An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids

Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described in a large family with a dominant inheritance pattern. The initial stage of the disease is dominated by frontal lobe symptoms that develop into a rapidly advancing encephalopathy with pyramidal, deep sensory, extrapyramidal and optic tract symptoms. Median survival is less than 10 years. Recently, pathogenic mutations in CSF1R were reported in a clinically and histologically similar leukoencephalopathy segregating in several families. Still, the cause of HDLS-S remained elusive since its initial description in 1984, with no CSF1R mutations identified in the family. Here we update the original findings associated with HDLS-S after a systematic and recent assessment of several family members. We also report the results from exome sequencing analyses indicating the p.Cys152Phe variant in the alanyl tRNA synthetase (AARS) gene as the probable cause of this disease. The variant affects an amino acid located in the aminoacylation domain of the protein and does not cause differences in splicing or expression in the brain. Brain pathology in one case after 10 years of disease duration showed the end stage of the disease to be characterized by widespread liquefaction of the white matter leaving only some macrophages and glial cells behind the centrifugally progressing front. These results point to AARS as a candidate gene for rapidly progressing adult-onset CSF1R-negative leukoencephalopathies

Localization of a 64-kDa phosphoprotein in the lumen between the outer and inner envelopes of pea chloroplasts

The identification and localization of a marker protein for the intermembrane space between the outer and inner chloroplast envelopes is described. This 64-kDa protein is very rapidly labeled by [γ-32P]ATP at very low (30 nM) ATP concentrations and the phosphoryl group exhibits a high turnover rate. It was possible to establish the presence of the 64-kDa protein in this plastid compartment by using different chloroplast envelope separation and isolation techniques. In addition comparison of labeling kinetics by intact and hypotonically lysed pea chloroplasts support the localization of the 64-kDa protein in the intermembrane space. The 64-kDa protein was present and could be labeled in mixed envelope membranes isolated from hypotonically lysed plastids. Mixed envelope membranes incorporated high amounts of 32P from [γ-32P]ATP into the 64-kDa protein, whereas separated outer and inner envelope membranes did not show significant phosphorylation of this protein. Water/Triton X-114 phase partitioning demonstrated that the 64-kDa protein is a hydrophilic polypeptide. These findings suggest that the 64-kDa protein is a soluble protein trapped in the space between the inner and outer envelope membranes. After sonication of mixed envelope membranes, the 64-kDa protein was no longer present in the membrane fraction, but could be found in the supernatant after a 110000 × g centrifugation

Monitoring of Collaborative Assembly Operations: An OEE Based Approach

International audienceIn this paper we present requirements and concept generation principles for performance monitoring of a collaborative assembly task. Life cycle aspects are considered and an Overall Equipment Efficiency (OEE) based monitoring scenario for a developed passive collaborative robot (COBOT) test system is presented. In this case main benefits of applying COBOT are expected to be: improved productivity, improved quality, reduced production cost and improved ergonomics. Since human and COBOT are working co-operatively human actions have also affects on process performance, i.e. OEE. However a human's and machines or a COBOT's efficiency are undistinguishable directly from OEE factors. It is possible to infer cause of lower efficiency from the variables from which OEE factors are calculated. One such variable is cycle time, which is used to define performance efficiency

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Simultaneous medullary and papillary thyroid cancer: two case reports

<p>Abstract</p> <p>Background</p> <p>Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) have always been considered different from each other; in their incidence, their cell origin and their histopathological features.</p> <p>Case presentation</p> <p>This paper describes two rare cases of the simultaneous occurrence of MTC and PTC in the thyroid gland. Case 1 is unique for different reasons: (a) the patient was affected by both multicentric MTC and PTC; (b) a "composite thyroid carcinoma" with mixed feautures of MTC and PTC carcinomas was found in the istmus of the gland; and (c) these tumors were associated with diffuse lymphocytic-type thyroiditis (LT). Case 2 is notable for the long follow up: 16 years disease free.</p> <p>Conclusion</p> <p>There are only 16 reports in the English medical literature describing a total of 20 cases of concurrent occurrence of both PTC and MTC in the same thyroid gland. We discuss whether the finding of another cancer in these patients was coincidental or from possible activation of a common tumorigenic pathway for both follicular and parafollicular thyroid cells.</p

Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses

RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines