, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32981728

ABSTRACT

Four multiparous, lactating Holstein cows (average DIM 169.5 ± 20.5 d), fitted with ruminal and duodenal cannulas, were used in a 4 × 4 Latin square with a 2 × 2 factorial arrangement of treatments to investigate the effects of 2-hydroxy-4-methylthio-butanoic acid (HMTBA) when fed with diets differing in metabolizable protein (MP) supply and equal levels of crude protein on milk production and composition, rumen microbial activity, duodenal protein flow, and rumen bacterial community composition in vivo and in vitro. Experimental periods were 28 d in length. Cows were housed in individual tie stalls and were randomly assigned to 4 dietary treatments: low MP or high MP, supplemented with or without 25 g of HMTBA, which was top-dressed once daily at 0930 h. No interactions were observed between HMTBA and level of dietary MP, with the exception of ruminal acetate-to-propionate ratio. Milk yield was not affected by treatment and averaged 23.8 ± 2.06 kg/d. There was a tendency for increased milk protein percent in cows receiving low MP diets, averaging 3.30 ± 0.09% and 3.21 ± 0.09% for low MP and high MP, respectively. The total-tract apparent digestibility of organic matter, neutral detergent fiber, and nitrogen were greater in cows consuming the low MP diet. Rumen pH was lower in cows consuming high MP diets as well as in those consuming HMTBA. Rumen ammonia concentrations tended to be greater in cows consuming HMTBA, and volatile fatty acid concentrations were greater in cows consuming HMTBA. Duodenal dry matter flow, nitrogen flow, and microbial nitrogen flow did not differ between treatments. The bacterial community structure of cows receiving HMTBA was not affected at the phylum level. The relative abundance of bacterial phyla in vivo differed when compared with in vitro conditions for Firmicutes, Bacteroidetes, Proteobacteria, TM7, Tenericutes, Spirochaetes, SR1, and Verrucomicrobia.


Subject(s)
Diet/veterinary , Duodenum/metabolism , Methionine/analogs & derivatives , Microbiota/drug effects , Nitrogen/metabolism , Rumen/microbiology , Ammonia/metabolism , Animal Feed/analysis , Animals , Bacteria/classification , Bacteria/metabolism , Cattle , Dietary Proteins/administration & dosage , Dietary Proteins/metabolism , Dietary Supplements , Female , Fermentation , Lactation , Methionine/administration & dosage , Microbiota/physiology , Milk/chemistry , Rumen/metabolism
2.
Sci Rep ; 6: 30894, 2016 08 04.
Article in English | MEDLINE | ID: mdl-27488366

ABSTRACT

Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies.


Subject(s)
Anal Canal/transplantation , Aorta/transplantation , Mesenteric Artery, Inferior/transplantation , Plastic Surgery Procedures/methods , Portal Vein/transplantation , Anastomosis, Surgical/methods , Animals , Colostomy/adverse effects , Male , Quality of Life , Rats , Rats, Inbred Lew , Rats, Wistar , Transplantation, Homologous
3.
J Appl Microbiol ; 120(3): 588-99, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26726754

ABSTRACT

AIMS: Recent studies have demonstrated RAMP, a complete starter feed, to have beneficial effects for animal performance. However, how RAMP may elicit such responses is unknown. To understand if RAMP adaptation results in changes in the rumen bacterial community that can potentially affect animal performance, we investigated the dynamics of rumen bacterial community composition in corn-adapted and RAMP-adapted cattle. METHODS AND RESULTS: During gradual acclimation of the rumen bacterial communities, we compared the bacterial community dynamics in corn and RAMP-adapted using 16S rRNA gene amplicon sequencing. Significant shifts in bacterial populations across diets were identified. The shift in corn-adapted animals occurred between adaptation step3 and step4, whereas in RAMP-adapted cattle, the shift occurred between step2 and step3. As the adaptation program progressed, the abundance of OTUs associated with family Prevotellaceae and S24-7 changed in corn-adapted animals. In RAMP-adapted animals, OTUs belonging to family Ruminococcaceae and Lachnospiraceae changed in abundance. CONCLUSIONS: Rumen bacteria can be acclimated faster to high concentrate diets, such as RAMP, than traditional adaptation programs and the speed of bacterial community acclimation depends on substrate composition. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings may have implications for beef producers to reduce feedlot costs, as less time adapting animals would result in lower feed costs. However, animal feeding behavior patterns and other factors must be considered.


Subject(s)
Animal Feed/analysis , Bacteria/metabolism , Cattle/microbiology , Rumen/microbiology , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Cattle/metabolism , Diet/veterinary , Rumen/metabolism
4.
Vet Comp Oncol ; 13(2): 98-105, 2015 Jun.
Article in English | MEDLINE | ID: mdl-23432735

ABSTRACT

Imaging studies in humans with anal and rectal cancer indicate that magnetic resonance imaging (MRI) is a more sensitive technique than abdominal ultrasound (AUS) for the detection of abdominal lymphadenopathy. The purpose of this retrospective study was to directly compare the efficacy of these two techniques in detecting abdominal lymphadenopathy in dogs with apocrine gland adenocarcinoma of the anal sac (AGAAS). Six dogs with histologically confirmed AGAAS and histopathologic confirmation of metastasis to abdominal lymph nodes (LNs) had AUS and abdominal MRI. AUS identified lymphadenopathy in two of six dogs, whereas MRI identified lymphadenopathy in all the six dogs. Lymphadenopathy was predominantly sacral in location, with involvement of the medial iliac and hypogastric LNs in only two cases. These data suggest that MRI is more sensitive than AUS for detecting sacral abdominal lymphadenopathy in dogs with AGAAS. As such, MRI could be considered in any patient with AGAAS for initial staging of this disease.


Subject(s)
Adenocarcinoma/veterinary , Anal Gland Neoplasms/diagnosis , Anal Sacs , Apocrine Glands , Dog Diseases/diagnosis , Lymphatic Diseases/veterinary , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Anal Gland Neoplasms/diagnostic imaging , Anal Gland Neoplasms/pathology , Anal Sacs/diagnostic imaging , Anal Sacs/pathology , Animals , Apocrine Glands/diagnostic imaging , Apocrine Glands/pathology , Dog Diseases/diagnostic imaging , Dog Diseases/pathology , Dogs , Lymphatic Diseases/diagnostic imaging , Lymphatic Diseases/pathology , Lymphatic Metastasis , Magnetic Resonance Imaging/veterinary , Retrospective Studies , Ultrasonography/veterinary
5.
J Anim Sci ; 92(2): 733-43, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24664563

ABSTRACT

The objectives of this study were to evaluate the effect of dried distillers grains with solubles (DDGS) on ruminal biohydrogenation and duodenal flow of fatty acids, and to evaluate effects on the ruminal and duodenal microbial community using Roche 454 pyro-sequencing. Three crossbred steers (average BW 780 ± 137 kg) fitted with ruminal and duodenal cannulae were used in a 3-diet, 6-period crossover design. Animals were housed in individual free stalls and fed twice daily at 0700 and 1900 h. Diets (DM basis) were 1) CONTROL, 19.5% corn bran, 20% sorghum silage, 60% brome hay, 0.5% trace minerals, and 0.25% urea, but no DDGS; 2) LOW DDGS, inclusion of 9.75% DDGS replacing equal percentage of corn bran; 3) HIGH DDGS, inclusion of 19.5% DDGS completely replacing corn bran. Feed ingredients and duodenal digesta samples were analyzed for fatty acid composition. The DNA was extracted from isolated mixed ruminal bacterial samples and from intestinal digesta samples. The V1-V3 region of the 16S rRNA gene was sequenced, and bacterial phylogenetic analysis was conducted. Data were analyzed using the MIXED procedure of SAS. Biohydrogenation of C18:1 increased (P < 0.01) with DDGS inclusion; means were 68.3, 75.6, and 79.3 ± 4.3% for CONTROL, LOW DDGS, and HIGH DDGS, respectively. In the same order, means of biohydrogenation of C18:2 (P < 0.05) were 84.1, 91.5, and 93.3 ± 3.4%. Duodenal flow of total fatty acids increased (P < 0.01) with DDGS inclusion; means were 134, 168, and 223 ± 33 g/d for CONTROL, LOW DDGS, and HIGH DDGS, respectively. In the same order, means of C18:0 flow (P < 0.01) were 51, 86, and 121 ± 18 g/d. DDGS did not affect the predominant bacterial phyla in the gut, which were Bacteroidetes (P = 0.62) and Firmicutes (P = 0.71). However, the phylum Fibrobacteres decreased (P < 0.01) when DDGS was fed with means of 5.5, 6.0 and 3.7 ± 0.6% for CONTROL, LOW DDGS, and HIGH DDGS, respectively. Fibrobacteres were lower (P < 0.01) in isolated ruminal bacterial samples compared to duodenal digesta samples with means of 0.1 and 10.1 ± 0.6%, respectively. Overall, the inclusion of DDGS in diets increased ruminal biohydrogenation of C18:1 and C18:2, which increased duodenal flow of C18:0. In addition, the bacterial community of the rumen clustered separately from that of the duodenum suggesting different bacterial diversity between isolated ruminal bacteria and duodenal digesta.


Subject(s)
Animal Feed/analysis , Cattle/physiology , Diet/veterinary , Edible Grain/chemistry , Fatty Acids/metabolism , Rumen/physiology , Animal Nutritional Physiological Phenomena , Animals , Bacteria/classification , Bacteria/genetics , Cross-Over Studies , DNA, Bacterial/classification , DNA, Bacterial/genetics , Fatty Acids/chemistry , Intestinal Mucosa/metabolism , Intestines/microbiology , Male , Nucleic Acid Amplification Techniques
6.
Xenotransplantation ; 19(5): 298-304, 2012.
Article in English | MEDLINE | ID: mdl-22957972

ABSTRACT

INTRODUCTION: Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR. METHODS: We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods. RESULTS: No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium. CONCLUSIONS: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the liver's relative resistance to this immune response.


Subject(s)
Graft Rejection/immunology , Immunoglobulin G/metabolism , Transplantation, Heterologous/adverse effects , Transplantation, Heterologous/immunology , Acute Disease , Animals , Digestive System/immunology , Digestive System/pathology , Graft Rejection/etiology , Graft Rejection/pathology , Liver Transplantation/adverse effects , Liver Transplantation/immunology , Liver Transplantation/pathology , Male , Models, Animal , Organ Specificity , Rabbits , Sus scrofa , Transplantation Immunology
7.
J Vet Intern Med ; 25(2): 278-84, 2011.
Article in English | MEDLINE | ID: mdl-21314727

ABSTRACT

BACKGROUND: Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) administered in a metronomic fashion has not been evaluated in dogs. HYPOTHESIS: Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms. ANIMALS: Eighty-one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine. METHODS: Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84 mg/m² PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death. RESULTS: Starting dosage (median) was 2.84 mg/m² PO daily and treatment duration was 98 days (median, range, 1-770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard-care treatment options, and warrants evaluation in primary therapy.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dog Diseases/drug therapy , Lomustine/therapeutic use , Neoplasms/veterinary , Administration, Oral , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Disease Progression , Dogs , Female , Lomustine/administration & dosage , Lomustine/adverse effects , Male , Neoplasm Metastasis/drug therapy , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/veterinary , Neoplasms/drug therapy , Palliative Care , Prospective Studies , Thrombocytopenia/chemically induced , Thrombocytopenia/veterinary , Treatment Outcome
8.
Science ; 330(6006): 927-31, 2010 Nov 12.
Article in English | MEDLINE | ID: mdl-21071659

ABSTRACT

The Amazonian rainforest is arguably the most species-rich terrestrial ecosystem in the world, yet the timing of the origin and evolutionary causes of this diversity are a matter of debate. We review the geologic and phylogenetic evidence from Amazonia and compare it with uplift records from the Andes. This uplift and its effect on regional climate fundamentally changed the Amazonian landscape by reconfiguring drainage patterns and creating a vast influx of sediments into the basin. On this "Andean" substrate, a region-wide edaphic mosaic developed that became extremely rich in species, particularly in Western Amazonia. We show that Andean uplift was crucial for the evolution of Amazonian landscapes and ecosystems, and that current biodiversity patterns are rooted deep in the pre-Quaternary.


Subject(s)
Biodiversity , Climate Change , Geological Phenomena , Animals , Ecosystem , Fossils , Geography , Phylogeny , Rivers , South America , Time , Trees , Wetlands
9.
Placenta ; 31(2): 144-50, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20004972

ABSTRACT

The expression pattern of caveolin-1 and the distribution of caveolae in the murine placental labyrinth and visceral yolk sac have been determined. Immunoblot analysis demonstrates that both placenta and yolk sac express the protein caveolin-1. Immunofluorescence microscopy was used to determine which cell types in the placental labyrinth and yolk sac express caveolin-1. In yolk sac, detectable caveolin-1 was restricted to endothelial cells and smooth muscle cells of the vitelline vasculature and to mesothelial cells. Endoderm, the major cell type in the yolk sac, does not express caveolin-1 as assessed by this assay. In the labyrinth region of the placenta, endothelial cells express caveolin-1 but this protein was not detectable in any of the three trophoblast layers. These tissues were also examined by electron microscopy to determine which cell types contain the specialized plasma membrane microdomains known as caveolae. Morphologically detectable caveolae were present in endothelial and smooth muscle cells, as well as mesothelial cells of the yolk sac and in endothelial cells of the placental labyrinth. Neither endodermal cells of the yolk sac nor trophoblastic cells in the placental labyrinth contained caveolae-like structures. We conclude that caveolin-1 and caveolae have restricted distribution in the murine placenta and yolk sac and that this parallels the situation in human placenta.


Subject(s)
Caveolae/ultrastructure , Caveolin 1/metabolism , Placenta/metabolism , Placenta/ultrastructure , Pregnancy Proteins/metabolism , Yolk Sac/metabolism , Yolk Sac/ultrastructure , Animals , Cell Polarity , Endoderm/metabolism , Endoderm/ultrastructure , Endothelial Cells/metabolism , Endothelial Cells/ultrastructure , Female , Fluorescent Antibody Technique, Indirect , Humans , Mice , Mice, Inbred BALB C , Microscopy, Confocal , Microscopy, Fluorescence , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/ultrastructure , Pregnancy , Protein Transport , Species Specificity , Trophoblasts/metabolism , Trophoblasts/ultrastructure
10.
Inj Prev ; 15(6): 379-83, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19959729

ABSTRACT

OBJECTIVE: To estimate the effectiveness of booster seats and of seatbelts in reducing the risk of child death during traffic collisions and to examine possible effect modification by various collision and vehicle characteristics. METHODS: A matched cohort study was conducted using data from the Fatality Analysis Reporting System. Death risk ratios were estimated with conditional Poisson regression, bootstrapped coefficient standard errors, and multiply imputed missing values using chained equations. RESULTS: Estimated death risk ratios for booster seats used with seatbelts were 0.33 (95% CI 0.28 to 0.40) for children age 4-5 years and 0.45 (0.31 to 0.63) for children aged 6-8 years (Wald test of homogeneity p<0.005). The estimated risk ratios for seatbelt used alone were similar for the two age groups, 0.37 (0.32 to 0.43) and 0.39 (0.34 to 0.44) for ages 4-5 and 6-8, respectively (Wald p = 0.61). Estimated booster seat effectiveness was significantly greater for inbound seating positions (Wald p = 0.05) and during rollovers collisions (Wald p = 0.01). Significant variability in risk ratio estimates was not observed across levels of calendar year, vehicle model year, vehicle type, or land use. CONCLUSIONS: Seatbelts, used with or without booster seats, are highly effective in preventing death among motor vehicle occupants aged 4-8 years. Booster seats do not appear to improve the performance of seatbelts with respect to preventing death (risk ratio 0.92, 95% CI 0.79 to 1.08, comparing seatbelts with boosters to seatbelts alone), but because several studies have found that booster seats reduce non-fatal injury severity, clinicians and injury prevention specialists should continue to recommend the use of boosters to parents of young children.


Subject(s)
Accidents, Traffic/mortality , Child Restraint Systems/statistics & numerical data , Motor Vehicles/statistics & numerical data , Seat Belts/statistics & numerical data , Wounds and Injuries/prevention & control , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Risk Assessment/methods , United States/epidemiology , Wounds and Injuries/etiology , Wounds and Injuries/mortality
11.
Br J Pharmacol ; 149(5): 481-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16967046

ABSTRACT

BACKGROUND AND PURPOSE: Fluoxetine (Prozac) is a widely prescribed drug in adults and children, and it has an active metabolite, norfluoxetine, with a prolonged elimination time. Although uncommon, Prozac causes QT interval prolongation and arrhythmias; a patient who took an overdose of Prozac exhibited a prolonged QT interval (QTc 625 msec). We looked for possible mechanisms underlying this clinical finding by analysing the effects of fluoxetine and norfluoxetine on ion channels in vitro. EXPERIMENTAL APPROACH: We studied the effects of fluoxetine and norfluoxetine on the electrophysiology and cellular trafficking of hERG K+ and SCN5A Na+ channels heterologously expressed in HEK293 cells. KEY RESULTS: Voltage clamp analyses employing square pulse or ventricular action potential waveform protocols showed that fluoxetine and norfluoxetine caused direct, concentration-dependent, block of hERG current (IhERG). Biochemical studies showed that both compounds also caused concentration-dependent reductions in the trafficking of hERG channel protein into the cell surface membrane. Fluoxetine had no effect on SCN5A channel or HEK293 cell endogenous current. Mutations in the hERG channel drug binding domain reduced fluoxetine block of IhERG but did not alter fluoxetine's effect on hERG channel protein trafficking. CONCLUSIONS AND IMPLICATIONS: Our findings show that both fluoxetine and norfluoxetine at similar concentrations selectively reduce IhERG by two mechanisms, (1) direct channel block, and (2) indirectly by disrupting channel protein trafficking. These two effects are not mediated by a single drug binding site. Our findings add complexity to understanding the mechanisms that cause drug-induced long QT syndrome.


Subject(s)
Ether-A-Go-Go Potassium Channels/metabolism , Fluoxetine/adverse effects , Long QT Syndrome/chemically induced , Adult , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/pharmacology , Blotting, Western , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/physiology , Cisapride/pharmacology , Dose-Response Relationship, Drug , Drug Overdose , Ether-A-Go-Go Potassium Channels/antagonists & inhibitors , Ether-A-Go-Go Potassium Channels/genetics , Female , Fluoxetine/analogs & derivatives , Fluoxetine/pharmacology , Humans , Long QT Syndrome/metabolism , Long QT Syndrome/physiopathology , Membrane Potentials/drug effects , Muscle Proteins/antagonists & inhibitors , Muscle Proteins/genetics , Muscle Proteins/metabolism , Mutation/genetics , NAV1.5 Voltage-Gated Sodium Channel , Patch-Clamp Techniques , Piperidines/pharmacology , Protein Transport/drug effects , Pyridines/pharmacology , Sodium Channels/genetics , Sodium Channels/metabolism , Time Factors , Transfection
12.
Clin Genet ; 66(4): 327-32, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15355435

ABSTRACT

Non-random X-chromosome inactivation (XCI) has been associated with X-linked diseases, neoplastic diseases, recurrent pregnancy loss, and trisomy risk. It also occurs more commonly in older female populations. To understand the etiology of non-random XCI and utilize this assay appropriately in clinical research and practice, the age-related alteration in XCI patterns in normal females needs to be clearly defined. In the present study, we evaluated the XCI status in 350 unselected women aged 0-88 years with unknown history of genetic disorders or abnormal pregnancies. DNA samples were extracted from peripheral blood and analyzed by a methylation-based assay at the androgen receptor locus. A weak but significant positive correlation was observed between age and degree of skewing in XCI over the whole age range (r = 0.23, p < 0.0001), and skewing values become non-normally distributed at older ages. However, the increase in skewed XCI appears to be more pronounced after age 30 than at younger ages. This trend supports the model of increased skewing with age as a consequence of hematopoietic stem cell senescence. An alternative possibility is that there is allele-specific loss of methylation with time that results in the appearance of increased XCI skewing using a methylation-based assay.


Subject(s)
Aging/genetics , Chromosomes, Human, X/genetics , DNA Methylation , Dosage Compensation, Genetic , Sex Chromosome Aberrations , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Middle Aged , Receptors, Androgen/genetics
13.
J Mol Evol ; 55(4): 460-9, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12355265

ABSTRACT

The structural and functional analysis of rRNA molecules has attracted considerable scientific interest. Empirical studies have demonstrated that sequence variation is not directly translated into modifications of rRNA secondary structure. Obviously, the maintenance of secondary structure and sequence variation are in part governed by different selection regimes. The nature of those selection regimes still remains quite elusive. The analysis of individual bacterial models cannot adequately explore this topic. Therefore, we used primary sequence data and secondary structures of a mitochondrial 16S rRNA fragment of 558 insect species from 15 monophyletic groups to study patterns of sequence variation, and variation of secondary structure. Using simulation studies to establish significance levels of change, we found that despite conservation of secondary structure, the location of sequence variation within the conserved rRNA structure changes significantly between groups of insects. Despite our conservative estimation procedure we found significant site-specific rate changes at 56 sites out of 184. Additionally, site-specific rate variation is somewhat clustered in certain helices. Both results confirm what has been predicted from an application of non-stationary maximum likelihood models to rRNA sequences. Clearly, constraints on sequence variation evolve and leave footprints in the form of evolutionary plasticity in rRNA sequences. Here, we show that a better understanding of the evolution of rRNA sequences can be obtained by integrating both phylogenetic and structural information.


Subject(s)
Drosophila melanogaster/genetics , Evolution, Molecular , Mitochondria/genetics , RNA, Ribosomal, 16S/genetics , Animals , Phylogeny
14.
BMC Evol Biol ; 1: 10, 2001.
Article in English | MEDLINE | ID: mdl-11734058

ABSTRACT

BACKGROUND: Although closely related, the alpha-proteobacteria Wolbachia and the Rickettsiaceae (Rickettsia and Ehrlichia), employ different evolutionary life history strategies. Wolbachia are obligate endocellular symbionts that infect an extraordinary host range and, in contrast to the infectious and pathogenic Rickettsia and Ehrlichia, profoundly influence host reproductive biology. RESULTS: Phylogenies of the Rickettsia, Ehrlichia, and Wolbachia were independently inferred from 16S rDNA sequences and GroEL amino acid sequences. Topologies inferred from both sets of sequence data were consistent with one another, and both indicate the genus Wolbachia shared a common ancestor most recently with Ehrlichia. These two genera are a sister group to the genus Rickettsia. Mapping biological properties onto this phylogeny reveals that manipulation of host reproduction, characteristic of Wolbachia strains, is a derived characteristic. This evolutionary novelty is accompanied by the loss of the ability to infect vertebrate hosts. CONCLUSIONS: Because of the contrasting transmission strategies employed by each, Wolbachia is expected to maximize efficiency of vertical transmission, while Ehrlichia and Rickettsia will optimize horizontal transfer of infection. Wolbachia manipulation of host reproduction could thus be viewed as strategy employed by this bacterium to foster its own propagation via vertical transmission.


Subject(s)
Evolution, Molecular , Rickettsia/genetics , Rickettsia/pathogenicity , Wolbachia/genetics , Wolbachia/pathogenicity , Chaperonin 60/chemistry , Chaperonin 60/genetics , DNA, Bacterial/genetics , DNA, Ribosomal/genetics , Ehrlichia/genetics , Ehrlichia/pathogenicity , Phylogeny , Protein Structure, Secondary/genetics , RNA, Ribosomal, 16S/genetics , Symbiosis/physiology
15.
Accid Anal Prev ; 33(4): 499-506, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11426680

ABSTRACT

To guide interventions to prevent injuries to pickup-truck occupants, we characterized pickup truck ownership, drivers and use in the 1995 National Personal Transportation Survey, which collects travel data from the civilian noninstitutionalized population of the US. SUDAAN software was used to account for the complex nature of the sample. Pickup truck ownership was more common in households with more vehicles, in rural households, in households living in single family homes and mobile homes, and in middle-income households. Among US regions, pickup truck ownership was highest among households in the mountain west. Pickup truck ownership was greater in households with two adults, whether or not children or youths were present, but this was largely due to the number of vehicles in these households. Driving a pickup on the sample day was more frequent among men, among drivers with less education and among full-time workers. A higher proportion of trips to work, work-related trips, longer trips and trips with fewer people were by pickup truck. Seat belt use was lower among pickup truck drivers than drivers of other vehicles. For only 0.5% of households (those with three or more members and a pickup truck as their only vehicle), restrictions on travel in cargo areas might be burdensome. Restrictions on cargo area travel, strengthening existing seat belt laws and social marketing strategies might increase the safety of pickup truck occupants.


Subject(s)
Accidents, Traffic/prevention & control , Motor Vehicles/statistics & numerical data , Ownership/statistics & numerical data , Adolescent , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Residence Characteristics , Risk Factors , Socioeconomic Factors
16.
J Parasitol ; 87(2): 379-85, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11318568

ABSTRACT

Recent progress in understanding the etiology of proliferative kidney disease (PKD) includes the identification of freshwater bryozoans as the natural hosts of the myxozoan parasite that causes the disease in salmonid fish and formal description of the parasite as Tetracapsula bryosalmonae. This paper presents data on patterns of occurrence of T. bryosalmonae and sequence variation among isolates. T. bryosalmonae infects bryozoans that range from primitive to more derived genera within the Phylactolaemata and that differ in growth form and habits. Infected bryozoans have been collected in diverse habitats including cold, clear streams and warm, eutrophic lakes. Temporal surveys reveal intra- and interannual variation in infection levels, and spatial variation in incidence of infection is implicit by the apparent absence of T. bryosalmonae from many bryozoan populations. The significance of minor variation in partial sequences of 18S rDNA requires further investigation. The information presented here provides the first significant insights into the ecology of T. bryosalmonae.


Subject(s)
Bryozoa/parasitology , DNA, Ribosomal/chemistry , Eukaryota/classification , Fish Diseases/parasitology , Kidney Diseases/veterinary , Protozoan Infections, Animal/epidemiology , Animals , Canada/epidemiology , Eukaryota/genetics , Eukaryota/isolation & purification , Fish Diseases/epidemiology , Genetic Variation , Host-Parasite Interactions/genetics , Kidney Diseases/epidemiology , Kidney Diseases/parasitology , Life Cycle Stages , Oncorhynchus mykiss , Prevalence , Protozoan Infections, Animal/parasitology , RNA, Ribosomal, 18S/genetics , Sequence Analysis, DNA , United States/epidemiology
17.
Soc Sci Med ; 52(7): 1081-91, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11266051

ABSTRACT

Several studies indicate that rates of serious pediatric injury are higher among Hispanics than among non-Hispanic whites in the USA. To investigate possible contributory factors, we interviewed 50 Mexican, 30 Mexican American, and 30 non-Hispanic white mothers in their own homes in the same low-income neighborhoods of Southern California. Mothers were identified via door-to-door canvassing in areas with high rates of pediatric injury. We observed household conditions and behaviors and obtained a detailed family history, including accounts of any occurrence of serious injury in a child under 5 years old, the highest-risk age group for pediatric injury. Results show that Mexican families were poorer, less educated, and lived in more hazardous and crowded conditions than did families in the other two groups. Nevertheless, they benefited from strong family bonds and a cultural tradition in which responsible older children typically supervise younger siblings. In contrast, a number of Mexican American and white mothers had been abused as children and were estranged from their own mothers; hence they lacked support and models of good parenting. There was much less self-reported smoking, drug use, and mental dysfunction among the Mexican mothers and their male partners as well as much less excessively active and/or aggressive behavior among their children. The nature of the injuries reported by the various groups seemed to reflect these differences. Appropriate interventions for each group are discussed. The study illustrates the importance of using ethnographic methods to examine the context of pediatric injury at the household level.


Subject(s)
Child Welfare/statistics & numerical data , Family Characteristics , Mexican Americans/statistics & numerical data , Poverty/ethnology , Social Support , White People/statistics & numerical data , Wounds and Injuries/epidemiology , Adult , Anthropology, Cultural , California/epidemiology , Child, Preschool , Health Behavior , Health Surveys , Humans , Infant , Interviews as Topic , Mothers , Risk Factors , Socioeconomic Factors
18.
J Immunol ; 166(6): 3882-9, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11238632

ABSTRACT

To evaluate the potential role of human placental endothelial cells in the transport of IgG from maternal to fetal circulation, we studied Fc gamma receptor (Fc gamma R) expression by immunohistology and immunoblotting. Several pan-Fc gamma RII Abs that label the placental endothelium displayed a distribution pattern that correlated well with transport functions, being intense in the terminal villus and nil in the cord. In contrast, the MHC class 1-like IgG transporter, FcRn, and the classical Fc gamma RIIa were not expressed in transport-related endothelium of the placenta. Our inference, that Fc gamma RIIb was the likely receptor, we confirmed by analyzing purified placental villi, enriched in endothelium, by immunoblotting with a new Ab specific for the cytoplasmic tail of Fc gamma RIIb. These experiments showed that the Fc gamma RII expressed in villus endothelium was the b2 isoform whose cytoplasmic tail is known to include a phosphotyrosyl-based motif that inhibits a variety of immune responses. We suggest that this receptor is perfectly positioned to transport IgG although as well it may scavenge immune complexes.


Subject(s)
Antigens, CD/biosynthesis , Chorionic Villi/immunology , Chorionic Villi/metabolism , Endothelium, Vascular/immunology , Endothelium, Vascular/metabolism , Receptors, IgG/biosynthesis , Antibodies, Monoclonal/metabolism , Antibody Specificity , Antigens, CD/immunology , Antigens, CD/metabolism , Chorionic Villi/blood supply , Endothelium, Vascular/cytology , Female , Glycosylation , Humans , Microscopy, Fluorescence , Pregnancy , Protein Isoforms/biosynthesis , Protein Isoforms/immunology , Protein Isoforms/metabolism , Receptors, IgG/immunology , Receptors, IgG/metabolism , Reproducibility of Results , Tumor Cells, Cultured , U937 Cells , Umbilical Cord/blood supply , Umbilical Cord/immunology , Umbilical Cord/metabolism
19.
Article in English | MEDLINE | ID: mdl-12214368

ABSTRACT

We used reports of additional occupants on trips from the Nationwide Personal Transportation Survey to estimate travel in cars and trucks for children age nine years and younger. For children age five to nine years these indirect estimates were 98% of directly reported travel. Using this travel data, the death rate was 4.0 per billion km of travel for children less than age one year and decreased to 1.7 for children age nine years. Infants have a higher exposure-based death rate for travel in cars and trucks than older children despite greater restraint use.


Subject(s)
Accidents, Traffic/mortality , Automobile Driving/statistics & numerical data , Child , Child, Preschool , Humans , Infant , United States/epidemiology
20.
Child Abuse Negl ; 24(6): 829-38, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10888021

ABSTRACT

OBJECTIVE: This study explored the main and interactive effects of sexual abuse history and relationship satisfaction on self-reported parenting, controlling for histories of physical abuse and parental alcoholism. METHOD: The community sample consisted of 90 mothers of 5- to 8-year-old children. The sample was limited to those mothers currently in an intimate relationship, 19 of whom reported a history of childhood sexual abuse. Participants completed the Child Behavior Checklist, the Parenting Stress Inventory, the Family Cohesion Index, and questions assessing parent-child role reversal, history of abuse and parental alcoholism, and current relationship satisfaction. RESULTS: Results of analyses and multivariate analyses of covariance suggested that sexual abuse survivors with an unsatisfactory intimate relationship were more likely than either sexual abuse survivors with a satisfactory relationship or nonabused women to endorse items on a questionnaire of role reversal (defined as emotional overdependence upon one's child). Role reversal was not significantly predicted by histories of physical abuse or parental alcoholism or child's gender. While parenting stress was inversely predicted by the significant main effect of relationship satisfaction, neither parenting stress nor child behavior problems were predicted by the main effect of sexual abuse history or by the interaction between sexual abuse history and relationship satisfaction. CONCLUSIONS: These results suggest the unique relevance of sexual abuse history and relationship satisfaction in the prediction of a specific type of parent-child role reversal--namely, a mother's emotional overdependence upon her child.


Subject(s)
Child Abuse, Sexual/psychology , Parenting , Role Playing , Adult , Alcoholism , Analysis of Variance , Child , Child, Preschool , Educational Status , Female , Humans , Interpersonal Relations , Male , Middle Aged
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