Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.     

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and follicular reservoir. However, the mechanism of melanocyte disappearance has never been clearly understood, and the intervention of cellular and humoral autoimmune phenomena as primary events remains unproven. In this review, is discussed the data supporting the major theories of vitiligo, namely melanocyte destruction (autoimmune, neural and impaired redox status) and melanocyte inhibition or defective adhesion. Based on recent morphologic findings in vivo supporting a chronic detachment and transepidermal loss of melanocytes in common generalized vitiligo, a new theory is suggested proposing melanocytorrhagy as the primary defect underlying melanocyte loss, integrating most of the possible triggering/precipitating/enhancing effects of other known factors.     

A cycle ergometer mounted on a standard force platform for three-dimensional pedal forces measurement during cycling

This report describes a new method allowing to measure the three-dimensional forces applied on right and left pedals during cycling. This method is based on a cycle ergometer mounted on a force platform. By recording the forces applied on the force platform and applying the fundamental mechanical equations, it was possible to calculate the instantaneous three-dimensional forces applied on pedals. It was validated by static and dynamic tests. The accuracy of the present system was -7.61 N, -3.37 N and -2.81 N, respectively, for the vertical, the horizontal and the lateral direction when applying a mono-directional force and -4.52 N when applying combined forces. In pedaling condition, the orientation and magnitude of the pedal forces were comparable to the literature. Moreover, this method did not modify the mechanical properties of the pedals and offered the possibility for pedal force measurement with materials often accessible in laboratories. Measurements obtained showed that this method has an interesting potential for biomechanical analyses in cycling.     

Application of the multiple antigenic peptides (MAP) strategy to the production of prophormone convertases antibodies: Synthesis,characterization and use of 8-branched immunogenic peptides

Antiserum against an N-terminal sequence of murine prohormone convertase-1 (mPC1) incorporating the sequence immediatley following the junction between the putative pro-region and the active enzyme was obtained. This was accomplished using the multiple antigenic peptide (MAP) approach whereupon an 8-branched polylysine core to which are grafted multiple copies of a 16 amino acid peptide representing the N-terminal sequence of mPC1 (positions 84–99) was synthesized by solid-phase Fmoc chemistry. The ensuing peptide was purified and fully characterized by RP-HPLC, ¹H-NMR, amino acid composition, peptide sequencing and ion-spray mass spectrometry. The immunological properties of the resulting antibodies in detecting recombinant PC1 in both crude and purified preparations were compared with antibodies raised against a similar N-terminal segment of PC1 but using the conventioanl method of peptide–carrier protein conjugation and also developed against a C-terminal fusion protein of PC1. Our data indicate that the MAP antibody was as efficient as both the amino and carboxy-terminal antibodies in qualitative as well as quantitative analysis of PC1 encoded protein by radioimmunoassay. Following an identical approach, antibodies against other prohormone convertases like furin, PC5/6 and PACE4 were also developed and subsequently applied to a number of biochemical and immunological studies. In each case, the ease of preparation and high immunogenicity of the MAP approach were confirmed and reside in the simplicity and rapidity with which a potent and useful antiserum is obtained.     

A chemical investigation by headspace SPME and GC-MS of volatile and semi-volatile terpenes in various olibanum samples

Six different olibanum samples with certified botanical origin were analyzed by headspace SPME-GC/MS in order to define their mono-, sesqui- and diterpenic composition, as pertinent criteria of identification. Boswellia carteri and Boswellia sacra olibanum have quite similar chemical composition, with isoincensole acetate as the main diterpenic biomarker. Although Boswellia serrata olibanum also exhibits this biomarker, the presence of methylchavicol, methyleugenol and an unidentified oxygenated sesquiterpene distinguishes B. serrata olibanum from the two other species. The characteristic chemical compounds of Boswellia papyrifera are the diterpenic biomarkers incensole and its oxide and acetate derivatives, n-octanol and n-octyl acetate. Boswellia frereana olibanum is devoid of diterpenes of the incensole family but contains a high amount of many dimers of alpha-phellandrene. The chemical composition of olibanum, which is demonstrated to be different for each Boswellia species allowed the determination of the taxonomic origin of frankincense samples purchased on various markets in East Africa, in the Near East and in Yemen. Moreover, terpenic fingerprints allowed the botanical origin of olibanum used in traditional incense mixtures to be identified. Furthermore, this study gave us the opportunity to assign a botanical origin to an archaeological frankincense sample.     

Ectomycorrhizal fungal diversity and saprotrophic fungal diversity are linked to different tree community attributes in a field‐based tree experiment

Exploring the link between above‐ and belowground biodiversity has been a major theme of recent ecological research, due in large part to the increasingly well‐recognized role that soil microorganisms play in driving plant community processes. In this study, we utilized a field‐based tree experiment in Minnesota, USA, to assess the effect of changes in plant species richness and phylogenetic diversity on the richness and composition of both ectomycorrhizal and saprotrophic fungal communities. We found that ectomycorrhizal fungal species richness was significantly positively influenced by increasing plant phylogenetic diversity, while saprotrophic fungal species richness was significantly affected by plant leaf nitrogen content, specific root length and standing biomass. The increasing ectomycorrhizal fungal richness associated with increasing plant phylogenetic diversity was driven by the combined presence of ectomycorrhizal fungal specialists in plots with both gymnosperm and angiosperm hosts. Although the species composition of both the ectomycorrhizal and saprotrophic fungal communities changed significantly in response to changes in plant species composition, the effect was much greater for ectomycorrhizal fungi. In addition, ectomycorrhizal but not saprotrophic fungal species composition was significantly influenced by both plant phylum (angiosperm, gymnosperm, both) and origin (Europe, America, both). The phylum effect was caused by differences in ectomycorrhizal fungal community composition, while the origin effect was attributable to differences in community heterogeneity. Taken together, this study emphasizes that plant‐associated effects on soil fungal communities are largely guild‐specific and provides a mechanistic basis for the positive link between plant phylogenetic diversity and ectomycorrhizal fungal richness.     

Safely Discharging Infants with Bronchiolitis from an Emergency Department: A Five Step Guide for Pediatricians

Recent publications have established the pulse oxygen saturation (SpO₂) threshold of 90% for the hospitalization and discharge of infant patients with bronchiolitis. However, there is no clear recommendation regarding the Emergency Department (ED) observation period necessary before allowing safe home discharge for patients with SpO₂ above 90%-92%. Our primary aims were to evaluate the risk factors associated with delayed desaturation in infants with SpO₂ ≥ 92% on arrival at the ED as well as the ED observation period necessary before allowing safe home discharge. A secondary aim was to identify the risk factors for ED readmission. Of 581 episodes of bronchiolitis in patients < 1 year old admitted to the ED, only 47 (8%) had SpO₂ < 92% on arrival there, although 106 (18%) exhibited a delayed desaturation (to < 92%) during ED observation. Female sex, age < 3 months old, ED readmission, more severe initial clinical presentation, and higher pCO₂ level (> 6KPa) were risk factors for delayed desaturation with OR varying from 1.7 to 7.5. In patients < 3 months old, mean desaturation occured later than in older patients [6.0 hours (IQR 3.0–14.0) vs. 3.0 hours (IQR 2.0–6.0), P = 0.0018]. In 95% of patients with a delayed desaturation this decrease occurred within 25 hours for patients < 3 months old and within 11 hours for patients ≥ 3 months old. In patients < 3 months old with respiratory rates above the normal range for their age the desaturation occurred earlier than in patients < 3 months with normal respiratory rates [4.4 hours (IQR 3.0–11.7) vs. 14.6 hours (IQR 7.6–22.2), P = 0.037]. Based on the present study’s results, we propose a five step guide for pediatricians on discharging children with bronchiolitis from the ED. By using the threshold of an 11 hour ED observation period for patients ≥ 3 months old and a 25 hour period for patients < 3 months old we are able to detect 95% of the patients with bronchiolitis who are at risk of delayed desaturation.     

Les industries acheuléennes de la France septentrionale

The excavations of several open air sites in Northern France and, especially in the Somme basin, have given numerous data concerning the age and the environment of the human occupations for the period from MIS 12 to MIS 8. The quality of the raw material and the function of the different sites have a great effect on the composition of the lithic assemblages as it has been seen for the different sites located near the confluence of the Somme and Avre (Cagny-la Garenne, Cagny-l’Épinette, Ferme de l’Épinette, Gentelles). The characteristics of the lithic industries of Gouzeaucourt show the complexity of the transition from Lower to Middle Palaeolithic.     

Cultivating the uncultured: limits, advances and future challenges

Since the invention of the Petri dish, there have been continuous efforts to improve efficiency in microbial cultivation. These efforts were devoted to the attainment for diverse growth conditions, simulation of in situ conditions and achievement of high-throughput rates. As a result, prokaryotes catalysing novel redox reactions as well as representatives of abundant, but not-yet cultured taxa, were isolated. Significant insights into microbial physiology have been made by studying the small number of prokaryotes already cultured. However, despite these numerous breakthroughs, microbial cultivation is still a low-throughput process. The main hindrance to cultivation is likely due to the prevailing lack of knowledge on targeted species. In this review, we focus on the limiting factors surrounding cultivation. We discuss several cultivation obstacles, including the loss of microbial cell–cell communication following species isolation. Future research directions, including the refinement of culture media, strategies based on cell–cell communication and high-throughput innovations, are reviewed. We further propose that a combination of these approaches is urgently required to promote cultivation of uncultured species, thereby dawning a new era in the field.