para‐Quinone methides (p‐QMs) are naturally occurring molecules that have been finding increasing synthetic applications in the last few years. The presence of two electronically different exocyclic ...conjugate substituents in their structure, carbonyl and methylidene, leads to a pronounced reactivity owing to the polarization of the molecule. In this sense, those are prone to undergo the attack of nucleophiles in the terminal carbon exocyclic double bond, behaving as vinylogous electrophiles and generating 1,6‐addition products. In this context, in the last few years the development of catalytic approaches for 1,6‐nucleophilic addition reactions involving p‐QMs has attracted considerable attention. Considering the extensive applications that such molecules have found in the last decades in 1,6‐addition reactions, in this review we comprehensively discuss the historical development of this field, starting with early approaches on natural product synthesis, going through seminal non‐stereoselective processes and progressing to cutting‐edge asymmetric‐catalyzed approaches.
para‐Quinone methides (p‐QMs) are naturally occurring molecules with two electronically different exocyclic conjugate substituents in their structure, carbonyl and methylidene, which gives them a pronounced reactivity owing to the polarization of the molecule. By attack of nucleophiles in the terminal carbon exocyclic double bond, they generate 1,6‐addition products.
Local extinctions have cascading effects on ecosystem functions, yet little is known about the potential for the rapid evolutionary change of species in human-modified scenarios. We show that the ...functional extinction of large-gape seed dispersers in the Brazilian Atlantic forest is associated with the consistent reduction of the seed size of a keystone palm species. Among 22 palm populations, areas deprived of large avian frugivores for several decades present smaller seeds than nondefaunated forests, with negative consequences for palm regeneration. Coalescence and phenotypic selection models indicate that seed size reduction most likely occurred within the past 100 years, associated with human-driven fragmentation. The fast-paced defaunation of large vertebrates is most likely causing unprecedented changes in the evolutionary trajectories and community composition of tropical forests.
Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and ...childhood cancer susceptibility.
We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants.
A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes.
We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis.
Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.
Seed dispersal constitutes a pivotal process in an increasingly fragmented world, promoting population connectivity, colonization and range shifts in plants. Unveiling how multiple frugivore species ...disperse seeds through fragmented landscapes, operating as mobile links, has remained elusive owing to methodological constraints for monitoring seed dispersal events. We combine for the first time DNA barcoding and DNA microsatellites to identify, respectively, the frugivore species and the source trees of animal‐dispersed seeds in forest and matrix of a fragmented landscape. We found a high functional complementarity among frugivores in terms of seed deposition at different habitats (forest vs. matrix), perches (isolated trees vs. electricity pylons) and matrix sectors (close vs. far from the forest edge), cross‐habitat seed fluxes, dispersal distances and canopy‐cover dependency. Seed rain at the landscape‐scale, from forest to distant matrix sectors, was characterized by turnovers in the contribution of frugivores and source‐tree habitats: open‐habitat frugivores replaced forest‐dependent frugivores, whereas matrix trees replaced forest trees. As a result of such turnovers, the magnitude of seed rain was evenly distributed between habitats and landscape sectors. We thus uncover key mechanisms behind “biodiversity–ecosystem function” relationships, in this case, the relationship between frugivore diversity and landscape‐scale seed dispersal. Our results reveal the importance of open‐habitat frugivores, isolated fruiting trees and anthropogenic perching sites (infrastructures) in generating seed dispersal events far from the remnant forest, highlighting their potential to drive regeneration dynamics through the matrix. This study helps to broaden the “mobile‐link” concept in seed dispersal studies by providing a comprehensive and integrative view of the way in which multiple frugivore species disseminate seeds through real‐world landscapes.
Urinary kidney injury molecule-1 in renal disease Moresco, Rafael N.; Bochi, Guilherme V.; Stein, Carolina S. ...
Clinica chimica acta,
December 2018, 2018-Dec, 2018-12-00, 20181201, Letnik:
487
Journal Article
Recenzirano
Kidney injury molecule-1 (KIM-1), a type l transmembrane glycoprotein, is recognized as a potential biomarker for detection of tubular injury in the main renal diseases. Urinary KIM-1 increases ...rapidly upon the tubular injury, and its levels are associated with the degree of tubular injury, interstitial fibrosis, and inflammation in the injured kidney. Currently, the investigation of kidney diseases is usually performed through the assessment of serum creatinine and urinary albumin. However, these biomarkers are limited for the early detection of changes in renal function. Besides, the tubular injury appears to precede glomerular damage in the pathophysiology of renal diseases. For these reasons, the search for sensitive, specific and non-invasive biomarkers is of interest. Therefore, the purpose of this article is to review the physiological mechanisms of KIM-1, as well to present clinical evidence about the association between elevated urinary KIM-1 levels and the main renal diseases such as chronic kidney disease, diabetic kidney disease, acute kidney injury, and IgA nephropathy.
•The KIM-1 expression is increased in tubular proximal tubule cells after injury.•Urinary KIM-1 is increased in renal diseases such as CKD, AKI, and IgA nephropathy.•Changes in urinary KIM-1 are observed before changes in serum creatinine.•Urinary KIM-1 presents value for the diagnosis and prognosis of the main renal diseases.
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Intestinal helminths are prevalent in individuals who live in rural areas of developing countries, where obesity, type 2 diabetes, and metabolic syndrome are rare. In the present ...study, we analyzed the modulation of the gut microbiota in mice infected with the helminth Strongyloides venezuelensis, and fed either a standard rodent chow diet or high-fat diet (HFD). To investigate the effects of the microbiota modulation on the metabolism, we analyzed the expression of tight-junction proteins present in the gut epithelium, inflammatory markers in the serum and tissue and quantified glucose tolerance and insulin sensitivity and resistance. Additionally, the levels of lipids related to inflammation were evaluated in the feces and serum. Our results show that infection with Strongyloides venezuelensis results in a modification of the gut microbiota, most notably by increasing Lactobacillus spp. These modifications in the microbiota alter the host metabolism by increasing the levels of anti-inflammatory cytokines, switching macrophages from a M1 to M2 pattern in the adipose tissue, increasing the expression of tight junction proteins in the intestinal cells (thereby reducing the permeability) and decreasing LPS in the serum. Taken together, these changes correlate with improved insulin signaling and sensitivity, which could also be achieved with HFD mice treated with probiotics. Additionally, helminth infected mice produce higher levels of oleic acid, which participates in anti-inflammatory pathways. These results suggest that modulation of the microbiota by helminth infection or probiotic treatment causes a reduction in subclinical inflammation, which has a positive effect on the glucose metabolism of the host.
Although habitat loss has large, consistently negative effects on biodiversity, its genetic consequences are not yet fully understood. This is because measuring the genetic consequences of habitat ...loss requires accounting for major methodological limitations like the confounding effect of habitat fragmentation, historical processes underpinning genetic differentiation, time-lags between the onset of disturbances and genetic outcomes, and the need for large numbers of samples, genetic markers, and replicated landscapes to ensure sufficient statistical power. In this paper we overcame all these challenges to assess the genetic consequences of extreme habitat loss driven by mining in two herbs endemic to Amazonian savannas. Relying on genotyping-by-sequencing of hundreds of individuals collected across two mining landscapes, we identified thousands of neutral and independent single-nucleotide polymorphisms (SNPs) in each species and used these to evaluate population structure, genetic diversity, and gene flow. Since open-pit mining in our study region rarely involves habitat fragmentation, we were able to assess the independent effect of habitat loss. We also accounted for the underlying population structure when assessing landscape effects on genetic diversity and gene flow, examined the sensitivity of our analyses to the resolution of spatial data, and used annual species and cross-year analyses to minimize and quantify possible time-lag effects. We found that both species are remarkably resilient, as genetic diversity and gene flow patterns were unaffected by habitat loss. Whereas historical habitat amount was found to influence inbreeding; heterozygosity and inbreeding were not affected by habitat loss in either species, and gene flow was mainly influenced by geographic distance, pre-mining land cover, and local climate. Our study demonstrates that it is not possible to generalize about the genetic consequences of habitat loss, and implies that future conservation efforts need to consider species-specific genetic information.
Lymphangioleiomyomatosis (LAM) is included within group 5 of the current PH classification (unclear multifactorial mechanisms). However, data regarding the occurrence of PH in LAM are scarce. The ...aims of the study were to describe the prevalence and characteristics of PH in a large cohort of LAM patients with different levels of severity, and to evaluate the role of echocardiography and carbon monoxide diffusion capacity (DL
) as screening methods for PH in LAM.
One hundred five LAM patients underwent transthoracic echocardiography, pulmonary function tests (PFTs) and 6-min walk test (6MWT). Patients with a suspicion of PH on echocardiography, defined by the presence of estimated systolic pulmonary artery pressure (PAP) over 35 mmHg or PFT showing DLco below 40% of the predicted value, underwent right heart catheterisation to confirm the diagnosis of PH.
Eight patients (7.6%) had PH confirmed on right heart catheterisation, six patients (5.7%) had a pre-capillary pattern and two patients (1.9%) had a post-capillary profile. Only one patient (1%) had mean PAP over 35 mmHg. Patients with PH had lower FEV
and DL
in PFTs and greater oxygen desaturation and dyspnea intensity during 6MWT compared with those without PH. In 63% of the patients with confirmed PH, the right heart catheterisation was performed based only on DL
result.
The prevalence of PH is low in LAM patients. Pulmonary hypertension in LAM is typically mild and significantly associated with pulmonary parenchymal involvement. Carbon monoxide diffusion capacity significantly improved the identification of PH in LAM patients.
Gunshot residue (GSR) is an evidence of major importance in firearm-related crimes. The recent introduction of nontoxic ammunition has made impossible the characterization of GSR particles by the ...current methods employed by forensic experts. To overcome this drawback, the introduction of luminescent markers was proposed, allowing on-site visual detection of luminescent gunshot residue (LGSR) at the crime scene. Three different luminescent markers coordinated with europium for specific and selective encoding of ammunition have been proposed. To promote a variety of versatile tools for GSR analysis, spectroscopic techniques combined with chemometric methods can be applied to achieve a reliable, fast, and nondestructive means to identify LGSR and discriminate among the different markers. Luminescence (emission and excitation), normal, and resonance Raman spectroscopies associated with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were evaluated. The classification model using the complementary information on emission and excitation spectra, a.k.a. data fusion, provided a 100% correct classification for all markers. A comprehensive study has been developed to show that the insertion of luminescent markers enables not only the easy localization of GSR residues but also the possibility of ammunition encoding through the use of multivariate classification methods.
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