Alteration of a Nonconserved Active Site Residue in the Chemotaxis Response Regulator CheY Affects Phosphorylation and Interaction with CheZ

CheY is a response regulator in the well studied two-component system that mediates bacterial chemotaxis. Phosphorylation of CheY at Asp(57) enhances its interaction with the flagellar motor. Asn(59) is located near the phosphorylation site, and possible roles this residue may play in CheY function were explored by mutagenesis. Cells containing CheY59NR or CheY59NH exhibited hyperactive phenotypes (clockwise flagellar rotation), and CheY59NR was characterized biochemically. A continuous enzyme-linked spectroscopic assay that monitors P(i) concentration was the primary method for kinetic analysis of phosphorylation and dephosphorylation. CheY59NR autodephosphorylated at the same rate as wild-type CheY and phosphorylated similarly to wild type with acetyl phosphate and faster (4-14x) with phosphoramidate and monophosphoimidazole. CheY59NR was extremely resistant to CheZ, requiring at least 250 times more CheZ than wild-type CheY to achieve the same dephosphorylation rate enhancement, whereas CheY59NA was CheZ-sensitive. However, several independent approaches demonstrated that CheY59NR bound tightly to CheZ. A submicromolar K(d) for CheZ binding to CheY59NR-P or CheY.BeF(3)(-) was inferred from fluorescence anisotropy measurements of fluoresceinated-CheZ. A complex between CheY59NR-P and CheZ was isolated by analytical gel filtration, and the elution position from the column was indistinguishable from that of the CheZ dimer. Therefore, we were not able to detect large CheY-P.CheZ complexes that have been inferred using other methods. Possible structural explanations for the specific inhibition of CheZ activity as a result of the arginyl substitution at CheY position 59 are discussed

Religious Freedom in Faith-Based Educational Institutions in the Wake of \u27Obergefell v. Hodges\u27: Believers Beware

Solicitor General Donald Verrilli’s fateful words, uttered in response to a question posed by Justice Samuel Alito during oral arguments in Obergefell v. Hodges,2 likely sent chills up the spines of leaders in faith-based educational institutions, from pre-schools to universities. In Obergefell, a bare majority of the Supreme Court legalized same-sex unions in the United States. Verrilli’s words, combined with the outcome in Obergefell, have a potentially chilling effect on religious freedom. The decision does not only impact educational institutions—the primary focus of this article—but also a wide array of houses of worship. Other religiously affiliated institutions that may be affected include health and social services agencies, such as those working with adoptions 3 and ministering to the needy.4 These educational institutions and other agencies designed to assist the common good run the risk of being shuttered as a form of punishment, to the detriment of many, if they remain true to their faith—a decidedly un- American prospect

Religious Freedom in Faith Based Educational Institutions in the Wake of Obergefell v. Hodges: Believers beware

Solicitor General Donald Verrilli’s fateful words, uttered in response to a question posed by Justice Samuel Alito during oral arguments in Obergefell v. Hodges,2 likely sent chills up the spines of leaders in faith-based educational institutions, from pre-schools to universities. In Obergefell, a bare majority of the Supreme Court legalized same-sex unions in the United States. Verrilli’s words, combined with the outcome in Obergefell, have a potentially chilling effect on religious freedom. The decision does not only impact educational institutions—the primary focus of this article—but also a wide array of houses of worship. Other religiously affiliated institutions that may be affected include health and social services agencies, such as those working with adoptions 3 and ministering to the needy.4 These educational institutions and other agencies designed to assist the common good run the risk of being shuttered as a form of punishment, to the detriment of many, if they remain true to their faith—a decidedly un- American prospect

JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with rheumatoid arthritis

BackgroundJanus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.MethodsTo this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on in-vitro B cell activation, proliferation, and class switch recombination and involved pathways.ResultsWhile B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an in-vitro model of T-cell-independent B cell activation we observed that JAK1/2 and selective JAK1 inhibitor treatment led to a dose-dependent decrease of total B cell numbers. We detected an altered B cell differentiation with a significant increase in MZ-like B cells and an increase in plasmablast differentiation in the first days of culture, most pronounced with the pan-JAK inhibitor tofacitinib, although there was no increase in immunoglobulin secretion in-vitro. Notably, we further observed a profound reduction of switched memory B cell formation, especially with JAK1/2 inhibition. JAK inhibitor treatment led to a dose-dependent reduction of STAT3 expression and phosphorylation as well as STAT3 target gene expression and modulated the secretion of pro- and anti-inflammatory cytokines by B cells.ConclusionJAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis

NASA Patent Abstracts October 2006: A Continuing Bibliography

Several thousand inventions result each year from research supported by the National Aeronautics and Space Administration. NASA seeks patent protection on inventions to which it has title if the invention has important use in government programs or significant commercial potential. These inventions cover a broad range of technologies and include many that have useful and valuable commercial application. NASA inventions best serve the interests of the United States when their benefits are available to the public. In many instances, the granting of nonexclusive or exclusive licenses for the practice of these inventions may assist in the accomplishment of this objective. This bibliography is published as a service to companies, firms, and individuals seeking new, licensable products for the commercial market. The NASA Patent Abstracts Bibliography is an annual NASA publication containing comprehensive abstracts of NASA-owned inventions covered by U.S. patents. The citations included were originally published in NASA s Scientific and Technical Aerospace Reports (STAR) and cover STAR announcements made since May 1969. The citations published in this issue cover the period July 2005 through September 2006. The range of subjects covered includes the NASA Scope and Subject Category Guide's 10 broad subject divisions separated further into 76 specific categories. However, not all categories contain citations during the dates covered for this issue; therefore, the Table of Contents does not include all divisions and categories. This scheme was devised in 1975 and last revised in 2005 in lieu of the 34 category divisions which were utilized in supplements (01) through (06) covering STAR abstracts from May 1969 through January 1974. Each entry consists of a citation accompanied by an abstract and, when appropriate, a key illustration taken from the patent or application for patent. Entries are arranged by subject category in ascending order. When available, citations contain a link to the full-text document online. Two indexes, Subject Term and Personal Author, are available within the publication

Sustentabilidade da produção de cacau em São Tomé e Príncipe

A produção de cacau de São Tomé e Príncipe é uma atividade importante, quer em termos socioculturais e ambientais, quer económicos, sendo a maior contribuinte para o PIB e para as exportações nacionais. Contudo, os pequenos produtores que a asseguram, deparam-se com várias dificuldades relacionadas à manutenção da atividade face a vantagens de superior valor de mercado de outras culturas mais rentáveis. O objetivo deste trabalho foi o de conhecer a sustentabilidade da produção de cacau em São Tomé e Príncipe. Para tal, para além da revisão da literatura sobre a temática, os procedimentos metodológicos incluíram a realização de um estudo empírico com uma abordagem mista (qualitativa e quantitativa), com levantamento de informação documental e bibliográfica oriunda de fontes secundárias e, de informação primária através da aplicação de um guião de entrevista a distintos intervenientes da cadeia de valor e de um questionário a uma amostra de 200 agregados familiares produtores de cacau. Os resultados permitem concluir ser o conceito de sustentabilidade percebido como importante e a certificação do cacau biológico considerada essencial para melhorar, nas dimensões económica, social e ambiental, o atual estado de sustentabilidade. Foram identificados três perfis de estratégias de subsistência dos produtores, suportadas sobretudo na diversidade de escolhas culturais com base no cacau, relacionados à produção do cacau em monocultura, à produção conjunta de cacau e banana, e à produção de cacau, banana e outras culturas. A forma como as famílias alocam os recursos, sobretudo mão-de-obra-familiar, depende da sua expetativa de geração de autoabastecimento e de rendimento para a família. Não existem diferenças de perceção entre os membros das duas cooperativas em relação aos riscos que enfrentam, à sua gravidade e impacto na roça e ao seu grau de controlo. As famílias com uma baixa proporção da terra atribuída apresentam estratégias de diversificação de rendimento mais altas e vice-versa. Uma política nacional de promoção da produção de cacau e de maior transição para a sustentabilidade é necessária, para evitar o abandono e assegurar bem-estar e maior rendimento às comunidades rurais que mais dependem do cultivo de cacau e têm menor dotação de ativos; Sustainability of cocoa production in São Tomé and Príncipe - Abstract: Cocoa production in São Tomé and Príncipe is an important activity, both in socio-cultural and environmental terms, as well as in economic terms, being the largest contributor to GDP and national exports. However, the small producers who ensure it, are faced with several difficulties related to maintaining the activity in the face of the advantages of higher market value of other more profitable crops. The objective of this work was to know the sustainability of cocoa production in São Tomé and Príncipe. To this end, in addition to reviewing the literature on the subject, the methodological procedures included carrying out an empirical study with a mixed approach (qualitative and quantitative), with a survey of documental and bibliographical information from secondary sources, and of primary information through the application of an interview guide to different players in the value chain and a questionnaire to a sample of 200 cocoa-producing households. The results allow to conclude that the concept of sustainability is perceived as important and the certification of organic cocoa is considered essential to improve, in the economic, social and environmental dimensions, the current state of sustainability. Three profiles of producers' subsistence strategies were identified, supported by the diversity of cultural choices based on cocoa, related to the production of cocoa in monoculture, the joint production of cocoa and banana, and the production of cocoa, banana and other crops. The way families allocate resources, especially family labour, depends on their expectation of generating self-sufficiency and income for the family. There are no differences in perception between the members of the two cooperatives in relation to the risks they face, their severity and impact on the fields and their degree of control. Households with a low proportion of allocated land have higher income diversification strategies and vice versa. A national policy to promote cocoa production and a greater transition towards sustainability is needed to avoid abandonment and ensure the well-being and higher income of rural communities that are most dependent on cocoa cultivation and have the lowest endowment of assets

A Brief History of Human Time: Exploring a database of 'notable people'

This paper describes a database of 1,243,776 notable people and 7,184,575 locations (Geolinks) associated with them throughout human history (3000BCE-2015AD). We first describe in details the various approaches and procedures adopted to extract the relevant information from their Wikipedia biographies and then analyze the database. Ten main facts emerge. 1. There has been an exponential growth over time of the database, with more than 60% of notable people still living in 2015, with the exception of a relative decline of the cohort born in the XVIIth century and a local minimum between 1645 and 1655. 2. The average lifespan has increased by 20 years, from 60 to 80 years, between the cohort born in 1400AD and the one born in 1900AD. 3. The share of women in the database follows a U-shape pattern, with a minimum in the XVIIth century and a maximum at 25% for the most recent cohorts. 4. The fraction of notable people in governance occupations has decreased while the fraction in occupations such as arts, literature media and sports has increased over the centuries; sports caught up to arts and literature for cohorts born in 1870 but remained at the same level until the 1950s cohorts; and eventually sports came to dominate the database after 1950. 5. The top 10 visible people born before 1890 are all non-American and have 10 different nationalities. Six out of the top 10 born after 1890 are instead U.S. born citizens. Since 1800, the share of people from Europe and the U.S. in the database declines, the number of people from Asia and the Southern Hemisphere grows to reach 20% of the database in 2000. Coincidentally, in 1637, the exact barycenter of the base was in the small village of Colombey-les-Deux-Eglises (Champagne Region in France), where Charles de Gaulle lived and passed away. Since the 1970s, the barycenter oscillates between Morocco, Algeria and Tunisia. 6. The average distance between places of birth and death follows a U-shape pattern: the median distance was 316km before 500AD, 100km between 500 and 1500AD, and has risen continuously since then. The greatest mobility occurs between the age of 15 and 25. 7. Individuals with the highest levels of visibility tend to be more distant from their birth place, with a median distance of 785km for the top percentile as compared to 389km for the top decile and 176km overall. 8. In all occupations, there has been a rise in international mobility since 1960. The fraction of locations in a country different from the place of birth went from 15% in 1955 to 35% after 2000. 9. There is no positive association between the size of cities and the visibility of people measured at the end of their life. If anything, the correlation is negative. 10. Last and not least, we find a positive correlation between the contemporaneous number of entrepreneurs and the urban growth of the city in which they are located the following decades; more strikingly, the same is also true with the contemporaneous number or share of artists, positively affecting next decades city growth; instead, we find a zero or negative correlation between the contemporaneous share of “militaries, politicians and religious people” and urban growth in the following decades

Ametiühingud, transformism ja Vene autoritarismi püsimine

Väitekiri uurib Venemaal toimuvate sotsiaalsete ja tööprotestide ohjeldamise ja neutraliseerimise mehhanisme. Kuigi majandusraskused ja valitsuse poliitika põhjustavad regulaarselt rohujuuretasandil rahulolematust ja sütitavad konflikte, ei kujuta need režiimile mingit poliitilist katsumust. Nendest arvukatest protestidest mõned saavutavad formaalse võidu, kui võimud rahuldavad altpoolt esitatud nõudmisi. Samal ajal jääb see edu lokaalseks, mis aitab kaasa valitseva režiimi elujõulisusele ega suurenda protestijate mobiliseerimise võimet. Käesolev uuring põhineb transformismi kontseptsioonil, mille pakkus välja Antonio Gramsci ja mille poststrukturalistliku tõlgenduse esitas Ernesto Laclau. Transformism viitab protsessidele, mille käigus protestijate nõudmisi rahuldatakse valdava poliitilise ja ühiskondliku korra raames. Selle mõistega kaasneb demokraatliku ja populistliku poliitika eristamine. Demokraatlik poliitika areneb olemasoleva valitsussüsteemi piirides, populistlik poliitika on aga valitseva korra suhtes antagonistlik. Transformistliku paradigma lõksu jäädes tekitavad rohujuuretasandi protestid demokraatlikku poliitikat, kuna väldivad režiimi vastu astumist ega tegele populistliku poliitikaga. Väitekiri uurib transformismi toimimist Vene ametiühingute näitel. Analüüsitakse ametiühingute struktuuri, diskursusi ja seejärel keskendutakse konkreetsetele juhtumitele kolmes Loode-Venemaa regioonis ning 2018. aasta üleriigilisele pensionireformi vastasele kampaaniale. Ametiühingud osalevad regulaarselt sotsiaalsetes ja töökonfliktides, korraldades kohalikke proteste, mille käigus sageli võidetakse järeleandmisi nii tööandjatelt kui ka võimudelt. Läbirääkimiste jooksul suunatakse sotsiaalsed ja töökonfliktid aga lokaalsetesse kokkulepetesse võimude ja töötajate vahel. Seega neutraliseerib transformism protestiliikumised ja aitab kaasa autoritaarse režiimi püsimisele.  This study explores the mechanisms of domestication and neutralization of social and labor protests in Russia. While economic difficulties and governmental policies regularly provoke grassroots discontent and spark conflicts, these do not present any political challenge to the regime. Some of the numerous protests formally succeed as the authorities satisfy the demands from below. At the same time, the success remains localized. Local victories contribute to the sustainability of the existing regime and do not enhance the capacity for protest mobilization. This dissertation uses the concept of transformism proposed by Antonio Gramsci and developed, in a poststructuralist setting, by Ernesto Laclau. Transformism refers to processes accommodating protesters’ demands from below within the current political and social order. This concept comes along with the distinction between democratic and popular politics. Democratic politics unfolds within the confines of the existing system of rule, while popular politics is antagonistic toward the present order. When trapped in the transformist paradigm, grassroots protests generate democratic politics, but avoid confronting the regime and thus do not engage in popular politics. This study demonstrates how transformism works by studying Russian trade unions. It analyzes the structure of the unions, their discourses, and then focuses on concrete cases of unions’ activities in three North-Western regions of Russia, as well as the 2018 nation-wide campaign against the pension reform. Trade unions are regularly involved in social and labor conflicts by spearheading local protests, which often succeed in getting concessions from the employers and the authorities. In the process, however, social and labor conflicts are channeled into local agreements between the authorities and the workers. Thus, transformism neutralizes protest movements and contributes to the survival of the authoritarian regime.https://www.ester.ee/record=b538682

Tomus Nominum Eriastri: The Nomenclature and Taxonomy of Eriastrum (Polemoniaceae: Loeselieae)

A revised taxonomy for the genus Eriastrum is presented, including type information, synonymy, descriptions, and keys for identification. The nomenclature of Hugelia lanata, Gilia floccosa, and Gilia virgata var. yageri is clarified. Additionally, issues pertaining to August Brand’s, Thomas Nuttall’s, and Asa Gray’s names in Eriastrum are reviewed. An illustrated glossary of important descriptive terms is provided, along with photographs and illustrations of taxa and features. Lectotypes are proposed for 14 taxa. There is further discussion about the nomenclature and type localities for each taxon, comparison of circumscriptions from previous authors, and some field observations. Discussion of identifying characteristics, geographic range, habitat, demographics, threats, conservation, and etymology is included for each taxon. A listing of unpublished herbarium names is also supplied, with the corresponding currently accepted names. One new combination, Eriastrum densifolium subsp. patens, is presented. Five new subspecies, Eriastrum diffusum subsp. coachellae, Eriastrum diffusum subsp. utahense, Eriastrum eremicum subsp. markianum, Eriastrum pluriflorum subsp. albifaux, and Eriastrum sapphirinum subsp. brevibracteatum, and one new species, Eriastrum calocyanum, are described and illustrated. As treated here, Eriastrum includes 18 species and 14 subspecies, for a total of 32 taxa