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Abstract Background Evidence briefs for policy (EBP) draw on best-available data and research evidence (e.g., systematic reviews) to help clarify policy problems, frame options for addressing them, and identify implementation considerations for policymakers in a given context. An increasing number of governments, non-governmental organizations and research groups have been developing EBP on a wide variety of topics. However, the reporting characteristics of EBP vary across organizations due to a lack of internationally accepted standard reporting guidelines. This project aims to develop a STandard reporting guideline of Evidence briefs for Policy (STEP), which will encompass a reporting checklist and a STEP statement and a user manual. Methods We will refer to and adapt the methods recommended by the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network. The key actions include: (1) developing a protocol; (2) establishing an international multidisciplinary STEP working group (consisting of a Coordination Team and a Delphi Panel); (3) generating an initial draft of the potential items for the STEP reporting checklist through a comprehensive review of EBP-related literature and documents; (4) conducting a modified Delphi process to select and refine the reporting checklist; (5) using the STEP to evaluate published policy briefs in different countries; (6) finalizing the checklist; (7) developing the STEP statement and the user manual (8) translating the STEP into different languages; and (9) testing the reliability through real world use. Discussion Our protocol describes the development process for STEP. It will directly address what and how information should be reported in EBP and contribute to improving their quality. The decision-makers, researchers, journal editors, evaluators, and other stakeholders who support evidence-informed policymaking through the use of mechanisms like EBP will benefit from the STEP. Registration We registered the protocol on the EQUATOR network. ( https://www.equator-network.org/library/reporting-guidelines-under-development/#84 )

In response to the climate change, it is essential to provide smallholder farmers with improved field crop genotypes that may increase the resilience of their farming system. This requires a fast turnover of varieties in a system capable of injecting significant amounts of genetic diversity into productive landscapes. Crop improvement is a pivotal strategy to cope with and adapt to climate change. Modern breeding may rely on the genomics revolution to speed up the development of new varieties with adaptive potential. However, centralized breeding may not adequately address smallholder farmers’ needs for more locally acclimatized varieties or groups of varieties. This, in turn, constrains adoption of new varieties that reduces the effectiveness of a resource-intensive breeding process, an issue that may be overcome with participatory, decentralized approaches. Whether high-tech centralized breeding or decentralized participatory approaches are better suited for smallholder farmers in the global South is hotly debated. Sidestepping any false dichotomies and ideological issues in these debates, this review provides a perspective on relevant advances in a breeding approach that combines the two approaches and uses genomics for trait mining from ex situ collections of genetic materials, participatory multilocation trials and crowdsourced citizen science. It argues that this new combination of high-tech centralized and participatory decentralized methods can provide a coherent and effective approach to breeding for climate adaptation and the present review advocates on a different way forward for the future research.

Abstract Smallholder farming communities face highly variable climatic conditions that threaten locally adapted, low-input agriculture. The benefits of modern crop breeding may fail to reach their fields when broadly adapted genetic materials do not address local requirements. To date, participatory methods only scratched the surface of the exploitability of farmers’ traditional knowledge in breeding. In this study, 30 smallholder farmers in each of two locations in Ethiopia provided quantitative evaluations of earliness, spike morphology, tillering capacity and overall quality on 400 wheat genotypes, mostly traditional varieties, yielding altogether 192,000 data points. Metric measurements of ten agronomic traits were simultaneously collected, allowing to systematically break down farmers’ preferences on quantitative phenotypes. Results showed that the relative importance of wheat traits differed by gender and location. Farmer traits were variously contributed by metric traits, and could only partially be explained by them. Eventually, farmer trait values were used to produce a ranking of the 400 wheat varieties identifying the trait combinations most desired by farmers. The study scale and methods lead to a better understanding of the quantitative basis of Ethiopian smallholder farmer preference in wheat, broadening the discussion for the future of local, sustainable breeding efforts accommodating farmers’ knowledge.

Septoria tritici blotch (STB) is a devastating fungal disease affecting durum and bread wheat cultivation worldwide. The identification, development, and employment of resistant wheat genetic material is the key to overcoming costs and limitations of fungicide treatments. The search for resistance sources in untapped genetic material may speed up the deployment of STB genetic resistance in the field. Ethiopian durum wheat landraces represent a valuable source of such diversity. In this study, 318 Ethiopian durum wheat genotypes, for the most part traditional landraces, were phenotyped for resistance to different aspects of STB infection. Phenology, yield and yield component traits were concurrently measured the collection. Here we describe the distribution of STB resistance traits in modern varieties and in landraces, and the relation existing between STB resistance and other agronomic traits. STB resistance sources were found in landraces as well as in modern varieties tested, suggesting the presence of alleles of breeding relevance. The genetic material was genotyped with more than 16 thousand genome-wide polymorphic markers to describe the linkage disequilibrium and genetic structure existing within the panel of genotypes, and a genome-wide association (GWA) study was run to allow the identification of genomic loci involved in STB resistance. High diversity and low genetic structure in the panel allowed high efficiency GWA. The GWA scan detected five major putative QTL for STB resistance, only partially overlapping those already reported in the wheat literature. We report four putative loci for Septoria resistance with no match in previous literature: two highly significant ones on Chr 3A and 5A, and two suggestive ones on Chr 4B and 5B. Markers underlying these QTL explained as much as 10% of the phenotypic variance for disease resistance. We found three cases in which putative QTL for agronomic traits overlapped marker trait association deriving from STB GWA. Our results show that the Ethiopian untapped allelic diversity bears a great value in studying the molecular basis of STB resistance and in breeding for resistance in local and international material.

Smallholder agriculture involves millions of farmers worldwide. A methodical utilization of their traditional knowledge in modern breeding efforts may help the production of locally adapted varieties better addressing their needs. In this study, a combination of participatory approaches, genomics, and quantitative genetics is used to trace the genetic basis of smallholder farmer preferences of durum wheat traits. Two smallholder communities evaluated 400 Ethiopian wheat varieties, mostly landraces, for traits of local interest in two locations in the Ethiopian highlands. For each wheat variety, farmers provided quantitative evaluations of their preference for flowering time, spike morphology, tillering capacity, and overall quality. Ten agronomic and phenology traits were simultaneously measured on the same varieties, providing the means to compare them with farmer traits. The analysis of farmer traits showed that they were partially influenced by gender and location but were repeatable and heritable, in some cases more than metric traits. The durum wheat varieties were genotyped for more than 80,000 SNP markers, and the resulting data was used in a genome wide association (GWA) study providing the molecular dissection of smallholder farmers' choice criteria. We found 124 putative quantitative trait loci (QTL) controlling farmer traits and 30 putative QTL controlling metric traits. Twenty of such QTL were jointly identified by farmer and metric traits. QTL derived from farmer traits were in some cases dependent on gender and location, but were consistent throughout. The results of the GWA study show that smallholder farmers' traditional knowledge can yield QTL eluding metric measurements of phenotypes. We discuss the potential of including farmer evaluations based on traditional knowledge in crop breeding, arguing for the utilization of this untapped resource to develop better adapted genetic materials for local agriculture.

Several road sections have failed due to volume changes of expansive soils during moisture variation. While there are various common stabilization techniques, the use of agricultural byproducts in stabilization works can minimize costs and environmental effects when compared to ordinary stabilization methods. This paper discusses an experimental approach used to study the influence of lupine hull ash on expansive soil as a subgrade material. The laboratory results show that the expansive soils belong to A-7-5 and CH classes according to AASHTO and USCS, respectively. The expansive soil was mixed with varying concentrations of lupine hull ash, namely, 3%, 6%, 9%, and 12%. The plasticity index and free swell index were reduced by 68.19% and 62.67%, respectively, when treated with a 12% lupine hull ash concentration. The compaction test revealed a decrement of MDD and increment in OMC values as the percentage of the stabilizer material increased. Additionally, the UCS and CBR values increased significantly as the concentration of the expansive soil increased. The mineralogical analysis showed that the untreated soil is composed of 46.2% silica, 28.7% montmorillonite, and 25.1% kaolinite minerals. The SEM and XRD analysis proved the microstructural and mineralogical changes when the expansive soil is mixed with the optimum lupine hull ash concentration. While the CBR value of natural soil is unsuitable for subgrade material, mixing it with a 9% concentration of lupine hull ash ensures that the expansive soil complies with the standard as subgrade material. The experimental findings of this study emphasize the suitability of lupine hull ash for treating expansive soil encountered in rural road construction works.

Though engaging communities in research processes has several advantages and implications, research efforts are poorly embedded in and linked with communities, especially in low- and middle-income countries (LMICs). There is also a need for more empirical evidence on effectively engaging communities in research in LMICs, specifically in Sub-Saharan Africa (SSA). Thus, there is an urgent need to synthesize existing evidence on community engagement experiences in research in SSA. Therefore, this review aimed to synthesize the existing community engagement experiences and related barriers to engaging communities in health research focusing on infectious diseases of poverty in SSA. The systematic review was conducted following the JBI methodology for qualitative systematic reviews. The review included both published and unpublished studies. A thematic analysis approach was used for data synthesis. A total of 40 studies were included in the review. Community engagement in the conceptualization of the research project, analysis, dissemination, and interpretation of the result was rare. On top of this, almost all the research projects engaged the community at a lower level of engagement (i.e., informing or consulting the community at some point in the research process), suggesting the importance of integrating communities in the entire research cycle. The lack of shared control over the research by the community was one of the significant challenges mentioned. This review uncovered that community engagement in the research process is minimal. Nevertheless, the review generated valuable evidence that can inform researchers and research stakeholders to promote effective community engagement in the research process addressing infectious diseases of poverty. Despite these, it requires rigorous primary studies to examine the applicability and usefulness of community engagement, including developing valid metrics of engagement, standardizations of reporting community engagements, and views and understandings of communities and stakeholders on the values, expectations, and concepts of community engagement in research.

AbstractEfficient conservation and subsequent utilization of genetic resources are primarily dependent on the strength in the assessment of variation among genotypes. An experiment was carried out aiming at determining the extent of phenotypic variability present in a panel of 320 barley genotypes and identifying candidate lines for further evaluation in improvement programs and successive utilization. It was conducted at two locations in Ethiopia, Aris Negelle and Holetta in the 2017/18 and 2018/19 cropping seasons. Among the best 30 lines for grain yield across all the environments, lines from farmers’ varieties constitute 73% and lines that mature in less than 85 days were identified. Based on the spike row number, the best-performing lines combined across all the environments were six-rowed types. Based on the two years’ data at Arsi Negelle the two-rowed spike type dominates, and at Holetta the six-rowed type. After principal component analysis, the first three PCs with an eigenvalue greater than one explained 70% of the variation. The correlation coefficient between grain and biomass yield was significant and though low (r = 0.38***). Significant, high, and negative correlation coefficient (−0.72***) was observed between 1000 kernel weight and the number of seeds per spike. A positive correlation between biomass and grain yield attracts farmers as a feed and food crop as it has also been signified in the current research. Having the improved barley gene pool largely from international sources, combining the improved materials with farmers’ varieties may minimize the existing gap between the local and improved barley gene pool.

Abstract Background The serum lipid and immunohematological values of tuberculosis lymphadenitis (TBLN) patients is poorly documented relative to pulmonary tuberculosis (PTB) cases. Therefore, the aim of this study was to investigate the serum lipid and immunohematological values of patients with TBLN in comparison with PTB (PTB) patients. Methods An institution-based comparative cross-sectional study was conducted in Northwest Ethiopia from March to December 2021. The study participants were bacteriologically confirmed PTB (n = 82) and TBLN (n = 94) cases with no known comorbidity and whose ages was greater than 18 years and with no current pregnancy. Independent sample t-test, one-way ANOVA, box plot, and correlation matrix were used to analyze the data. Results The body mass index (BMI), CD4 + T cell count, and high-density lipoprotein-Cholesterol (HDL-C) values were significantly higher among TBLN cases compared with PTB cases. Additionally, the total white blood cell (WBC) count, hemoglobin (Hb), total Cholesterol (CHO) and creatinine (Cr) values were relatively higher among TBLN than PTB (P > 0.05). On the reverse, the platelet count and triacylglycerol (TAG) values were relatively higher among PTB than in TBLN cases. While the mean days of culture positivity were 11.6 days for TBLN, the mean days of culture positivity were 14.0 days for PTB. Anemia and serum lipid values showed no correlation with sputum bacilli load and time to culture positivity. Conclusion Tuberculous lymphadenitis patients were well-endowed with serum lipid, immunological and nutritional status compared with PTB cases. Hence, the high incidence rate of TBLN in Ethiopia could not be explained by low peripheral immunohematological values, malnutrition, Anemia, and dyslipidemia. Further study for identifying the predictors for TBLN in Ethiopia is highly desirable.

Aim and Background: Women with marital conflict have less resilience in their lives, for this reason, the present study was conducted to determine the effectiveness of the therapeutic package of originality in the three worlds based on Rollo May existential theory on the resilience of women with marital conflict. Methods and Materials: The current research method was quantitative and of the type of quasi-experimental studies and pre-test and post-test design with a control group and a two-month follow-up period. The statistical population of this study included women who refer to the psychological clinics of Isfahan city, from which 26 were selected by convenience sampling method and randomly placed in two experimental and control groups. Resilience questionnaires were used to collect information. The experimental group received the therapeutic package during 14 sessions of 75 minutes, and the control group did not receive any intervention during this period. Data analysis was done with spss-24 software and with the statistical method of analysis of variance with repeated measures and chi-square test at the level of 0.05. Findings: Based on the chi-square test, no significant difference was observed in terms of age, education, and job between the two groups (P

microRNAs (miRNAs) are small non-coding RNAs (sncRNAs) that play an important role in the life cycle of human viruses. We sought to characterize human immunodeficiency virus 1 (HIV-1)-encoded miRNAs and determine their role in viral replication. Initially, a bioinformatic analysis was used to predict HIV-1-encoded miRNAs. Next, a representative number of these predicted sequences were verified using a miRNA microarray chip, reverse transcription PCR (RT-PCR), and the deep sequencing of RNA extracted from HIV-1-infected cells. Eight HIV-1-encoded sncRNA sequences conforming to the criteria that define miRNAs were identified in HIV-1-infected immortalized T cells and human primary CD4+ lymphocytes; five of the eight sequences have not been previously reported. Deep sequencing validated the presence of these virus-encoded miRNA sequences and uncovered large numbers of atypical sncRNA sequences, lacking characteristics of conventional miRNAs. We named these sequences small RNAs (smRNAs). The overexpression of four candidate HIV-1-encoded miRNAs and silencing of two smRNAs significantly increased HIV-1 viral replication. Our study uncovered novel HIV-1-encoded sncRNAs that, upon deregulated expression, alter viral titers in HIV-1-infected cells, suggesting that miRNAs and smRNAs play an important role in regulating viral replication. Future studies may reveal the function of HIV-1-encoded sncRNAs and their possible implications for diagnosis and treatment.

The vegetative coverage throughout the world is rapidly changing, which also directly affects the land degradation. Therefore, this study was intended to investigate the vegetation vulnerability analysis triggered by land use/land cover (LULC) dynamics as an indicator of land degradation conditions using Remote Sensing and GIS in Guna-tana watershed. Trend studies and cross-sectional research design was employed, which produces data from the population at a particular point in time and to examine patterns of change with a mixed research approach to examine the degree of influence to measure the sensitivity analysis. A multi-criteria decision evaluation was used to create a vegetation vulnerability map for the research area. The vulnerability model was run using four sets of parameters: closeness to the road, slope, settlement closeness, and land use planning. Landsat imageries of 1995 and 2020 was used to conduct a comparative study of land use pattern. The study area has experienced a sequence of land degradation from 1995 to 2020, according to the results of multitemporal data. Agricultural and built-up lands have increased throughout this time, while forest and shrub land has decreased. The vegetation vulnerability of the area also shows that 19.23% extreme vulnerable and 67.03% very strongly vulnerable which is more than 80% of the area is highly vulnerable to vegetation. Vegetation suitability and land management evaluation is critical for determining the risk of land deterioration, that shows the adverse effects on ecological elements due to a decrease in metabolic capacity and patch disintegration processes.

Abstract This study provides one of the earliest examples of fruit tree cultivation worldwide, demonstrating that olive (Olea europaea) and fig (Ficus carica) horticulture was practiced as early as 7000 years ago in the Central Jordan Valley, Israel. It is based on the anatomical identification of a charcoal assemblage recovered from the Chalcolithic (7200–6700 cal. BP) site of Tel Tsaf. Given the site’s location outside the wild olive’s natural habitat, the substantial presence of charred olive wood remains at the site constitutes a strong case for horticulture. Furthermore, the occurrence of young charred fig branches (most probably from pruning) may indicate that figs were cultivated too. One such branch was 14C dated, yielding an age of ca. 7000 cal. BP. We hypothesize that established horticulture contributed to more elaborate social contracts and institutions since olive oil, table olives, and dry figs were highly suitable for long-distance trade and taxation.

Robotic Process Automation (RPA) adalah teknologi yang diyakini akan terus berkembang karena banyak memberikan manfaat terutama dalam membantu mengerjakan pekerjaan yang sifatnya berulang-ulang dan jumlah besar. Tulisan ini berisi tentang penelitian penggunaan perangkat lunak RPA dalam melakukan input data pada proses rekrutmen mahasiswa magang di PT. Telkom Indonesia. Proses rekrutmen ini ada 2 langkah proses yang dilakukan yaitu proses seleksi administrasi dan proses seleksi wawancara sehingga perlu dibuatkan sebuah bot RPA untuk mengotomatisasi masing-masing proses tersebut. Perangkat lunak RPA yang digunakan adalah perangkat lunak RPA yang dikembangkan oleh PT. Telkom Indonesia berbasis platform Open RPA. Penelitian dilakukan di laboratorium dan di lapangan melalui implementasi RPA secara langsung untuk proses rekrutmen mahasiswa magang. Penelitian di laboratorium untuk melihat perbandingan kecepatan proses dan akurasi antara proses menggunakan RPA dan dengan cara manual. Penelitian di lapangan untuk melihat sejauh mana keberhasilan menggunakan RPA dalam membantu proses rekrutmen mahasiswa magang serta mengetahui pendapat dari pegawai sebagai pengguna RPA. Penelitian di laboratorium menggunakan data simulasi sebanyak 40 sampel data, baik untuk proses seleksi administrasi maupun proses seleksi wawancara, Dari hasil percobaan dapat dilaporkan bahwa dengan menggunakan RPA dapat menghemat waktu sampai dengan 76% dan akurasi sebesar100%. Sementara itu untuk implementasi di lapangan, jumlah sampel data yang diproses sebanyak 1204 data untuk proses seleksi administrasi dan sebanyak 303 data untuk proses seleksi wawancara. Dari hasil implementasi RPA di lapangan, pegawai merasa sangat terbantu dan senang dengan keberadaan RPA Abstract Robotic Pocess Automation (RPA) is a technology that is believed to continue to grow because it provides many benefits, especially in helping to do repetitive and large amounts of work. This paper contains research on the use of RPA software in inputting data in the recruitment process of internship students at PT. Telkom Indonesia. This recruitment process has two processes, that are the administrative selection process and the interview selection process, so it is necessary to build an RPA bot to automate each of these processes. The RPA software used is the RPA software developed by PT. Telkom Indonesia is based on the Open RPA platform. Research is carried out in the laboratory and in the field through direct implementation of RPA for the recruitment process of internship students. Research in the laboratory to see the comparison of process speed and accuracy between processes using RPA and the manual method. Research in the field to see the extent to which the success of using RPA in helping the recruitment process of internship students and knowing the opinions of employees as users of RPA. Research in the laboratory using simulation data as much as 40 data samples, both for the administrative selection process and the interview selection process. From the experimental results it can be reported that using RPA can save time up to 76% and accuracy is 100%. Meanwhile, for implementation in the field, the number of data samples processed was 1204 data for the administrative selection process and 303 data for the interview selection process. From the results of the implementation of RPA in the field, employees feel very helpful and happy with the existence of RPA.

de Sousa et al. present a data-driven decentralized crop breeding approach called 3D-breeding that is geared toward improving yields for smallholder farmers. 3D-breeding is applied to a case study of durum wheat in Ethiopia, which demonstrates higher prediction accuracies for grain yield than the existing model.

Abstract Background Septoria tritici blotch (STB) (Zymoseptoria tritici) is a major disease of durum wheat, an economic crop grown in the highlands of Wollo in Ethiopia. Methods To determine the status of this disease, we conducted surveys in five districts of Wollo (Meket, Woreilu, Wadila, Jama, and Dessie Zuria) during the 2015 cropping season. We visited 75 farm plots to determine the prevalence, incidence, and severity of STB. Results STB prevalence varied among locations, genotypes, planting dates, growth stages, previous crops, plant population, weed population, and soil types. Similarly, disease intensity also varied along all independent variables. The level of incidence was high in all the visited districts, and the level severity ranged from 9.9 to 59.3% while the incidence varied from 50 to 100%. The mean differences in incidence and severity within the districts’ variable classes, altitude, varieties, growth stage, plant population, planting date, previous crop, weed population, and soil type were high. The independent variables, districts, altitude, varieties, growth stage, plant population, planting date, previous crops, weed population, and soil type, were significantly associated with high incidence and severity of STB as single predictor in the logistic regression model. A reduced multiple variable model was fitted using districts, altitude, varieties, growth stage, plant population, planting date, previous crop, weed population, and soil type as independent variables. High incidence (> 50%) and severity (> 25%) had a high probability of association to all independent variables, except previous crop. Low disease incidence (≤ 50%) and low disease severity (≤ 25%) had high probability of association to the previous crop. Conclusion Environmental variables, cultivation practice, and responses were important for the development of STB. Therefore, these factors must be considered in designing strategies for the effective management of STB.

Mandibuloacral dysplasias (MADs) are rare progeroid syndromes characterized by nuclear morphological and functional abnormalities. Here the authors report that loss of mitochondrial membrane protein MTX2 causes a progeroid MAD sharing clinical features with lamin-associated progeroid syndromes.

AbstractThe Ethiopian health system faces persistent inequities in health-care utilization and outcomes, despite continued efforts to expand health service coverage. There is little evidence in the literature describing the status of equity in the quality of healthcare. This paper aims to understand the disparities in quality of antenatal care (ANC) and family planning (FP) among the poor and non-poor communities. We used the 2016 Ethiopia Demographic and Health Survey (DHS) data to compute a Multidimensional Poverty Index (MPI), and the 2014 Service Provision Assessment (SPA) data to assess quality of ANC and FP services—defined as the level of adherence to World Health Organization (WHO) clinical and service guidelines. We merged the two datasets using geographical coordinates, and aggregated service users into facility catchment area clusters using a 2-km radius for urban and 10-km radius for rural facilities. We computed ANC and FP quality and MPI indices for each facility and assigned these to catchment areas. Using the international cutoff point for deprivation (MPI = 33.3%), we evaluated whether the quality of ANC and FP services varies by poor and non-poor catchment areas. We found that most of catchment areas (75.7%) were deprived. While the overall quality of ANC and FP services are low (33% and 34% respectively), we found little variation in the distribution of the quality of these services between poor and non-poor areas, urban and rural settings, or regionally. The short-term focus needs to be on improving the overall quality of services rather than on its distribution.

Titanium alloys have good biocompatibility and good mechanical properties, making them particularly suitable for dental and orthopedic implants. Improving their osseointegration with human bones is one of the most essential tasks. This can be achieved by developing hydroxyapatite (HA) on the treating surface using the plasma electrolytic oxidation (PEO) method in molten salt. In this study, a coating of titanium oxide-containing HA nanoparticles was formed on Ti-6Al-7Nb alloy by PEO in molten salt. Then, samples were subjected to hydrothermal treatment (HTT) to form HA crystals sized 0.5 to 1 μm. The effect of the current and voltage frequency for the creation of the coating on the morphology, chemical, and phase composition was studied. The anti-corrosion properties of the samples were studied using the potentiodynamic polarization test (PPT) and electrochemical impedance spectroscopy (EIS). An assessment of the morphology of the sample formed at a frequency of 100 Hz shows that the structure of this coating has a uniform submicron porosity, and its surface shows high hydrophilicity and anti-corrosion properties (4.90 × 106 Ohm·cm2). In this work, for the first time, the process of formation of a bioactive coating consisting of titanium oxides and HA was studied by the PEO method in molten salts.

Statement of the Problem: Quercetin is a pharmacological flavonoid that can inhibit high mobility group box1 (HMGB1) protein, a non-histone nuclear protein that is implicated in inflammation. Th17 cells are important cells in the pathogenesis of inflammation. Pulpitis is the inflammation of dental pulp, which usually is accompanied by pain. Quercetin may alleviate this inflammation. Purpose: The current study aimed to compare blocking of HMGB1 function and stimulation of HMGB1 function with quercetin and investigate the effects of the blockage on T helper 17 (Th17) cells and mitogen-activated protein kinase Toll-like receptor 4 (MAPK-TLR4) signaling pathway. Materials and Method: T cells isolated from the pulp involved with pulpitis and the normal pulp were cultured. The cells suspensions were plated in 6-wells culture plates and stimulated with 0.5 µg/ml of HMGB1 for 2, 4, 8, and 12 hours. For blocking TLR4, 10 µg/ml rabbit anti-human TLR4 antibody was added 1 hour before treatment with HMGB1. Results: The level of these cytokines decreased; moreover, western blot data showed that quercetin could decrease MAPK signaling pathway by means of inhibition of HMGB1 on T cells. The results showed the reduction of TLR4 pathway and Th17 cell polarization. Conclusion: Our results indicated that the levels of IL-17, IL-33, and IL-6 in supernatants from patients’ cultured T cells were increased after stimulation with HMGB-1 following employing quercetin. It also could inhibit MAPK signaling pathway, which subsequently could decrease Th17 production and IL-17. Quercetin could decrease pro-inflammatory cytokines and IL-17 production.

The interfacial electrochemical characteristics of unpassivated Mg metal electrodes have been studied using Staircase Galvano Electrochemical Impedance Spectroscopy (SGEIS) in THF/C6H5MgCl/AlCl3 solutions over a wide range of applied dc currents. The results shed light on the mechanism of electrochemical deposition and dissolution of Mg. We found that at the stationary condition (at the OCV, when no current flows) there is a very high interfacial charge-transfer resistance of around 40,000 Ωcm2. The impedance decreases to several hundred Ωcm2 when dynamic, though steady, processes of Mg deposition or dissolution take place. The alternating process through which impedance spectroscopy is measured is superimposed on this system. We show that the high impedance measured at the OCV with a low direct current is due to interfacial adsorption phenomena. However, the adsorption phenomena affect the interfacial charge transfer in different ways depending on the direction of the reaction. During steady-state deposition, the adsorbed layer leads to a large distance for electron tunneling, which translates to a high charge-transfer impedance across the interface. Application of relatively large steady-state negative currents leads to changes in the composition of the adsorbed layer and a significant reduction in the charge-transfer resistance. During the opposite process, dissolution, the high interfacial impedance measured is probably predominantly due to migration of Mg ions away from the Mg metal surface, across the adsorbed layer, to the bulk solution. At relatively high direct currents (and overpotentials >100 mV) the interfacial resistivity obeys Butler–Volmer kinetics, which are not complicated by adsorption phenomena.

In the present study, the diversity of medicinal plants (MPs) and associated traditional knowledge of rural community herbalists to treat human and animals’ diseases were assessed in two districts in the Tigray Region, Ethiopia. Study participants were randomly selected for survey and focus group discussions, while key informant traditional healers were identified through snowball/chain-referral sampling. The informant consensus factor (FIC) by ailment category and fidelity level (FL) for some MPs were determined. About 97 MP species were identified. Leaves, roots, and seeds are the parts predominantly used for phytomedication preparation to treat 30 human and 5 animal diseases. Diseases, such as epilepsy, arthritis, otitis media, and fever, are treated with a combination of 2–4 MPs. The FIC value ranged from 0.29–1.00, with most human diseases showing an FIC value of above 0.7. The FL value for the MPs ranged from 53–100%, with plants used to treat more than one disease tending to have lower FL values. Higher values of FIC and FL indicate high levels of traditional knowledge used to identify and administer medicinal preparations. Despite the frequent use of MPs, the four-cell analysis showed that most of them risk extinction due anthropogenic and climate factors. We recommend botanical gardens as a solution to sustainable conservation, study, education and a source for these declining MP species.

Modeling the simple assembly line balancing (SALB) problem has covered a wide range of real-world applications. The recent advances in optimization problems have created the opportunities to tackle more challenging problems. This paper presents a multi-objective decision making problem to consider two objectives, cost and cycle time, for simple assembly line balancing. The problem is formulated as a mixed integer nonlinear optimization and the proposed study of this paper uses two metaheuristics to solve the resulted problem on some benchmark problems. The preliminary results have indicated that multi objective particle swarm optimization (MOPSO) has provided better quality solutions while the hybrid method based on MOPSO and simulated annealing has yielded more non-dominated Pareto solutions.

Our goal in this study was to behaviorally characterize the property (or properties) that render negative quantifiers more complex in processing compared to their positive counterparts (e.g. the pair few/many). We examined two sources: (i) negative polarity; (ii) entailment reversal (aka downward monotonicity). While negative polarity can be found in other pairs in language such as dimensional adjectives (e.g. the pair small/large), only in quantifiers does negative polarity also reverse the entailment pattern of the sentence. By comparing the processing traits of negative quantifiers with those of non-monotone expressions that contain negative adjectives, using a verification task and measuring reaction times, we found that negative polarity is cognitively costly, but in downward monotone quantifiers it is even more so. We therefore conclude that both negative polarity and downward monotonicity contribute to the processing complexity of negative quantifiers.

One of the important aspects of human life in urban areas is the problem of leisure time and how to spend it. Leisure spaces in cities are the most important functional areas where a person turns in his spare time in order to escape the tensions of urban life.Shahinshahr is one of the cities that its recreational and leisure spaces do not have proper conditions to meet the needs of citizens. The aim of this study is to examine the condition and vulnerability of cultural- recreational centers and the places of leisure that the municipality of Shahinshahr city created to meet the cultural and recreational needs of the citizens. The research method is descriptive – analytical and its purpose is practical. Data collection is based on survey (field study), and document. Target population includes Shahinshahr citizens. Sample size of study is 383 subjects according to Cochran formula and Cronbach's alpha values of the questionnaire for reliability is %86. Analyzing citizens’ questionnaires is done through SPSS software and the relationship between citizens’ satisfaction of cultural - recreational centers and their demographic characteristics were identified by Pearson and Spearman tests. Moreover, these centers were evaluated in terms of meeting to citizens' leisure time requirements. The results showed that cultural - recreational centers allocated to women, ranked 6th in Friedman test in terms of meeting the citizens’ leisure time needs, face more difficulties and shortages. The status of women’s cultural - recreational centers was lower than the expected by the society with the average of 2.890 (statistical value of -3.051, and significance level of 0.002).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Parokhet, or sacred curtain, was an important item of cultic paraphernalia in the ancient Near East. It is known from the Sumerian and Akkadian texts, the biblical tradition, the Second Temple in Jerusalem, Greek temples, and synagogues of the Roman and Byzantine eras, and is still in use today. We suggest that such a sacred curtain is depicted on several of the miniature clay objects known as portable shrines. In Egypt, thanks to the dry climate, a miniature curtain of this kind has indeed been preserved in association with a portable shrine. Depictions of shrines on Egyptian sacred barks also include life-size curtains.

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity.

América Central ha sufrido el impacto de diversos eventos hidrometeorológicos extremos, dentro de los cuales se destaca la sequía. Esta ha tenido efectos adversos de distinta índole en la región denominada como el Corredor Seco Centroamericano (CSC). El objetivo de este trabajo fue describir los impactos que han sufrido la agricultura, la ganadería y la economía de los países del CSC debidos a las sequías: agrícola, hidrológica y socioeconómica. Se realizó una revisión a partir de fuentes primarias y secundarias como artículos científicos, reportes de prensa y reportes de estudios de instituciones estatales e internacionales. Los impactos más recurrentes se dan a nivel de granos básicos y ganado vacuno, debidos también en parte al fenómeno del ENOS (El Niño-Oscilación del Sur). Debido a que el CSC es una región con alta vulnerabilidad a la sequía y a otros eventos hidrometeorológicos extremos, es necesario realizar una caracterización adecuada del CSC tomando como línea de base estudios similares a este, que originen un proceso de discusión para el diseño y la implementación de estrategias y políticas públicas anticipadas de adaptación y mitigación de la sequía en el CSC y por ende, conduzca a mejorar la calidad de vida de su población.

Ecological destinations are one of the manifestations of tourists interests to regions with the aim of spending their leisure time with nature are often set up in different areas. This study is conducted with the aim to investigate the role of ecological destinations in the development of sustainable tourism of Hanza region. This is a practical study and the method used is descriptive- analytical. The target population consist of people living in Hanza (four towns and villages with the population of 897 households). A total of 270 questionnaires (household) using Cochran formula were chosen as samples .The Cronbach's alpha was calculated for 0.87 reliability questionnaire. The Data collected in GIS software and SPSS were analyzed using single sample T- test, F (ANOVA) and Waller-Duncan Test. The results indicated that setting up the ecological destinations have effects on economical, social, environmental and physical consequences. The positive effects of ecological destinations in the study area (with mean 3.13) is moderate and between the areas studied , in terms of ecological destinations effects (except economically) there were significant differences in the 0.95 reliability. The negative effects of ecological destinations in the study area are higher than moderate (with mean 4.3) and among the areas studied in terms of the ecological impacts of the destinations there is a significant difference in the 0.95 reliability.

In this research the relationship between autumn precipitation rate in north west and western region stations of Iran and north Caspian sea teleconnection pattern in a time period of 29 years (1977-2005) have been calculated and analyzed. Results of the Pearson correlation analysis between the Northern Caspian sea pattern (NCP) index and North West and western regions autumn precipitation rates showed that in Positive phase of NCP autumn rainfall is increased from normal limit and in negative phase the rainfall is decreased. A relatively good linking between the northwest and west regions’ fall rainfalls with NCP was calculated. The signficance coefficient was calculated 0.31 for autumn long term mean rainfall of studied stations. The monthly correlation analyzes calculated indicated the highest correlation between monthly rainfall of stations and the NCP in December with an 0.52 correlation coefficient. Results also showed that Khoy station was affected more from NCP. This study established that In addition to the ENSO, common pattern of the effects on the autumn rainfall was previously approved and new NCP also affected rainfall fluctuations and autumn wet and dry spells occurrences in northwest and west regions of Iran.

Background: Toxoplasma gondii is the most common parasite causing latent cerebral infections in human. It has been shown that some anti-psychotic drugs are able to inhibit the proliferation of the parasite in in vitro study. There is very limited data regarding the inhibitory effect of anti-psychotics on Toxoplasma in in vivo. In this study, we evaluated anti-Toxoplasma activity of fluphenazine and thioridazine drugs on T. gondii in mice. Methods: Mice were divided into six groups: Control, sesame as vehicle, thioridazine 10 mg/kg, thioridazine 20 mg/kg, fluphenazine 0.06 mg/kg and fluphenazine 0.6 mg/kg. They were inoculated intraperitoneally with brain suspension containing tissue cysts of T. gondii Tehran strain. Two months after inoculation, the number of cysts in crushed smears of mice brain were counted microscopically and considered as an indicator of anti-Toxoplasma activity. This work has conducted in Qazvin, central Iran, 2014. Results: Our study showed that fluphenazine and thioridazine could not significantly inhibit the brain cystogenesis of T. gondii in mice. However, the number of brain cysts was less at higher dose compared to lower doses for both drugs. Conclusion: Further studies need to clear the mechanism of different structure of anti-psychotic drugs on activity of Toxoplasma.

1 Kings preserves a long and detailed description of the construction of a temple and palace in Jerusalem by King Solomon in the 10th century BCE. Previous generations of scholars accepted this description as an authentic account. Accordingly, much literature on this text and the relevant archeological discoveries has accumulated. Since the 1980s, skeptical approaches to the early part of the Kingdom of Judah, the biblical text, and the archaeological record have been expressed. Some scholars doubt whether any temple at all was constructed in Jerusalem in the 10th century BCE. In the last few years, the picture has been changed by new discoveries from two Judean sites: a building model of the early 10th century BCE from Khirbet Qeiyafa and an actual temple building of the 9th century BCE from Motza. In this article, we present the history of research, some aspects of the biblical text and the contribution of the new discoveries. These enable us to place in context both the biblical text and the building it describes.

In this Survey, the climatic comfort conditions of Tabriz megalopolis have been examined with regard to the thermal sense of people. The evaluation of the thermal conditions has been made based on the calculations which are based on the human energy balance, and has been made for recognizing lack of comfort against the hot or cold weather for the people walking outdoors with suitable clothing. Hot and cold hours are defined depending on the extent and duration of thermal discomfort against the cold and warm conditions.Major methods used in this study are American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) standard 55-2004 Predicted Mean Vote (PMV) method and it's put out to Givoni psychometric diagram. This is possible using hourly data for analyzing of monthly, seasonal and total 44 yearly (1961-2004) study period. Achieved results shows that maximum hourly rate of climatic comfort centralizations located in August, July and September months and minimum hourly rate of climatic comfort is in November, December, January, February and March months. From consecutive Distribution of months of the highest climatic comfort point of view, thermal period of April to October to have highest rates of hourly climatic comfort and while November to March period have not climatic comfort hours. From the view point of seasonal distribution of climatic comfort hours, summer with total mean of 989 hours and 64 percent seasonal distribution has allocated itself the most climatic comfort hours of Tabriz, after that, spring with 437 hours has 28 percent of seasonal distribution of hourly climatic comfort. Autumn with 123 hours and 8 percent of the seasonal distribution of hourly climatic comfort is located in next Place and winter has no role in seasonal distribution of hourly climatic comfort in Tabriz and total hours of winter season of Tabriz are discomfort hours. The total mean of climatic comfort hours of Tabriz in Statistical period shows 1549 hours from total 8760 hours that it shows 17.7 percent relation of climatic comfort hours to climatic discomfort hours in Tabriz. This means that in 82.3 percent of cases, for Creating balanced climate with human physiological conditions, energy shall be consumed, which in addition to the Expense, requires professional issues.

Gelian anticline is located at south of Shirvan in North Khorasan Province, and geologically considered as a is part of Aladagh-Binaloud construction zone. The aim of this research is to evaluate the active tectonics of Gelian anticline based on geo-morphological indices. The purpose of this study is evaluating the active tectonics of Gelian anticline by using geo-morphologic indices. For achieving the above said objective, the required data were extracted from 1/100000 geological map and 1/50000 topographic maps as well as from Quickbird satellite images. Also, the field studies of Geo-morphological landforms and processes were made. Required data for calculation of ” K indices, triangular facets, wine-glass valleys, mountain front sinuosity, and stream spacing ratio(R) were extracted after importing into ILWIS (Integrated Land and Water Information System) software and the under study anticline was divided into 3 tectonic zones based on height, width and slope. Results of this study reveal that the rates of K, W (maximum width of wine-glass valley divided by width of wine-glass valley in outlet), R, slope, base length and area of triangular facets in zone 1 are higher than those of other zones. The values of mountain front sinuosity in 3 zones are about one. Generally, the evaluation of geo-morphological indices represent firstly, that Gelian anticline is tectonically active and secondly, that the rate of tectonic activity increases from southeast to northwest.

The pedestalled bowls described here are part of the ground stone tool assemblage discovered during the Hebrew University of Jerusalem excavations at Tel Tsaf (2004-2007). This site, located in the Central Jordan Valley, is the first well-documented and large-scale excavation of the Middle Chalcolithic period in the southern Levant. The inhabitants used two types of raw materials for their stone items: basalt and limestone. While the first is commonly used in the stone-vessel industry of the Chalcolithic period, the second is rarer. We present here the preliminary results of our analysis of the typology and function of the pedestalled bowls, a small but important component of the local ground stone tool assemblage.

The present study has been conducted in a 90 degrees sharp bend to investigate the effect of bank roughness on flow patterns. Tests conducted under two different flow conditions, with Froude numbers equal to 0.17 and 0.4 and two different roughness sizes of 0.5 and 5.0 mm. In each test three components of flow velocity at 576 point were measured. Plot of flow velocity vectors and stream lines were done by SURFER and TECPLOT softwares. The results show that the region of maximum flow at the beginning of bend occurs at the inner bank then gradually shifted toward the outer bank at the end of bend. Comparison of flow patterns in two different roughnesses shows that by increasing the roughness height, the strength of secondary flow decreases while the number of smaller rotational cells is increased. In general it may be said that in a sharp bend up to cross section of 70, the region of high shear stress is very closed to the inner bank and from that place to the downstream, it shifted to the outer bank. The increases of bank roughness causes that the maximum shear stress is decreases. The location of maximum and minimum shear stress at two roughness of 0.5 and 5.0 mm are at 20 and 90 respectively, their values have been calculated to be 1.47 and 0.54 N/m2 for 0.5 mm roughness and 2.2 and 0.46 N/m2 for 5.0 mm roughness, respectively.

Abstract In this study the data relating to the maximum daily temperatures of Tehran Mehrabad synoptic station during the statistical period of 1951-2010 (60 years) have been analyzed. The regression models along with Mann-Kendal statistic were employed for detecting the significance of trend in temperature series. Considering the long-term average high extreme temperatures and compared with the average six decades in the statistical series revealed those three decades of temperature 50, 80 and 90 are below the 60 years long-term average and instead of three decades of 60, 70 and the first decade of the 21st century, temperature changes are higher than from long term average. In this regard the decade 80 is the coldest and the first decade of the 21st century, according to the minimum and the higher range of 60 and 70 decades are the warmest decades of Tehran Mehrabad station. Overall results of this study revealed the existence of seasonal fluctuations in the high extreme temperatures series of Tehran which do not have significant trend. Trend of high extreme temperature changes of Tehran was positive, meaning the increasing the intensity of summer warming. The results of high extreme temperatures forecasting indicated that the high extreme temperatures in Tehran in years 2018 will lift up to the 43.25 degree of centigrade. The results of goodness to fit test proved that the Halt-Winters model is the appropriate model to forecasting of future high extreme temperatures of Tehran

Attenuation and group delay effects on millimeter wave (MMW) propagation in clouds and fog are studied theoretically and verified experimentally using high resolution radar in an indoor space filled with artificial fog. In the theoretical analysis, the frequency-dependent attenuation and group delay were derived via the permittivity of the medium. The results are applied to modify the millimeter-wave propagation model (MPM) and employed to study the effect of fog and cloud on the accuracy of the Frequency-Modulated Continuous-Wave (FMCW) radar operating in millimeter wavelengths. Artificial fog was generated in the experimental study to demonstrate ultra-low visibility in a confined space. The resulted attenuation and group delay were measured using FMCW radar operating at 320–330 GHz. It was found that apart from the attenuation, the incremental group delay caused by the fog also played a role in the accuracy of the radar. The results were compared to the analytical model. It was shown that although the artificial fog has slight different characteristics compare to the natural fog and clouds, in particle composition, size, and density, the model predictions were good, pointing out that the dispersive effects should be considered in the design of remote sensing radars operating in millimeter and sub-millimeter wavelengths.

The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases (‘laminopathies’). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385–646), with no detectable modification of lamin B1, lamin C, or ‘progerin’ (Δ50) tails. Using mass spectrometry, we identified 11 O-GlcNAc sites in a ‘sweet spot’ unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites. By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson–Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622–625 and 639–645) homologous to that in mouse Tet1. These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function. The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.

Carbon dioxide (CO2) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO2 levels remain largely unknown. Here we report that acute CO2 exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO2 avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO2 levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO2 avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO2 levels on animals at the organism-wide level.

The beginning of metallurgy in the ancient Near East attracts much attention. The southern Levant, with the rich assemblage of copper artifacts from the Nahal Mishmar cave and the unique gold rings of the Nahal Qanah cave, is regarded as a main center of early metallurgy during the second half of the 5th millennium CalBC. However, a recently discovered copper awl from a Middle Chalcolithic burial at Tel Tsaf, Jordan Valley, Israel, suggests that cast metal technology was introduced to the region as early as the late 6th millennium CalBC. This paper examines the chemical composition of this item and reviews its context. The results indicate that it was exported from a distant source, probably in the Caucasus, and that the location where it was found is indicative of the social status of the buried individual. This rare finding indicates that metallurgy was first diffused [corrected] to the southern Levant through exchange networks and only centuries later involved local productionThis copper awl, the earliest metal artifact found in the southern Levant, indicates that the elaborate Late Chalcolithic metallurgy developed from a more ancient tradition.

The quantity of PCR products that are simultaneously amplified from two different loci in a duplex amplification (DA) are significantly lower for one of the loci, as compared to identical PCR amplification in separate single-band amplifications (SBA). This difference in amplification probably occurs already after the second cycle of amplification. To further analyze this phenomenon, we tested different reaction conditions, including annealing times, a wide range of temperatures, various quantities of the template, several nucleotide concentrations, different amounts of TaqI DNA Polymerase, number of amplification cycles and various amounts of primers and primers ratio. Changing the ratio between the sets of primers in DA had the most significant effect on the relative levels of amplification of the loci with an optimal ratio of 4:1 in favor of the set of primers used to amplify the underrepresented fragment. The optimal annealing temperatures for the tested sets of primers were identical in SBA and different in DA. Possible reasons for this phenomenon are discussed.

Matefin/SUN-1 is an evolutionary conserved C. elegans inner nuclear membrane SUN-domain protein. By creating a bridge with the KASH-domain protein ZYG-12, it connects the nucleus to cytoplasmic filaments and organelles. Matefin/SUN-1 is expressed in the germline where it undergoes specific phosphorylation at its N-terminal domain, which is required for germline development and homologous chromosome pairing. The maternally deposited matefin/SUN-1 is then essential for embryonic development. Here, we show that in embryos, serine 43 of matefin/SUN-1 (S43) is phosphorylated in a CDK-1 dependent manner and is localized throughout the cell cycle mostly to centrosomes. By generating animals expressing phosphodead S43A and phosphomimetic S43E mutations, we show that phosphorylation of S43 is required to maintain centrosome integrity and function, as well as for the localization of ZYG-12 and lamin. Expression of S43E in early embryos also leads to an increase in chromatin structural changes, decreased progeny and to almost complete embryonic lethality. Down regulation of emerin further increases the occurrence of chromatin organization abnormalities, indicating possible collaborative roles for these proteins that is regulated by S43 phosphorylation. Taken together, these results support a role for phosphorylation of serine 43 in matefin/SUN-1 in mitosis.

Cylindrical objects made usually of fired clay but sometimes of stone were found at the Yarmukian Pottery Neolithic sites of Sha'ar HaGolan and Munhata (first half of the 8(th) millennium BP) in the Jordan Valley. Similar objects have been reported from other Near Eastern Pottery Neolithic sites. Most scholars have interpreted them as cultic objects in the shape of phalli, while others have referred to them in more general terms as "clay pestles," "clay rods," and "cylindrical clay objects." Re-examination of these artifacts leads us to present a new interpretation of their function and to suggest a reconstruction of their technology and mode of use. We suggest that these objects were components of fire drills and consider them the earliest evidence of a complex technology of fire ignition, which incorporates the cylindrical objects in the role of matches.

Elevated CO(2) levels (hypercapnia) occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK) in CO(2) signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO(2) levels rapidly induced activation of JNK leading to downregulation of Na,K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK) and protein kinase C-ζ leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO(2) levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO(2)-induced downregulation of Na,K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO(2) signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO(2) signaling in mammals, diptera and nematodes.

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage - possibly by promoting the reorganization of damaged chromatin.

Indications for dancing activities in prehistoric Europe appeared as early as modern humans, at the start of the Upper Palaeolithic era. However, only limited data are available for this stage. In the Neolithic period, evidence for dancing appeared at many more sites, but the territory is confined to south-eastern Europe. The dancing in this case is probably part of the ‘Neolithic pack- age’, which diffused from the Near East.

The Caenorhabditis elegans inner nuclear envelope protein matefin/SUN-1 plays a conserved, pivotal role in the process of genome haploidization. CHK-2-dependent phosphorylation of SUN-1 regulates homologous chromosome pairing and interhomolog recombination in Caenorhabditis elegans. Using time-lapse microscopy, we characterized the movement of matefin/SUN-1::GFP aggregates (the equivalent of chromosomal attachment plaques) and showed that the dynamics of matefin/SUN-1 aggregates remained unchanged throughout leptonene/zygotene, despite the progression of pairing. Movement of SUN-1 aggregates correlated with chromatin polarization. We also analyzed the requirements for the formation of movement-competent matefin/SUN-1 aggregates in the context of chromosome structure and found that chromosome axes were required to produce wild-type numbers of attachment plaques. Abrogation of synapsis led to a deceleration of SUN-1 aggregate movement. Analysis of matefin/SUN-1 in a double-strand break deficient mutant revealed that repair intermediates influenced matefin/SUN-1 aggregate dynamics. Investigation of movement in meiotic regulator mutants substantiated that proper orchestration of the meiotic program and effective repair of DNA double-strand breaks were necessary for the wild-type behavior of matefin/SUN-1 aggregates.