The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions

The evolutionary conserved CCR4-NOT complex functions in the cytoplasm as the main mRNA deadenylase in both constitutive mRNA turnover and regulated mRNA decay pathways. The versatility of this complex is underpinned by its modular multi-subunit organization, with distinct structural modules actuating different functions. The structure and function of all modules are known, except for that of the N-terminal module. Using different structural approaches, we obtained high-resolution data revealing the architecture of the human N-terminal module composed of CNOT1, CNOT10, and CNOT11. The structure shows how two helical domains of CNOT1 sandwich CNOT10 and CNOT11, leaving the most conserved domain of CNOT11 protruding into solvent as an antenna. We discovered that GGNBP2, a protein identified as a tumor suppressor and spermatogenic factor, is a conserved interacting partner of the CNOT11 antenna domain. Structural and biochemical analyses thus pinpoint the N-terminal CNOT1-CNOT10-CNOT11 module as a conserved protein-protein interaction platform

Multidomain switching in the ferroelectric nanodots

Controlling the polarization switching in the ferroelectric nanocrystals, nanowires and nanodots has an inherent specificity related to the emergence of depolarization field that is associated with the spontaneous polarization. This field splits the finite-size ferroelectric sample into polarization domains. Here, based on 3D numerical simulations, we study the formation of 180$^{\circ }$ polarization domains in a nanoplatelet, made of uniaxial ferroelectric material, and show that in addition to the polarized monodomain state, the multidomain structures, notably of stripe and cylindrical shapes, can arise and compete during the switching process. The multibit switching protocol between these configurations may be realized by temperature and field variations

Parasitic Worms: Knowledge, Attitudes, and Practices in Western Côte d’Ivoire with Implications for Integrated Control

There is a need to better understand communities' knowledge, attitudes, and practices (KAP) of neglected tropical diseases to improve prevention and control efforts. We studied the socio-cultural aspects of parasitic worm infections in two villages (Mélapleu and Zouatta II) of western Côte d'Ivoire, where research and control activities have been implemented. Zouatta II was exposed to a community-based approach, while school-based interventions were implemented in Mélapleu. KAP surveys were carried out using qualitative and quantitative methods. Although there was some knowledge of parasitic worm infections in both villages, we found important differences between the two villages regarding intestinal schistosomiasis: there was a better understanding of this disease in Zouatta II. However, even the community-based research and control efforts implemented in Zouatta II were ineffective in transforming the information conveyed into preventive behavior related to water contact. Our results suggest that KAP of parasitic worm infections conveyed by research and control activities targeting only school-aged children have shortcomings as older population groups are left out. Hence, for effective control of parasitic worms, children and adults must be educated and interventions should include access to deworming drugs, clean water and sanitation

ETIOLOGIES DES PLEURESIES DU SUJET AGE AU TOGO

Objective: The aim of this study was to review the current aetiologic profile of pleurisies in the elderly people. Materials and method: We carried out a retrospective study based on the data of 126 patients, old of at least 55 years, hospitalised from January 2007 to December 2011 for pleurisy in the pneumology department of Sylvanus Olympio teaching hospital of Lome. Results: Pleurisies represent 23,11 % of elderly people’s hospitalisation motives. The Sex-ratio was 1 and the average age of the patients 65 ± 09 years old. The clinical aspect was dominated by thoracic pain (88,88 %) and cough (69,84 %). The chest X-ray revealed pleural effusion at the left side in 48,41 %, at right side in 46,83% and of medium abundance in 57,93 %. The liquid was citrine in 53,97 %, haematic in 30,95% and purulent in 15,08% . Pleurisies were of cancerous origin in 32,54 %, tubercular in 17,46 % and bacterial not tubercular in 14,58%. No aetiology had been found in 33,33 %. The mortality was 27,78 % and due to cancers and idiopathic pleurisies in 86 % during three months’ follow up. Conclusion: Cancers are the first aetiology of pleurisies followed by tuberculosis in elderly people. The acquisition of the new means of pleural exploration is important to reduce the proportion of idiopathic pleurisies

Nucleic Acids Res

Developmentally Regulated GTP-binding (DRG) proteins are highly conserved GTPases that associate with DRG Family Regulatory Proteins (DFRP). The resulting complexes have recently been shown to participate in eukaryotic translation. The structure of the Rbg1 GTPase, a yeast DRG protein, in complex with the C-terminal region of its DFRP partner, Tma46, was solved by X-ray diffraction. These data reveal that DRG proteins are multimodular factors with three additional domains, helix-turn-helix (HTH), S5D2L and TGS, packing against the GTPase platform. Surprisingly, the S5D2L domain is inserted in the middle of the GTPase sequence. In contrast, the region of Tma46 interacting with Rbg1 adopts an extended conformation typical of intrinsically unstructured proteins and contacts the GTPase and TGS domains. Functional analyses demonstrate that the various domains of Rbg1, as well as Tma46, modulate the GTPase activity of Rbg1 and contribute to the function of these proteins in vivo. Dissecting the role of the different domains revealed that the Rbg1 TGS domain is essential for the recruitment of this factor in polysomes, supporting further the implication of these conserved factors in translation

Rna

Complex cellular functions involve large networks of interactions. Pre-mRNA splicing and transcription are thought to be coupled by the C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II). In yeast, the U1 snRNP subunit Prp40 was proposed to mediate cotranscriptional recruitment of early splicing factors through binding of its WW domains to the Pol II CTD. Here we investigate the role of Prp40 in splicing with an emphasis on the role of the WW domains, which might confer protein-protein interactions among the splicing and transcriptional machineries. Affinity purification revealed that Prp40 and Snu71 form a stable heterodimer that stably associates with the U1 snRNP only in the presence of Nam8, a known regulator of 5' splice site recognition. However, the Prp40 WW domains were dispensable for yeast viability. In their absence, no defect in splicing in vivo, U1 or U2 snRNP recruitment in vivo, or early splicing complex assembly in vitro was detected. We conclude that the WW domains of Prp40 do not mediate essential coupling between U1 snRNP and Pol II. Instead, delays in cotranscriptional U5 snRNP and Prp19 recruitment and altered spliceosome formation in vitro suggest that Prp40 WW domains assist in late steps of spliceosome assembly

ETIOLOGIES DES PLEURESIES DU SUJET AGE AU TOGO

Objective: The aim of this study was to review the current aetiologic profile of pleurisies in the elderly people. Materials and method: We carried out a retrospective study based on the data of 126 patients, old of at least 55 years, hospitalised from January 2007 to December 2011 for pleurisy in the pneumology department of Sylvanus Olympio teaching hospital of Lome. Results: Pleurisies represent 23,11 % of elderly people’s hospitalisation motives. The Sex-ratio was 1 and the average age of the patients 65 ± 09 years old. The clinical aspect was dominated by thoracic pain (88,88 %) and cough (69,84 %). The chest X-ray revealed pleural effusion at the left side in 48,41 %, at right side in 46,83% and of medium abundance in 57,93 %. The liquid was citrine in 53,97 %, haematic in 30,95% and purulent in 15,08% . Pleurisies were of cancerous origin in 32,54 %, tubercular in 17,46 % and bacterial not tubercular in 14,58%. No aetiology had been found in 33,33 %. The mortality was 27,78 % and due to cancers and idiopathic pleurisies in 86 % during three months’ follow up. Conclusion: Cancers are the first aetiology of pleurisies followed by tuberculosis in elderly people. The acquisition of the new means of pleural exploration is important to reduce the proportion of idiopathic pleurisies

The C-terminal domain from S. cerevisiae Pat1 displays two conserved regions involved in decapping factor recruitment

Eukaryotic mRNA decay is a highly regulated process allowing cells to rapidly modulate protein production in response to internal and environmental cues. Mature translatable eukaryotic mRNAs are protected from fast and uncontrolled degradation in the cytoplasm by two cis-acting stability determinants: a methylguanosine (m(7)G) cap and a poly(A) tail at their 5' and 3' extremities, respectively. The hydrolysis of the m(7)G cap structure, known as decapping, is performed by the complex composed of the Dcp2 catalytic subunit and its partner Dcp1. The Dcp1-Dcp2 decapping complex has a low intrinsic activity and requires accessory factors to be fully active. Among these factors, Pat1 is considered to be a central scaffolding protein involved in Dcp2 activation but also in inhibition of translation initiation. Here, we present the structural and functional study of the C-terminal domain from S. cerevisiae Pat1 protein. We have identified two conserved and functionally important regions located at both extremities of the domain. The first region is involved in binding to Lsm1-7 complex. The second patch is specific for fungal proteins and is responsible for Pat1 interaction with Edc3. These observations support the plasticity of the protein interaction network involved in mRNA decay and show that evolution has extended the C-terminal alpha-helical domain from fungal Pat1 proteins to generate a new binding platform for protein partners