Anti‐HSV‐1 and HSV‐2 Flavonoids and a New Kaempferol Triglycoside from the Medicinal Plant Kalanchoe daigremontiana

Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside ( 1 ), was isolated from the AcOEt fraction (Kd‐AC). The BuOH‐soluble fraction afforded quercetin 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside ( 2 ) and the new kaempferol 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside‐7‐O‐β‐d ‐glucopyranoside ( 3 ), named daigremontrioside. The crude extract, Kd‐AC fraction, flavonoids 1 and 2 were evaluated using acyclovir‐sensitive strains of HSV‐1 and HSV‐2. Kd‐AC was highly active against HSV‐1 (EC₅₀ = 0.97 μg/ml, SI > 206.1) and HSV‐2 (EC₅₀ = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti‐HSV‐1 (EC₅₀ = 7.4 μg/ml; SI > 27 and EC₅₀ = 5.8 μg/ml; SI > 8.6, respectively) and anti‐HSV‐2 (EC₅₀ = 9.0 μg/ml; SI > 22.2 and EC₅₀ = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity.     

The role of floral structure and biotic factors in determining the occurrence of florivorous thrips in a dystilous shrub

Elucidating the factors determining the occurrence of florivorous organisms is an essential step for comprehending arthropod–plant interactions, especially when considering florivores that use flowers/inflorescences as microhabitats. In this study, we characterize the interaction between florivorous thrips (Thysanoptera) and Palicourea rigida (Rubiaceae), a distylous hummingbird-pollinated shrub. We investigated the relative role of different factors in determining thrips occurrence in the flower and inflorescence microhabitats. Furthermore, we experimentally examined the protective role of corolla influencing thrips exploration of floral buds. Frankliniella musaeperda (Thripidae) was the only species recorded on P. rigida, feeding on floral tissue, pollen and nectar. Thrips occurrence was not related to distyly, but rather to floral stage. Open flowers presented the highest abundance of thrips, followed by senescent flowers and then buds. The experimental opening of buds translated in increased thrips occurrence, indicating that F. musaeperda manage to explore the microhabitat offered by the floral chamber, as long as there is an opening in the corolla. In inflorescences, thrips abundance was negatively related to the number of ants visiting extrafloral nectaries. We found that the marked difference between floral morphs of distylous plants is not necessarily reflected in the abundance of florivores. Thrips seek for floral cavities, preferentially those with fresh tissue, which may confer nutrient-rich food and protection. Buds also provide this; however, the enclosed petals are an effective barrier against F. musaeperda entrance. At inflorescence scale, presence of mutualistic ants in high numbers can drive away these flower-feeding insects. Despite the abundance of thrips in the flowers, there was no evidence of any functional relationship, either of pollination for flowers or of breeding for insects. We demonstrate here that in the flower/inflorescence microhabitat, structural and biotic factors play a key role in the exploitation and occupation by insect florivores.     

Paleodistribution modeling suggests glacial refugia in Scandinavia and out‐of‐Tibet range expansion of the Arctic fox

Quaternary glacial cycles have shaped the geographic distributions and evolution of numerous species in the Arctic. Ancient DNA suggests that the Arctic fox went extinct in Europe at the end of the Pleistocene and that Scandinavia was subsequently recolonized from Siberia, indicating inability to track its habitat through space as climate changed. Using ecological niche modeling, we found that climatically suitable conditions for Arctic fox were found in Scandinavia both during the last glacial maximum (LGM) and the mid‐Holocene. Our results are supported by fossil occurrences from the last glacial. Furthermore, the model projection for the LGM, validated with fossil records, suggested an approximate distance of 2000 km between suitable Arctic conditions and the Tibetan Plateau well within the dispersal distance of the species, supporting the recently proposed hypothesis of range expansion from an origin on the Tibetan Plateau to the rest of Eurasia. The fact that the Arctic fox disappeared from Scandinavia despite suitable conditions suggests that extant populations may be more sensitive to climate change than previously thought.     

Age-Dependent Changes in Geometry,Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves

There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation–but more pronounced in aortic valves–the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.     

Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease

Background

Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.

Methods and Findings

Our data established that CH displayed increased expression of CD32⁺ and CD56⁺ in monocytes and enhanced frequency of NK Granzyme A⁺ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8⁺ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8⁺ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8⁺ T-cells, as the most reliable biomarkers of potential use for clinical applications.

Conclusions

Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease.     

The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP)

Background

About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors.

Methods and Findings

This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02–13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57–35.88), multiple pregnancy (OR 12.49; 4.86–32.05), and chronic diabetes (OR 5.24; 2.68–10.25) were the most significant factors independently associated with pi-PTB.

Conclusions

pi-PTB is responsible for about one-third of all preterm births, requiring special attention. The decision-making process relative to the choice of provider-initiated birth is complex, and many factors should be elucidated to improve strategies for its prevention, including evidence-based guidelines on proper management of the corresponding clinical conditions.