Les génotypes responsables de mucoviscidose ou d’absence bilatérale des canaux déférents ABCD

Over the last decade, the genetic basis for CBAVD has been identified by its association with CFTR gene mutations, and CBAVD is now generally considered to be a mild or incomplete form of CF. In this review, the author summarizes the main results of compilation of CFTR gene analysis conducted in French laboratories for 3,923 patients with CF and 800 males with CABVD. The degree of clinical expression can be affected by several variables, including the molecular mechanisms by which the various CFTR mutations impair or disrupt the function of the CFTR chloride channel. Phenotypic expression of CFTR mutational genotypes varies from severe, progressive pulmonary disease with pancreatic insufficiency (CF-PI), to mild pulmonary disease with pancreatic sufficiency (PS) or singleorgan forms of “CFTR-opathies”. In CF, a total of 310 different CFTR mutations accounting for 94% of 7,846 CF alleles have generated almost 500 different genotypes, comprising 2 severe mutations in 88% of cases (CF-PI), one severe mutation in trans to a mild mutation in 11% (CF-PS), and 2 mild mutations in 1% of identified genotypes. In CBAVD, 137 mutations scattered over the whole gene were identified in 60% of 1,600 CBAVD alleles during the study. Among the 150 characterized mutational CFTR genotypes, compound heterozygosity was the rule, and the most frequent CBAVD combinations were ΔF508/5T (35%), ΔF508/other mutation (30%, including ΔF508/R117H-7T: 5,6%), and 5T/other mutation (17%). No combination of two severe mutations was found in CBAVD (0%); by contrast with the CF population, 88% of genotypes identified in CBAVD comprised a severe mutation in trans to a mild mutation, and 12% consisted of 2 mild mutations. A total of 22 genotypes were shared by both CF and CBAVD. The role of the 5T allele as a splicing variant with variable, incomplete disease penetrance in CBAVD is reviewed. Other haplotype backgrounds, such as the TG12 sequence and the M470V polymorphism, may influence CFTR splicing and/or function. This study confirms the high molecular heterogeneity of CFTR mutations in CBAVD and emphasizes the importance of extensive CFTR analysis in these patients. Longterm follow-up studies of CBAVD patients are necessary in order to predict the phenotypic consequences of numerous CFTR mutational genotypes.     

Muon disrupts AKT hydrogen bond network in cancer

A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon-catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype.     

Identification of potentially critical genes in the development of heart failure after ST-segment elevation myocardial infarction (STEMI)

Heart failure (HF) remains a common complication after acute ST-segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post-infarct HF and eight patients without post-infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein-protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow-up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix-receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post-infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.     

A journey through time: exploring temporal patterns amongst digitized plant specimens from Australia

Online access to species occurrence records has opened new windows into investigating biodiversity patterns across multiple scales. The value of these records for research depends on their spatial, temporal, and taxonomic quality. We assessed temporal patterns in records from the Australasian Virtual Herbarium, asking: (1) How temporally consistent has collecting been across Australia? (2) Which areas of Australia have the most reliable records, in terms of temporal consistency and inventory completeness? (3) Are there temporal trends in the completeness of attribute information associated with records? We undertook a multi-step filtering procedure, then estimated temporal consistency and inventory completeness for sampling units (SUs) of 50?km ×?50?km. We found temporal bias in collecting, with 80% of records collected over the period 1970–1999. South-eastern Australia, the Wet Tropics in north-east Queensland, and parts of Western Australia have received the most consistent sampling effort over time, whereas much of central Australia has had low temporal consistency. Of the SUs, 18% have relatively complete inventories with high temporal consistency in sampling. We also determined that 25% of digitized records had missing attribute information. By identifying areas with low reliability, we can limit erroneous inferences about distribution patterns and identify priority areas for future sampling.     

From mutations to mechanisms and dysfunction via computation and mining of protein energy landscapes

Background

The protein energy landscape underscores the inherent nature of proteins as dynamic molecules interconverting between structures with varying energies. Reconstructing a protein’s energy landscape holds the key to characterizing a protein’s equilibrium conformational dynamics and its relationship to function. Many pathogenic mutations in protein sequences alter the equilibrium dynamics that regulates molecular interactions and thus protein function. In principle, reconstructing energy landscapes of a protein’s healthy and diseased variants is a central step to understanding how mutations impact dynamics, biological mechanisms, and function.

Results

Recent computational advances are yielding detailed, sample-based representations of protein energy landscapes. In this paper, we propose and describe two novel methods that leverage computed, sample-based representations of landscapes to reconstruct them and extract from them informative local structures that reveal the underlying organization of an energy landscape. Such structures constitute landscape features that, as we demonstrate here, can be utilized to detect alterations of landscapes upon mutation.

Conclusions

The proposed methods detect altered protein energy landscape features in response to sequence mutations. By doing so, the methods allow formulating hypotheses on the impact of mutations on specific biological activities of a protein. This work demonstrates that the availability of energy landscapes of healthy and diseased variants of a protein opens up new avenues to harness the quantitative information embedded in landscapes to summarize mechanisms via which mutations alter protein dynamics to percolate to dysfunction.

     

Consistent associations with beneficial bacteria in the seed endosphere of barley (Hordeum vulgare L.)

The importance of the plant microbiome for host fitness has led to the concept of the “plant holobiont”. Seeds are reservoirs and vectors for beneficial microbes, which are very intimate partners of higher plants with the potential to connect plant generations. In this study, the endophytic seed microbiota of numerous barley samples, representing different cultivars, geographical sites and harvest years, was investigated. Cultivation-dependent and -independent analyses, microscopy, functional plate assays, greenhouse assays and functional prediction were used, with the aim of assessing the composition, stability and function of the barley seed endophytic bacterial microbiota. Associations were consistently detected in the seed endosphere with Paenibacillus, Pantoea and Pseudomonas spp., which were able to colonize the root with a notable rhizocompetence after seed germination. In greenhouse assays, enrichment with these bacteria promoted barley growth, improved mineral nutrition and induced resistance against the fungal pathogen Blumeria graminis. We demonstrated here that barley, an important crop plant, was consistently associated with beneficial bacteria inside the seeds. The results have relevant implications for plant microbiome ecology and for the holobiont concept, as well as opening up new possibilities for research and application of seed endophytes as bioinoculants in sustainable agriculture.     

Failure of neutralizing gp120 monoclonal antibodies to prevent HIV infection of choriocarcinoma-derived trophoblasts

Although placental trophoblasts, the only fetal cells in direct contact with infectious maternal blood, can be infected with HIV, the precise cause for the low transmission rate of virus across the placental barrier is unknown. One of the most common conjectures is that maternal anti-HIV antibodies (Abs) contribute to the protection of the fetus. This hypothesis has been tested in vitro by infecting the CD4-negative placental trophoblast line, BeWo, with HIV-1_IIIB in the presence of serial dilutions of neutralizing monoclonal Abs against the V3 loop (No. 694) or CD4-binding conformational domain (No. 588). The results, based on measurement of p24 production from virus-exposed cells, reveal that the titers of Abs, adequate in preventing the infection of control MT-4 T lymphocytes, were less effective in protecting trophoblasts. Furthermore, PCR analysis of HIV DNA formed after a single round of infection has shown no significant decrease in the number of viral copies in Ab-protected BeWo cells. An anti-HIV serum from a pregnant woman did also have no effect. Although our in vitro observations do not necessarily apply to the in vivo situation, the results suggest that the humoral immune response sustained by neutralizing Abs may be able to protect T lymphocytes, but not placental trophoblasts. The findings are consistent with recent clinical studies demonstrating a lack of correlation between the presence of neutralizing anti-HIV Abs in pregnant women and HIV transmission in utero.     

Female Choice in the Synchronously Waving Fiddler Crab Uca annulipes

In the fiddler crab, Uca annulipes, males attract receptive females into their burrows by waving their greatly enlarged major claw. We have previously shown that males clustered around a female wave in close synchrony. Females may have a preference for leading signals and synchronised waving may arise as an epiphenomenon of competition between males to signal first. Indeed, the males in clusters that females approach and visit in their burrows are more likely to produce leading waves than are their neighbours. Here we document two other differences in the waving behaviour of visited males and their neighbours. First, visited males complete the downward component of the wave more rapidly than their neighbours. Second, the interval between the end of one wave and the start of the next is shorter for visited males. How can waving be synchronous if visited males wave faster than their neighbours? While only 9% (40/431) of waves by neighbours did not overlap those of the visited male, 22% (110/501) of visited male waves did not overlap the wave of a focal neighbour (111 visited male-neighbour dyads). Hence, while overlapping waves are nearly synchronous, visited males produce additional, ‘nonoverlapping’ waves that result in a higher wave rate than that of their neighbours.     

Photosynthetic activity of developing leaves of Zea mays is less affected by heat stress than that of developed leaves

Various physiological and biochemical characters of a leaf change with stages of its ontogeny. It is likely that the photosynthetic functions of leaves of different ontogeny have different levels of heat tolerance. This study was initiated to analyze the photosynthetic heat tolerance of fully-developed, nearly-developed (more than 2/3 expanded) and developing (10–12 cm visible) leaves of two maize genotypes, F223 and F250. The results indicate that the photosynthetic CO₂ assimilation rate (P_n) of developing leaves was less affected by heat stress (42°C in the dark for 90 min) than that of developed leaves. The impaired P_n recovered within 24 h in the developing leaves, while the P_n of developed and nearly-developed leaves did not reach the non-stress level, even after 72 h. The P_n of the developed leaves of genotype F250 was less affected by heat stress than that of genotype F223. After heat stress, the slightly affected P_n of the developing leaf was associated with the almost unchanged photochemical efficiency of photosystem II (F_v/F_m) and the quantum yield of photosystem II electron transport. The chlorophylls a and b were degraded by heat stress; the degradation was pronounced in the developed leaves. As a result of heat stress, the antheraxanthin and zeaxanthin of the xanthophyll cycle accumulated in both the nearly-developed and developed leaves but not in the developing leaves. Injury to the plasma membrane due to heat stress was much less severe in developing leaves than that in the developed leaves. From the physiological characters which we determined it would appear that the P_n functions of the developing leaves are more resistant to heat stress than those of nearly-developed and developed leaves.