Rheological Evaluation of Softened Binders Blended with Aged Asphalt Selected with a High-Temperature Mixing Chart

Reclaimed asphalt pavements (RAP) provide economic and environmental benefits. In recent decades, their use has increased, but rheological properties are affected by RAP aging, increasing stiffness, cracking, and susceptibility to water. To counteract these effects, rejuvenating agents are used, but they must be properly dosed to design quality mixtures. Therefore, different binders were analyzed, including virgin binder (VBB), binder modified by SBS polymer (MB), AC-RAP, binder softened using a rejuvenating agent, and binders softened with doses (15%, 30%, and 45%) of AC-RAP. The rheological properties were evaluated by dynamic shear rheometry (DSR) and beam-bending rheometry (BBR) tests, while the linear amplitude sweep (LAS) test was used to measure fatigue cracking and the multiple stress creep recovery (MSCR) test was used to measure rutting. A mixing chart was constructed based on a high temperature AC-RAP to satisfy the performance grade (PG 76-22). The results showed that softened binders become flexible, but when AC-RAP is added, they turn stiff and behave better than MB. Moreover, combining a rejuvenating agent and AC-RAP reduces the aging stiffness of RAP, improving its rheological properties without compromising the rutting or cracking resistance.     

Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity

Old–world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus–caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS–associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus–infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus–infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.     

Síndrome cardiorrenal: clasificación,fisiopatología,diagnóstico y tratamiento. Una revisión de las publicaciones médicas

The cardiorenal syndrome is a complex entity in which a primary heart dysfunction causes kidney injury (Types 1 and 2) and vice versa (Types 3 and 4), being either acute or chronic events, or maybe the result of a systemic disease that involves both organs (Type 5). Approximately 49% of heart failure cases present some grade of kidney dysfunction, significantly increasing morbidity and mortality rates. Its pathogenesis involves a variety of hemodynamic, hormonal and immunological factors that in the majority of cases produce fluid overload; the diagnosis and treatment of such constitutes the disease’s management basis. Currently, a clinical based diagnosis is insufficient and the use of biochemical markers, such as natriuretic peptides, or lung and heart ultrasound is required. These tools, along with urinary sodium levels, allow the evaluation of therapy effectiveness. The preferred initial decongestive strategy is based on a continuous infusion of a loop diuretic with a step-up dosing regimen, aiming for a minimal daily urine volume of 3 liters, with the possibility to sequentially add potassium sparing diuretics, thiazide diuretics and carbonic anhydrase inhibitors to reach the diuresis goal, leaving ultrafiltration as a last resource due to its higher rate of complications. Finally, evidence-based therapy should be given to improve quality of life, decrease mortality, and delay the deterioration of kidney and heart function over the long term.     

Areca catechu—From farm to food and biomedical applications

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases.     

From the Cover: Complex history of the amphibian-killing chytrid fungus revealed with genome resequencing data

Understanding the evolutionary history of microbial pathogens is critical for mitigating the impacts of emerging infectious diseases on economically and ecologically important host species. We used a genome resequencing approach to resolve the evolutionary history of an important microbial pathogen, the chytrid Batrachochytrium dendrobatidis (Bd), which has been implicated in amphibian declines worldwide. We sequenced the genomes of 29 isolates of Bd from around the world, with an emphasis on North, Central, and South America because of the devastating effect that Bd has had on amphibian populations in the New World. We found a substantial amount of evolutionary complexity in Bd with deep phylogenetic diversity that predates observed global amphibian declines. By investigating the entire genome, we found that even the most recently evolved Bd clade (termed the global panzootic lineage) contained more genetic variation than previously reported. We also found dramatic differences among isolates and among genomic regions in chromosomal copy number and patterns of heterozygosity, suggesting complex and heterogeneous genome dynamics. Finally, we report evidence for selection acting on the Bd genome, supporting the hypothesis that protease genes are important in evolutionary transitions in this group. Bd is considered an emerging pathogen because of its recent effects on amphibians, but our data indicate that it has a complex evolutionary history that predates recent disease outbreaks. Therefore, it is important to consider the contemporary effects of Bd in a broader evolutionary context and identify specific mechanisms that may have led to shifts in virulence in this system.Emerging infectious diseases (EIDs) pose significant challenges for human health, agricultural crops, and economically and ecologically important populations in nature (1–4). The incidence of EIDs has been steadily rising over the last several decades (5, 6), and EIDs are of particular concern in an increasingly globalized world. For example, the majority of human EIDs is zoonoses that originate in wildlife (5) and subsequently, create a significant burden for global economies and public health (7, 8). Therefore, scientific efforts to understand and respond to EIDs are critical in diverse fields from biomedicine to conservation biology.Although EIDs result from a complex interplay of factors, many studies focus primarily on the emergence of novel microbial pathogens. There are, in fact, high-profile examples of EIDs caused by the rapid appearance of novel, hypervirulent, or host-switching strains (9–11), but EIDs are not always caused by rapid or recent evolution of the pathogen itself. Virulence itself is an emergent property of microbe–host–environment interactions (12). Thus, EIDs can result from shifts in any factor—or combination of factors—in the microbe–host–environment epidemiological triangle (13). Characterizing the evolutionary history of emerging pathogens is, thus, critical, allowing us to determine whether observed EIDs result from rapid, recent shifts in organisms with pathogenic potential.Chytridiomycosis is an EID responsible for declines in amphibian species around the world. The chytrid fungus Batrachochytrium dendrobatidis (Bd) was discovered and linked to amphibian declines in 1998 (14, 15). Chytridiomycosis is caused by Bd and kills amphibians by disrupting the integrity of their skin, a physiologically important organ that is involved in gas exchange, electrolyte balance, hydration, and protection from other pathogens (16, 17). Bd infects hundreds of species of amphibians, is found on all continents where amphibians occur, and is responsible for declines and extirpations in a diversity of amphibian hosts (18).Soon after Bd was discovered, researchers proposed two competing hypotheses for the emergence of chytridiomycosis. The emerging pathogen hypothesis posited that a novel disease agent caused chytridiomycosis, and the endemic pathogen hypothesis proposed that an environmental shift disrupted a previously benign microbe–host interaction (19). Over the years, spatiotemporal and genetic data have supported the emerging pathogen hypothesis (reviewed in refs. 20 and 21). Spatiotemporal data provided clear evidence that Bd arrived and spread through geographic regions where it was not present historically (22–24). Early genetic studies also found very little genetic differentiation in Bd with no geographic signal, consistent with a recent, rapid spread of a novel disease agent (25–27). Recently, genetic and genomic data have been used to describe a geographically widespread Bd lineage [termed the global panzootic lineage (GPL)] (28) and several putatively endemic Bd lineages (28–30). However, different studies have used different methods and focused sampling in different parts of the world, precluding integration across studies to determine the evolutionary history leading to the emergence of Bd as a global threat to amphibians.Here, we present whole-genome sequencing from a global panel of Bd isolates to show that Bd has a historically deeper and more complex evolutionary history than previously appreciated. We sequenced Bd genomes from around the world and also, a non-Bd chytrid outgroup that does not attack amphibians [Homolaphlyctis polyrhiza (Hp)] (31). Our focus was primarily on the evolutionary dynamics of Bd in the Americas, because many of the most devastating outbreaks have occurred in the New World. We address outstanding questions about the origins, genetic diversity, and genome structure of Bd that can be resolved using whole-genome data. We also integrate our genomic data with those data from a previous study with complementary geographic sampling (28). Our results reveal that the evolutionary history of Bd is complex, with multiple divergent lineages, heterogeneous patterns of genomic evolution, and no simple link between a single evolutionary event and observed amphibian declines.     

A proteomic approach to the identification of tegumental proteins of male and female Schistosoma bovis worms

Schistosoma bovis, a parasite of ruminants, can live for years in the bloodstream in spite of the immune response of its host. The parasite tegument covers the entire surface of the worm and plays a key role in the host-parasite relationship. The parasite molecules involved in host immune response evasion mechanisms must be expressed on the tegument surface and are potential targets for immune or drug intervention. The purpose of the present work was to identify the tegumental proteomes of male and female S. bovis worms, in particular the proteins expressed on the outermost layers of the tegument structure. Adult worms of each sex were treated separately with trypsin in order to digest their tegumental proteins, after which the peptides released were analysed by LC-MS/MS for identification. This experimental approach afforded valuable information about the protein composition of the tegument of adult S. bovis worms. A range of tegumental proteins was identified, most of which had not been identified previously in this species. Although an absolute purification of the proteins expressed on the outermost layers of the tegument structure was not achieved, it is likely that present among the proteins identified are some of the molecules most closely associated with the tegument surface. Our study also suggests that there may be differences in the protein composition of the tegument of male and female schistosomes. Finally, the presence of actin and GAPDH on the surface of male and female worms and the presence of enolase exclusively on the surface of male worms were verified by confocal microscopy.     

Potential effectiveness of stored cord blood (non-frozen) for emergency use

Bone marrow has been used for a number of years to assist patients who have accidentally received potentially lethal levels of irradiation. The intent of the transplant is to replace the victim's own bone marrow that has been injured from the irradiation or to act as temporary support to allow the patient's own marrow to recover. Following the Chernobyl disaster, some victims received bone marrow that was HLA matched or partially matched. However, donor marrows were difficult to obtain in adequate numbers; as a substitute for bone marrow, frozen fetal liver cells were used as a source of hematopoietic stem cells. The use of fetal livers, however, was unsuccessful. Human umbilical cord blood, currently considered an excellent source of hematopoietic stem cells, was not used at Chernobyl. For several years, we have been able experimentally to keep SJL/J mice alive with the use of human umbilical cord blood after the animals received lethal levels of irradiation. This finding suggests that under certain conditions human cord blood does not have to be HLA matched to facilitate rescue from irradiation. In addition, there are reports of unmatched HLA cord blood being used successfully for marrow transplantation. If human cord blood does not have to be matched for HLA, there may be emergency cataclysmic circumstances where the availability of umbilical cord blood may be of considerable value. To simulate a clinical situation such as a nuclear accident, in which human cord blood might serve as a source of stem cells for marrow transplantation, we attempted to rescue immunocompetent mice after 900 cGY of irradiation with the use of (nonfrozen) human cord blood stored in a blood bank. The blood was stored under routine conditions (3–6 °C) for 5 and 7 days in special bags that allow transmission of oxygen. Following lethal levels of irradiation, the cord blood was administered to the animals and a significant survival rate was obtained.     

Selective antileishmania activity of 13,28‐epoxy‐oleanane and related triterpene saponins from the plant families Myrsinaceae,Primulaceae, Aceraceae and Icacinaceae

Maesa saponins with the 13,28‐epoxy‐oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure‐based literature search was carried out to explore a structure‐activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC‐5_SV2 cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28‐epoxy‐oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28‐epoxy‐oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery. Copyright © 2009 John Wiley & Sons, Ltd.