Complex molecular architecture of beet yellows virus particles

Closteroviruses possess exceptionally long filamentous virus particles that mediate protection and active transport of the genomic RNA within infected plants. These virions are composed of a long “body” and short “tail” whose principal components are the major and minor capsid proteins, respectively. Here we use biochemical, genetic, and ultrastructural analyses to dissect the molecular composition and architecture of particles of beet yellows virus, a closterovirus. We demonstrate that the virion tails encapsidate the 5′-terminal, ≈650-nt-long, part of the viral RNA. In addition to the minor capsid protein, the viral Hsp70-homolog, 64-kDa protein, and 20-kDa protein are also incorporated into the virion tail. Atomic force microscopy of virions revealed that the tail possesses a striking, segmented morphology with the tip segment probably being built of 20-kDa protein. The unexpectedly complex structure of closterovirus virions has important mechanistic and functional implications that may also apply to other virus families.     

Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase,MitoEbselen-2, as a Radiation Mitigator

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Objective cervical portio length measurements: consistency and efficacy of screening for a short cervix

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Alcohol septal ablation for obstructive hypertrophic cardiomyopathy

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Nanomedicine and nanotoxicology: two sides of the same coin

Current advances in nanotechnology have led to the development of the new field of nanomedicine, which includes many applications of nanomaterials and nanodevices for diagnostic and therapeutic purposes. The same unique physical and chemical properties that make nanomaterials so attractive may be associated with their potentially calamitous effects on cells and tissues. Our recent study demonstrated that aspiration of single-walled carbon nanotubes elicited an unusual inflammatory response in the lungs of exposed mice with a very early switch from the acute inflammatory phase to fibrogenic events resulting in pulmonary deposition of collagen and elastin. This was accompanied by a characteristic change in the production and release of proinflammatory to anti-inflammatory profibrogenic cytokines, decline in pulmonary function, and enhanced susceptibility to infection. Chemically unmodified (nonfunctionalized) carbon nanotubes are not effectively recognized by macrophages. Functionalization of nanotubes results in their increased recognition by macrophages and is thus used for the delivery of nanoparticles to macrophages and other immune cells to improve the quality of diagnostic and imaging techniques as well as for enhancement of the therapeutic effectiveness of drugs. These observations on differences in recognition of nanoparticles by macrophages have important implications in the relationship between the potentially toxic health effects of nanomaterials and their applications in the field of nanomedicine.     

Toward oxidative lipidomics of cell signaling

Involvement and role of oxidatively modified lipids become increasingly evident in different signaling pathways, although specific mechanisms remain to be explored. The current forum focuses on several aspects of signaling by oxidatively modified lipid molecules during apoptosis and implications of different oxidized phospholipids in elimination of apoptotic cells and regulation of inflammatory response. Studies of signaling mechanisms by oxidatively modified lipids represent a rapidly expanding field of oxidative lipidomics, a new and exciting research focus at the interface of traditional lipid/membrane biochemistry and biophysics with free radical chemistry and cell biology.     

Perceived HIV-related Stigma and HIV Disclosure to Relationship Partners after Finding Out about the Seropositive Diagnosis

The present study examined how perceived HIV-related stigma (how much HIV-infected persons believe that the public stigmatizes someone with HIV) influences both reasons for and against HIV disclosure and self-reports of HIV disclosure to a friend, intimate partner and a parent. The research participants were 145 men and women living with HIV. They were asked to recall when they first learned about their HIV diagnosis. Then they indicated how much specific reasons might have influenced disclosing or not disclosing about the HIV diagnosis to a friend, intimate partner and a parent. Findings, based on the total sample, indicated that perceived HIV-related stigma was associated with the endorsement of various reasons against disclosing to a friend and a parent, including concerns about self-blame, fear of rejection, communication difficulties and a desire to protect the other person. Perceived HIV-related stigma was not associated with the endorsement of any reasons for disclosing to a friend, intimate partner or a parent, including catharsis, test other's reactions, duty to inform/educate, similarity and a close/supportive relationship with the other. In addition, perceived HIV-related stigma predicted self-reports of disclosure to a parent but not to a friend or intimate partner. Specific reasons for and against self-disclosure predicted HIV disclosure based on the type of relationship with the potential disclosure recipient. The data analyses were also stratified by gender; these results were, with some exceptions, consistent with the findings with the total sample. The research introduces scales that quantify individuals' reasons for HIV disclosure and/or nondisclosure.     

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = ?0.81); most patients with low-medium (39–55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39–55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow’s index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.     

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OBJECTIVE: Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered. METHODS: Using controlled cortical impact as a model of traumatic brain injury, we employed a newly developed oxidative lipidomics approach to qualitatively and quantitatively characterize the lipid peroxidation response. RESULTS: Electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry analysis of rat cortical mitochondrial/synaptosomal fractions demonstrated the presence of highly oxidizable molecular species containing C(22:6) fatty acid residues in all major classes of phospholipids. However, the pattern of phospholipid oxidation at 3 hours after injury displayed a nonrandom character independent of abundance of oxidizable species and included only one mitochondria-specific phospholipid, cardiolipin (CL). This selective CL peroxidation was followed at 24 hours by peroxidation of other phospholipids, most prominently phosphatidylserine, but also phosphatidylcholine and phosphatidylethanolamine. CL oxidation preceded appearance of biomarkers of apoptosis (caspase-3 activation, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positivity) and oxidative stress (loss of glutathione and ascorbate). INTERPRETATION: The temporal sequence combined with the recently demonstrated role of CL hydroperoxides (CL-OOH) in in vitro models of apoptosis suggest that CL-OOH may be both a key in vivo trigger of apoptotic cell death and a therapeutic target in experimental traumatic brain injury.