Clonality and intracellular polyploidy in virus evolution and pathogenesis

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.     

Computational fluid dynamics evaluation of flow reversal treatment of giant basilar tip aneurysm

Therapeutic parent artery flow reversal is a treatment option for giant, partially thrombosed basilar tip aneurysms. The effectiveness of this treatment has been variable and not yet studied by applying computational fluid dynamics. Computed tomography images and blood flow velocities acquired with transcranial Doppler ultrasonography were obtained prior to and after bilateral endovascular vertebral artery occlusion for a giant basilar tip aneurysm. Patient-specific geometries and velocity waveforms were used in computational fluid dynamics simulations in order to determine the velocity and wall shear stress changes induced by treatment. Therapeutic parent artery flow reversal lead to a dramatic increase in aneurysm inflow and wall shear stress (30 to 170 Pa) resulting in an increase in intra-aneurysmal circulation. The enlargement of the circulated area within the aneurysm led to a re-normalization of the wall shear stress and the aneurysm remained stable for more than 8 years thereafter. Therapeutic parent artery flow reversal can lead to unintended, potentially harmful changes in aneurysm inflow which can be quantified and possibly predicted by applying computational fluid dynamics.     

Evolutionary trajectories of two distinct avian influenza epidemics: Parallelisms and divergences

Influenza A virus can quickly acquire genetic mutations that may be associated with increased virulence, host switching or antigenic changes. To provide new insights into the evolutionary dynamics and the adaptive strategies of distinct avian influenza lineages in response to environmental and host factors, we compared two distinct avian influenza epidemics caused by the H7N1 and H7N3 subtypes that circulated under similar epidemiological conditions, including the same domestic species reared in the same densely populated poultry area for similar periods of time.The two strains appear to have experienced largely divergent evolution: the H7N1 viruses evolved into a highly pathogenic form, while the H7N3 did not. However, a more detailed molecular and evolutionary analysis revealed several common features: (i) the independent acquisition of 32 identical mutations throughout the entire genome; (ii) the evolution and persistence of two sole genetic groups with similar genetic characteristics; (iii) a comparable pattern of amino acid variability of the HA proteins during the low pathogenic epidemics; and (iv) similar rates of nucleotide substitutions. These findings suggest that the evolutionary trajectories of viruses with the same virulence level circulating in analogous epidemiological conditions may be similar. In addition, our deep sequencing analysis of 15 samples revealed that 17 of the 32 parallel mutations were already present at the beginning of the two epidemics, suggesting that fixation of these mutations may occur with different mechanisms, which may depend on the fitness gain provided by each mutation. This highlighted the difficulties in predicting the acquisition of mutations that can be correlated to viral adaptation to specific epidemiological conditions or to changes in virus virulence.     

改革开放以来医疗保障行政管理体制的变迁

改革开放以来，中国医疗保障行政管理职能和机构设置不断调整，形成了不同的医疗保障行政管理体制，改革朝着更加科学、更为规范的方向发展。但是，当前医疗保障行政管理体制还没有调整到位，主要是医疗保障制度由不同的部门分割管理，造成了重复建设、本位主义、社会不公、难以适应人口流动等诸多许多问题。下一步应在政府职能转变的前提下，统筹卫生服务和医疗保障职能，建立健康保障大部门体制。     

Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice

Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia.     

Urinary endometriosis: MR Imaging appearance with surgical and histological correlations

ObjectivesThe goals of the study were to describe the MR imaging features of endometriosis of the urinary tract and identify those that suggest intrinsic involvement of ureteric wall.Materials and methodsThirty-five women with proven urinary tract endometriosis and who had preoperative MR imaging between 2001 and 2011 were included retrospectively. MR images were intrepreted by one junior and one senior radiologists. To characterize the intrinsic parietal involvement, the ureteric circumference involved by the lesion of endometriosis was noted.ResultsThirty-eight ureteric and 13 bladder lesions were analyzed. They were found in association in nine women. Ureteric lesions were bilateral in seven women. Of the 38 ureteric lesions, 27 were extrinsic and 11 intrinsic at histopathological analysis. Sixteen women with extrinsic lesions and 10 with intrinsic ones were correctly identified on MR imaging. When the ureter was included less than 360° in the lesion, extrinsic involvement was confirmed in 80% of cases.ConclusionMR imaging appears to be more sensitive (91%vs 82%) but less specific (59% vs 67%) than surgery for the diagnosis of intrinsic form of ureteric location.