γ‐Unsaturated Aldehydes as Potential Lilial Replacers

A series of Claisen rearrangements was undertaken in order to find a replacement for Lilial (=3‐(4‐(tert‐butyl)phenyl)‐2‐methylpropanal), a high‐tonnage perfumery ingredient with a lily‐of‐the‐valley odour, which is a CMR2 material [1]. 5,7,7‐Trimethyl‐4‐methyleneoctanal ( 10 ), the synthesis of which is described, became the main lead. It possesses an odour which is very close to that of Lilial but lacks its substantivity. Aldehydes with higher molecular weights than that of 10 were, therefore, synthesised in order to boost substantivity and to understand the structural requirements for a ‘Lilial’ odour. The aldehydes were obtained via Claisen rearrangements of ‘exo‐methylidene’ vinyl ethers, allenyl vinyl ethers, or allenyl allyl ethers. Alternatively, coupling of terminal alkynes with allyl alcohols led to the desired aldehydes. Derivatives of 10 and their sila analogues were also synthesised. The olfactory properties of all synthesised molecules were evaluated for possible structure? odour relationships (SOR).     

Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological,Molecular and Genetics Study

Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients≤45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease.     

The effects of N-ethylmaleimide on active amino acid transport in Escherichia coli.

N-Ethylmaleimide (MalNEt) binds covalently and without specificity to accessible sulfhydryl residues in proteins. In some cases specificity has been imposed on this reaction by manipulating reaction conditions, yielding information concerning both enzyme mechanism and the identity of specific proteins (for example C.F. Fox and E.P. Kennedy (1965) Proc. Natl. Acad. Sci. u.s. 54, 891-899) and R.E. McCarty and J. Fagan (1973) Biochemistry 12, 1503-1507). We have examined the effects of MalNEt on the active accumulation of nine amino acids by Escherichia coli strains ML 308-225 and DL 54. Whole cells have been used in order that transport systems both dependent on and independent of periplasmic binding proteins could be studied under various conditions of energy supply for transport. Our results suggest that the systems transporting ornithine, phenylalanine and proline are those most likely to undergo inactivation by direct reaction of MalNEt with the transport apparatus, rather than merely via side effects such as interruption of their energy supply. The inhibition of proline transport is specifically enhanced by the presence of proline, competitive inhibitors of proline transport, or carbonylcyanide p-trifluoromethyoxyphenylhydrazone during MalNEt treatment. The other eight systems tested showed no analogous effects.     

The effects of N-ethylmaleimide on active amino acid transport in Escherichia coli

N-Ethylmaleimide (MalNEt) binds covalently and without specificity to accessible sulfhydryl residues in proteins. In some cases specificity has been imposed on this reaction by manipulating reaction conditions, yielding information concerning both enzyme mechanism and the identity of specific proteins (for example C.F. Fox and E.P. Kennedy (1965) Proc. Natl. Acad. Sci. U.S. 54, 891–899) and R.E. McCarty and J. Fagan (1973) Biochemistry 12, 1503–1507). We have examined the effects of MalNEt on the active accumulation of nine amino acids by Escherichia coli strains ML 308-225 and DL 54. Whole cells have been used in order that transport systems both dependent on and independent of periplasmic binding proteins could be studied under various conditions of energy supply for transport. Our results suggest that the systems transporting ornithine, phenylalanine and proline are those most likely to undergo inactivation by direct reaction of MalNEt with the transport apparatus, rather than merely via side effects such as interruption of their energy supply. The inhibition of proline transport is specifically enhanced by the presence of proline, competitive inhibitors of proline transport, or carbonylcyanide p-trifluoromethoxyphenylhydrazone during MalNEt treatment. The other eight systems tested showed no analogous effects.     

Seroprevalence of chikungunya virus infection among HIV-infected adults in French Caribbean Islands of Martinique and Guadeloupe in 2015: A cross-sectional study

BackgroundIn 2014, a first outbreak of chikungunya hit the Caribbean area where chikungunya virus (CHIKV) had never circulated before.Methodology/Principal findingsWe conducted a cross-sectional study to measure the seroprevalence of CHIKV immediately after the end of the 2014 outbreak in HIV-infected people followed up in two clinical cohorts at the University hospitals of Guadeloupe and Martinique. Study patients were identified during the first months of 2015 and randomly selected to match the age and sex distribution of the general population in the two islands. They were invited to complete a survey that explored the symptoms consistent with chikungunya they could have developed during 2014 and to have a blood sample drawn for CHIKV serology.The study population consisted of 377 patients (198 in Martinique and 179 in Guadeloupe, 178 men and 199 women), 182 of whom reported they had developed symptoms consistent with chikungunya. CHIKV serology was positive in 230 patients, which accounted for an overall seroprevalence rate of 61% [95%CI 56–66], with only 153 patients who reported symptoms consistent with chikungunya. Most frequent symptoms included arthralgia (94.1%), fever (73.2%), myalgia (53.6%), headache (45.8%), and skin rash (26.1%).Conclusions/SignificanceThis study showed that the seroprevalence of CHIKV infection was 61% after the 2014 outbreak, with one third of asymptomatic infections.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 02553369","term_id":"NCT02553369"}}NCT 02553369.