Architectology® : architectural knowledge construction

Recent theoretical debates on the sources of architectural knowledge tend to dissect architecture into a set of atomized disciplines, or else define it as a multidisciplinary matter. Such are for instance the most recent debates held by the EAAE on the issue of architectural theory between 2006 and 2010. However, as Pedro Vieira de Almeida (2005) and other theoreticians – i.e. Alexander Tzonis, Liane Lefaivre – have long claimed, architectural theory – here considered a part of architectology – has its own knowledge sources within architecture itself. Despite its lacking a clearly defined corpus which may let us establish clear boundaries, architectural theory does not belong to science, history, social studies, philosophy or aesthetics. All these fields have their own requirements and means to articulate a universal discourse of their own, not always or often coincidental with that of architecture. Thus it seems easier to define what architectural knowledge is not than to establish what it is in fact. Architectural knowledge does not own ‘the’ truth, but rather it is constructive in the terms described by Popper (1934), Kuhn (1962) or Bourdieu (1967). Architectology draws from the example of cousin disciplines like music – where it is but a natural, almost inherent consequence – or that of the ‘French school’ – where architectural theory is a discipline in its own right, established as such since 1968 – this article aims to claim the right of architecture to own a global process of its own through which to understand architectural knowledge as a whole. It is constituted as a system of subbodies of knowledge central to the major field of architecture. All of these are considered as timely contributors of knowledge to this field, and therefore having played a central role throughout times, to the present moment. Architectology comes to adopt all of the methods needed in architectural research and knowledge construction

A role for palindromic structures in the cis-region of maize Sirevirus LTRs in transposable element evolution and host epigenetic response

Transposable elements (TEs) proliferate within the genome of their host, which responds by silencing them epigenetically. Much is known about the mechanisms of silencing in plants, particularly the role of siRNAs in guiding DNA methylation. In contrast, little is known about siRNA targeting patterns along the length of TEs, yet this information may provide crucial insights into the dynamics between hosts and TEs. By focusing on 6456 carefully annotated, full-length Sirevirus LTR retrotransposons in maize, we show that their silencing associates with underlying characteristics of the TE sequence and also uncover three features of the host–TE interaction. First, siRNA mapping varies among families and among elements, but particularly along the length of elements. Within the cis-regulatory portion of the LTRs, a complex palindrome-rich region acts as a hotspot of both siRNA matching and sequence evolution. These patterns are consistent across leaf, tassel, and immature ear libraries, but particularly emphasized for floral tissues and 21- to 22-nt siRNAs. Second, this region has the ability to form hairpins, making it a potential template for the production of miRNA-like, hairpin-derived small RNAs. Third, Sireviruses are targeted by siRNAs as a decreasing function of their age, but the oldest elements remain highly targeted, partially by siRNAs that cross-map to the youngest elements. We show that the targeting of older Sireviruses reflects their conserved palindromes. Altogether, we hypothesize that the palindromes aid the silencing of active elements and influence transposition potential, siRNA targeting levels, and ultimately the fate of an element within the genome

Detection of mecC-Methicillin-resistant Staphylococcus aureus isolates in river water : a potential role for water in the environmental dissemination

Methicillin-resistant Staphylococcus aureus (MRSA) is a public health concern due to limited treatment options. The recent description of a mecA homologue, mecC in human and cattle, led to studies to detect this new variant in human and other animal species. Detection of mecC in wild boar and fallow deer in a Spanish game estate led us to further investigate the presence of mecC-MRSA at this location. Samples from cattle, wild animals, workers and river water were tested. A further three mecC-MRSA isolates were obtained from river water. Molecular characterization (multilocus sequence typing and spa typing) and antimicrobial susceptibility testing (broth microdilution) showed that isolates were similar to those detected in wild animals. Whole genome sequencing confirmed that the isolates from the river water and wild animals in the same geographic area were all closely related isolates of ST425 mecC-MRSA. The presence of mecC-MRSA in the river water highlights the potential role of water in the dissemination of mecC-MRSA

Persistent HIV-controllers are more prone to spontaneously clear HCV: a retrospective cohort study.

HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4+ T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure.This work was supported by the Instituto de Salud Carlos III (research contracts CPII014/00025 to E.R.‐M., and FI14/00431 to L.T.‐D. and research projects PI12/02283, PI16/00684, PI19/01127 to E.R.‐M.) and Red Temática de Investigación Cooperativa en SIDA (Projects RD12/0017/0029, RD12/0017/0031, and RD16/0025/0020 and RD16/0025/0013), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008 to 2011 and 2013 to 2016, Instituto de Salud Carlos III, Fondos FEDER. E.R.‐M. was supported by Consejería de Salud y Bienestar Social of Junta de Andalucía through the Nicolás Monardes program (C‐0032/17), N Rallón is a Miguel Servet investigator from the Spanish Carlos III Institute of Health (ISCIII), grant CP14/00198, Madrid, Spain and B.D.M. received a grant from The Spanish Ministry of Education (FPU13/02451). Work in CL‐G’s laboratory was supported by grants SAF (2010 to 17226) and (2016‐77894‐R) from MINECO (Spain) and FIS (PI 13/02269, ISCIII) and in part by the RIS‐RETIC grants RD06/006/0036 and RD12/0017/0028 funded by the ISC III‐FEDER. MP has a contract of RIS‐RETIC RD12/0017/0036.S

A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Three groups of transposable elements with contrasting copy number dynamics and host responses in the maize (Zea mays ssp. mays) genome

Most angiosperm nuclear DNA is repetitive and derived from silenced transposable elements (TEs). TE silencing requires substantial resources from the plant host, including the production of small interfering RNAs (siRNAs). Thus, the interaction between TEs and siRNAs is a critical aspect of both the function and the evolution of plant genomes. Yet the co-evolutionary dynamics between these two entities remain poorly characterized. Here we studied the organization of TEs within the maize (Zea mays ssp mays) genome, documenting that TEs fall within three groups based on the class and copy numbers. These groups included DNA elements, low copy RNA elements and higher copy RNA elements. The three groups varied statistically in characteristics that included length, location, age, siRNA expression and 24: 22 nucleotide (nt) siRNA targeting ratios. In addition, the low copy retroelements encompassed a set of TEs that had previously been shown to decrease expression within a 24 nt siRNA biogenesis mutant (mop1). To investigate the evolutionary dynamics of the three groups, we estimated their abundance in two landraces, one with a genome similar in size to that of the maize reference and the other with a 30% larger genome. For all three accessions, we assessed TE abundance as well as 22 nt and 24 nt siRNA content within leaves. The high copy number retroelements are under targeted similarly by siRNAs among accessions, appear to be born of a rapid bust of activity, and may be currently transpositionally dead or limited. In contrast, the lower copy number group of retrolements are targeted more dynamically and have had a long and ongoing history of transposition in the maize genome

The number of significantly differences in pairwise comparisons between genotypes for TE, 22

a<p>The standard χ² test based on a 2×2 table of the relative proportions of hits.</p>b<p>The χ² corrected by the coverage to the FGS.</p>c<p>The χ² test of proportionality; see text and Supplement <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004298#pgen.1004298.s007" target="_blank">Text S1</a>.</p

Pairwise comparisons between accessions for: a) TE hits; b) 22 nt siRNA hits per RPKM_TE and c) 24 nt siRNA hits per RPKM_TE.

<p>For all the cases the <i>x</i>- and <i>y</i>-axis indicate accessions under comparison (B73, PT or OAXA). Each dot represents a TE subfamily, with the regression (<i>y</i>) and correlations (<i>r²</i>) between accessions indicated. The solid line represents the regression fit, while the dashed line represents the null hypothesis. The color of the dots represents significance: red dots are significant differences between accessions at a FDR of <i>q</i><0.001, based on the χ²_Corr in panel a and the χ²_Prop for panels b and c. Blue dots are not significant.</p