Teaching old NCATs new tricks: using non-canonical amino acid tagging to study neuronal plasticity

The non-canonical amino acid labeling techniques BONCAT (bioorthogonal non-canonical amino acid tagging) and FUNCAT (fluorescent non-canonical amino acid tagging) enable the specific identification and visualization of newly synthesized proteins. Recently, these techniques have been applied to neuronal systems to elucidate protein synthesis dynamics during plasticity, identify stimulation-induced proteomes and subproteomes and to investigate local protein synthesis in specific subcellular compartments. The next generation of tools and applications, reviewed here, includes the development of new tags, the quantitative identification of newly synthesized proteins, the application of NCAT to whole animals, and the ability to genetically restrict NCAT labeling. These techniques will enable not only improved detection but also allow new scientific questions to be tackled

Unified Description of Aging and Rate Effects in Yield of Glassy Solids

The competing effects of slow structural relaxations (aging) and deformation at constant strain rate on the shear yield stress $\tau^y$ of simple model glasses are examined using molecular simulations. At long times, aging leads to a logarithmic increase in density and $\tau^y$. The yield stress also rises logarithmically with rate, but shows a sharp transition in slope at a rate that decreases with increasing age. We present a simple phenomenological model that includes both intrinsic rate dependence and the change in properties with the total age of the system at yield. As predicted by the model, all data for each temperature collapse onto a universal curve.Comment: 4 pages, 3 figure

Tod bei der Arbeit - eine Analyse tödlicher Arbeitsunfälle von 2005 bis 2016 im Obduktionsgut des Instituts für Rechtsmedizin in Frankfurt am Main

Hintergrund: Das genaue Wissen um die Umstände eines jeden tödlichen Arbeitsunfalls ist Voraussetzung für die Identifizierung von Unfallschwerpunkten und ermöglicht eine effektive Präventionsarbeit. Mit dieser rechtsmedizinischen Studie zum Arbeitsunfallgeschehen soll ein Beitrag dazu geleistet werden, die Zahl tödlicher Arbeitsunfälle in Deutschland zu senken. Material und Methode: Zur Untersuchung kamen die tödlichen Arbeitsunfälle, die sich im Einzugsbereich des rechtsmedizinischen Instituts Frankfurt am Main in den Jahren von 2005 bis 2016 ereigneten. Ausgewertet wurden Obduktionsprotokolle sowie die dem Institut zur Verfügung gestellten staatsanwaltschaftlichen Ermittlungsakten. Ergebnisse: Es fanden sich 87 tödliche Arbeitsunfälle in dem genannten Zwölfjahreszeitraum. Die Altersstruktur reichte vom jugendlichen Alter bis in das Rentenalter. Betroffen waren zum größten Teil männliche Arbeiter (96,6 %, p < 0,0001), verhältnismäßig häufig ausländischer Nationalität (34,5 %). Die meisten Unfälle ereigneten sich in der 2. Jahreshälfte (58,6 %), an Montagen (26,4 %), kurz vor und nach der Mittagspause. In 3 Fällen lag die Blutalkoholkonzentration über 0,5‰. Die Baubranche (55,2 %) war der unfallträchtigste Wirtschaftszweig. Der Absturz (28,7 %) war der häufigste Unfallmechanismus und das Polytrauma (39,1 %) gemeinsam mit dem Schädel-Hirn-Trauma (24,1 %) gemäß dem ISS die häufigste Todesursache. Diskussion: Nach den Ergebnissen dieser Studie sollten Alter der Arbeiter sowie die Tages‑, Wochen- und Jahreszeit bei der Ausführung risikoreicher Arbeiten im Baugewerbe berücksichtigt werden. Besonderes Augenmerk sollten Arbeitgeber auf die Kontrolle von Sicherheitsvorkehrungen bei Arbeiten in der Höhe sowie auf die Durchsetzung der Helmpflicht gerade auch bei ausländischen Arbeitnehmern legen.Background: Precise knowledge of the circumstances of each fatal work accident is a prerequisite to identify accident hot spots and to enable effective preventive measures. This forensic medical study on work accidents was initiated to contribute to attempts to reduce the number of fatal work accidents in Germany. Methods: Fatal work accidents that occurred between 2005 and 2016 in the catchment area of the Institute of Legal Medicine in Frankfurt am Main were investigated. Besides autopsy protocols the files of the public prosecutor’s office were also evaluated. Results: During the 12-year period 87 fatal work accidents were documented. The age structure of the persons involved ranged from adolescence to retirement age. Male workers (96.6%, p < 0.0001), often of foreign nationality (34.5%) represented the majority of cases. Most accidents occurred in the second half of the year (58.6%), on Mondays (26.4%), shortly before and after the lunch break. In three cases the blood alcohol concentration was found to be above 0.05%. The highest number of accidents occurred in the building sector (55.2%). Falling from heights (28.7%) was the most frequent accident and polytrauma (39.1%) together with craniocerebral trauma (24.1%) were the most frequent causes of death according to the ISS. Conclusion: According to the results of this study when high-risk work in the building industry is carried out, the age of workers, the time of day, week and year should be taken into consideration. Employers should pay special attention to the control of safety precautions when work is done at heights, enforcing the obligation to wear helmets, particularly when foreign workers are concerned

Tod bei der Arbeit - eine Analyse tödlicher Arbeitsunfälle von 2005 bis 2016 im Obduktionsgut des Instituts für Rechtsmedizin in Frankfurt am Main

Hintergrund: Das genaue Wissen um die Umstände eines jeden tödlichen Arbeitsunfalls ist Voraussetzung für die Identifizierung von Unfallschwerpunkten und ermöglicht eine effektive Präventionsarbeit. Mit dieser rechtsmedizinischen Studie zum Arbeitsunfallgeschehen soll ein Beitrag dazu geleistet werden, die Zahl tödlicher Arbeitsunfälle in Deutschland zu senken. Material und Methode: Zur Untersuchung kamen die tödlichen Arbeitsunfälle, die sich im Einzugsbereich des rechtsmedizinischen Instituts Frankfurt am Main in den Jahren von 2005 bis 2016 ereigneten. Ausgewertet wurden Obduktionsprotokolle sowie die dem Institut zur Verfügung gestellten staatsanwaltschaftlichen Ermittlungsakten. Ergebnisse: Es fanden sich 87 tödliche Arbeitsunfälle in dem genannten Zwölfjahreszeitraum. Die Altersstruktur reichte vom jugendlichen Alter bis in das Rentenalter. Betroffen waren zum größten Teil männliche Arbeiter (96,6 %, p < 0,0001), verhältnismäßig häufig ausländischer Nationalität (34,5 %). Die meisten Unfälle ereigneten sich in der 2. Jahreshälfte (58,6 %), an Montagen (26,4 %), kurz vor und nach der Mittagspause. In 3 Fällen lag die Blutalkoholkonzentration über 0,5‰. Die Baubranche (55,2 %) war der unfallträchtigste Wirtschaftszweig. Der Absturz (28,7 %) war der häufigste Unfallmechanismus und das Polytrauma (39,1 %) gemeinsam mit dem Schädel-Hirn-Trauma (24,1 %) gemäß dem ISS die häufigste Todesursache. Diskussion: Nach den Ergebnissen dieser Studie sollten Alter der Arbeiter sowie die Tages‑, Wochen- und Jahreszeit bei der Ausführung risikoreicher Arbeiten im Baugewerbe berücksichtigt werden. Besonderes Augenmerk sollten Arbeitgeber auf die Kontrolle von Sicherheitsvorkehrungen bei Arbeiten in der Höhe sowie auf die Durchsetzung der Helmpflicht gerade auch bei ausländischen Arbeitnehmern legen.Background: Precise knowledge of the circumstances of each fatal work accident is a prerequisite to identify accident hot spots and to enable effective preventive measures. This forensic medical study on work accidents was initiated to contribute to attempts to reduce the number of fatal work accidents in Germany. Methods: Fatal work accidents that occurred between 2005 and 2016 in the catchment area of the Institute of Legal Medicine in Frankfurt am Main were investigated. Besides autopsy protocols the files of the public prosecutor’s office were also evaluated. Results: During the 12-year period 87 fatal work accidents were documented. The age structure of the persons involved ranged from adolescence to retirement age. Male workers (96.6%, p < 0.0001), often of foreign nationality (34.5%) represented the majority of cases. Most accidents occurred in the second half of the year (58.6%), on Mondays (26.4%), shortly before and after the lunch break. In three cases the blood alcohol concentration was found to be above 0.05%. The highest number of accidents occurred in the building sector (55.2%). Falling from heights (28.7%) was the most frequent accident and polytrauma (39.1%) together with craniocerebral trauma (24.1%) were the most frequent causes of death according to the ISS. Conclusion: According to the results of this study when high-risk work in the building industry is carried out, the age of workers, the time of day, week and year should be taken into consideration. Employers should pay special attention to the control of safety precautions when work is done at heights, enforcing the obligation to wear helmets, particularly when foreign workers are concerned

Fluorescence Visualization of Newly Synthesized Proteins in Mammalian Cells

Modern proteomic methods enable efficient identification of the hundreds or thousands of proteins present in whole cells or in isolated organelles. However, a thorough understanding of the proteome requires insight into protein localization as well as protein identity. Recently, visualization of newly synthesized proteins in bacterial cells was demonstrated through co-translational introduction of an alkynyl amino acid followed by selective CuI-catalyzed ligation of the alkynyl side chain to the fluorogenic dye 3-azido-7-hydroxycoumarin. Here we report that selective fluorescence labeling and imaging of newly synthesized proteins can be accomplished in a diverse set of mammalian cells

Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey

Background: The study evaluates the scope of non-uniform classification practices concerning breast carcinomas with non-inflammatory skin involvement. Patients and methods: We compared the clinical course of patients with histologically proven non-inflammatory skin involvement: 119 (65.4%) with clinically obvious ‘classical' skin changes (Group A) and 63 (34.6%) with no or only discreet changes (Group B). A questionnaire was circulated to pathology departments in 24 countries to assess the practice concerning the placement of skin- involved breast carcinomas in the TNM classification. Results: Patients in Group B showed a significantly better disease specific survival (P = 0.0002). Eighty-six respondents (70.5%) of the survey preferred the ‘histological view' and classified tumors with only histological proven skin involvement as T4b/stage IIIB. The opposing classification principle (‘clinical view'), which dictates that T4b breast cancer is a clinical diagnosis and the classical signs must be present, was supported by 31 respondents (25.4%). Conclusions: A large number of breast cancer patients with non-inflammatory skin involvement are only histologically proven and show, compared with cases exhibiting the classical clinical signs, significant differences in clinical course and prognosis. In general, both subsets were aggregated in one T category/stage (T4b/IIIB). This results in a considerable distortion of the reported statistical dat

Boundary lubrication with a glassy interface

Recently introduced constitutive equations for the rheology of dense, disordered materials are investigated in the context of stick-slip experiments in boundary lubrication. The model is based on a generalization of the shear transformation zone (STZ) theory, in which plastic deformation is represented by a population of mesoscopic regions which may undergo non affine deformations in response to stress. The generalization we study phenomenologically incorporates the effects of aging and glassy relaxation. Under experimental conditions associated with typical transitions from stick-slip to steady sliding and stop start tests, these effects can be dominant, although the full STZ description is necessary to account for more complex, chaotic transitions

Rheology of a confined granular material

We study the rheology of a granular material slowly driven in a confined geometry. The motion is characterized by a steady sliding with a resistance force increasing with the driving velocity and the surrounding relative humidity. For lower driving velocities a transition to stick-slip motion occurs, exhibiting a blocking enhancement whith decreasing velocity. We propose a model to explain this behavior pointing out the leading role of friction properties between the grains and the container's boundary.Comment: 9 pages, 3 .eps figures, submitted to PR