Precision Mass Measurement of the Proton Dripline Halo Candidate

We report the first mass measurement of the proton-halo candidate ^{22}Al performed with the low energy beam ion trap facility's 9.4 T Penning trap mass spectrometer at facility for rare isotope beams. This measurement completes the mass information for the lightest remaining proton-dripline nucleus achievable with Penning traps. ^{22}Al has been the subject of recent interest regarding a possible halo structure from the observation of an exceptionally large isospin asymmetry [J. Lee et al., Large isospin asymmetry in Si22/O22 Mirror Gamow-Teller transitions reveals the halo structure of ^{22}Al, Phys. Rev. Lett. 125, 192503 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.192503]. The measured mass excess value of ME=18 092.5(3) keV, corresponding to an exceptionally small proton separation energy of S_{p}=100.4(8) keV, is compatible with the suggested halo structure. Our result agrees well with predictions from sd-shell USD Hamiltonians. While USD Hamiltonians predict deformation in the ^{22}Al ground state with minimal 1s_{1/2} occupation in the proton shell, a particle-plus-rotor model in the continuum suggests that a proton halo could form at large quadrupole deformation. These results emphasize the need for a charge radius measurement to conclusively determine the halo nature.

Genome-wide gene expression responses to experimental manipulation of Saccharomyces cerevisiae repressor activator protein 1 (Rap1) expression level.

Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.

Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Impact of Nuclear Deformation and Pairing on the Charge Radii of Palladium Isotopes.

The impact of nuclear deformation can been seen in the systematics of nuclear charge radii, with radii generally expanding with increasing deformation. In this Letter, we present a detailed analysis of the precise relationship between nuclear quadrupole deformation and the nuclear size. Our approach combines the first measurements of the changes in the mean-square charge radii of well-deformed palladium isotopes between A=98 and A=118 with nuclear density functional calculations using Fayans functionals, specifically Fy(std) and Fy(Δr,HFB), and the UNEDF2 functional. The changes in mean-square charge radii are extracted from collinear laser spectroscopy measurements on the 4d^{9}5s ^{3}D_{3}→4d^{9}5p ^{3}P_{2} atomic transition. The analysis of the Fayans functional calculations reveals a clear link between a good reproduction of the charge radii for the neutron-rich Pd isotopes and the overestimated odd-even staggering: Both aspects can be attributed to the strength of the pairing correlations in the particular functional which we employ.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Trueness, 3D Deviation, Time and Cost Comparisons Between Milled and 3D-Printed Resin Single Crowns.

The purpose of this in-vitro study was to compare trueness, 3D deviation, production time and costs of milled and 3D-printed resin single crowns. A total of 20 CAD-CAM resin single crowns were fabricated from 10 digital wax patterns designed on 10 tooth preparations available in a reference model. Standardized control linear measurements were performed with a CAD software. Each STL file was then used to fabricate two resins crowns - one milled and one 3D-printed. All crowns underwent physical linear measurements using a digital caliper. The crowns were then scanned using an intraoral scanner for assessing 3D deviation. Finally, time to produce a single crown, as well as costs and production rates of both methods were also compared. Both CAM methods did not present statistically significant differences in linear measurements, as compared to controls (P⟩.05). Furthermore, 3D-printed crowns had significantly greater deviations in cervical margins (P=.032) and occlusal surfaces (P=.041), as compared with milled crowns. Finally, 3D-printing took significantly longer to produce one single crown (P=.001), but with a cheaper and higher production rate than milling. These findings suggest that milling devices produce resin single crowns with smaller 3D deviations but more expensive costs, as compared with low-cost 3D printers.

Replication of Marek's disease vaccines in turkey embryos and their effect on TLR-3 and IFN-γ transcripts.

Understanding the pathogenesis of herpesvirus of turkeys (HVT) in its natural host is necessary before recombinant HVT (rHVT) can be used efficiently in turkey flocks. The objectives of this study were to evaluate when commercial turkey flocks get infected with wild type HVT, to study replication of HVT (conventional and recombinant rHVT-Newcastle disease, rHVT-ND) and other Marek's disease (MD) vaccines (SB-1 and CVI988) in turkey embryonic tissues, and to evaluate the expression of TLR-3 and IFN-γ in the lung and spleen of one-day-old turkeys after in ovo vaccination with MD vaccines. Our results demonstrated that commercial turkeys got exposed to wild type HVT within the first days of life; therefore, there is a potential of interaction between wild type HVT and rHVT when administered at day of age. On the other hand, all evaluated vaccines (especially HVT and rHVT-ND) replicated very well in turkey embryonic tissues. In ovo vaccination with HVT and CVI988 increased transcription of TLR-3 in the spleen of one-day-old turkeys. However, no effect on the transcription of TLR-3 or IFN-γ in the lungs and IFN-γ in the spleen in newly hatched turkeys was detected in the present study. Because of the limitations of evaluated genes, timepoints, and studied tissues, future studies are warranted to better understand the effect of MD vaccines on the turkey embryo immune responses.RESEARCH HIGHLIGHTS Commercial turkey flocks get infected with wild type HVT within the first days of life.HVT and rHVT replicates readily in turkey embryonic tissues.SB-1 and CVI988 also replicate in turkey embryonic tissues, but at lower rates than HVT and rHVT.HVT and CVI988 increase transcription of TLR-3 in the spleen.

Characterization of Md5-BAC-REV-LTR virus as Marek's disease vaccine in commercial meat-type chickens: protection and immunosuppression.

Md5-BAC-REV-LTR is a recombinant Marek's disease virus (MDV), with an insertion of the long terminal repeat (LTR) of reticuloendotheliosis virus (REV) into the genome of the highly virulent MDV strain rMd5. It has been shown that Md5-BAC-REV-LTR does not induce tumours and confers high protection against challenge with MDV in 15 × 7 chickens. The objective of the present study was to evaluate the protection and safety (in terms of oncogenicity and immunosuppression) of Md5-BAC-REV-LTR in commercial meat-type chickens bearing maternal antibodies against MDV. Our results show that sub-cutaneous administration of Md5-BAC-REV-LTR at 1 day of age conferred high protection (protection index PI = 84.2) against an early challenge (1 day) by contact exposure to shedder birds infected with the vv+ MDV 648A strain. In such stringent challenge conditions, Md5-BAC-REV-LTR was more protective than a commercial CVI988 (PI = 12.4) and similar to the experimental vaccine Md5-BACΔmeq (PI = 92.4). Furthermore, Md5-BAC-REV-LTR did not induce either tumours or immunosuppression in this study. Immunosuppression was evaluated by the relative lymphoid organ weights and also by the ability of the vaccine to induce late-MDV-induced immunosuppression associated with reactivation of the virus. This study shows that Md5-BAC-REV-LTR has the potential to be used as a MD vaccine and is highly protective against early challenge with vv+ MDV.RESEARCH HIGHLIGHTSMd5-BAC-REV-LTR is highly protective against early challenge with vv+ MDV in commercial meat-type chickens.Md5-BAC-REV-LTR does not cause early immunosuppression.Md5-BAC-REV-LTR does not cause late immunosuppression.Unlike other serotype 1 vaccines, Md5-BAC-REV-LTR is not detected in feather pulp at 7 days post vaccination.

Dental Public Health in Action: Experiences and Responses of Oral Health Care Professionals during the First Wave of the COVID-19 Pandemic in Malta.

Initial impetus for action: Maltese Oral Health Care Professionals (OHCP) experienced changes to clinical practice and redeployment during the COVID-19 pandemic. In the early stages, there were few data on the resultant changes to the provision of dental services or their impact on the wellbeing of dental professionals. Solutions Suggested: Two questionnaires were designed to explore different domains in OHCP working on the frontline of the COVID-19 pandemic as well as in other areas/sectors. The findings were intended to inform guidance documents and to better support the profession. Findings: Anxiety-provoking factors, challenges, and areas of concern of OHCP were identified and practical recommendations to support transitioning to the 'new normal' were presented. OHCP expressed anxiety about contracting COVID-19 from their workplace and passing infection to other family members, friends, or patients. As a result, OHCP expressed the need for better protective clothing, workplace ventilation, and air filtration systems. Future implications: Provision of adequate PPE for OHCP was a priority. New guidelines for dental practice were informed by the experiences of the particpating OHCP. University modules to enhance the resilience of OHCP were among the recommendations to support practitioners.

Influence of Gingival Contour on Marginal Fit of CAD-CAM Zirconia Copings on Implant Stock Abutments.

PURPOSE: Intraoral scanning subgingival finish lines has been described as challenging. The purpose of this study was to assess the impact of gingival contour around margins of implant stock abutments on marginal fit of Computer-aided Design - Computer-aided Manufacturing (CAD-CAM) zirconia copings. This in-vitro study was conducted on 40 analogues of implant stock abutments that were embedded into individual phantoms composed by a resin block. All 40 phantoms underwent two intraoral scans - one with (test group) and one without artificial gingiva (control group) - using a closed system intraoral scanner. Zirconia copings were then digitally designed and milled, followed by high-speed sintering, before being analyzed for marginal adaptation and internal surface roughness with scanning electron microscopy. Statistically significant differences between groups were assessed with the Mann-Whitney test. Median marginal gap values were 149.78 µm (95% CI: 112.39-216.66) for the test group and 94.90 µm (95% CI: 83.89-107.74) for the control group. A statistically significant difference was found between groups (p=0.0001). However, there were no subjective differences between groups for internal surface roughness. Within the limitations of this study, the present findings suggest that a gingival contour one millimeter higher than the finishing line affects marginal adaptation of CAD-CAM zirconia copings.

Highly virulent Marek's disease virus strains affect T lymphocyte function and viability of splenocytes in commercial meat-type chickens.

In previous studies, we have demonstrated that very virulent plus Marek's disease viruses (vv+MDV) are highly immunosuppressive in commercial meat-type chickens. The specific objectives of this work were to evaluate if vv+MDV immunosuppression (MDV-IS) is induced by reduction of lymphocyte responsiveness and/or viability. Three experiments were conducted to (i) compare vv+MDV 686 with a partially attenuated 686-BAC; (ii) compare vv+MDV strains (648A and 686) with vMDV (GA) and vvMDV (Md5); and (iii) compare chickens vaccinated with Md5-BACΔMEQ and with CVI988 + HVT. In each experiment, spleens were collected at 28-30 days post infection and lymphocytes were isolated and investigated in three ways: their proliferative response to Concanavalin A (ConA) was analysed by MTT proliferation assay; cell death, and expression of CD45 and MHC-I was studied by flow cytometry; and MHC-IA and ß-2 microglobulin (B2M) expression was evaluated by real time RT-PCR. Splenocytes of chickens inoculated with vv+MDV were severely impaired to proliferate when exposed to ConA. Furthermore, vv+MDV induced severe splenocyte death that did not occur after infection with v or vvMDV strains. Vaccination with CVI988 + HVT, and at less level with Md5-BACΔMEQ reduced these negative effects. This is in contrast to our previous results in which Md5-BACΔMEQ but not CVI988 + HVT protected against MDV-IS suggesting that although cell death and decrease lymphocyte function seem to be related to MDV virulence and certainly will be associated with immunosuppression, they might not fully explain the previously reported MDV-IS. RESEARCH HIGHLIGHTS vv+MDV induces extensive death in splenocytes in meat-type chickens 28-30 dpi. vv+MDV impairs lymphocyte function in meat-type chickens 28-30 dpi. Vaccination protects against splenocyte death and reduced lymphocyte function. Cell lysis and reduced lymphocyte function do not fully explain MDV-IS.

Copper(I)-Catalyzed Click Chemistry as a Tool for the Functionalization of Nanomaterials and the Preparation of Electrochemical (Bio)Sensors.

Proper functionalization of electrode surfaces and/or nanomaterials plays a crucial role in the preparation of electrochemical (bio)sensors and their resulting performance. In this context, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been demonstrated to be a powerful strategy due to the high yields achieved, absence of by-products and moderate conditions required both in aqueous medium and under physiological conditions. This particular chemistry offers great potential to functionalize a wide variety of electrode surfaces, nanomaterials, metallophthalocyanines (MPcs) and polymers, thus providing electrochemical platforms with improved electrocatalytic ability and allowing the stable, reproducible and functional integration of a wide range of nanomaterials and/or different biomolecules (enzymes, antibodies, nucleic acids and peptides). Considering the rapid progress in the field, and the potential of this technology, this review paper outlines the unique features imparted by this particular reaction in the development of electrochemical sensors through the discussion of representative examples of the methods mainly reported over the last five years. Special attention has been paid to electrochemical (bio)sensors prepared using nanomaterials and applied to the determination of relevant analytes at different molecular levels. Current challenges and future directions in this field are also briefly pointed out.

[Exposure to contaminants from coal-fired thermoelectric plants and children's health: What is the international and national evidence?] / Exposición a contaminantes provenientes de termoeléctricas a carbón y salud infantil: ¿Cuál es la evidencia internacional y nacional?

Coal-fired power plants (CFPP) represent a health risk to the exposed communities. A review of national and international scientific literature was made focused on the health effects on children and exposure to air emissions from CFPP. Twenty-one articles were included for full-text review, where effects on child health mainly related to the biomarkers presence of exposure and effect, pe rinatal, neurobehavioral and respiratory damages were measured. Exposure to CFPP emissions in pregnancy was associated with low birth weight and very low birth weight, shorter height, smaller head circumference (HC) diameter, and prematurity; the HC diameter increased in newborns after the CFPP closure. Lower coefficient of development (CD) and intelligence quotient (IQ) were found in children exposed to CFPP emissions compared with unexposed ones; CD increased when the plant was closed. On the other hand, living in areas with mercury emission sources (associated with CFPP and cement plants that work with coal) was associated with an increased risk of autism. In respira tory health, the articles were consistent with reporting lower pulmonary function in children living in areas exposed to coal combustion sources compared with groups of unexposed children. There is a great need to open the debate in Chile on the controllable risks faced by the child population as a result of power generation plants located in Chile.

Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication. METHODS: Hearts and placentas from 16 IUGR-offspring and 14 controls were included to characterize mitochondrial function. RESULTS: Enzymatic activities of complexes II, IV and II + III in IUGR-hearts (-11.96 ±â€¯3.16%; -15.58 ±â€¯5.32%; -14.73 ±â€¯4.37%; p < 0.05) and II and II + III in IUGR-placentas (-17.22 ±â€¯3.46%; p < 0.005 and -29.64 ±â€¯4.43%; p < 0.001) significantly decreased. This was accompanied by a not significant reduction in CI-stimulated oxygen consumption and significantly decreased complex II SDHB subunit expression in placenta (-44.12 ±â€¯5.88%; p < 0.001). Levels of mitochondrial content, Coenzyme Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in IUGR-hearts (-39.02 ±â€¯4.35%; p < 0.001), but not significantly increased in IUGR-placentas. Sirtuin3 protein expression significantly increased in IUGR-hearts (84.21 ±â€¯31.58%; p < 0.05) despite conserved anti-oxidant SOD2 protein expression and activity in both tissues. CONCLUSIONS: IUGR is associated with cardiac and placental mitochondrial CII dysfunction. Up-regulated expression of Sirtuin3 may explain attenuation of cardiac oxidative damage and preserved ATP levels under CII deficiency. GENERAL SIGNIFICANCE: These findings may allow the design of dietary interventions to modulate Sirtuin3 expression and consequent regulation of mitochondrial imbalance associated with IUGR and derived cardiovascular remodeling.

Approximal morphology as predictor of approximal caries in primary molar teeth.

OBJECTIVE: To evaluate the predictive power of the morphology of the distal surface on 1st and mesial surface on 2nd primary molar teeth on caries development in young children. SAMPLE AND METHODS: Out of 101 3-to 4-year-old children from an on-going study, 62 children, for whom parents' informed consent was given, participated. Upper and lower molar teeth of one randomly selected side received a 2-day temporarily separation. Bitewing radiographs and silicone impressions of interproximal area (IPA) were obtained. One-year procedures were repeated in 52 children (84%). The morphology of the distal surfaces of the first molar teeth and the mesial surfaces on the second molar teeth (n=208) was scored from the occlusal aspect on images from the baseline resin models resulting in four IPA variants: concave-concave; concave-convex; convex-concave, and convex-convex. Approximal caries on the surface in question was radiographically assessed as absent/present. RESULTS: Of the 52 children examined at follow-up, 31 children (60%) had 1-4 concave surfaces. In total 53 (25%) of the 208 surfaces were concave. A total of 22 children (43%) had 1-4 approximal lesions adding up to 59 lesions. Multiple logistic regression analyses disclosed that gender, surface morphology on one of the approximal surfaces (focus-surface), and adjacent-surface morphology were significantly related to caries development (p values ≤ 0.03). The odds ratio for developing caries in the focus-surface/adjacent-surface in the four IPA variants were convex-convex, 1.0; convex-concave, 5.5 (CI 2.0-14.7); concave-convex, 12.9 (CI 4.1-40.3); and concave-concave, 15.7 (CI 5.1-48.3). CONCLUSION: Morphology of approximal surfaces in primary molar teeth, in particular both surfaces being concave, significantly influences the risk of developing caries. CLINICAL RELEVANCE: The concave morphology of approximal surfaces can predict future caries lesions supporting specific home-care and in-office preventive strategies.

Effects of 25-hydroxycholecalciferol with two D3 vitamin levels on production and immunity parameters in broiler chickens.

This study was performed in Ross 308 chickens aged 1-21 days and aimed to evaluate whether the addition of 25-hydroxycholecalciferol (25(OH)D3 ) to broiler chicken diets affects their growth performance and immunity. A completely random 2 × 2 factorial arrangement was used with two levels of vitamin D3 and the absence or presence of 25(OH)D3 , corresponding to four treatments based on sorghum + soya bean diets: (i) 200 IU of vitamin D3 /kg of feed (Diet 1) (NRC, ), (ii) Diet 1 + 69 µg of 25(OH)D3 /kg of feed (Diet 2), (iii) 5,000 IU of vitamin D3 /kg of feed (Diet 3) and (iv) Diet 3 + 69 µg of 25(OH)D3 /kg of feed (Diet 4). Each treatment was conducted with six replicates of 10 chickens each. Water and feed was supplied ad libitum. The results showed significantly increased growth and tibia ash (p < .05) in the birds fed 5,000, IU of vitamin D3 /kg + 25(OH)D3 . Additionally, the cellular immune response increased significantly (p < .05) in both treatments with added 25(OH)D3. Based on the results obtained under the current test conditions, the addition of 25(OH)D3 at a rate of 69 µg/kg to diets containing vitamin D3 improved the cellular immune response and mineral deposition in the bones of broilers aged 1-21 days. Because these parameters are very important in modern poultry farming, these results indicate that supplementation with 25(OH)D3 should improve broiler production.

[Exposure to nitrates in drinking water and its association with thyroid gland dysfunction]. / Exposición a nitratos en agua y su relación con disfunción de la glándula tiroides: revisión sistemática ¿Existen riesgos para la salud de la población?

BACKGROUND: Nitrate exposure may be associated with thyroid gland dysfunction. AIM: To review the available evidence about the relationship between nitrates in drinking water and thyroid gland dysfunction. MATERIAL AND METHODS: A wide search was performed using Medline, Cochrane, Lilacs, IBECS and Scielo databases using pertinent keywords, finding a total of 66 related studies. After filtering and in depth reviewing, a total of 12 studies were included in this review. RESULTS: The main results reveal the importance of this ion for human health, finding evidence both in animals and human beings that suggest pathological changes in the gland as its relationship with the occurrence of subclinical hypothyroidism, and potentially cancer of the thyroid gland. In Chile, nitrate is not considered a critical contaminant so its regular measuring and control is not enforced. CONCLUSIONS: In light of the present review we believe that there is evidence to consider nitrate as a critical contaminant whose measurement, registration and correct implementation of valid policies would have a direct benefit for the population of this country. Without this information, it is not possible to quantify the damage to human health, especially in vulnerable groups residing in areas at greatest risk of exposure.

Investigation of a possible extended risk haplotype in the IL23R region associated with ankylosing spondylitis.

The IL23R region on chromosome 1 exhibits complex associations with ankylosing spondylitis (AS). We used publicly available epigenomic information and historical genetic association data to identify a putative regulatory element (PRE) in the intergenic region between IL23R and IL12RB2, which includes two single-nucleotide polymorphisms (SNPs) independently associated with AS-rs924080 (P=2 × 10-3) and rs11578380 (P=2 × 10-4). In luciferase reporter assays, this PRE showed silencer activity (P<0.001). Haplotype and conditional analysis of 4230 historical AS cases and 9700 controls revealed a possible AS-associated extended haplotype, including the PRE and risk variants at three SNPs (rs11209026, rs11209032 and rs924080), but excluding the rs11578380 risk variant. However, the rs924080 association was absent after conditioning on the primary association with rs11209032, which, in contrast, was robust to conditioning on all other AS-associated SNPs in this region (P<2 × 10-8). The role of this putative silencer on some IL23R extended haplotypes therefore remains unclear.

Study of the Huntington's disease IT-15 gene in different ethnic groups in Ecuador.

This study aims to establish the current state of the IT-15 (HTT) gene in different Ecuadorian ethnic groups and patients by determining CAG triplet repeats, compared with the ethnicity of individuals. A total of 412 individuals were studied using nested polymerase chain reaction and Sanger sequencing: 75 individuals were indigenous (Kichwas), 211 mestizos, and 65 Afro-Ecuadorians. We included 31 patients who were clinically diagnosed with Huntington's disease (HD) and relatives of the affected patients (n = 30). Moreover, we correlated the presence of HD in Ecuadorian patients with 46 genetic ancestry-informative insertion-deletion polymorphic markers. We found that 77.20% had <28 CAG repetitions, 18.80% had mutable alleles, 2.27% had incomplete penetrance, and 1.70% reflected >39 repetitions. The average of CAG repetitions was 24 ± 3 for indigenous people; 28 ± 2 for mestizos; and 24 ± 3.2 repetitions for the Afro-Ecuadorians. The ancestral component showed that the main ancestry corresponded to Native Americans (0.873) and European ascendants (0.145), Africans were less represented in the evaluated population (0.018). There was a significant difference between the number of CAG repeats in mestizos and indigenous people (P < .01), suggesting that the Ecuadorian mestizo population has a risk factor for the gene mutation.

[Planar molecular arrangements aid the design of MHC class II binding peptides].

The coupling between peptides and MHC-II proteins in the human immune system is not well understood. This work presents an evidence-based hypothesis of a guiding intermolecular force present in every human MHC-II protein (HLA-II). Previously, we examined the spatial positions of the fully conserved residues in all HLA-II protein types. In each one, constant planar patterns were revealed. These molecular planes comprise of amino acid groups of the same chemical species (for example, Gly) distributed across the protein structure. Each amino acid plane has a unique direction and this directional element offers spatial selectivity. Constant within all planes, too, is the presence of an aromatic residue possessing electrons in movement, leading the authors to consider that the planes generate electromagnetic fields that could serve as an attractive force in a single direction. Selection and attraction between HLA-II molecules and antigen peptides would, therefore, be non-random, resulting in a coupling mechanism as effective and rapid as is clearly required in the immune response. On the basis of planar projections onto the HLA-II groove, modifications were made by substituting the key residues in the class II-associated invariant chain peptide-a peptide with a universal binding affinity-resulting in eight different modified peptides with affinities greater than that of the unmodified peptide. Accurate and reliable prediction of MHC class II-binding peptides may facilitate the design of universal vaccine-peptides with greatly enhanced binding affinities. The proposed mechanisms of selection, attraction and coupling between HLA-II and antigen peptides are explained further in the paper.