Malaria vectors and transmission in an area deforested for a new international airport in Southern Cameroon

Dans le village de Nsimalen au Sud du Cameroun, la construction récente d'un aéroport international a nécessité une déforestation sur 370 hectares. Une enquête entomologique des vecteurs et de la transmission du paludisme a été réalisée pendant un an dans deux hameaux de ce village. L'un était situé en bordure de l'aire de déforestation, l'autre 3 kilomètres plus loin. L'enquête était basée sur les captures nocturnes de moustiques sur sujets humains à l'intérieur des habitations. Les résultats obtenus montrent que #Anopheles moucheti$est le vecteur principal du paludisme dans ce village, il représente en effet 90$ est plus abondant en bordure de l'aire de déforestation (5% des effectifs capturés) que 3 kilomètres plus loin (2%). Le faible taux de parturité de cette dernière espèce dans le hameau proche de la zone aéroportuaire (54,9%) montre que la déforestation a créé des gîtes qui lui sont favorables. Le taux d'inoculation entomologique a été estimé à 106 et 68 piqûres infectées par homme par an respectivement dans les hameaux proches et éloignés. #Anopheles gambiae$ assurait 13% de la transmission à côté de l'aéroport alors que sa transmission était nulle 3 kilomètres plus loin. (Résumé d'auteur

Understanding the mechanism of recognition of gab2 by the N-SH2 domain of SHP2

Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and it is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds, through its two SH2 domains, specific consensus sequences presenting a phosphorylated tyrosine located on the disordered tail of Gab2. To shed light on the details of such a fundamental interaction for the physiology of the cell, we present a complete mutational analysis of the kinetics of binding between the N-SH2 domain of SHP2 and a peptide mimicking a specific region of Gab2. By analyzing kinetic data, we determined structural features of the transition state of the N-SH2 domain binding to Gab2, highlighting a remarkable cooperativity of the binding reaction. Furthermore, comparison of these data with ones previously obtained for another SH2 domain suggests the presence of underlying general features characterizing the binding process of SH2 domains. Data are discussed under the light of previous works on SH2 domains

Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy

Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy.BackgroundCalcium channel blockers (CCBs) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy. No clinical study, however, has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability. We, therefore, tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane, hence changing its permeability.MethodsTwenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were randomized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure, urinary protein excretion, glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearances were obtained. Glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearance were measured every three months, arterial pressure and heart rate every month. Patients were followed for 21months.ResultsAt 21months, both patient groups had similar levels of blood pressure control, however, only the diltiazem group had a change in proteinuria (4 ± 10%Δ, nifedipine vs. -57 ± 18%Δ, diltiazem; P < 0.001) with improvement in glomerular size selectivity and change in IgG clearance.ConclusionsThese data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so, in part, by improving glomerular size permselectivity

The kinetics of folding of the NSH2 domain from p85

SH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics. Taking advantage of double mixing stopped flow experiments and site directed mutagenesis we demonstrate that such behavior is due to the cis/trans isomerization of the peptide bond between D73 and P74, being in a cis conformation in the native protein. Our data are discussed in comparison with previous works on the folding of other SH2 domains

Pengendalian Biologi Nematoda Meloidogyne Spp. Dengan Jamur Paecilomyces Fumosoroseus Dan Bakteri Pasteuria Penetrans Serta Pengaruhnya Terhadap Tanaman Buncis (Phaseolus Vulgaris L.)

Produksi buncis di Indonesia masih rendah dibandingkan dengan negara-negara lain. Hal ini diakibatkan oleh serangan nematoda bengkak akar (Meloidogyne spp.). Usaha pengendalian Meloidogyne spp. dapat dilakukan dengan beberapa cara, salah satunya dengan pemanfaatan musuh alami Meloidogyne spp. yaitu Paecilomyces fumosoroseus dan Pasteuria penetrans. Penelitian ini bertujuan untuk memperoleh efektifitas P. fumosoroseus, dan P. penetrans, atau campuran keduanya terhadap indeks gall akar, jumlah telur, berat segar bagian atas tanaman, jumlah larva II Meloidogyne spp. dalam 100 ml tanah, dan hasil tanaman buncis. Penelitian menggunakan metode percobaan dengan Rancangan Acak Kelompok, terdiri atas 8 perlakuan dan 4 ulangan. Perlakuan tersebut adalah tanaman buncis diinokulasi dengan: 1). Meloidogyne spp. + P. fumosoroseus, 2). Meloidogyne spp. + Pasteuria penetrans, 3). Meloidogyne spp. + P. fumosoroseus + P. penetrans, 4). Hanya Meloidogyne spp., 5). Hanya P. fumosoroseus, 6). Hanya P. penetrans, 7). P. fumosoroseus + P. penetrans. 8). Kontrol tanpa perlakuan. Data hasil percobaan dianalisis dengan menggunakan analisis ragam. Hasil percobaan menunjukkan, bahwa perlakuan yang mengandung Meloidogyne spp. dan P. fumosoroseus, atau Meloidogyne spp. dan P. penetrans, atau Meloidogyne spp. ditambah P. fumosoroseus dan P. penetrans mampu menurunkan indeks gall akar, jumlah telur, mampu meningkatkan berat segar bagian atas tanaman, menurunkan jumlah larva II Meloidogyne spp. dalam 100 ml tanah, dan meningkatkan hasil tanaman buncis. P. fumosoroseus dan P. penetrans yang diaplikasikan bersama mampu menurunkan jumlah telur, dan jumlah larva II Meloidogyne spp. dalam 100 ml tanah, dan hasil buncis lebih tinggi dibandingkan jika diaplikasikan secara sendiri-sendiri

Understanding the binding induced folding of intrinsically disordered proteins by protein engineering: Caveats and pitfalls

Many proteins lack a well-defined three-dimensional structure in isolation. These proteins, typically denoted as intrinsically disordered proteins (IDPs), may display a characteristic disorder-to-order transition when binding their physiological partner(s). From an experimental perspective, it is of great importance to establish the general grounds to understand how such folding processes may be explored. Here we discuss the caveats and the pitfalls arising when applying to IDPs one of the key techniques to characterize the folding of globular proteins, the Φ value analysis. This method is based on measurements of the free energy changes of transition and native states upon conservative, non-disrupting, mutations. On the basis of available data, we reinforce the validity of Φ value analysis in the study of IDPs and suggest future experiments to further validate this powerful experimental method

Experimental characterization of the interaction between the n-terminal sh3 domain of crkl and c3g

Crkl is a protein involved in the onset of several cancer pathologies that exerts its function only through its protein–protein interaction domains, a SH2 domain and two SH3 domains. SH3 domains are small protein interaction modules that mediate the binding and recognition of proline-rich sequences. One of the main physiological interactors of Crkl is C3G (also known as RAPGEF1), an interaction with key implications in regulating cellular growth and differentiation, cell morphogenesis and adhesion processes. Thus, understanding the interaction between Crkl and C3G is fundamental to gaining information about the molecular determinants of the several cancer pathologies in which these proteins are involved. In this paper, through a combination of fast kinetics at different experimental conditions and site-directed mutagenesis, we characterize the binding reaction between the N-SH3 domain of Crkl and a peptide mimicking a specific portion of C3G. Our results show a clear effect of pH on the stability of the complex, due to the protonation of negatively charged residues in the binding pocket of N-SH3. Our results are discussed under the light of previous work on SH3 domains

Double mutant cycles as a tool to address folding, binding, and allostery

Quantitative measurement of intramolecular and intermolecular interactions in protein structure is an elusive task, not easy to address experimentally. The phenomenon denoted ‘energetic coupling’ describes short- and long-range interactions between two residues in a protein system. A powerful method to identify and quantitatively characterize long-range interactions and allosteric networks in proteins or protein-ligand complexes is called double-mutant cycles analysis. In this review we describe the thermodynamic principles and basic equations that underlie the double mutant cycle methodology, its fields of application and latest employments, and caveats and pitfalls that the experimentalists must consider. In particular, we show how double mutant cycles can be a powerful tool to investigate allosteric mechanisms in protein binding reactions as well as elusive states in protein folding pathways