The structure and migration patterns of the population of Uruguay through isonymy.

Surname distribution can be a useful tool for studying the genetic structure of a human population. In South America, the Uruguay population has traditionally been considered to be of European ancestry, despite its trihybrid origin, as proved through genetics. The aim of this study was to investigate the structure of the Uruguayan population, resulting from population movements and surname drift in the country. The distribution of the surnames of 2,501,774 people on the electoral register was studied in the nineteen departments of Uruguay. Multivariate approaches were used to estimate isonymic parameters. Isolation by Distance was measured by correlating isonymic and geographic distances. In the study sample, the most frequent surnames were consistently Spanish, reflecting the fact that the first immigration waves occurred before Uruguayan independence. Only a few surnames of Native origin were recorded. The effective surname number (α) for the entire country was 302, and the average for departments was 235.8 ± 19. Inbreeding estimates were lower in the south-west of the country and in the densely populated Montevideo area. Isonymic distances between departments were significantly correlated with linear geographic distance (p < 0.001) indicating continuously increasing surname distances up to 400 km. Surnames form clusters related to geographic regions affected by different historical processes. The isonymic structure of Uruguay shows a radiation towards the east and north, with short-range migration playing a major role, while the contribution of drift, considering the small variance of α, appears to be minor.

Factors affecting SPF in vitro measurement and correlation with in vivo results.

OBJECTIVE: The in vitro evaluation of SPF is still a problem due to the lack of repeatability and correlation between the in vitro and in vivo data, and many authors are currently working to develop an internationally harmonized method. Very recently, the use of several "adjuvant" ingredients such as boosters, antioxidants, immunomodulators, solvents and film-forming ingredients have further complicated the pattern for product developers that should frequently run in vivo test. The aim of this study was to understand whether a simple and cheap in vitro method could be optimized in order to provide both statistically repeatable and predictive SPF measurement. METHODS: In vitro SPF assessments were carried out on 75 commercial products. The SPF was measured according to two laboratory methods (A and B), using different substrates (PMMA and surgical tape Transpore™), quantity of product and spectrophotometers. In order to evaluate whether a standard technique of spreading could lead to a statistically reliable result, we applied different spreading pressure (100 g and 200 g). Furthermore, we investigate whether other parameters characterizing the product (SPF category, filter and texture) might represent statically significant variables affecting the measures. We then compared the results obtained from in vitro SPF measure of 11 products to in vivo SPF, in order to assess the predictability of in vitro methods. RESULTS: Several problems were encountered in confirming the weakness of the in vitro procedures. Pressure, SPF category, filter and texture did not affect significantly the results. Overall best results were obtained with the B2 method that in terms of repeatability and predictivity provided statistically better results. Method A with Transpore™ tape showed better in vitro-in vivo correlation than Method B with PMMA plates. CONCLUSION: In our investigation, we demonstrated that it is possible for a single laboratory to optimize internal methods and protocols to achieve repeatable and predictive in vitro results, but it is extremely difficult to develop methods reproducible and equally reliable in different laboratories, probably due to "external variables" (e.g. environmental, operator), which are difficult to control.

Surnames in Chile: a study of the population of Chile through isonymy.

In Chile, the Hispanic dual surname system is used. To describe the isonymic structure of this country, the distribution of 16,277,255 surnames of 8,178,209 persons was studied in the 15 regions, the 54 provinces, and the 346 communes of the nation. The number of different surnames found was 72,667. Effective surname number (Fisher's α) for the entire country was 309.0, the average for regions was 240.8 ± 17.6, for provinces 209.2 ± 8.9, and for communes 178.7 ± 4.7. These values display a variation of inbreeding between administrative levels in the Chilean population, which can be attributed to the 'Prefecture effect' of Nei and Imaizumi. Matrices of isonymic distances between units within administrative levels were tested for correlation with geographic distance. The correlations were highest for provinces (r = 0.630 ± 0.019 for Euclidean distance) and lowest for communes (r = 0.366 ± 0.009 for Lasker's). The geographical distribution of the first three-dimensions of the Euclidean distance matrix suggests that population diffusion may have taken place from the north of the country toward the center and south. The prevalence of European plus European-Amerindian (95.4%) over Amerindian ethnicity (4.6%, CIA World Factbook) is compatible with diffusion of Caucasian groups over a low-density area populated by indigenous groups. The significant excess of maternal over paternal indigenous surnames indicates some asymmetric mating between nonAmerindian and Amerindian Chileans. The available studies of Y-markers and mt-markers are in agreement with this asymmetry. In the present work, we investigate the Chilean population with the aim of detecting its structure through the study of isonymy (Crow and Mange,1965) in the three administrative levels of the nation, namely 15 regions, 54 provinces, and 346 communes.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

Gene--gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis.

Aggressive periodontitis (AgP) is a multifactorial disease. The distinctive aspect of periodontitis is that this disease must deal with a large number of genes interacting with one another and forming complex networks. Thus, it is reasonable to expect that gene-gene interaction may have a crucial role. Therefore, we carried out a pilot case-control study to identify the association of candidate epistatic interactions between genetic risk factors and susceptibility to AgP, by using both conventional parametric analyses and a higher order interactions model, based on the nonparametric Multifactor Dimensionality Reduction algorithm. We analyzed 122 AgP patients and 246 appropriate periodontally healthy individuals, and genotyped 28 polymorphisms, located within 14 candidate genes, chosen among the principal genetic variants pointed out from literature and having a role in inflammation and immunity. Our analyses provided significant evidence for gene--gene interactions in the development of AgP, in particular, present results: (a) indicate a possible role of two new polymorphisms, within SEPS1 and TNFRSF1B genes, in determining host individual susceptibility to AgP; (b) confirm the potential association between of IL-6 and Fc γ- receptor polymorphisms and the disease; (c) exclude an essential contribution of IL-1 cluster gene polymorphisms to AgP in our Caucasian-Italian population.

Surnames in Siberia: a study of the population of Yakutia through isonymy.

We studied the isonymic structure of the Republic of Sakha (Yakutia), in the Russian Federation, using the surname distributions of 491,259 citizens above 18 years registered as residents in 2002. These were distributed in 35 districts and 497 towns and settlements of the Republic. The number of different surnames was 44,625. Matrices of isonymic distances between the 35 districts were tested for correlation with the geographic distance between the population centers of gravity of the districts. We found that, for the whole of Yakutia, Nei's distance was correlated with geographic distance (r = 0.693 +/- 0.027). A dendrogram of the 35 districts was built from the distance matrix, using the UPGMA method. The clusters identified by the dendrogram correlate with the geographic position of the districts. The correlation of random inbreeding calculated from isonymy, F(ST), with latitude was positive and highly significant but weak (r = 0.23). So, inbreeding was highest in the Arctic districts, and lowest in the South. Average alpha for 497 towns was 107, for 35 districts it was 311, and for the Republic 433. The value of alpha was higher for Russian than for the local languages. The geographical distribution of alpha, high in the Center and South-East and lower in the North-West, is compatible with the settlement of groups of migrants moving from the South-East toward the center and the North of Yakutia. It is proposed that low-density demic diffusion of human populations results in high inbreeding and may have been a general phenomenon in the early phases of human radiations.

General preadaptation of viral infectors to their hosts.

We tested the hypothesis of optimal adaptation of viral infectors to eukaryotic hosts, using (1) correlation in codon and amino acid usage between organisms, and (2) canonical correlation between groups of hosts and infectors. The codon correlations between parasites and hosts vary, being low between swine and African swine fever virus (ASF; r = 0.18), and highest between potato and potato virus X (r = 0.60). The correlations might indicate different stages of evolution toward optimal adaptation of the parasite codon distribution to the host tRNA pools. The amino acid correlations vary from r = 0.71 between pig and ASF, to 0.88 between catfish and its herpesvirus. It was observed that both in virus and hosts, there is a negative correlation between frequency of an amino acid and molecular weight. Therefore, it was advanced that viral infectors might be preadapted to their hosts because of similarities of the tRNA pools of hosts, and that evolution toward optimization would be dependent on the size of the divergence between the codon distributions of infector and host. Preadaptation does not imply origin of the virus by lateral transfer from the present host, since the correlation of the molecular weight of amino acids with their abundance in proteins is a general phenomenon.

Enhanced solubility and antibacterial activity of lipophilic fluoro-substituted N-benzoyl-2-aminobenzothiazoles by complexation with ß-cyclodextrins.

Some lipophilic fluoro-substituted N-benzoyl-2-aminobenzothiazole antibacterial agents have been evaluated for their activity in the presence of cyclodextrins (CDs) containing aqueous solutions where CDs are adopted as solubilizing excipients for improving the poor water solubility of these compounds. For such purpose both the natural ß-CD and one of FDA/EMA approved CDs for parenteral use (i.e. HP-ß-CD) have been employed. The solubility rank order observed was accounted for by thermal analysis (Differential Scanning Calorimetry) and FT-IR spectroscopy. The most promising compound was subjected to further NMR spectroscopic studies and molecular modelling simulations to verify the interactions between the guest molecule and the CD cavity. The assessment of the antibacterial activity of such compounds against selected Gram positive and Gram negative bacterial strains clearly showed that their antimicrobial effectiveness may, quite in all instances, be positively affected by complexation with ß-CD and HP-ß-CD. These results, which are in some ways in contrast with those already reported in the literature, are herein discussed on the basis of plausible mechanisms. Moreover, this investigation also reveals that the described methodology of complexing both lipophilic and hydrophilic antimicrobial agents with CDs may be an useful approach to enhance their effectiveness as well as a promising strategy to overcome even the microbial resistance problem.

Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.1.3.22), a molybdenum-containing hydroxylase that produces superoxide and uric acid from purine substrates and molecular oxygen, is involved in the oxidative stress underlying several human pathologies including lung diseases. An enzymatic activity similar to xanthine oxidase was previously reported in bronchoalveolar lavage fluid of patients with chronic obstructive pulmonary disease (COPD-BAL), by fluorometric analysis of DNA unwinding and cytochrome c reduction kinetics. Here we report the detection of xanthine oxidase activity products by electron paramagnetic resonance (EPR) in presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and reversed-phase high-performance liquid chromatography (RP-HPLC) in COPD-BAL (n = 14, average age of patients 65 years, range 38-81) and BAL from healthy nonsmoker controls (n = 6, average age 64 years, range 44-73). Superoxide DMPO adducts were detected in COPD-BAL and in an in vitro system containing xanthine and xanthine oxidase (XA/XO), but not in BAL controls and when superoxide dismutase (SOD, 1000 I.U./ml) was added to COPD-BAL. The HPLC analyses after addition of xanthine showed production of uric acid in COPD-BAL and in the XA/XO system but not in BAL controls. These results support the involvement of xanthine oxidase in the mechanisms of superoxide production by BAL supernatant, which increases oxidative stress in chronic obstructive pulmonary disease.

Ligands of neuronal nicotinic acetylcholine receptor (nAChR): inferences from the Hansch and 3-D quantitative structure-activity relationship (QSAR) Models.

Neuronal acetylcholine ion channel receptors (nAChRs), that exist in several subtypes resulting from a different organisation of various subunits around the central ion channel, are involved in a variety of functions and disorders of the central nervous system. There is evidence to implicate a deficit of nAChRs in the symptomatology of severe neurologic pathologies, such as Alzheimer s and Parkinson s diseases. Reliable three-dimensional structures of nAChRs are not available yet, and this hampers adopting structure-based approaches in designing new ligands. Also pharmacophore models are not reliable enough to be used in ligand-based approaches to drug design and little structure-activity work has been reported so far. This paper deals with structure-activity relationships of a wide series of nicotinic ligands. It provides results from a study of the quantitative structure activity relationships (QSARs) based on literature data of about 270 nicotinic agonists, belonging to various chemical classes. The QSAR study was carried out by using either a classical Hansch approach or a Comparative Molecular Field Analysis (CoMFA). Within each congeneric series, Hansch-type equations revealed detrimental steric effects as the factors mainly modulating the receptor affinity, whereas CoMFA allowed us to merge progressively models obtained for each class of congeners into a more general one that showed good cross-validation statistics. The CoMFA coefficient isocontour maps illustrated, at the 3-D level, the most relevant interactions responsible for a high receptor affinity, whereas the robustness of the global three-dimensional QSAR/CoMFA (n = 206, q(2) = 0.749, r(2) = 0.847, s= 0.600) model was supported by the high value of the prediction statistics (r(2)pred = 0.961) and confirmed by the satisfactory predictions of the affinity data of an external set of 18 recently published ligands with chemical structures even quite diverse from those included in the training set.

Conformationally constrained butyrophenones with mixed dopaminergic (D(2)) and serotoninergic (5-HT(2A), 5-HT(2C)) affinities: synthesis, pharmacology, 3D-QSAR, and molecular modeling of (aminoalkyl)benzo- and -thienocycloalkanones as putative atypical antipsychotics.

A series of novel conformationally restricted butyrophenones (2-(aminoethyl)- and 3-(aminomethyl)thieno- or benzocycloalkanones bearing (6-fluorobenzisoxazolyl)piperidine, (p-fluorobenzoyl)piperidine, (o-methoxyphenyl)piperazine, or linear butyrophenone fragments) were prepared and evaluated as atypical antipsychotic agents by in vitro assays of affinity for dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(2A), 5-HT(2C)) and by in vivo assays of antipsychotic potential and the risk of inducing extrapyramidal side effects. Potency and selectivity depended mainly on the amine fragment connected to the cycloalkanone structure. As a group, compounds with a benzisoxazolyl fragment had the highest 5-HT(2A) activities, followed by the benzoylpiperidine derivatives; in general, alpha-substituted cycloalkanone derivatives were more active than the corresponding beta-substituted congeners. CoMFA (comparative molecular field analysis) and docking studies showed electrostatic, steric, and lipophilic determinants of 5-HT(2A) and D(2) affinities and 5-HT(2A)/D(2) selectivity. The in vitro and in vivo pharmacological profiles of N-[(4-oxo-4H-5, 6-dihydrocyclopenta[b]thiophene-5-yl)ethyl]-4-(6-fluorobenzisox azol-3 -yl)piperidine (23b, QF 0510B), N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]thiophene-5-yl)ethyl]-4-(6-fluorobenzisoxazol- 3-y l)piperidine (24b, QF 0610B), and N-[(7-oxo-4,5,6, 7-tetrahydrobenzo[b]thiophene-6-yl)ethyl]-4-(6-fluorobenzisoxazol- 3-y l)piperidine (29b, QF 0902B) suggest that they may be effective antipsychotic drugs with low propensity to induce extrapyramidal side effects.

Lipophilicity of teicoplanin antibiotics as assessed by reversed phase high-performance liquid chromatography: quantitative structure-property and structure-activity relationships.

Structure-lipophilicity relationships of a large series of 63-COX teicoplanin antibiotic derivatives were examined, by correlating their capacity factors (log kw), measured through reversed-phase high-performance liquid chromatography on Deltabond C8 stationary phase, with some computed molecular properties such as fragmental log P constants (pi x), molecular volumes (Vx) and factors imparting hydrophilicity (e.g. amino groups in the X chain, nN). A number of equations were derived which demonstrate that variations of log kw are mainly related to changes in bulk (modelled by Vx) and polarity (primarily modelled by nN) of X chains of teicoplanin derivatives. QSAR analysis revealed that in-vitro activity against E. coli increases as lipophilicity decreases and isoelectric point increases.

Codon and aminoacid usage patterns in mycobacteria.

The large number of organisms and of genes sequenced at the present time permits now to study molecular evolution in such lower clades as genera, species, and subspecies. Here, we focus our attention on the genus Mycobacterium, in which we examined codon and aminoacid usage in 13 species, and in 12 subspecies for a total of 8,836,513 codons from 26,755 sequences. Within the genus Mycobacterium, frequencies of codon and aminoacid usage correlate between species and between subspecies. In the groups studied, aminoacid molecular weight and codon degeneracy influence correlations between frequencies, while GC content is the main factor influencing the effective number of codons. The coding GC, which is highly correlated with total genomic GC content, seems to be the main factor influencing present synonymous codon usage in the genus. In particular, the GC content at the 3rd base position seems to shape heavily the effective number of codons, giving indication that here mutational bias dominates over translational selection. Evolutionary trees based on codon and aminoacid usage are consistent with traditional phylogenies of species within the genus.

Modeling the structural basis of human CCR5 chemokine receptor function: from homology model building and molecular dynamics validation to agonist and antagonist docking.

This article describes the construction and validation of a three-dimensional model of the human CCR5 receptor using a homology-based approach starting from the X-ray structure of the bovine rhodopsin receptor. The reliability of the model is assessed through molecular dynamics and docking simulations using both natural agonists and a synthetic antagonist. Some important structural and functional features of the receptor cavity and the extracellular loops are identified, in agreement with data available from site-directed mutagenesis. The results of this study help to explain the structural basis for the recognition, activation, and inhibition processes of CCR5 and may provide fresh insights for the design of HIV-1 entry blockers.

Panoramic infrared-imaging spectroradiometer model with reverse phase-modulated beam broadcasting.

The optical design of a passive remote sensor, a panoramic spectroradiometer (PANSPEC), and its computer-simulated image performance are presented. PANSPEC monitors the surrounding infrared environment for chemical clouds, detecting a presence once absorption or emission spectra characteristic of the chemical species are resolved. PANSPEC broadcasts chemical presence and cloud heading when equipped with a laser transmitter that projects a polarized laser beam source with phase encryption back through the optical system into object space. Various merit functions were programmed and accessed during computer optimization runs for shaping and positioning of the instrument's semishell entrance window, collector, collimator, interferometer, and imager. The result is a balanced near-diffraction-limited circular image, 6.3 mm across with 10-line pairs/mm spatial resolution at 50% modulation, and an f/2.3 working speed.

Neural network pattern recognition by means of differential absorption Mueller matrix spectroscopy.

Artificial neural network systems were built for detecting amino acids, sugars, and other solid organic matter by pattern recognition of their polarized light scattering signatures in the form of a Mueller matrix. Backward-error propagation and adaptive gradient descent methods perform network training. The product of the training is a weight matrix that, when applied as a filter, discerns the presence of the analytes on the basis of their cued susceptive Mueller matrix difference elements. This filter function can be implemented as a software or a hardware module to a future differential absorption Mueller matrix spectrometer.

Infrared detection of liquids on terrestrial surfaces by CO(2) laser heating.

The strong mid-infrared bands of contaminant liquids wetting sand and soil can be remotely detected by 0.103-eV laser irradiation with beam intensity well below that which chars the terrain. Emissions from heated nonvolatile interstitial liquid layers and extinction of thermoluminescence by beam-generated vapors of volatile contaminants are spectrally distinct within the infrared contaminant fingerprint spectral region-as measured by a Michelson interferometer based FT-IR radiometer instrument. The contaminant's vibrational resonance intensities change proportionally in magnitude and sign in measured contiguous difference FFT spectra, within a specific beam-to-sample dwell period. The onset irradiation time and period for detecting these bands can differ according to amount and volatility of contaminant, beam intensity and its time of dwell necessary to produce sufficient thermoluminescence flux, and on the quantity of interferogram data acquisitions.

Neural network pattern recognition of thermal-signature spectra for chemical defense.

We treat infrared patterns of absorption or emission by nerve and blister agent compounds (and simulants of this chemical group) as features for the training of neural networks to detect the compounds' liquid layers on the ground or their vapor plumes during evaporation by external heating. Training of a four-layer network architecture is composed of a backward-error-propagation algorithm and a gradient-descent paradigm. We conduct testing by feed-forwarding preprocessed spectra through the network in a scaled format consistent with the structure of the training-data-set representation. The bestperformance weight matrix (spectral filter) evolved from final network training and testing with software simulation trials is electronically transferred to a set of eight artificial intelligence integrated circuits (ICs') in specific modular form (splitting of weight matrices). This form makes full use of all input-output IC nodes. This neural network computer serves an important real-time detection function when it is integrated into pre- and postprocessing data-handling units of a tactical prototype thermoluminescence sensor now under development at the Edgewood Research, Development, and Engineering Center.