163 research outputs found

    Revascularization of skeletal muscle transplanted into the hamster cheek pouch: Electron microscopy

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    Revascularization of bundles of skeletal muscle fibers transplanted into the cheek pouch of hamsters was examined previously by intravital and light microscopy. Some blood vessels survived the ischemia of transplantation and revascularization resulted from the growth of surviving vessels. We have now examined the cellular events of graft revascularization by electron microscopy (EM). Approximately 20 skeletal muscle fibers were autografted into the hamster cheek pouch. Segments of the graft were prepared for EM from 0.5 to 5 days after transplantation. At 0.5 day, the endothelial cells of surviving blood vessels had short processes extending from them. By 1.0 day, some endothelial cells had separated. At 1.5 days, many endothelial cells were undergoing mitosis. Blood vessels at 2 to 2.5 days were of narrow diameter and most were densely packed with erythrocytes. Circulation was reestablished between 2.5 and 3 days. The fine structure of the blood vessels changed little after 3 days except for a decrease in the number of vesicles in the endothelial cell cytoplasm and the formation of normal endothelial cell injections. After 5 days, blood vessels were larger in diameter, but otherwise similar to control capillaries. We conclude that, despite the initial absence of circulation, surviving blood vessels underwent a rapid, orderly sequence of growth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25167/1/0000605.pd

    Revascularization of skeletal muscle transplanted into the hamster cheek pouch: Intravital and light microscopy

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    Small fiber bundles from the extensor digitorum longus (EDL) muscle were transplanted into the hamster cheek pouch to observe the process of revascularization. We tested the hypothesis that blood vessels of a graft degenerate and that revascularization results from the ingrowth of blood vessels from the cheek pouch into the graft. Degeneration and regeneration of muscle fibers followed a pattern similar to that reported for autografts of whole muscles in rats. Blood vessels in the graft that were adjacent to vascularized host tissue survived. At 1 day, surviving blood vessels in the graft had normal structure but erythrocytes were packed tightly in the lumen. At 2 days, sprouts from surviving graft vessels had grown into the cheek pouch. Between 2 and 2.5 days, anastomoses of blood vessels from the graft with those of the cheek pouch reestablished circulation. After circulation was established, the blood vessels contained well-spaced erythrocytes. By 3 days, blood vessels which increased in number and diameter throughout the graft occupied 40-60% of the graft. Over the next 24 hr, blood vessels in the graft regressed toward the control value. We conclude that blood vessels in muscle grafts in the cheek pouch survive transplantation, and that circulation in grafts is reestablished by the anastomoses of blood vessel sprouts from the graft with the blood vessels of the host.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25166/1/0000604.pd

    Inheritance and Inequality Among Nomads of South Siberia

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    At the headwaters of the Yenisei River in Tuva and northern Mongolia, nomadic pastoralists move between camps in a seasonal rotation that facilitates their animals\u27 access to high-quality grasses and shelter. The use and informal ownership of these camps depending on season helps illustrate evolutionary and ecological principles underlying variation in property relations. Given relatively stable patterns of precipitation and returns to capital improvement, families generally benefit from reusing the same camps year after year. We show that locations with higher economic defensibility and capital investment—winter camps and camps located in mountain/river valleys—are claimed and inherited more frequently than summer camps and camps located in open steppe. Camps are inherited patrilineally and matrilineally at a ratio of 2 : 1. Despite its practical importance, camp inheritance is not associated with livestock wealth today, which is better predicted by education and wealth outside the pastoral economy. The relationship between the livestock wealth of parents and their adult children is significantly positive, but relatively low compared to other pastoralists. The degree of inequality in livestock wealth, however, is very close to that of other pastoralists. This is understandable considering the durability and defensibility of animal wealth and economies of scale common across pastoralists. This article is part of the theme issue ‘Evolutionary ecology of inequality’

    Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.

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    A limited number of Methicillin-resistant Staphylococcus aureus (MRSA) clones are responsible for MRSA infections worldwide, and those of different lineages carry unique Type I restriction-modification (RM) variants. We have identified the specific DNA sequence targets for the dominant MRSA lineages CC1, CC5, CC8 and ST239. We experimentally demonstrate that this RM system is sufficient to block horizontal gene transfer between clinically important MRSA, confirming the bioinformatic evidence that each lineage is evolving independently. Target sites are distributed randomly in S. aureus genomes, except in a set of large conjugative plasmids encoding resistance genes that show evidence of spreading between two successful MRSA lineages. This analysis of the identification and distribution of target sites explains evolutionary patterns in a pathogenic bacterium. We show that a lack of specific target sites enables plasmids to evade the Type I RM system thereby contributing to the evolution of increasingly resistant community and hospital MRSA

    Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

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    In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

    A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

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    Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral

    A Novel Putative miRNA Target Enhancer Signal

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    It is known that miRNA target sites are very short and the effect of miRNA-target site interaction alone appears as being unspecific. Recent experiments suggest further context signals involved in miRNA target site recognition and regulation. Here, we present a novel GC-rich RNA motif downstream of experimentally supported miRNA target sites in human mRNAs with no similarity to previously reported functional motifs. We demonstrate that the novel motif can be found in at least one third of all transcripts regulated by miRNAs. Furthermore, we show that motif occurrence and the frequency of miRNA target sites as well as the stability of their duplex structures correlate. The finding, that the novel motif is significantly associated with miRNA target sites, suggests a functional role of the motif in miRNA target site biology. Beyond, the novel motif has the impact to improve prediction of miRNA target sites significantly

    Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

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    Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition
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