Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

<p>Abstract</p> <p>Background</p> <p>Gram-negative bacteria use periplasmic-binding proteins (bPBP) to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo) and closed (ligated) conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding.</p> <p>Results</p> <p>We use a distance constraint model (DCM) to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR) are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings) also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network.</p> <p>Conclusion</p> <p>Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect intrinsic flexibility. Moreover, varying numbers of H-bonds and their strengths control the likelihood for energetic fluctuations as H-bonds break and reform, thus directly affecting thermodynamic properties. Consequently, these results demonstrate how unexpected large differences, especially within cooperativity correlation, emerge from subtle differences within the underlying H-bond network. This inference is consistent with well-known results that show allosteric response within a family generally varies significantly. Identifying the hydrogen bond network as a critical determining factor for these large variances may lead to new methods that can predict such effects.</p

Detection of 1014F kdr mutation in four major Anopheline malaria vectors in Indonesia

Background: Malaria is a serious public health problem in Indonesia, particularly in areas outside Java and Bali. The spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. To better understand patterns of transmission and resistance in Indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, Purworejo in Central Java, South Lampung District in Sumatera and South Halmahera District in North Mollucca.\ud Methods: Mosquitoes were collected from the three areas through indoor and outdoor human landing catches (HLC) and indoor restinging catches. Specimens were identified morphologically by species and kept individually in 1.5 ml Eppendorf microtube. A fragment of the VGSC gene from 95 mosquito samples was sequenced and kdr allelic variation determined.\ud Results: The molecular analysis of these anopheline mosquitoes revealed the existence of the 1014F allele in 4 major malaria vectors from South Lampung. These species include, Anopheles sundaicus, Anopheles aconitus, Anopheles subpictus\ud andAnopheles vagus. The 1014F allele was not found in the other areas.\ud Conclusion: The finding documents the presence of this mutant allele in Indonesia, and implies that selection pressure on the Anopheles population in this area has occurred. Further studies to determine the impact of the resistance allele on the efficacy of pyrethroids in control programmes are neede

Trends in popularity of some morphological traits of purebred dogs in Australia.

Background The morphology of dogs can provide information about their predisposition to some disorders. For example, larger breeds are predisposed to hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in popularity of dog morphology can reveal potential disease pervasiveness in the future. There have been reports on the popularity of particular breeds and behavioural traits but trends in the morphological traits of preferred breeds have not been studied. Methods This study investigated trends in the height, dog size and head shape (cephalic index) of Australian purebred dogs. One hundred eighty-one breeds derived from Australian National Kennel Council (ANKC) registration statistics from 1986 to 2013 were analysed. Weighted regression analyses were conducted to examine trends in the traits by using them as outcome variables, with year as the explanatory variable and numbers of registered dogs as weights. Linear regression investigated dog height and cephalic index (skull width/skull length), and multinomial logistic regression studied dog size. Results The total number of ANKC registration had decreased gradually from 95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and weighted maximal height (p < 0.001) decreased significantly over time, and the weighted cephalic index increased significantly (p < 0.001). The odds of registration of medium and small breeds increased by 5.3 % and 4.2 %, respectively, relative to large breeds (p < 0.001) and by 12.1 % and 11.0 %, respectively, relative to giant breeds (p < 0.001) for each 5-year block of time. Conclusions Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Mean cephalic index has increased, which indicates that Australians have gradually favoured breeds with shorter and wider heads (brachycephalic). These significant trends indicate that the dog morphological traits reported here may potentially influence how people select companion dogs in Australia and provide valuable predictive information on the pervasiveness of diseases in dogs. Keywords: Purebred dogs, Dog popularity, Dog height, Dog size, Cephalic index, Brachycephalic Disease, predisposition, Australia. Plain English Summary Some diseases in dogs are related to certain physical characteristics. For example, larger breeds have a higher risk of getting hip dysplasia and certain neoplastic diseases while breeds with wider and shorter heads, such as Pug and French bulldog, are more likely to experience breathing problems and dystocia. Therefore, if we know the trends in popularity of dogs of a certain morphology, we may be able to predict disease pervasiveness. The study aimed to investigate the trends in the height, dog size and head shape of Australian purebred dogs. The numbers of dogs registered within the 181 breeds in Australian National Kennel Council (ANKC) every year from 1986 to 2013 were obtained and analysed. The total number of ANKC registration had decreased from 95,792 in 1986 to 66,902 in 2013. Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Also, the data suggest that Australians increasingly favour dogs with shorter and wider heads for whose welfare veterinarians often express concern [1, 2]. The results indicate that dog height, dog size and dog head shape may potentially influence how people select companion dogs in Australia and provide valuable predictive information on trends in disease prevalence, enabling the veterinary profession and industry to prepare for potential future caseloads

Mycorrhizas in South American Anthropic Environments

The agricultural expansion has leaded to increase the irrigated cropland area and the use of fertilizers, resulting in water degradation, increased energy use, and common pollution. Of particular concern is the increased interest to reduce the environmental impacts of high quantities of water dedicated to irrigation by agricultural activities We are now truly recognizing the importance of sustainable measures in agriculture such as conservation of the vegetation cover and management approach to understand surface and deep soil responses to global change. The agroecology management based on key processes from natural ecosystems can help to solve some agricultural difficulties. Increasing studies on the Arbuscular mycorrhizal fungi (AMF) has showed their importance for soil ecology and studies on their biodiversity have spread in some agro-ecosystems such as corn and soybean monocultures. Therefore, it is needed to deeply study the mycorrhizal functions under global change. In this chapter, we examine the major developments and advances on mycorrhizal fungi based on recent research from South American countries. New reports on the occurrence of mycorrhizas in Amazonian dark earth, as well as the inoculum production of arbuscular mycorrhizal fungi native of soils under native forest covers, have resulted in a more detailed understanding of the soil biology from South America. Reports from Amazonian dark earth or “Terra preta do índio” soil has stimulated the use of biochar worldwide as a soil conditioner that can add value to non-harvested agricultural products and promote plant growth. Few reports from Brazil showed that the addition of inorganic fertilizer, compost and chicken manure resulted in increases in plant cover and plant species richness. In this sense, the biochar/mycorrhizae interactions also can be prioritized for sequestration of carbon in soils to contribute to climate change mitigation