According to the World Health Organization, malaria remains one of the biggest public health problems in the world. The development of resistance is a current concern, mainly because the number of ...safe drugs for this disease is limited. Artemisinin-based combination therapy is recommended by the World Health Organization to prevent or delay the onset of resistance. Thus, the need to obtain new drugs makes artemisinin the most widely used scaffold to obtain synthetic compounds. This review describes the drugs based on artemisinin and its derivatives, including hybrid derivatives and dimers, trimers and tetramers that contain an endoperoxide bridge. This class of compounds is of extreme importance for the discovery of new drugs to treat malaria.
An open and dry vegetation belt separates Amazonia (AM) and the Atlantic Forest (AF). Evidence from palaeoclimatic and phylogenetic studies suggests past connections between these forests during ...cycles of increased humidity through the formation of forest corridors. The distinctive northern AF avifauna is known to have affinities both with AM and the southern AF. Still, the extent of how these two regions contributed to the assemblage of this avifauna remains poorly understood. Using historical demographic analyses and comparative phylogeography based on sub‐genomic genetic sampling, we assessed how past connections between AM and AF led to shared vicariance and colonization events in four avian AF endemic taxa. Our results supported the occurrence of humid forest corridors promoting the contact between AF and AM populations and suggested two vicariant events and two colonization events from AF to AM. Population divergences were mostly non‐synchronous and occurred multiple times during the Pleistocene. Historical gene flow was prevalent across study groups, supporting migration flows after the initial separation between AM and AF – a pattern previously unknown in birds between these regions. Idiosyncratic histories and divergent demographic syndromes suggest that organisms' responses to climate‐driven habitat shifts broadly depend on their ecological attributes. This study strengthened our knowledge of past connections between AM and AF and provided demographic scenarios amenable for testing in other groups of co‐distributed organisms.
Valine Radiolysis by H+, He+, N+, and S15+ MeV Ions Costa, Cíntia A. P. da; Muniz, Gabriel S. Vignoli; Boduch, Philippe ...
International journal of molecular sciences,
03/2020, Letnik:
21, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Radiolysis of biomolecules by fast ions has interest in medical applications and astrobiology. The radiolysis of solid D-valine (0.2–2 μm thick) was performed at room temperature by 1.5 MeV H+, He+, ...N+, and 230 MeV S15+ ion beams. The samples were prepared by spraying/dropping valine-water-ethanol solution on ZnSe substrate. Radiolysis was monitored by infrared spectroscopy (FTIR) through the evolution of the intensity of the valine infrared 2900, 1329, 1271, 948, and 716 cm−1 bands as a function of projectile fluence. At the end of sample irradiation, residues (tholins) presenting a brownish color are observed. The dependence of the apparent (sputtering + radiolysis) destruction cross section, σd, on the beam stopping power in valine is found to follow the power law σd = aSen, with n close to 1. Thus, σd is approximately proportional to the absorbed dose. Destruction rates due to the main galactic cosmic ray species are calculated, yielding a million year half-life for solid valine in space. Data obtained in this work aim a better understanding on the radioresistance of complex organic molecules and formation of radioproducts.
Chronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active ...alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.
Self-Capacitance of High-Voltage Transformers Dalessandro, L.; da Silveira Cavalcante, F.; Kolar, J.W.
IEEE transactions on power electronics,
09/2007, Letnik:
22, Številka:
5
Journal Article
Recenzirano
The calculation of a transformer's parasitics, such as its self capacitance, is fundamental for predicting the frequency behavior of the device, reducing this capacitance value and moreover for more ...advanced aims of capacitance integration and cancellation. This paper presents a comprehensive procedure for calculating all contributions to the self-capacitance of high-voltage transformers and provides a detailed analysis of the problem, based on a physical approach. The advantages of the analytical formulation of the problem rather than a finite element method analysis are discussed. The approach and formulas presented in this paper can also be used for other wound components rather than just step-up transformers. Finally, analytical and experimental results are presented for three different high-voltage transformer architectures.
Brazil's protected areas under threat Silveira, F A O; Ferreira, M C; Perillo, L N ...
Science (American Association for the Advancement of Science),
08/2018, Letnik:
361, Številka:
6401
Journal Article
Display omitted
•PCE avifauna is closely related to that in the southern-central Atlantic Forest.•Study species exhibited a pattern of divergence with gene flow and stable population size.•PCE ...species showed patterns of divergence during middle Pleistocene.•Pleistocene Refugia and connections with Amazonia shaped extant genetic diversity.
The Pernambuco Center of Endemism (PCE) is the northernmost strip of the Atlantic Forest (AF). Biogeographic affinities among avifaunas in the PCE, the southern-central Atlantic Forest (SCAF), and Amazonia (AM) have not been studied comprehensively, and current patterns of genetic diversity in the PCE remain unclear. The interplay between species’ ecological attributes and historical processes, such as Pleistocene climate fluctuations or the appearance of rivers, may have affected population genetic structures in the PCE. Moreover, the role of past connections between the PCE and AM and the elevational distribution of species in assembling the PCE avifauna remain untested. Here, we investigated the biogeographic history of seven taxa endemic to the PCE within a comparative phylogeographic framework based on a mean of 3,618 independent single nucleotide polymorphisms (SNPs) extracted from flanking regions of ultraconserved elements (UCEs) and one mitochondrial gene. We found that PCE populations were more closely related to SCAF populations than they were to those in AM, regardless of their elevational range, with divergence times placed during the Mid-Pleistocene. These splits were consistent with a pattern of allopatric divergence with gene flow until the upper Pleistocene and no signal of rapid changes in population sizes. Our results support the existence of a Pleistocene refugium driving current genetic diversity in the PCE, thereby rejecting the role of the São Francisco River as a primary barrier for population divergence. Additionally, we found that connections with Amazonia also played a significant role in assembling the PCE avifauna through subsequent migration events.
Background.Risk factors for Nocardia infection in organ transplant recipients have not been formally assessed in the current era of transplantation. Methods.We performed a matched case-control study ...(1 : 2 ratio) between January 1995 and December 2005. Control subjects were matched for transplant type and timing. Univariate matched odds ratios were determined and conditional logistic regression was performed to identify independent risk factors. Clinical and microbiological characteristics of all case patients were reviewed. Results.Among 5126 organ transplant recipients, 35 (0.6%) were identified as having cases of Nocardia infection. The highest frequency was among recipients of lung transplants (18 3.5% of 521 patients), followed by recipients of heart (10 2.5% of 392), intestinal (2 1.3% of 155), kidney (3 0.2% of 1717), and liver (2 0.1% of 1840) transplants. In a comparison of case patients with 70 matched control subjects, receipt of high-dose steroids (odds ratio, 27; 95% confidence interval, 3.2–235; P = .003) and cytomegalovirus disease (odds ratio, 6.9; 95% confidence interval, 1.02–46; P = .047) in the preceding 6 months and a high median calcineurin inhibitor level in the preceding 30 days (odds ratio, 5.8; 95% confidence interval, 1.5–22; P = .012) were found to be independent risk factors for Nocardia infection. The majority of case patients (27 77% of 35) had pulmonary disease only. Seven transplant recipients (20%) had disseminated disease. Nocardia nova was the most common species (found in 17 49% of the patients), followed by Nocardia farcinica (9 28%), Nocardia asteroides (8 23%), and Nocardia brasiliensis (1 3%). Of the 35 case patients, 24 (69%) were receiving trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. Thirty-one case patients (89%) experienced cure of their Nocardia infection. Conclusions.Receipt of high-dose steroids, history of cytomegalovirus disease, and high levels of calcineurin inhibitors are independent risk factors for Nocardia infection in organ transplant recipients. Our study provides insights into the epidemiology of Nocardia infection in the current era, a period in which immunosuppressive and prophylactic regimens have greatly evolved.
South American dry forests have a complex and poorly understood biogeographic history. Based on the fragmented distribution of many Neotropical dry forest species, it has been suggested that this ...biome was more widely distributed and contiguous under drier climate conditions in the Pleistocene. To test this scenario, known as the Pleistocene Arc Hypothesis, we studied the phylogeography of the Rufous‐fronted Thornbird (Phacellodomus rufifrons), a widespread dry forest bird with a disjunct distribution closely matching that of the biome itself. We sequenced mtDNA and used ddRADseq to sample 7,167 genome‐wide single‐nucleotide polymorphisms from 74 P. rufifrons individuals across its range. We found low genetic differentiation over two prominent geographic breaks — particularly across a 1,000 km gap between populations in Bolivia and Northern Peru. Using demographic analyses of the joint site frequency spectrum, we found evidence of recent divergence without subsequent gene flow across those breaks. By contrast, parapatric morphologically distinct populations in northeastern Brazil show high genetic divergence with evidence of recent gene flow. These results, in combination with our paleoclimate species distribution modelling, support the idea that currently disjunct patches of dry forest were more connected in the recent past, probably during the Middle and Late Pleistocene. This notion fits the major predictions of the Pleistocene Arc Hypothesis and illustrates the importance of comprehensive genomic and geographic sampling for examining biogeographic and evolutionary questions in complex ecosystems like Neotropical dry forests.
Secondary contact between species often results in the formation of a hybrid zone, with the eventual fates of the hybridizing species dependent on evolutionary and ecological forces. We examine this ...process in the Amazon Basin by conducting the first genomic and phenotypic characterization of the hybrid zone formed after secondary contact between two obligate army‐ant‐followers: the White‐breasted Antbird (Rhegmatorhina hoffmannsi) and the Harlequin Antbird (Rhegmatorhina berlepschi). We found a major geographic displacement (∼120 km) between the mitochondrial and nuclear clines, and we explore potential hypotheses for the displacement, including sampling error, genetic drift, and asymmetric cytonuclear incompatibilities. We cannot exclude roles for sampling error and genetic drift in contributing to the discordance; however, the data suggest expansion and unidirectional introgression of hoffmannsi into the distribution of berlepschi.
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