Murine coronavirus ubiquitin-like domain is important for papain-like protease stability and viral pathogenesis

Ubiquitin-like domains (Ubls) now are recognized as common elements adjacent to viral and cellular proteases; however, their function is unclear. Structural studies of the papain-like protease (PLP) domains of coronaviruses (CoVs) revealed an adjacent Ubl domain in severe acute respiratory syndrome CoV, Middle East respiratory syndrome CoV, and the murine CoV, mouse hepatitis virus (MHV). Here, we tested the effect of altering the Ubl adjacent to PLP2 of MHV on enzyme activity, viral replication, and pathogenesis. Using deletion and substitution approaches, we identified sites within the Ubl domain, residues 785 to 787 of nonstructural protein 3, which negatively affect protease activity, and valine residues 785 and 787, which negatively affect deubiquitinating activity. Using reverse genetics, we engineered Ubl mutant viruses and found that AM2 (V787S) and AM3 (V785S) viruses replicate efficiently at 37°C but generate smaller plaques than wild-type (WT) virus, and AM2 is defective for replication at higher temperatures. To evaluate the effect of the mutation on protease activity, we purified WT and Ubl mutant PLP2 and found that the proteases exhibit similar specific activities at 25°C. However, the thermal stability of the Ubl mutant PLP2 was significantly reduced at 30°C, thereby reducing the total enzymatic activity. To determine if the destabilizing mutation affects viral pathogenesis, we infected C57BL/6 mice with WT or AM2 virus and found that the mutant virus is highly attenuated, yet it replicates sufficiently to elicit protective immunity. These studies revealed that modulating the Ubl domain adjacent to the PLP reduces protease stability and viral pathogenesis, revealing a novel approach to coronavirus attenuation. IMPORTANCE Introducing mutations into a protein or virus can have either direct or indirect effects on function. We asked if changes in the Ubl domain, a conserved domain adjacent to the coronavirus papain-like protease, altered the viral protease activity or affected viral replication or pathogenesis. Our studies using purified wild-type and Ubl mutant proteases revealed that mutations in the viral Ubl domain destabilize and inactivate the adjacent viral protease. Furthermore, we show that a CoV encoding the mutant Ubl domain is unable to replicate at high temperature or cause lethal disease in mice. Our results identify the coronavirus Ubl domain as a novel modulator of viral protease stability and reveal manipulating the Ubl domain as a new approach for attenuating coronavirus replication and pathogenesis.

First international external quality assessment of molecular diagnostics for Mers-CoV

BACKGROUND: Since the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, diagnostic protocols were quickly published and deployed globally. OBJECTIVES: We set out to assess the quality of MERS-CoV molecular diagnostics worldwide. STUDY DESIGN: Both sensitivity and specificity were assessed using 12 samples containing different viral loads of MERS-CoV or common coronaviruses (OC43, 229E, NL63, HKU1). RESULTS: The panel was sent to more than 106 participants, of which 99 laboratories from 6 continents returned 189 panel results.Scores ranged from 100% (84 laboratories) to 33% (1 laboratory). 15% of respondents reported quantitative results, 61% semi-quantitative (Ct-values or time to positivity) and 24% reported qualitative results. The major specific technique used was real-time RT-PCR using the WHO recommended targets upE, ORF1a and ORF1b. The evaluation confirmed that RT-PCRs targeting the ORF1b are less sensitive, and therefore not advised for primary diagnostics. CONCLUSIONS: The first external quality assessment MERS-CoV panel gives a good insight in molecular diagnostic techniques and their performances for sensitive and specific detection of MERS-CoV RNA globally. Overall, all laboratories were capable of detecting MERS-CoV with some differences in sensitivity. The observation that 8% of laboratories reported false MERS-CoV positive single assay results shows room for improvement, and the importance of using confirmatory targets.

Atlas of cancer mortality in the United Arab Emirates aided by application of geographic information system methods

The aim of this study was to determine cancer mortality rates for the United Arab Emirates (UAE) and to create an atlas of cancer mortality for the UAE. This atlas is the first of its kind in the Gulf country and the Middle East. Death certificates were reviewed for a period from January 1, 1990 to December 31, 1999 and cancer deaths were identified. Cancer mortality cases were verified by comparing with medical records. Age-adjusted cancer mortality rates were calculated by gender, emirate/medical district and nationality (UAE nationals and overall UAE population). Individual rates for each emirate were compared to the overall rate of the corresponding population for the same cancer site and gender. Age-adjusted rates were mapped using MapInfo software. High rates for liver, lung and stomach cancer were observed in Abu Dhabi, Dubai and the northern emirates, respectively. Rates for UAE nationals were greater compared to the overall UAE population. Several factors were suggested that may account for high rates of specific cancers observed in certain emirates. It is hoped that this atlas will provide leads that will guide further epidemiologic and public health activities aimed at preventing cancer. ^

Practice and attitude differences in physician cigarette use: A study of prevalence, physicians' role, and smoking policy awareness in Dubai, UAE

The use of tobacco products ruins the health of millions of people around the world. On average, tobacco users die nearly seven years earlier than non-tobacco users. n1 Cigarette smoking is a particular concern in the developing countries of the Middle East and Gulf Cooperation Council (GCC) region where smoking prevalence is expected to increase. This is due to the tobacco industry's vigorous commercial and marketing activities. n3 Smoking prevalence among physicians is considered to be an effective indicator of a society's readiness to identify the smoking epidemic and its related health diseases. n4 There is a lack of detailed data on the smoking prevalence among healthcare professionals, particularly physicians, in the United Arab Emirates (UAE). This cross sectional study is the first to address smoking practices among physicians working at the Department of Health and Medical Services (DOHMS); in Dubai, UAE. ^ This study describes the cigarette smoking prevalence among DOHMS Physicians, physician attitudes towards tobacco use and tobacco bans; physician attitudes towards smoking cessation techniques (among smokers and non-smokers); and physician awareness of official anti-smoking policies. Data for the study was collected through the use of an adapted WHO standardized questionnaire, the Global Health Professionals Survey. The questionnaire was administered by the researcher to physicians (n=288) at their work place. Date was analyzed using the SPSS analytic software program. ^ Twelve percent of DOHMS physicians smoked cigarettes. Regardless of smoking status, the majority supported a tobacco ban in hospitals and public places, and a ban on tobacco advertising. There is a significant relationship between physician smoking status and discussing risks of tobacco use (p < 0.05). Non-smoking physicians reported spending more time with patients discussing hazards of smoking (p < 0.01). Non-smokers reported providing more counseling than their smoking colleagues. The majority of DOHMS physicians (63%) reported a lack of knowledge about 5As/ 5Rs. The majority of physicians also reported they are aware of hospital smoking policies that restrict smoking. Regardless of physician smoking status, DOHMS physicians are not very actively involved in smoking cessation activities. This cross sectional study is the first to address smoking programs, policies, and practices among physicians in Dubai, UAE. Findings support the need for increased physical smoking cessation training as well as the development of smoking cessation programs for tobacco control, and programs with a focus on physician participation in reducing tobacco and cigarette use among the general population.^

Les Tribus Dans l´histoire et face aux états. En: Avá, nº 17

Este brevísimo libro de Maurice Godelier, cuyo texto procede de la conferencia inaugural del coloquio internacional The Political Role of Tribes in the Middle East (Ammán, Jordania, Octubre de 2009), ofrece en apenas unas 80 páginas un panorama general de cuestiones de antropología política, con una vertiente de comparación histórica en diversos períodos y lugares, sobre la naturaleza de las sociedades tribales y su relación con las organizaciones estatales.

Varved sediments of the Arabian Sea

The upper Holocene marine section from a kasten core taken from the oxygen minimum zone off Karachi (Pakistan) at water depth 700 m contains continuously laminated sediments with a sedimentation rate of 1.2 mm/yr and a unique record of monsoonal climatic variability covering the past 5000 years. Our chronostratigraphy is based on varve counts verified by conventional and AMS14C dating. Individual hemipelagic varve couplets are about 0.8-1.5 mm thick, with light-colored terrigenous laminae (A) deposited mainly during the winter monsoon alternating with dark-colored laminae (B) rich in marine organic matter, coccoliths, and fish debris that reflect deposition during the high-productivity season of the late summer monsoon (August-October). Precipitation and river runoff appear to control varve thickness and turbidite frequency. We infer that precipitation decreased in the river watershed (indicated by thinning varves) after 3500-4000 yr B.P. This is about the time of increasing aridification in the Near East and Middle East, as documented by decreasing Nile River runoff data and lake-level lowstands between Turkey and northwestern India. This precipitation pattern continued until today with precipitation minima about 2200-1900 yr B.P., 1000 yr B.P., and in the late Middle Ages (700-400 yr B.P.), and precipitation maxima in the intervening periods. As documented by spectral analysis, the thickness of varve couplets responds to the average length of a 250-yr cycle, a 125-yr cycle, the Gleissberg cycle of solar activity (95 yr), and a 56-yr cycle of unknown origin. Higher frequency cycles are also present at 45, 39, 29-31, and 14 yr. The sedimentary gray-value also shows strong variability in the 55-yr band plus a 31-yr cycle. Because high-frequency cyclicity in the ENSO band (ca. 3.5 and 5 yr) is only weakly expressed, our data do not support a straightforward interaction of the Pacific ENSO with the monsoon-driven climate system of the Arabian Sea.

Aerosols over the Arabian Sea

This paper provides an overview of dust transport pathways and concentrations over the Arabian Sea during 1995. Results indicate that the transport and input of dust to the region is complex, being affected by both temporally and spatially important processes. Highest values of dust were found off the Omani coast and in the entrance to the Gulf of Oman. Dust levels were generally lower in summer than the other seasons, although still relatively high compared to other oceanic regions. The Findlater jet, rather than acting as a source of dust from Africa, appears to block the direct transport of dust to the open Arabian Sea from desert dust source regions in the Middle East and Iran/Pakistan. Dust transport aloft, above the jet, rather than at the surface, may be more important during summer. In an opposite pattern to dust, sea salt levels were exceedingly high during the summer monsoon, presumably due to the sustained strong surface winds. The high sea salt aerosols during the summer months may be impacting on the strong aerosol reflectance and absorbance signals over the Arabian Sea that are detected by satellite each year.

Stable isotope analysis of Porites coral core EILAT-1

The environmental interpretation of the 13C/12C variations in the skeletons of massive corals is still a matter of debate. A 19-year seasonal skeletal 13C/12C record of a shallow-water Pontes coral from the northern Red Sea (Gulf of Aqaba) documents interannual events of extraordinarily large plankton blooms, indicated by anomalous 13C depletions in the coral skeleton. These blooms are caused by deep vertical water mass mixing, convectively driven in colder winters, which results in increased supplies of nutrients to the surface waters. The deep vertical mixings can sometimes be driven by the cooling occurring throughout the Middle East after large tropical volcanic eruptions. We therefore have evidence in our coral skeletal 13C/12C record for an indirect volcanic signal of the eruptions of El Chichón (1982) and Mount Pinatubo (1991). Deep mixing induced 13C/12C variations of the dissolved inorganic carbon in the surface waters can be neglected at this location. We therefore suggest that the 13C skeletal depletions can be best explained by changes in the coral's autotrophy-heterotrophy diet, through increased heterotrophic feeding on Zooplankton during the blooms. Increased feeding on 13C-depleted Zooplankton or increased heterotrophy at the expense of autotrophy can both result in a 13C-depleted coral skeleton. However, this suggestion requires more testing. If our conclusions are substantiated, seasonal skeletal 13C/12C records of corals which change from autotrophy under normal conditions to increased heterotrophy during bloom events may be used as indicators of ocean paleoproductivity at interannual resolution, available from no other source.

Una cuestión de patrones y clientes. Acerca de la organización social y el poder político en la antigua palestina

Durante las últimas tres décadas, los métodos de la investigación histórica de las sociedades de la antigua Palestina han experimentado un considerable progreso desde los días en que la Biblia era tomada como fuente primaria y principal de reconstrucción histórica. Las nuevas perspectivas privilegian el aporte de múltiples disciplinas sociales, entre otras, la antropología, la sociología, la etnografía. En la presente comunicación hacemos uso de la información del registro etnográfico contemporáneo junto con perspectivas de la teoría antropológica para tratar de resolver la cuestión de la organización social de Palestina en la antigüedad así como de la práctica del poder político en las sociedades "tribales" de Medio Oriente. La integración de esta información junto con el análisis de fuentes históricas antiguas nos indica que las relaciones de parentesco y, fundamentalmente, las de patronazgo fueron las prácticas sociopolíticas dominantes en estas sociedades. Como resultado, el predominio de estas prácticas constituyó un obstáculo considerable para la aparición de una práctica estatal indígena en esta región. En consecuencia, una aceptación de la primacía analítica del concepto de "sociedades de patronazgo" por sobre el de "sociedades estatales" o "sociedades de clase" nos puede conducir a un mejor entendimiento de la dinámica sociopolítica en la antigua Palestina.

Una cuestión de patrones y clientes. Acerca de la organización social y el poder político en la antigua palestina

Durante las últimas tres décadas, los métodos de la investigación histórica de las sociedades de la antigua Palestina han experimentado un considerable progreso desde los días en que la Biblia era tomada como fuente primaria y principal de reconstrucción histórica. Las nuevas perspectivas privilegian el aporte de múltiples disciplinas sociales, entre otras, la antropología, la sociología, la etnografía. En la presente comunicación hacemos uso de la información del registro etnográfico contemporáneo junto con perspectivas de la teoría antropológica para tratar de resolver la cuestión de la organización social de Palestina en la antigüedad así como de la práctica del poder político en las sociedades "tribales" de Medio Oriente. La integración de esta información junto con el análisis de fuentes históricas antiguas nos indica que las relaciones de parentesco y, fundamentalmente, las de patronazgo fueron las prácticas sociopolíticas dominantes en estas sociedades. Como resultado, el predominio de estas prácticas constituyó un obstáculo considerable para la aparición de una práctica estatal indígena en esta región. En consecuencia, una aceptación de la primacía analítica del concepto de "sociedades de patronazgo" por sobre el de "sociedades estatales" o "sociedades de clase" nos puede conducir a un mejor entendimiento de la dinámica sociopolítica en la antigua Palestina.

Dust flux in the Arabian Sea

Eolian grain size and flux were measured on samples from 11 Arabian Sea sediment traps deployed 200-1250 km offshore. The timing of increased grain size is coincident with the onset of strong summer monsoon winds and dust storm activity over the Arabian Peninsula and Middle East. Data spanning a full annual cycle show that eolian grain size is highly correlated with barometric pressure (r=-0.91) and wind speed (r=0.84), enabling calibration of the downcore record in terms of these primary meteorological variables. Eolian flux is highly correlated with organic carbon flux (r=0.80); both increase 6-8 weeks after the grain size increase and summer monsoon onset. This lag, and the low correlation between eolian grain size and eolian flux (r=0.36), likely result from the differential sinking rates of large and small dust particles in the surface waters as well as biological scavenging associated with monsoon-induced productivity.

Una cuestión de patrones y clientes. Acerca de la organización social y el poder político en la antigua palestina

Durante las últimas tres décadas, los métodos de la investigación histórica de las sociedades de la antigua Palestina han experimentado un considerable progreso desde los días en que la Biblia era tomada como fuente primaria y principal de reconstrucción histórica. Las nuevas perspectivas privilegian el aporte de múltiples disciplinas sociales, entre otras, la antropología, la sociología, la etnografía. En la presente comunicación hacemos uso de la información del registro etnográfico contemporáneo junto con perspectivas de la teoría antropológica para tratar de resolver la cuestión de la organización social de Palestina en la antigüedad así como de la práctica del poder político en las sociedades "tribales" de Medio Oriente. La integración de esta información junto con el análisis de fuentes históricas antiguas nos indica que las relaciones de parentesco y, fundamentalmente, las de patronazgo fueron las prácticas sociopolíticas dominantes en estas sociedades. Como resultado, el predominio de estas prácticas constituyó un obstáculo considerable para la aparición de una práctica estatal indígena en esta región. En consecuencia, una aceptación de la primacía analítica del concepto de "sociedades de patronazgo" por sobre el de "sociedades estatales" o "sociedades de clase" nos puede conducir a un mejor entendimiento de la dinámica sociopolítica en la antigua Palestina.