Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving functional recovery after CNS injuries. It has been shown that Sema3A adheres to the proteoglycan component of the extracellular matrix (ECM) and selectively binds to heparin and chondroitin sulfate-E (CS-E) glycosaminoglycans (GAGs). We hypothesize that the biologically relevant interaction between Sema3A and GAGs takes place at Sema3A C-terminal polybasic region (SCT). The aims of this study were to characterize the interaction of the whole Sema3A C-terminal polybasic region (Sema3A 725–771) with GAGs and to investigate the disruption of this interaction by small molecules. Recombinant Sema3A basic domain was produced and we used a combination of biophysical techniques (NMR, SPR, and heparin affinity chromatography) to gain insight into the interaction of the Sema3A C-terminal domain with GAGs. The results demonstrate that SCT is an intrinsically disordered region, which confirms that SCT binds to GAGs and helps to identify the specific residues involved in the interaction. NMR studies, supported by molecular dynamics simulations, show that a new peptoid molecule (CSIC02) may disrupt the interaction between SCT and heparin. Our structural study paves the way toward the design of new molecules targeting these protein–GAG interactions with potential therapeutic applications. ; This work was funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Project VISION, grant No. 304884, the Spanish Ministry of Science and Innovation/Spanish Research Agency (MCI/AEI/FEDER, RTI2018–096182-B-I00) and AGAUR (2017 SGR 208). ; Peer reviewed
10 páginas.- 4 figuras.- referencias.-Data Availability Statement: All data underlying this article are available in the main publication and in its Supplementary Materials online. ; Unspecific peroxygenases (UPOs), the extracellular enzymes capable of oxygenating a potpourri of aliphatic and aromatic substrates with a peroxide as co-substrate, come out with a new reaction: carbon-chain shortening during the conversion of fatty acids with the well-known UPOs from Coprinopsis cinerea (rCciUPO) and Cyclocybe (Agrocybe) aegerita (AaeUPO). Although a pathway (Cα-oxidation) for shortening the hydrocarbon chain of saturated fatty acids has already been reported for the UPO from Marasmius rotula (MroUPO), it turned out that rCciUPO and AaeUPO shorten the chain length of both saturated and unsaturated fatty acids in a different way. Thus, the reaction sequence does not necessarily start at the Cα-carbon (adjacent to the carboxyl group), as in the case of MroUPO, but proceeds through the subterminal (ω-1 and ω-2) carbons of the chain via several oxygenations. This new type of shortening leads to the formation of a dicarboxylic fatty acid reduced in size by two carbon atoms in the first step, which can subsequently be further shortened, carbon by carbon, by the UPO Cα-oxidation mechanism. View Full-Text ; This research was funded by BioBased Industries Joint Undertaking under the European Union's Horizon 2020 Research and Innovation Programme, grant number 792063 (SusBind project; https://susbind.eu; to A.G., Á.T.M. and M.H.), the PID2020-118968RB-100 project by the Spanish MCIN/AEI/ 10.13039/501100011033 to A.G., and the CSIC projects PIE-202040E185 (to A.G.) and PIE-202120E019 (to Á.T.M.). ; Peer reviewed
At the end of the 1870s, the oppressive policies of the Argentine State were intensified towards the indigenous people linked to the Southern Border, visible in the punitive expeditions of 1878-1879. In the case of theranqueles, located in the centralPampa, these actions were part of previous strategies of attrition, carried out by the military commanders ofSan LuisandCórdobathrough the diplomatic channel, softening campaigns and co-optation of contingents who, both forced and voluntarily, migrated to the fortsVilla MercedesandSarmiento. From a line of investigation that seeks to reconstruct the itineraries of theranquelessubmitted in the aforementioned context, the article characterizes the imprisonment of the indigenous people taken by the 3rd Expeditionary Division (April-August 1879) under the leadership of Colonel Eduardo Racedo. Its purpose is to describe their living conditions while they were in thePitral Lauquencamp (nearPoitagué), understanding that it simultaneously acted as a place of concentration and distribution of prisoners. ; Al terminar la década de 1870 se intensificaron las políticas opresivas del Estado argentino para con los indígenas ligados a la Frontera Sur, visibles en las expediciones punitivas de 1878-1879. En el caso de los ranqueles, situados en la pampa central, estas acciones se enmarcan en estrategias previas de desgaste ejecutadas por los mandos militares de San Luis y Córdoba a través de la vía diplomática, las campañas de ablandamiento y cooptación de contingentes que migrabande manera forzaday por presentación a los fuertes Villa Mercedes y Sarmiento. Desde una línea de investigación que busca reconstruir los itinerarios de los ranqueles sometidos en ese contexto, el artículo caracteriza elaprisionamiento de los indígenas tomados por la 3aDivisión Expedicionaria (abril-agosto de 1879) bajo el liderazgo del coronel Eduardo Racedo. Su finalidad es describir sus condiciones de vida mientras estuvieron depositados en el campamento Pitral Lauquen (cercano a Poitagué), lugar de concentración y distribución de prisioneros.
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The writings of the Indian Diaspora have received a great deal of attention and critical acclaim throughout the world. Rohinton Mistry is a well renowned author in the contemporary commonwealth literature and occupies a significant place among the writers of Indian Diaspora. Even though he is settled in Canada; it is his upbringing in Mumbai that reflects in all his writings. The distinct Mumbai culture, particularly the Parsee way of life, the people of the city and even the politics of India are major themes in his novels. Rohinton Mistry as a writer of Diaspora has carved a niche for himself. His works such as: "Tales from Firozsha Baag", "Such A Long Journey", "A Fine Balance" and "Family Matters";mark a new kind of writing, resulting from a fragmented, splintered world. As a Diasporic Parsi writer, very sensitively he has recalled his community's journey through time and history with a sense of loss and nostalgia. His books portray diverse facets of Indian socioeconomic life; as well as Parsi Zoroastrian life, customs, and religion. Many of his writings are markedly "Indo-nostalgic". Rohinton Mistry through his Diasporic discourse has well depicted his ancestral background, his community's engaged situation in a metropolis like Bombay and his deep attachment with and nostalgia for a world gone by. In this paper an attempt has been made to delineate diasporic discourse in the works of Rohinton Mistry. Although he is obsessed with the colonial and postcolonial experiences in India, we can find some traces of Canada in his literature. His characters dream of being integrated into, and accepted by, Canadian society on the one hand and on the other hand, these same characters are torn by an insatiable desire to be true to their native culture; to honor and cherish their own, distinct cultural identity.
The writings of the Indian Diaspora have received a great deal of attention and critical acclaim throughout the world. Rohinton Mistry is a well renowned author in the contemporary commonwealth literature and occupies a significant place among the writers of Indian Diaspora. Even though he is settled in Canada; it is his upbringing in Mumbai that reflects in all his writings. The distinct Mumbai culture, particularly the Parsee way of life, the people of the city and even the politics of India are major themes in his novels. Rohinton Mistry as a writer of Diaspora has carved a niche for himself. His works such as: "Tales from Firozsha Baag", "Such A Long Journey", "A Fine Balance" and "Family Matters"; mark a new kind of writing, resulting from a fragmented, splintered world. As a Diasporic Parsi writer, very sensitively he has recalled his community's journey through time and history with a sense of loss and nostalgia. His books portray diverse facets of Indian socioeconomic life; as well as Parsi Zoroastrian life, customs, and religion. Many of his writings are markedly "Indo-nostalgic". Rohinton Mistry through his Diasporic discourse has well depicted his ancestral background, his community's engaged situation in a metropolis like Bombay and his deep attachment with and nostalgia for a world gone by. In this paper an attempt has been made to delineate diasporic discourse in the works of Rohinton Mistry. Although he is obsessed with the colonial and postcolonial experiences in India, we can find some traces of Canada in his literature. His characters dream of being integrated into, and accepted by, Canadian society on the one hand and on the other hand, these same characters are torn by an insatiable desire to be true to their native culture; to honor and cherish their own, distinct cultural identity.Keywords: Diaspora, Cultural identity, Contemporary Canadian literature, Parsi.
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An deutschen Schulen sollen bald mehr als 80.000 Lehrerstellen unbesetzt sein. Verfehlte Personalpolitik der meisten Bundesländer, nennt das der Bildungsforscher Klemm – erschienen in der ZEIT am 17. Juni 2009.
Es ist eine besorgniserregende Rechnung, die der Essener Bildungsforscher Klaus Klemm aufstellt: Die gegenwärtig anlaufende Pensionswelle unter Lehrern werde dazu führen, dass allein bis 2015 an deutschen Schulen mehr als 80.000 Pädagogenstellen unbesetzt sein werden. Anstatt kontinuierlich Junglehrer einzustellen, hätten die Bundesländer oft bis zum letzten Moment gewartet, um Kosten zu sparen – und so den seit Jahrzehnten bekannten Wechsel zwischen bitterer Lehrerarbeitslosigkeit und eklatantem Mangel für die Zukunft zementiert.
Klemms Rechnung verwirrt allerdings auch ein wenig – hat doch derselbe Wissenschaftler früher über Jahre prognostiziert, dass sämtliche Szenarien einer drohenden Pädagogenknappheit übertrieben seien: Es werde zu einem zumindest quantitativen Ausgleich zwischen Lehrerstellen und Bewerbern kommen, so lautete seine Vorhersage. Was ist passiert?
Im Grunde gar nichts. Klemm steht nämlich zu seiner alten Prognose. Der einzige Unterschied ist, dass er einmal etwas getan hat, was Bildungsforscher sonst meist bewusst unterlassen: Er hat sich in seinen neuen Berechnungen auf die Versprechungen der Politik gestützt – speziell auf jene, die Bundeskanzlerin und Ministerpräsidenten der Länder vergangenen Herbst auf dem Dresdner Bildungsgipfel gemacht haben.
Seit 25 Jahren beschäftigte ich mich mit Hochschulen, Bildung und Wissenschaft. Viel ist passiert in dieser Zeit, vieles davon durfte ich als Journalist begleiten. Der Blick zurück zeigt, wie aktuell einige meiner Themen von einst geblieben sind – obwohl sich fast alles verändert hat. Machmal allerdings auch, weil sich fast gar nichts verändert hat. Der 21. Teil einer Serie. Einen Überblick über die gesamte Serie "Blick zurück" finden Sie hier.
Die mutige wie notwendige Zusage damals: Man wolle die sogenannte demografische Rendite größtenteils im System belassen. In normalem Deutsch formuliert bedeutet das: Die Schülerzahlen gehen derzeit zwar zurück, doch um eine bessere Betreuungsrelation zu erreichen, soll die Zahl der Lehrer in etwa stabil gehalten werden. Ein Versprechen, das enorme Folgen für die Lehrerbedarfsprognosen hat, denn so fehlen plötzlich bis 2015 nicht maximal 1000 Lehrer, sondern 12.000 – und zwar Jahr für Jahr.
Vielleicht verfluchen die Ministerpräsidenten ja angesichts der enormen Steuerausfälle mittlerweile ihre eigene Courage von damals. Umso wichtiger ist es, dass Bildungsforscher Klemm sie mit seiner aktualisierten Prognose an ihre Selbstverpflichtung erinnert. Womöglich aber sind die Landespolitiker auch gar nicht so unglücklich über die neuen Zahlen, liefert der absehbare Lehrermangel ihnen doch die perfekte Ausrede: Angesichts der gegenwärtigen Absolventenzahlen wird es ihnen faktisch unmöglich sein, ihre Zusagen zu erfüllen – zu ihrem großen Bedauern, versteht sich.
So könnte Klemms ursprüngliche Vorhersage von einem Ausgleich zwischen Stellen und Bewerbern ironischerweise doch noch Wirklichkeit werden.
Wahr ist allerdings auch: Trotz stärkstem Lehrermangel werden nicht alle Absolventen einen Job finden. Ihre berufliche Zukunft hängt von ihrer Fächerkombination ab und der studierten Schulform. So werden es Mathe- und Physiklehrer auf jeden Fall viel leichter haben als etwa Studienräte für Deutsch und Geschichte. Dabei spielt keine Rolle, ob nun 1000 Lehrstellen im Jahr unbesetzt bleiben – oder doch 12.000.
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Nach dem PISA-Schock 22: Bildungswende – jetzt! Noch nie haben deutsche Schüler so schlecht bei PISA abgeschnitten wie in der […] Der Beitrag Nach dem PISA-Schock 22: Bildungswende – jetzt! erschien zuerst auf GESPRÄCHSKREIS BILDUNGSPOLITIK.
With new proposals and development initiatives, the government aims to maintain the momentum of economic growth. There is emphasis on keeping poverty and job losses to a minimum with no new taxes, expansion of social protection schemes, and increase in salaries. Initiatives to protect both formal and informal Small and Medium Enterprises (SMEs) have been announced in view of the stresses faced by private enterprises amid COVID-19.
Throughout this internship, I, Abhi Pasupula, have worked with my internship mentor, Barry Federici, in order to help him start up a new service. This service is targeted specifically towards veterans and their paths in their lives after they retire from the military. The service is split up into two categories, those being Jobs and Veteran Benefits. Jobs entailed creating and implement a job board into our website for retired veterans to search for. Veteran benefits showcase a list of benefits that veterans are eligible for, divided up by Federal Benefits, State Benefits, Local Benefits, and a page for all available benefits. For the Job Board page on the website, we got into contact with a job board service known as Hiring Opps and spent many days working through the features and seeing which features would serve us the best for the website. In addition, we set up a Sandbox so that we could physically see the service in action. The benefits required more menial work, such as compiling the list of total benefits and categorizing them into states with links that lead to the state Veteran Benefits commission for more information. Once organized, the benefits were organized into 4 sections, each section having its own page on the website. Both of these websites were connected back to the original website, which served as a homepage for all the services. The homepage also had services to meet with my mentor, Mr. Federici. Working on both of these websites and services really opened my eyes to the professional world of Software Development, where there was so much more apart from just programming. Similar to this internship, the real world will require me to be able to voice my thoughts as well as put them down on paper and be able to explain them well to others, something that I believe this internship set me up for very well. ; https://digitalcommons.imsa.edu/intern_reports_2021/1004/thumbnail.jpg
This study evaluates the consolidated financial condition and performance of local water districts (LWDs) in the Philippines. Water districts are government-owned or controlled corporations (GOCCs) tasked to construct, operate, maintain, and expand water and sanitation systems in the countryside. They are instrumental in the Philippines' objective to attain 100-percent water supply and sanitation access by 2036. National data show that the consolidated financial performance of LWDs has improved from 2009 to 2018, as reflected in their high and stable cash flows, high debt service coverage ratios, and lower debt ratios. With the aggressive spending program of the government on water infrastructure, lower debt ratios are needed to prepare LWDs to achieve the 2023 and the 2030 goals of universal access to water supply and sanitation. However, the government's spending plans are so ambitious that the current balance sheets of LWDs cannot sustain the planned investments financed through debt. The national government needs to bolster the balance sheets of LWDs by infusing fresh equity of PHP 22 billion to PHP 56 billion to achieve the Philippines' 2030 water supply and sanitation targets. The study likewise shows a significant disparity in water investments across the country's different regions, which impacts the uneven water service coverage throughout the Philippines.
This study evaluates the consolidated financial condition and performance of local water districts (LWDs) in the Philippines. Water districts are government-owned or controlled corporations (GOCCs) tasked to construct, operate, maintain, and expand water and sanitation systems in the countryside. They are instrumental in the Philippines' objective to attain 100-percent water supply and sanitation access by 2036. National data show that the consolidated financial performance of LWDs has improved from 2009 to 2018, as reflected in their high and stable cash flows, high debt service coverage ratios, and lower debt ratios. With the aggressive spending program of the government on water infrastructure, lower debt ratios are needed to prepare LWDs to achieve the 2023 and the 2030 goals of universal access to water supply and sanitation. However, the government's spending plans are so ambitious that the current balance sheets of LWDs cannot sustain the planned investments financed through debt. The national government needs to bolster the balance sheets of LWDs by infusing fresh equity of PHP 22 billion to PHP 56 billion to achieve the Philippines' 2030 water supply and sanitation targets. The study likewise shows a significant disparity in water investments across the country's different regions, which impacts the uneven water service coverage throughout the Philippines.
In der deutschen Rechtswissenschaft scheint bereits die Idee von Open Access (OA) einen schweren Stand zu haben: Eine Reihe von Wissenschaftler:innen üben offen Kritik an der Idee oder bezweifeln sogar die Verfassungsmäßigkeit von Open-Access-Vorgaben oder -Richtlinien. Nichtsdestotrotz sind in den letzten Jahren innovative digitale Formate entstanden, die hochwertige rechtswissenschaftliche Inhalte OA veröffentlichen. Nennenswerte Beispiele sind der Verfassungsblog und der Völkerrechtsblog. Diese Plattformen nennen sich "Blogs", stellen als qualitätsgesicherte Multi-Author-Blogs (QMABs) aber tatsächlich eine neue, innovative, frei verfügbare und genuin digitale Form des wissenschaftlichen Publizierens dar, die zwischen wissenschaftlichen Zeitschriften und traditionellen Medien/Presse angesiedelt ist. In einem QMAB können Expert:innen (in der Regel Wissenschaftler:innen) tagesaktuell Ereignisse analysieren, einordnen und kommentieren. QMABs in der Rechtswissenschaft und den Geistes- und Sozialwissenschaften haben als innovatives Publikationsformat in den vergangenen Jahren eine wachsende Zahl an Autor:innen und Leser:innen hinzugewonnen. Auch die breite Öffentlichkeit nimmt zunehmend Notiz von diesen Plattformen. Gesellschaftspolitische Entwicklungen und Ereignisse sind häufig mit rechtlichen und rechtspolitischen Fragestellungen verknüpft, auf die auch Nicht-Wissenschaftler:innen Antworten suchen. Gleichzeitig haben Wissenschaftler:innen ein Interesse daran, ihre Expertise in den politischen Raum zu tragen. QMAB dienen somit nicht nur dem wissenschaftlichen Binnendiskurs, sondern ermöglichen es auch der breiten Öffentlichkeit, an Fachdiskursen teilzunehmen, etwa über die Kommentarfunktion – und all dies über staatliche Grenzen hinweg. Damit fördern QMABs nicht nur den wissenschaftlichen Austausch und öffnen Diskurse für ein breites Publikum, sondern internationalisieren diese auch. Hierin offenbaren sie ihr partizipatives und kommunikatives Potenzial, das letztlich dem wissenschaftlichen Erkenntnisgewinn zugute ...
This week's guest is Ryan Busse, former senior executive in the firearms industry. Ryan's new book, Gunfight, is an intimate and revealing account of his experience in that industry, his growing disillusionment with it and his ultimate exit. In this conversation, we talk about rural household gun culture, the symbolism assault rifles take on in political division, and the rights and responsibilities of gun ownership in our country. ; https://scholarworks.umt.edu/anewangle_podcasts/1224/thumbnail.jpg