Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer

Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738–0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.     

Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9. Received: 20 January 1997 / Accepted: 5 November 1997     

Identification des cercaires de Schistosoma africains émises par Bulinus umbilicatus,B. truncatus et B. forskalii

Résumé Trois indices chétotaxiques AD, AL et U, des cercaires de quatre espèces pré-identifiées de Schistosoma africains, émises par des Mollusques infestés naturellement ou expérimentalement, ont été calculés. AD et AL correspondant respectivement à la distance relative entre les papilles dorsales et les papilles latérales. U correspond au nombre total des papilles du tronc caudal. La simple comparaison des moyennes arithmétiques d'un ou deux de ces trois indices permet de distinguer les cercaires de Schistosoma haematobium et de S. curassoni émises par Bulinus umbilicatus; les cercaires de S. haematobium et S. bovis émises par B. truncatus; les cercaires de S. bovis et S. intercalatum émises par B. forskalii.

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Identification des cercaires de Schistosoma africains émises par Bulinus umbilicatus, B. truncatus et B. forskalii

Three chaetotaxic indices, AD, AL and U, of cercariae of four pre-identified African Schistosoma species, obtained from natural or experimental infections, were established. AD and AL correspond respectively to the relative distance between the dorsal and lateral papillae. U corresponds to the total number of tail stem papillae. The simple comparison of average values of one or two of these three indices facilitated identification of the cercariae of Schistosoma haematobium and S. curassoni emitted by Bulinus umbilicatus, cercariae of S. haematobium and S. bovis shed by B. truncatus, and cercariae of S. bovis and S. intercalatum emitted by B. forskalii.

     

Myocardium proteome remodelling after nutritional deprivation of methyl donors

Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and α-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation.     

γ-Lactam-Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC₅₀ around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy.     

Synthesis of Racemic Carboacyclonucleosides Derived from Butane-1, 4-Diol and Hexane-1, 6-Diol

Abstract

The synthesis of racemic diethyl succinate and dimethyl adipate substituted in their 2 and 3 position respectively by usual heterocyclic bases are described via the Michael addition of nucleobases on diethyl maleate and dimethyl (E)-3-hexene-1, 6-dioate. The Michael adducts are further reduced to afford the corresponding carboacyclonucleosides.     

From Aggregation to Dispersion: How Habitat Fragmentation Prevents the Emergence of Consensual Decision Making in a Group

In fragmented landscape, individuals have to cope with the fragmentation level in order to aggregate in the same patch and take advantage of group-living. Aggregation results from responses to environmental heterogeneities and/or positive influence of the presence of congeners. In this context, the fragmentation of resting sites highlights how individuals make a compromise between two individual preferences: (1) being aggregated with conspecifics and (2) having access to these resting sites. As in previous studies, when the carrying capacity of available resting sites is large enough to contain the entire group, a single aggregation site is collectively selected. In this study, we have uncoupled fragmentation and habitat loss: the population size and total surface of the resting sites are maintained at a constant value, an increase in fragmentation implies a decrease in the carrying capacity of each shelter. For our model organism, Blattella germanica, our experimental and theoretical approach shows that, for low fragmentation level, a single resting site is collectively selected. However, for higher level of fragmentation, individuals are randomly distributed between fragments and the total sheltered population decreases. In the latter case, social amplification process is not activated and consequently, consensual decision making cannot emerge and the distribution of individuals among sites is only driven by their individual propensity to find a site. This intimate relation between aggregation pattern and landscape patchiness described in our theoretical model is generic for several gregarious species. We expect that any group-living species showing the same structure of interactions should present the same type of dispersion-aggregation response to fragmentation regardless of their level of social complexity.