Herpes zoster as a rare complication of liposuction

Liposuction typically has a low incidence of complications and is associated with significant cosmetic benefit. In this case, the patient developed a dermatomal rash with vesicles on an erythematous base consistent with herpes zoster 8 days after liposuction to the back and flanks. To the authors' knowledge, herpes zoster has not been previously reported as a complication of liposuction. Although the precise relationship of herpes zoster infection to the liposuction procedure is difficult to determine, mechanical irritation most likely reactivated the varicella zoster virus in the involved dermatomal distribution. The patient was treated with antiviral and analgesic medications and healed without any further complications.     

Structural Insights Into NMDA Ionotropic Glutamate Receptors via Molecular Modelling

Structural models have been produced for the agonist binding and transmembrane domains of two NMDA ionotropic glutamate receptors: homomeric NMDA-R2C and heteromeric NMDA-R1/R2C. These models--produced using homology modelling techniques in conjunction with distance restraints derived from the accessibility of substituted cysteines--have aided our understanding of (1) ligand selectivity and (2) channel activity. The model of the agonist binding domain of NMDA-R2C indicates that T691 forms an essential hydrogen bond with glutamate ligand. This interaction is absent in the NMDA-R1 model--where a valine replaces the threonine--explaining why NMDA-R1 binds glycine rather than glutamate. For the transmembrane region, the models suggest that a number of positive residues, located in the cytoplasmic loop between the M1 and M2 segments, create a large electrostatic energy barrier that could explain why homomeric NMDA-R2C channels are non-functional. Introducing NMDA-R1 to form heteromeric NMDA-R1/R2C channels is predicted to rescue channel activity because the corresponding region in NMDA-R1 contains negative residues that more than compensate for the electrostatic energy barrier in NMDA-R2C. These studies suggest that replacing the positively charged region in the M1-M2 loop of NMDA-R2C with the corresponding negatively charged region of NMDA-R1 could transform NMDA-R2C into a functional homomeric channel.     

A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis

Background

Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but the molecular basis for varying progression rates is poorly understood. The aim of the present study was to ascertain whether differential miRNA expression might provide one explanation for rapidly versus slowly progressing forms of IPF.

Methodology and Principal Findings

miRNA and mRNA were isolated from surgical lung biopsies from IPF patients with a clinically documented rapid or slow course of disease over the first year after diagnosis. A quantitative PCR miRNA array containing 88 of the most abundant miRNA in the human genome was used to profile lung biopsies from 9 patients with rapidly progressing IPF, 6 patients with slowly progressing IPF, and 10 normal lung biopsies. Using this approach, 11 miRNA were significantly increased and 36 were significantly decreased in rapid biopsies compared with normal biopsies. Slowly progressive biopsies exhibited 4 significantly increased miRNA and 36 significantly decreased miRNA compared with normal lung. Among the miRNA present in IPF with validated mRNA targets were those with regulatory effects on epithelial-mesenchymal transition (EMT). Five miRNA (miR-302c, miR-423-5p, miR-210, miR-376c, and miR-185) were significantly increased in rapid compared with slow IPF lung biopsies. Additional analyses of rapid biopsies and fibroblasts grown from the same biopsies revealed that the expression of AGO1 and AGO2 (essential components of the miRNA processing RISC complex) were lower compared with either slow or normal lung biopsies and fibroblasts.

Conclusion

These findings suggest that the development and/or clinical progression of IPF might be the consequence of aberrant miRNA processing.     

Ultra-fast and sensitive detection of non-typhoidal Salmonella using microwave-accelerated metal-enhanced fluorescence ("MAMEF")

Certain serovars of Salmonella enterica subsp. enterica cause invasive disease (e.g., enteric fever, bacteremia, septicemia, meningitis, etc.) in humans and constitute a global public health problem. A rapid, sensitive diagnostic test is needed to allow prompt initiation of therapy in individual patients and for measuring disease burden at the population level. An innovative and promising new rapid diagnostic technique is microwave-accelerated metal-enhanced fluorescence (MAMEF). We have adapted this assay platform to detect the chromosomal oriC locus common to all Salmonella enterica subsp. enterica serovars. We have shown efficient lysis of biologically relevant concentrations of Salmonella spp. suspended in bacteriological media using microwave-induced lysis. Following lysis and DNA release, as little as 1 CFU of Salmonella in 1 ml of medium can be detected in <30 seconds. Furthermore the assay is sensitive and specific: it can detect oriC from Salmonella serovars Typhi, Paratyphi A, Paratyphi B, Paratyphi C, Typhimurium, Enteritidis and Choleraesuis but does not detect Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae or Acinetobacter baumanii. We have also performed preliminary experiments using a synthetic Salmonella oriC oligonucleotide suspended in whole human blood and observed rapid detection when the sample was diluted 1:1 with PBS. These pre-clinical data encourage progress to the next step to detect Salmonella in blood (and other ordinarily sterile, clinically relevant body fluids).     

Kinesin-5/Eg5 is important for transport of CARTS from the trans-Golgi network to the cell surface

Here we report that the kinesin-5 motor Klp61F, which is known for its role in bipolar spindle formation in mitosis, is required for protein transport from the Golgi complex to the cell surface in Drosophila S2 cells. Disrupting the function of its mammalian orthologue, Eg5, in HeLa cells inhibited secretion of a protein called pancreatic adenocarcinoma up-regulated factor (PAUF) but, surprisingly, not the trafficking of vesicular stomatitis virus G protein (VSV-G) to the cell surface. We have previously reported that PAUF is transported from the trans-Golgi network (TGN) to the cell surface in specific carriers called CARTS that exclude VSV-G. Inhibition of Eg5 function did not affect the biogenesis of CARTS; however, their migration was delayed and they accumulated near the Golgi complex. Altogether, our findings reveal a surprising new role of Eg5 in nonmitotic cells in the facilitation of the transport of specific carriers, CARTS, from the TGN to the cell surface.     

Can Consumers Make Affordable Care Affordable? The Value of Choice Architecture

Tens of millions of people are currently choosing health coverage on a state or federal health insurance exchange as part of the Patient Protection and Affordable Care Act. We examine how well people make these choices, how well they think they do, and what can be done to improve these choices. We conducted 6 experiments asking people to choose the most cost-effective policy using websites modeled on current exchanges. Our results suggest there is significant room for improvement. Without interventions, respondents perform at near chance levels and show a significant bias, overweighting out-of-pocket expenses and deductibles. Financial incentives do not improve performance, and decision-makers do not realize that they are performing poorly. However, performance can be improved quite markedly by providing calculation aids, and by choosing a “smart” default. Implementing these psychologically based principles could save purchasers of policies and taxpayers approximately 10 billion dollars every year.     

Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast

Mitochondria accumulate at neuronal and immunological synapses and yeast bud tips and associate with the ER during phospholipid biosynthesis, calcium homeostasis, and mitochondrial fission. Here we show that mitochondria are associated with cortical ER (cER) sheets underlying the plasma membrane in the bud tip and confirm that a deletion in YPT11, which inhibits cER accumulation in the bud tip, also inhibits bud tip anchorage of mitochondria. Time-lapse imaging reveals that mitochondria are anchored at specific sites in the bud tip. Mmr1p, a member of the DSL1 family of tethering proteins, localizes to punctate structures on opposing surfaces of mitochondria and cER sheets underlying the bud tip and is recovered with isolated mitochondria and ER. Deletion of MMR1 impairs bud tip anchorage of mitochondria without affecting mitochondrial velocity or cER distribution. Deletion of the phosphatase PTC1 results in increased Mmr1p phosphorylation, mislocalization of Mmr1p, defects in association of Mmr1p with mitochondria and ER, and defects in bud tip anchorage of mitochondria. These findings indicate that Mmr1p contributes to mitochondrial inheritance as a mediator of anchorage of mitochondria to cER sheets in the yeast bud tip and that Ptc1p regulates Mmr1p phosphorylation, localization, and function.     

Evidence for 1-(Malonylamino)cyclopropane-1-Carboxylic Acid Being the Major Conjugate of Aminocyclopropane-1-Carboxylic Acid in Tomato Fruit

Tomato (Lycopersicon esculentum Miller) fruit discs fed with [2,3-¹⁴C]1-aminocyclopropane-1-carboxylic acid (ACC) formed 1-malonyl-ACC (MACC) as the major conjugate of ACC in fruit throughout all ripening stages, from immature-green through the red-ripe stage. Another conjugate of ACC, γ-glutamyl-ACC (GACC), was formed only in mature-green fruit in an amount about 10% of that of MACC; conjugation of ACC into GACC was not detected in fruits at other ripening stages. No GACC formation was observed from etiolated mung bean (Vigna radiata [L.] Wilczek) hypocotyls, etiolated common vetch (Vicia sativum L.) epicotyls, or pea (Pisum sativum L.) root tips, etiolated epicotyls, and green stem tissue, where active conversion of ACC into MACC was observed. GACC was, however, formed in vitro in extracts from fruit of all ripening stages. GACC formation in an extract from red fruit at pH 7.15 was only about 3% of that at pH 8.0, the pH at which most assays were run. Our present in vivo data support the previous contention that MACC is the major conjugate of ACC in plant tissues, whereas GACC is a minor, if any, conjugate of ACC. Thus, our data do not support the proposal that GACC formation could be more important than MACC formation in tomato fruit.