Involvement of a region of 23S ribosomal RNA of {\it E. coli\/} in decoding of termination codons

Involvement of E. coli 23S ribosomal RNA (rRNA) in decoding of termination codons was first indicated by the characterization of a 23S rRNA mutant that causes UGA-specific nonsense suppression. The work described here was begun to test the hypothesis that more 23S rRNA suppressors of specific nonsense mutations can be isolated and that they would occur non-randomly in the rRNA genes and be clustered in specific, functionally significant regions of rRNA.^ Approximately 2 kilobases of the gene for 23S rRNA were subjected to PCR random mutagenesis and the amplified products screened for suppression of nonsense mutations in trpA. All of the suppressor mutations obtained were located in a thirty-nucleotide part of the GTPase center, a conserved rRNA sequence and structure, and they and others made in that region by site-directed mutagenesis were shown to be UGA-specific in their suppression of termination codon mutations. These results proved the initial hypothesis and demonstrated that a group of nucleotides in this region are involved in decoding of the UGA termination codon. Further, it was shown that limitation of cellular availability or synthesis of L11, a ribosomal protein that binds to the GTPase center rRNA, resulted in suppression of termination codon mutations, suggesting the direct involvement of L11 in termination in vivo.^ Finally, in vivo analysis of certain site-specific mutations made in the GTPase center RNA demonstrated that (a) the G$\cdot$A base pair closing the hexanucleotide hairpin loop was not essential for normal termination, (b) the "U-turn" structure in the 1093 to 1098 hexaloop is critical for normal termination, (c) nucleotides A1095 and A1067, necessary for the binding to ribosomes of thiostrepton, an antibiotic that inhibits polypeptide release factor binding to ribosomes in vitro, are also necessary for normal peptide chain termination in vivo, and (d) involvement of this region of rRNA in termination is determined by some unique subset structure that includes particular nucleotides rather than merely by a general structural feature of the GTPase center.^ This work advances the understanding of peptide chain termination by demonstrating that the GTPase region of 23S rRNA participates in recognition of termination codons, through an associated ribosomal protein and specific conserved nucleotides and structural motifs in its RNA. ^

What Limits Bacterial Production in the Suboxic Region of Permanently Ice-Covered Lake Bonney, Antarctica?

Bacterial production assays (thymidine incorporation rates) were used to evaluate the activity of heterotrophic bacteria at the chemocline region in both the East (ELB) and West (WLB) Lobes of permanently ice-covered Lake Bonney, in the Taylor Valley of Antarctica. The magnitude of activity varied dramatically within the depth interval of 1 to 2 m from moderate to very low levels below the chemocline, especially in the East Lobe, where chemical distributions indicate the absence of a normally functioning nitrogen cycle. Several parameters (e.g. addition of nutrients or chelators, dilution) were manipulated in incubation experiments in order to identify factors that would enhance activity in the suboxic deep waters of the East Lobe. Activity, in terms of thymidine incorporation, was consistently detected in the deep-water communities, implying that, although the water may be 'toxic', the cells remain viable. None of the treatments resulted in consistent enhancement of thymidine incorporation rates in samples from below the chemocline. Bacterial populations above the chemocline appear to be phosphorus-limited. The nature of the limitation, toxicity or inhibition that limits bacterial activity in the suboxic waters has not been identified.

Cloning, sequencing and partial functional characterization of the 5' region of the human p75 tumor necrosis factor receptor-encoding gene (TNF-R)

A 1887-bp region at the 5' flank of the human p75 tumor necrosis factor receptor (p75 TNF-R)-encoding gene was found to be active in driving expression of the luc (luciferase-encoding) reporter gene, suggesting that it contains the promoter for the receptor. Rather unexpectedly, a 1827-bp region at the 3' end of the first intron of the p75 TNF-R gene also displayed promoter activity. This activity may be artefactual, reflecting only the presence of an enhancer in this region; yet it also raises the possibility that p75 TNF-R is controlled by more than one promoter and that it encodes various forms of the receptor, or even other proteins. We present here the nucleotide sequences of the 5' flanking and intron regions. Possible implications for the transcriptional regulation of the p75 TNF-R gene are discussed.

Possible open-system (hydraulic) pingos in and around the Argyre impact region of Mars

We report the observation of possible (hydraulic) open-system pingos (OSPs ) at the mid latitudes (∼37°S) in and around the Argyre impact-basin. OSPs are perennial (water)–ice cored mounds; they originate and evolve in periglacial and pro-glacial landscapes on Earth where intra- or sub-permafrost water under hydraulic/artesian pressure uplifts localised sections of surface or near-surface permafrost that then freezes in-situ. We invoke three lines of evidence in support of our analogue-based interpretation: (1) similarities of shape, size and summit traits between terrestrial OSPs and the Martian mounds; (2) clustered distribution and the slope-side location of the mounds, consistent with terrestrial permafrost-environments where OSPs are found; and, (3) spatially-associated landforms putatively indicative of periglacial and glacial processes on Mars that characterise OSP landscapes on Earth. This article presents five OSP candidate-locations and nests these mound locations within a new geological map of the Argyre impact-basin and margins. It also presents three periglacial hypotheses about the possible origin of the water required to develop the mounds. Alternative (non-periglacial) formation-hypotheses also are considered; however, we show that their robustness is not equal to that of the periglacial ones.

Preconceptional use of folic acid in the region of the Kantonsspital Münsterlingen/Thurgau: has it changed over the past 10 years?

BACKGROUND  Numerous studies have shown that the preconceptional use of folic acid prevents neural tube defects. We created a study to find out whether the preconceptional use of folic acid has improved in the past 10 years, in the area of Münsterlingen, Switzerland. MATERIAL AND METHODS  We interviewed 2 groups of patients who delivered at our Institution, namely between 2000 and 2002 (period A) involving 287 women and from 2009 to 2010 (period B) involving 305 pregnant women. We asked them whether they used folic acid by means of a standardised questionnaire. RESULTS  In period B significantly more women have taken folic acid preconceptionally (period A: 27.5% vs. period B: 40.7%; p=0.001). A significant increase in folic acid intake was seen in the German speaking group from period A to B (30.3% vs. 52.7%; p=0.0005), while this was not the case in the non-German speaking group (21.4% in both periods). More multiparaé women were taking folic acid compared to nulliparae. A significant increase from period A to B was noted only in the German speaking group. Unexpectedly, in nulliparae non-German speaking women, folic acid supplementation decreased from 14% to 6.1%. DISCUSSION  We have found a significant increase in preconceptional folic acid supplementation from 2001 to 2010. The percentage of women taking folic acid is disappointingly low in all groups, particularly in nulliparae women of non-German ethnicity.

Temporal morphological changes in the Imhotep region of comet 67P/Churyumov-Gerasimenko

Aims. We report on the first major temporal morphological changes observed on the surface of the nucleus of comet 67P/Churyumov-Gerasimenko in the smooth terrains of the Imhotep region. Methods. We used images of the OSIRIS cameras onboard Rosetta to follow the temporal changes from 24 May 2015 to 11 July 2015. Results. The morphological changes observed on the surface are visible in the form of roundish features that are growing in size from a given location in a preferential direction at a rate of 5.6-8.1 x 10(-5) m s(-1) during the observational period. The location where the changes started and the contours of the expanding features are bluer than the surroundings, which suggests that ices (H2O and/or CO2) are exposed on the surface. However, sublimation of ices alone is not sufficient to explain the observed expanding features. No significant variations in the dust activity pattern are observed during the period of changes.

THE NATURAL BACKGROUND GAMMA RADIATION EXPOSURE IN THE METROPOLITAN AREA OF THE VALLEY OF MEXICO

Measurements of the natural background radiation have been made at numerous places throughout the world. Very little work in this field has been done in developing countries. In Mexico the natural radiation to which the population is exposed has not been assessed. This dissertation represents a pioneer study in this environmental area. The radiation exposure which occupants within buildings receive as a result of naturally occurring radionuclides present in construction materials is the principal focus.^ Data were collected between August 1979 and November 1980. Continuous monitoring was done with TLDs placed on site for periods of 3 to 6 months. The instrumentation used for "real-time" measurements was a portable NaI (Tl) scintillation detector. In addition, radiometric measurements were performed on construction materials commonly used in Mexican homes.^ Based on TLD readings taken within 75 dwellings, the typical indoor exposure for a resident of the study area is 9.2 (mu)Rh('-1). The average reading of the 152 indoor scintillometer surveys was 9.5 (mu)Rh('-1), the outdoor reading 7.5 (mu)Rh('-1). Results of one-way and multi-way analyses of the exposure data to determine the effect due to building materials type, geologic subsoil, age of dwelling, and elevation are also presented. The results of 152 indoor scintillometer surveys are described. ^

Effects of air pollution on asthma hospitalization rates in different age groups in metropolitan cities of Korea

Many studies have shown relationships between air pollution and the rate of hospital admissions for asthma. A few studies have controlled for age-specific effects by adding separate smoothing functions for each age group. However, it has not yet been reported whether air pollution effects are significantly different for different age groups. This lack of information is the motivation for this study, which tests the hypothesis that air pollution effects on asthmatic hospital admissions are significantly different by age groups. Each air pollutant's effect on asthmatic hospital admissions by age groups was estimated separately. In this study, daily time-series data for hospital admission rates from seven cities in Korea from June 1999 through 2003 were analyzed. The outcome variable, daily hospital admission rates for asthma, was related to five air pollutants which were used as the independent variables, namely particulate matter <10 micrometers (μm) in aerodynamic diameter (PM10), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Meteorological variables were considered as confounders. Admission data were divided into three age groups: children (<15 years of age), adults (ages 15-64), and elderly (≥ 65 years of age). The adult age group was considered to be the reference group for each city. In order to estimate age-specific air pollution effects, the analysis was separated into two stages. In the first stage, Generalized Additive Models (GAMs) with cubic spline for smoothing were applied to estimate the age-city-specific air pollution effects on asthmatic hospital admission rates by city and age group. In the second stage, the Bayesian Hierarchical Model with non-informative prior which has large variance was used to combine city-specific effects by age groups. The hypothesis test showed that the effects of PM10, CO and NO2 were significantly different by age groups. Assuming that the air pollution effect for adults is zero as a reference, age-specific air pollution effects were: -0.00154 (95% confidence interval(CI)= (-0.0030,-0.0001)) for children and 0.00126 (95% CI = (0.0006, 0.0019)) for the elderly for PM 10; -0.0195 (95% CI = (-0.0386,-0.0004)) for children for CO; and 0.00494 (95% CI = (0.0028, 0.0071)) for the elderly for NO2. Relative rates (RRs) were 1.008 (95% CI = (1.000-1.017)) in adults and 1.021 (95% CI = (1.012-1.030)) in the elderly for every 10 μg/m3 increase of PM10 , 1.019 (95% CI = (1.005-1.033)) in adults and 1.022 (95% CI = (1.012-1.033)) in the elderly for every 0.1 part per million (ppm) increase of CO; 1.006 (95%CI = (1.002-1.009)) and 1.019 (95%CI = (1.007-1.032)) in the elderly for every 1 part per billion (ppb) increase of NO2 and SO2, respectively. Asthma hospital admissions were significantly increased for PM10 and CO in adults, and for PM10, CO, NO2 and SO2 in the elderly.^

Bioterrorism preparedness at a hospital level in the Southwest Region of the United States -- A systematic review

Since the tragic events of September, 11 2001 the United States bioterrorism and disaster preparedness has made significant progress; yet, numerous research studies of nationwide hospital emergency response have found alarming shortcomings in surge capacity and training level of health care personnel in responding to bioterrorism incidents. The primary goals of this research were to assess hospital preparedness towards the threat of bioterrorist agents in the Southwest Region of the United States and provide recommendations for its improvement. Since little formal research has been published on the hospital preparedness of Oklahoma, Arizona, Texas and New Mexico, this research study specifically focused on the measurable factors affecting the respective states' resources and level of preparedness, such as funding, surge capacity and preparedness certification status.^ Over 300 citations of peer-reviewed articles and 17 Web sites were reviewed, of which 57 reports met inclusion criteria. The results of the systematic review highlighted key gaps in the existing literature and the key targets for future research, as well as identified strengths and weaknesses of the hospital preparedness in the Southwest states compared to the national average. ^ Based on the conducted research, currently, the Southwest states hospital systems are unable fully meet presidential preparedness mandates for emergency and disaster care: the staffed beds to 1,000 population value fluctuated around 1,5 across the states; funding for the hospital preparedness lags behind hospital costs by millions of dollars; and public health-hospital partnership in bioterrorism preparedness is quite weak as evident in lack of joint exercises and training. However, significant steps towards it are being made, including on-going hospital preparedness certification by the Joint Commission of Health Organization. Variations in preparedness levels among states signify that geographic location might determine a hospital level of bioterrorism preparedness as well, tending to favor bigger states such as Texas.^ Suggested recommendations on improvement of the hospital bioterrorism preparedness are consistent with the existing literature and include establishment and maintenance of solid partnerships between hospitals and public health agencies, conduction of joint exercises and drills for the health care personnel and key partners, improved state and federal funding specific to bioterrorism preparedness objectives, as well as on-going training of the clinical personnel on recognition of the bioterrorism agents.^

Policy analysis of iron micronutrient programs at USAID: The FANTA program in East Africa and the micronutrient initiative in Bihar region of India, using comparative cost effective and cost benefit analysis

It is the aim of this paper to examine iron supplementation programs which receive funding from United States Agency for International Development (USAID) but approach combating iron deficiency anemia in two vastly different ways. A brief literature review and background information on iron deficiencies and the differences between supplementation programs and micronutrient fortification were reviewed. Two non-governmental organizations (NGO's) were examined for this paper: the Food and Nutrition Technical Assistance II (FANTA) and the MicroNutrient Initiative. The FANTA program included an educational component to their supplementation program while the MicroNutrient Initiative solely used supplementation of micronutrients to their population. Methods used were cost-benefit analysis and cost-effectiveness analysis to determine the overall effectiveness of each program in reducing iron deficiency anemia in each population, if the added costs of the incentives in the FANTA program changed the cost-effectiveness of the program compared to the MicroNutrient Initiative program and to determine which program imparted the greatest benefit to each population by reducing the disease burden in Disability Adjusted Life Years (DALY). Results showed that the unit cost of the FANTA program per person was higher than the MicroNutrient Initiative program due to the educational component. The FANTA program reduced iron deficiency anemia less overall but cost less for each percentage point of anemia decreased in their respective populations. The MicroNutrient Initiative program had a better benefit cost ratio for the populations it served. The MicroNutrient Initiative's large scale program imparted many advantages by reducing unit cost per person and decreasing iron deficiency anemia. The FANTA program was more effective at decreasing iron deficiency anemia with less money: $5,660 per 1% decrease in iron deficiency anemia versus $18,450 per 1% decrease in iron deficiency anemia for the MicroNutrient Initiative program. ^ In conclusion, economic analysis cannot measure all of the benefits associated with programs that contain an educational component or large scale supplementation. More information needs to be gathered by NGOs and reported to USAID, such as detailed prevalence rates of iron deficiency anemia among the populations served. Further research is needed to determine the effects an educational supplementation program has on compliance rates of participants and motivation to participate in supplementation programs whose aim is to decrease iron deficiency anemia in a targeted population.^

Commercial Sexual Exploitation and Missing Children in the Coastal Region of Sao Paulo State, Brazil

The commercial sexual exploitation of children (CSEC) has emerged as one of the world’s most heinous crimes. The problem affects millions of children worldwide and no country or community is fully immune from its effects. This paper reports first generation research of the relationship that exists between CSEC and the phenomenon of missing children living in and around the coastal regions of the state of Sao Paulo, Brazil, the country’s richest State. Data are reported from interviews and case records of 64 children and adolescents, who were receiving care through a major youth serving non-governmental organization (NGO) located in the coastal city of Sao Vicente. Also, data about missing children and adolescents were collected from Police Reports – a total of 858 Police Reports. In Brazil, prostitution is not a crime itself, however, the exploitation of prostitution is a crime. Therefore, the police have no information about children or adolescents in this situation, they only have information about the clients and exploiters. Thus, this investigation sought to accomplish two objectives: 1) to establish the relationship between missing and sexual exploited children; and 2) to sensitize police and child-serving authorities in both the governmental and nongovernmental sectors to the nature, extent, and seriousness of many unrecognized cases of CSEC and missing children that come to their attention. The observed results indicated that the missing children police report are significantly underestimated. They do not represent the number of children that run away and/or are involved in commercial sexual exploitation.

Post-transcriptional Regulation of Mammalian Gene Expression in Non-coding Region of Target RNA

Tumor Suppressor Candidate 2 (TUSC2) is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. TUSC2 mRNA transcripts could be detected on Northern blots in both normal lung and some lung cancer cell lines, but no endogenous TUSC2 protein could be detected in a majority of lung cancer cell lines. Mechanisms regulating TUSC2 protein expression and its inactivation in primary lung cancer cells are largely unknown. We investigated the role of the 5’- and 3’-untranslated regions (UTRs) of the TUSC2 gene in the regulation of TUSC2 protein expression. We found that two small upstream open-reading frames (uORFs) in the 5’UTR of TUSC2 could markedly inhibit the translational initiation of TUSC2 protein by interfering with the “scanning” of the ribosome initiation complexes. Site-specific stem-loop array reverse transcription-polymerase chain reaction (SLA-RT-PCR) verified several micoRNAs (miRNAs) targeted at 3’UTR and directed TUSC2 cleavage and degradation. In addition, we used the established let-7-targeted high mobility group A2 (Hmga2) mRNA as a model system to study the mechanism of regulation of target mRNA by miRNAs in mammalian cells under physiological conditions. There have been no evidence of direct link between mRNA downregulation and mRNA cleavages mediated by miRNAs. Here we showed that the endonucleolytic cleavages on mRNAs were initiated by mammalian miRNA in seed pairing style. Let-7 directed cleavage activities among the eight predicted potential target sites have varied efficiency, which are influenced by the positional and the structural contexts in the UTR. The 5’ cleaved RNA fragments were mostly oligouridylated at their 3’-termini and accumulated for delayed 5’–3’ degradation. RNA fragment oligouridylation played important roles in marking RNA fragments for delayed bulk degradation and in converting RNA degradation mode from 3’–5’ to 5’–3’ with cooperative efforts from both endonucleolytic and non-catalytic miRNA-induced silencing complex (miRISC). Our findings point to a mammalian miRNA-mediated mechanism for the regulation of mRNA that miRNA can decrease target mRNA through target mRNA cleavage and uridine addition