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Autophagy is a physiological process for the recycling and degradation of cellular materials. Forming the autophagosome from the phagophore, a cup-shaped double-membrane vesicle, is a critical step in autophagy. The origin of the cup shape of the phagophore is poorly understood. In yeast, fusion of a small number of Atg9-containing vesicles is considered a key step in autophagosome biogenesis, aided by Atg1 complexes (ULK1 in mammals) localized at the preautophagosomal structure (PAS). In particular, the S-shaped Atg17-Atg31-Atg29 subcomplex of Atg1 is critical for phagophore nucleation at the PAS. To study this process, we simulated membrane remodeling processes in the presence and absence of membrane associated Atg17. We show that at least three vesicles need to fuse to induce the phagophore shape, consistent with experimental observations. However, fusion alone is not sufficient. Interactions with 34-nm long, S-shaped Atg17 complexes are required to overcome a substantial kinetic barrier in the transition to the cup-shaped phagophore. Our finding rationalizes the recruitment of Atg17 complexes to the yeast PAS, and their unusual shape. In control simulations without Atg17, with weakly binding Atg17, or with straight instead of S-shaped Atg17, the membrane shape transition did not occur. We confirm the critical role of Atg17-membrane interactions experimentally by showing that mutations of putative membrane interaction sites result in reduction or loss of autophagic activity in yeast. Fusion of a small number of vesicles followed by Atg17-guided membrane shape-remodeling thus emerges as a viable route to phagophore formation.
Objectives: This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice.
Methods: We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval.
Results: The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2.
Conclusions: These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice.
We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into “clinical” benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.
Am Ende ging es dann doch recht fix. Hatte der Islamische Staat (IS) noch im März 2017 fast die Hälfte des Territoriums in Syrien unter seiner Kontrolle, ist das Möchtegern-Kalifat mittlerweile so gut wie von der Landkarte getilgt. Das heißt zwar nicht, dass er als Terrororganisation keine Rolle in dem Land mehr spielen wird. Doch als maßgeblicher Bürgerkriegsakteur mit territorialer Basis dürfte der IS weitestgehend aus dem Spiel genommen sein. Das macht diesen verworrenen Bürgerkrieg zunächst einmal ein wenig übersichtlicher. Andererseits wird damit aber auch der Vorhang für das nächste Kapitel geöffnet, das neue Wirrungen verspricht. Denn schließlich waren wegen des Kampfes gegen den IS einige Konfliktlinien erkaltet. Diese könnten nun wieder heiß werden. Allerdings lässt sich aufgrund der vielschichtigen Konstellationen nur schwer einschätzen, welche Dynamiken daraus erwachsen dürften. Der folgende Beitrag soll daher einen Überblick über die vergangenen und neuesten Entwicklungen im Syrischen Bürgerkrieg geben, um zumindest den Ist-Stand ermessen zu können. Die Anfertigung eines solchen Panoramas ist jedoch, zugegeben, eine kleine Herausforderung. Denn aufgrund der zahlreichen Konfliktparteien und multiplen Fronten sind die Entwicklungen derart konfus, dass sie sich nicht so einfach chronologisch zusammenfassen lassen. Der Beitrag stellt daher die jeweiligen Akteursgruppen und Allianzen dar und versucht, deren (ambivalenten) Verhältnisse untereinander zu sortieren und aufzuschlüsseln.
Not unlike the recent report Filling the ranks on the recruitment problems of the British Army shows for the UK, the German armed forces (Bundeswehr) struggle badly to meet their recruitment goals and to fulfill the “Trendwende Personal” (the turnaround in the personnel strength) as proclaimed by the German Defence Minister Ursula von der Leyen. Last year the recruitment department of the Bundeswehr tried a new way of targeting especially young people on YouTube. With a series of 59 episodes called Die Rekruten (The Recruits) YouTube users followed a couple of German Navy recruits through their basic training at the German Navy Technical School.
The series was widely criticised for not showing the serious implications of military service. Two weeks ago, the new series MALI on the deployment of German forces with the United Nations mission MINUSMA in Mali started as a sequel. But does the new series give a realistic impression of the challenges and risks of being a German soldier today and why should this be a requirement for a YouTube series?
In the Global South, private corporations and development aid programs are widely implementing information and communication technology (ICT). Stakeholders export infrastructure (including satellites, drones, and white spaces technology) as well as mobile and internet services (mobile money services, zero-rating), following the proclaimed goal to close the global digital divide. They particularly target under-connected regions in Africa, as Africa shows the lowest levels of internet connectivity (cf. International Telecommunications Union 2017). According to companies and development aid programs, these digitalization efforts in the Global South are key to development and security. However, an ethical perspective points to concerns about the practice of digitalization in the Global South. One central concern is that certain values are inscribed in ICT, and that they may be indirectly implemented through technology in the importing countries. Thus, the export of ICT by Western companies and development aid programs to the Global South may have a "neo-colonial" character. This raises ethical questions about global justice...
Warum werden Frauen Terroristinnen? Wider eine stereotype Betrachtung des weiblichen Terrorismus
(2017)
Punk-Band Frontfrau, Ex-Katholikin, Kosmetikverkäuferin – für die meisten klingt das nicht nach der Biographie einer der aktivsten Anhängerinnen des sogenannten Islamischen Staates (IS). Und doch: Bis Sally Jones jüngst bei einem US-Drohnenangriff ums Leben gekommen ist, war die Britin für mehr als vier Jahre das weibliche Gesicht des IS. Die Geschichte von Jones wirft eine grundlegende Frage auf: Wieso werden Frauen Terroristinnen? Ein Blick auf das breite Spektrum und die Geschichte des weiblichen Terrorismus zeigt, dass Terroristinnen weder neu noch selten, weder vor allem Opfer noch rein persönlich motiviert sind. Wenn an solchen Stereotypen festgehalten wird, steht dies nicht nur einer umfassenden Analyse der Gründe, sondern auch der Prävention von weiblichem Terrorismus im Wege.
Sally Jones Tod im Juni wurde erst vor Kurzem bekannt, und eine letztgültige Bestätigung steht noch aus – genauso wie die Antwort auf die Frage, ob der Drohnenangriff legal war, da angeblich auch ihr 12-jähriger Sohn getötet wurde. So wie Sally Jones möglicherweise posthum als erstes explizit weibliches Ziel eines solchen Angriffs Prominenz erlangen könnte, gibt ihre Person der regelmäßig wiederkehrenden öffentlichen wie wissenschaftlichen Diskussion über die Gründe für weiblichen Terrorismus neue Nahrung. In dieser Debatte sind Antworten auf die Frage, ob Frauen „auch“ Terroristinnen sein können, inzwischen zu einem Dickicht aus Stereotypen und Fantasien mutiert. Wird Religion – vulgo Islam – dieser Mischung hinzugefügt, begibt sich die Diskussion oft vollends auf Abwege. Von den vielen Argumenten, die dabei angeführt werden, halten sich drei mit besonderer Vehemenz: Weiblicher Terrorismus sei erstens ein neues und seltenes Phänomen; Frauen seien zweitens in der Regel Opfer; und drittens hätten Terroristinnen – im Gegensatz zu ihren männlichen Counterparts – in der Regel persönliche Motive. Die beiden ersten Argumente sind schlicht falsch und das dritte greift entschieden zu kurz. Es lohnt also, ein paar Breschen in das Dickicht zu schlagen...
This paper presents new evidence on the expectation formation process of firms from a survey of the German manufacturing sector. It focuses on the expectation about their future business conditions, which enters the widely followed economic sentiment index and which is an important determinant of their employment and investment decisions. We find that firms extrapolate their experience too much and make predictable forecasting errors. Moreover, firms do not seem to anticipate the upcoming reversals of business cycle peaks and troughs which causes suboptimal adjustment of investment and employment and affects their inventories and profits. However, the impact on expectation errors decreases with the size and the age of the firm as firms learn to reduce their extrapolation bias over time.
Facial Width-to-Height Ratio (fWHR) has been linked with dominant and aggressive behavior in human males. We show here that on portrait photographs published online, chief executive officers (CEOs) of companies listed in the Dow Jones stock market index and the Deutscher Aktienindex have a higher-than-normal fWHR, which also correlates positively with their company’s donations to charitable causes and environmental awareness. Furthermore, we show that leaders of the world’s most influential non-governmental organizations and even the leaders of the Roman Catholic Church, the popes, have higher fWHR compared to controls on public portraits, suggesting that the relationship between displayed fWHR and leadership is not limited to profit-seeking organizations. The data speak against the simplistic view that wider-faced men achieve higher social status through antisocial tendencies and overt aggression, or the mere signaling of such dispositions. Instead they suggest that high fWHR is linked with high social rank in a more subtle fashion in both competitive as well as prosocially oriented settings.