Los Murillos de Macharaviaya [Texto impreso]

Recorte de un artículo de la revista "Arte Español" , donde el investigador B.S. Crosa hace una descripción de los cuadros atribuidos popularmente a Murillo en la iglesia de Macharaviaya y que P. Madoz recoje en: Diccionario geográfico-estadístico-histórico de España y sus posesiones de ultramar. Madrid, 1845-1850. Descripciones del cuadro de La Virgen de Rosario atribuido a Murillo, que Crosa asemeja a la obra pictórica de Claudio Coello

Tree rings as ecological indicator of geomorphic activity in geoheritage studies

Mountain areas are characterized by geomorphic processes, especially mass wasting and snow avalanches, which may impact the landscape affecting also the biological component, trees included. If sites colonized by trees are characterized by geomorphic features with a high Global and Scientific Value, including Representativeness of geomorphological processes, Educational Exemplarity, and Integrity, they can be considered geomorphosites. In the framework of assessment of the Scientific Value of geomorphosites, Ecological Support Role is of great importance. Hence, tree rings derived information can be used as indicators to refine the Scientific Value of the sites and also to propose multidisciplinary approaches to understand landscape dynamics. In fact, trees colonizing sites of geomorphological interest are used for detecting past and present events and tree rings may be considered ecological indicators under different points of view. Arboreal vegetation can register growth disturbances in terms of morphological features, at macro- (particular morphologies of trunks) and micro-scale (annual growth rings, stress indicators like compression wood, traumatic resin ducts), becoming a powerful indicator of the geomorphic activity affecting the landscape. In some cases, combined with other techniques like climate data analysis, they may allow refining the often lacunose historical records of geomorphic events impacting different territories. The integrated analysis carried out in the Loana Valley (Sesia Val Grande UNESCO Geopark, Western Italian Alps), considering a selection of geomorphosites affected by mass wasting processes and snow avalanches and located along a touristic trail, allowed to detect which meteorological thresholds favour hydrogeological instability (i.e. overcome of Mean Annual Rainfall of 6\u201310%). Tree rings data coming from the investigated sites provided information on the recurrence of geomorphic activity, allowing filling gaps within the historical archives, by individuating years during which hydrogeological or snow-related events probably occurred and that were missed (i.e. 1986, 1989, 2001, 2007), and adding details on sites for which temporal constraints had not been found before (i.e. Pizzo Stagno Complex System). Finally, investigated sites demonstrated to differently record the history of instability affecting the area and this difference is mirrored in the sites values that are adopted in the framework of geoheritage analysis (Scientific Value, Ecological Support Role and Educational Exemplarity). The proposed multidisciplinary approach, including geomorphology, dendrogeomorphology and climatology, represents, hence, a useful tool in geoheritage valorisation and management strategies

Current and historical genetic variability of native brown trout populations in a southern alpine ecosystem: implications for future management

The highly polymorphic taxon European brown trout (genus Salmo) has high phenotypic plasticity, displaying a complex pattern of morphological and life-history variation, contributing to taxonomic confusion. Three main mitochondrial lineages (Adriatic, Mediterranean, and marmoratus) developed during the Pleistocene climatic events in the southern Alpine ecosystem. Here, the natural distribution of native brown trout S. trutta is controversial, complicated by introductions of the Atlantic strain. By investigating museum vouchers, this study aimed to retrace the historical presence of brown trout in the southern Alpine ecosystem before the beginning of mass introductions, which occurred since the middle of the 19th century. By examining the combination of historical and current genetic variability, this study aims to depict the actual impact of introductions of the introduced strain, increasing knowledge and informing conservation strategies and future management plans. The molecular approaches selected were: (i) sequencing of the mitochondrial control region and (ii) genotyping of the nuclear gene LDH-C1*. Vouchers dated the presence of the native Adriatic strain since 1821, while current genetic variability showed the widespread signature of introgression, a consequence of several decades of introductions. Focused plans to preserve local lineages are urgently needed, including short-term solution to avoid complete pauperization of this ecosystem

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Mechanistic Insights into a Novel Exporter-Importer System of Mycobacterium tuberculosis Unravel Its Role in Trafficking of Iron

Elucidation of the basic mechanistic and biochemical principles underlying siderophore mediated iron uptake in mycobacteria is crucial for targeting this principal survival strategy vis-à-vis virulence determinants of the pathogen. Although, an understanding of siderophore biosynthesis is known, the mechanism of their secretion and uptake still remains elusive.Here, we demonstrate an interplay among three iron regulated Mycobacterium tuberculosis (M.tb) proteins, namely, Rv1348 (IrtA), Rv1349 (IrtB) and Rv2895c in export and import of M.tb siderophores across the membrane and the consequent iron uptake. IrtA, interestingly, has a fused N-terminal substrate binding domain (SBD), representing an atypical subset of ABC transporters, unlike IrtB that harbors only the permease and ATPase domain. SBD selectively binds to non-ferrated siderophores whereas Rv2895c exhibits relatively higher affinity towards ferrated siderophores. An interaction between the permease domain of IrtB and Rv2895c is evident from GST pull-down assay. In vitro liposome reconstitution experiments further demonstrate that IrtA is indeed a siderophore exporter and the two-component IrtB-Rv2895c system is an importer of ferrated siderophores. Knockout of msmeg_6554, the irtA homologue in Mycobacterium smegmatis, resulted in an impaired M.tb siderophore export that is restored upon complementation with M.tb irtA.Our data suggest the interplay of three proteins, namely IrtA, IrtB and Rv2895c in synergizing the balance of siderophores and thus iron inside the mycobacterial cell

Prognostic Significance of Age Within the Adolescent and Young Adult Acute Ischemic Stroke Population after Mechanical Thrombectomy: Insights from STAR

Objective: Although younger adults have been shown to have better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the significance of this relationship in the adolescent and young adult (AYA) population is not well defined given its undefined rarity. Correspondingly, the goal of this study was to determine the prognostic significance of age in this specific demographic following MT for large-vessel occlusions. Methods: A prospectively maintained international multi-institutional database, STAR (Stroke Thrombectomy and Aneurysm Registry), was reviewed for all patients aged 12-18 (adolescent) and 19-25 (young adult) years. Parameters were compared using chi-square and t-test analyses, and associations were interrogated using regression analyses. Results: Of 7192 patients in the registry, 41 (0.6%) satisfied all criteria, with a mean age of 19.7 ± 3.3 years. The majority were male (59%) and young adults (61%) versus adolescents (39%). The median prestroke modified Rankin Scale (mRS) score was 0 (range 0-2). Strokes were most common in the anterior circulation (88%), with the middle cerebral artery being the most common vessel (59%). The mean onset-to-groin puncture and groin puncture-to-reperfusion times were 327 ± 229 and 52 ± 42 minutes, respectively. The mean number of passes was 2.2 ± 1.2, with 61% of the cohort achieving successful reperfusion. There were only 3 (7%) cases of reocclusion. The median mRS score at 90 days was 2 (range 0-6). Between the adolescent and young adult subgroups, the median mRS score at last follow-up was statistically lower in the adolescent subgroup (1 vs 2, p = 0.03), and older age was significantly associated with a higher mRS at 90 days (coefficient 0.33, p < 0.01). Conclusions: Although rare, MT for AIS in the AYA demographic is both safe and effective. Even within this relatively young demographic, age remains significantly associated with improved functional outcomes. The implication of age-dependent stroke outcomes after MT within the AYA demographic needs greater validation to develop effective age-specific protocols for long-term care across both pediatric and adult centers.info:eu-repo/semantics/publishedVersio

Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. v4

Studying the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores - soluble, low molecular weight compounds - have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition for acquiring iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of 'odd' siderophores can reveal the evolutionary strategy that led to their creation. Here, we here report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholerae vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.This work was supported by the National Institutes of Health (Grants GM82137 to R.K., and AI057159 and GM086258 to J.C.). M.R.S. acknowledges support from the NIH Pathway to Independence Award (Grant 1K99 GM098299-01). S.C. and M.J.V. acknowledge support from the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/38298/2007 to S.C.; Project PTDC/EBB-EBI/104263/2008 to M.J.V.)

The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

We previously showed that the facultative intracellular pathogen Rhodococcus equi produces a nondiffusible and catecholate-containing siderophore (rhequibactin) involved in iron acquisition during saprophytic growth. Here, we provide evidence that the rhbABCDE cluster directs the biosynthesis of a hydroxamate siderophore, rhequichelin, that plays a key role in virulence. The rhbC gene encodes a nonribosomal peptide synthetase that is predicted to produce a tetrapeptide consisting of N(5)-formyl-N(5)-hydroxyornithine, serine, N(5)-hydroxyornithine, and N(5)-acyl-N(5)-hydroxyornithine. The other rhb genes encode putative tailoring enzymes mediating modification of ornithine residues incorporated into the hydroxamate product of RhbC. Transcription of rhbC was upregulated during growth in iron-depleted medium, suggesting that it plays a role in iron acquisition. This was confirmed by deletion of rhbCD, rendering the resulting strain R. equi SID2 unable to grow in the presence of the iron chelator 2,2-dipyridyl. Supernatant of the wild-type strain rescued the phenotype of R. equi SID2. The importance of rhequichelin in virulence was highlighted by the rapid increase in transcription levels of rhbC following infection and the inability of R. equi SID2 to grow within macrophages. Unlike the wild-type strain, R. equi SID2 was unable to replicate in vivo and was rapidly cleared from the lungs of infected mice. Rhequichelin is thus a key virulence-associated factor, although nonpathogenic Rhodococcus species also appear to produce rhequichelin or a structurally closely related compound. Rhequichelin biosynthesis may therefore be considered an example of cooption of a core actinobacterial trait in the evolution of R. equi virulence

International Experience of Mechanical Thrombectomy During the COVID-19 Pandemic: Insights from STAR and ENRG

Background: In response to the COVID-19 pandemic, many centers altered stroke triage protocols for the protection of their providers. However, the effect of workflow changes on stroke patients receiving mechanical thrombectomy (MT) has not been systematically studied. Methods: A prospective international study was launched at the initiation of the COVID-19 pandemic. All included centers participated in the Stroke Thrombectomy and Aneurysm Registry (STAR) and Endovascular Neurosurgery Research Group (ENRG). Data was collected during the peak months of the COVID-19 surge at each site. Collected data included patient and disease characteristics. A generalized linear model with logit link function was used to estimate the effect of general anesthesia (GA) on in-hospital mortality and discharge outcome controlling for confounders. Results: 458 patients and 28 centers were included from North America, South America, and Europe. Five centers were in high-COVID burden counties (HCC) in which 9/104 (8.7%) of patients were positive for COVID-19 compared with 4/354 (1.1%) in low-COVID burden counties (LCC) (P<0.001). 241 patients underwent pre-procedure GA. Compared with patients treated awake, GA patients had longer door to reperfusion time (138 vs 100 min, P=<0.001). On multivariate analysis, GA was associated with higher probability of in-hospital mortality (RR 1.871, P=0.029) and lower probability of functional independence at discharge (RR 0.53, P=0.015). Conclusion: We observed a low rate of COVID-19 infection among stroke patients undergoing MT in LCC. Overall, more than half of the patients underwent intubation prior to MT, leading to prolonged door to reperfusion time, higher in-hospital mortality, and lower likelihood of functional independence at discharge.info:eu-repo/semantics/publishedVersio

Chemical Synthesis of Staphyloferrin B Affords Insight into the Molecular Structure, Iron Chelation, and Biological Activity of a Polycarboxylate Siderophore Deployed by the Human Pathogen

Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.Alfred Benzon Foundation (Postdoctoral fellowship)Pacific Southwest Regional Center of ExcellenceAlfred P. Sloan Foundatio