Investigation on masticatory muscular functionality following oral reconstruction – An inverse identification approach

The human masticatory system has received significant attention in the areas of biomechanics due to its sophisticated co-activation of a group of masticatory muscles which contribute to the fundamental oral functions. However, determination of each muscular force remains fairly challenging in vivo; the conventional data available may be inapplicable to patients who experience major oral interventions such as maxillofacial reconstruction, in which the resultant unsymmetrical anatomical structure invokes a more complex stomatognathic functioning system. Therefore, this study aimed to (1) establish an inverse identification procedure by incorporating the sequential Kriging optimization (SKO) algorithm, coupled with the patient-specific finite element analysis (FEA) in silico and occlusal force measurements at different time points over a course of rehabilitation in vivo; and (2) evaluate muscular functionality for a patient with mandibular reconstruction using a fibula free flap (FFF) procedure. The results from this study proved the hypothesis that the proposed method is of certain statistical advantage of utilizing occlusal force measurements, compared to the traditionally adopted optimality criteria approaches that are basically driven by minimizing the energy consumption of muscle systems engaged. Therefore, it is speculated that mastication may not be optimally controlled, in particular for maxillofacially reconstructed patients. For the abnormal muscular system in the patient with orofacial reconstruction, the study shows that in general, the magnitude of muscle forces fluctuates over the 28-month rehabilitation period regardless of the decreasing trend of the maximum muscular capacity. Such finding implies that the reduction of the masticatory muscle activities on the resection side might lead to non-physiological oral biomechanical responses, which can change the muscular activities for stabilizing the reconstructed mandible.     

Molecular dynamics approach to probe the antigenicity of PagN – an outer membrane protein of Salmonella Typhi

PagN is a highly immunogenic 27-kDa outer membrane adhesin present in Salmonella Typhi. It plays a major role in the pathogenesis of typhoid fever and has emerged as a strong vaccine candidate. In this report, we predict the three-dimensional structure of PagN and describe the conformational dynamics associated with its four extracellular loops based on two 100-ns molecular dynamics simulations at 300 and 310 K. The formation and deformation of the secondary structures on these loops were also investigated during the simulations which revealed loops L1 and L2 to be highly flexible, whereas the relative flexibility of loops L3 and L4 was minimal. Essential dynamics and principal component analysis deciphered more realistic dynamic behaviours of the loops, particularly at 310 K. Moreover, our epitope predictions suggest that the antigenic peptides for B-cell recognition are located within the loops L1 and L2, while those for T-cell recognition are located within the loops L3 and L4. The binding specificities of the antigenic peptides towards specific human MHC-I and MHC-II HLA alleles closely resembled the stability of the loops L3 and L4 inferred from the simulations. Finally, we identified potential antigenic peptides in the flexible (L1 and L2) as well as stable (L3 and L4) regions of PagN for both B- and T-cell recognitions, which can help in developing effective sub-unit vaccines.     

Characterization of haemoglobin from Actinorhizal plants – An in silico approach

Plant haemoglobins (Hbs), found in both symbiotic and non-symbiotic plants, are heme proteins and members of the globin superfamily. Hb genes of actinorhizal Fagales mostly belong to the non-symbiotic type of haemoglobin; however, along with the non-symbiotic Hb, Casuarina sp. posses a symbiotic one (symCgHb), which is expressed specifically in infected cells of nodules. A thorough sequence analysis of 26 plant Hb proteins, currently available in public domain, revealed a consensus motif of 29 amino acids. This motif is present in all the members of symbiotic class II Hbs including symCgHb and non-symbiotic Class II Hbs, but is totally absent in Class I symbiotic and non-symbiotic Hbs. Further, we constructed 3D structures of Hb proteins from Alnus and Casuarina through homology modelling and peeped into their structural properties. Structure-based studies revealed that the Casuarina symbiotic haemoglobin protein shows distinct stereochemical properties from that of the other Casuarina and Alnus Hb proteins. It also showed considerable structural similarities with leghemoglobin structure from yellow lupin (pdb id 1GDI). Therefore, sequence and structure analyses point to the fact that symCgHb protein shows significant resemblance to symbiotic haemoglobin found in legumes and may thus eventually play a similar role in shielding the nitrogenase from oxygen as seen in the case of leghemoglobin.     

Modeling the dynamics of woody plant–herbivore interactions with age-dependent toxicity

In this paper we study the effects that woody plant chemical defenses may have on interactions between boreal hares that in winter feed almost entirely on twigs. We focus particularly on the fact that toxin concentration often varies with the age of twig segments. The model incorporates the fact that the woody internodes of the youngest segments of the twigs of the deciduous angiosperm species that these hares prefer to eat are more defended by toxins than the woody internodes of the older segments that subtend and support the younger segments. Thus, the per capita daily intake of the biomass of the older segments of twigs by hares is much higher than their intake of the biomass of the younger segments of twigs. This age-dependent toxicity of twig segments is modeled using age-structured model equations which are reduced to a system of delay differential equations involving multiple delays in the woody plant-hare dynamics. A novel aspect of the modeling was that it had to account for mortality of non-consumed younger twig segment biomass when older twig biomass was bitten off and consumed. Basic mathematical properties of the model are established together with upper and lower bounds on the solutions. Necessary and sufficient conditions are found for the linear stability of the equilibrium in which the hare is extinct, and sufficient conditions are found for the global stability of this equilibrium. Numerical simulations confirmed the analytical results and demonstrated the existence of limit cycles over ranges of parameters reasonable for hares browsing on woody vegetation in boreal ecosystems. This showed that age dependence in plant chemical defenses has the capacity to cause hare-plant population cycles, a new result.     

Seasonal dynamics of chemotypes in a freshwater phytoplankton community – A metabolomic approach

Cyanobacteria are known to produce a huge variety of secondary metabolites. Many of these metabolites are toxic to zooplankton, fish, birds and mammals. Therefore, the toxicity of cyanobacterial blooms is strongly dependent on the cyanobacterial strain composition. These strains produce distinct bouquets of secondary metabolites, and thus constitute different chemotypes. Some of the cyanobacterial metabolites are potent inhibitors of gut proteases of the filter-feeder Daphnia. Here, we investigate the seasonal dynamics of secondary metabolites in a phytoplankton community from a hypertrophic pond, making use of a new metabolomic approach. Using liquid chromatography coupled with high-resolution mass spectrometry (LCMS), we obtained mass spectra of phytoplankton samples taken on different dates throughout the summer season. By applying multivariate statistics, we combined these data with the protease inhibition capacity of the same samples. This led to the identification of metabolites with cyanobacterial origin and as well of distinct cyanobacterial chemotypes being dominant on different dates. The protease inhibition capacity varied strongly with season, and only one out of 73 known cyanobacterial protease inhibitors could be confirmed in the natural samples. Instead, several so far unknown, putative protease inhibitors were detected. In conclusion, the creation of time series of mass spectral data of a natural phytoplankton community proved to be useful for elucidating seasonal chemotype succession in a cyanobacterial community. Additionally, correlating mass spectral data with a biological assay provides a promising tool for facilitating the search for new harmful metabolites prior to structure elucidation.     

Going with the wind – Adaptive dynamics of plant secondary meristems

The developmental plasticity of organisms is a natural consequence of adaptation. Classical approaches targeting developmental processes usually focus on genetics as the essential factor underlying phenotypic differences. However, such differences are often based on the inherent plasticity of developmental programs. Due to their dependence on environmental stimuli, plants represent ideal experimental systems in which to dissect the contribution of genetic and environmental variation to phenotypic plasticity. An evident example is the vast repertoire of growth forms observed in plant shoot systems. A fundamental factor underlying the broadness of this repertoire is the activity of secondary meristems, namely the axillary meristems that give rise to side shoots, and the cambium essential for stem thickening. Differential activities of both meristem types are crucial to the tremendous variation seen in higher plant architecture. In this review, we discuss the role of secondary meristems in the adaptation of plant growth forms, and the ways in which they integrate environmental input. In particular, we explore potential approaches for dissecting the degree to which this flexibility and its consequences for plant architecture is genetically predetermined and how much it represents an adaptive value.     

Prediction of the nutrients value and biochemical characteristics of swine slurry by measurement of EC – Electrical conductivity

Slurry samples, collected from 41 commercial swine farms in South Korea, were characterized in various physico-biochemical, macro and micronutrients, heavy metals and microbial parameters. Interestingly, significant variations were observed in all the parameters. However, positive relationships were noticed between EC and ammonia nitrogen (NH₃-N), total nitrogen (TN), total potassium (TK), specific gravity (SG), total solids (TS), volatile solids (VS), fixed solids (FS), total dissolved solids (TDS) at R² = 0.91, 0.74, 0.69, 0.60, 0.50, 0.48, 0.55, and 0.52, respectively. Whereas phosphorous and other nutrients shown poor correlation. Escherichia coli and Salmonella were counted at an average of 5.04 log₁₀ colony forming unit (CFU)/mL and 3.55 log₁₀ most probable number (MPN)/mL, respectively. Equations for predicting nutrients content in swine slurries are presented with EC, because it is an easily determinable parameter. The data obtained in this study could be used as a guideline for Good Management Practices in South Korean swine farms as well as other countries.     

Pocket analysis of the full-length cholix toxin. An assessment of the structure–dynamics of the apo catalytic domain

Cholix toxin from Vibrio cholerae is the third member of the diphtheria toxin (DT) group of mono-ADP-ribosyltransferase (mART) bacterial toxins. It shares structural and functional properties with Pseudomonas aeruginosa exotoxin A and Corynebacterium diphtheriae DT. Cholix toxin is an important model for the development of antivirulence approaches and therapeutics against these toxins from pathogenic bacteria. Herein, we have used the high-resolution X-ray structure of full-length cholix complexed with NAD⁺ to describe the properties of the NAD⁺-binding pocket at the residue level, including the role of crystallographic water molecules in the NAD⁺ substrate interaction. The full-length apo cholix structure is used to describe the putative NAD⁺-binding site(s) and to correlate biochemical with crystallographic data to study the stoichiometry and orientation of bound NAD⁺ molecules. We quantitatively describe the NAD⁺ substrate interactions on a residue basis for the main 22 pocket residues in cholix_f, a glycerol and 5 contact water molecules as part of the recognition surface by the substrate according to the conditions of crystallization. In addition, the dynamic properties of an in silico version of the catalytic domain were investigated in order to understand the lack of electronic density for one of the main flexible loops (R-loop) in the pocket of X-ray complexes. Implications for a rational drug design approach for mART toxins are derived.     

An anthropological approach to the demography of central Brazil Gê societies

In this paper, the author considers the spatial and social dynamics of the Akwen Xerente population and demonstrates the necessity of relying on both demographic and anthropological information. This population is characterised by a complex combination of distinct processes which at the same time maintain the ethnic identity and redistribute individuals among villages. Individuals moves in different villages following a rule of uxorilocal residence and as the result of the formation of new villages after conflicts between political factions, whereas the social belonging of the individual is organised by exogamous moieties and patrilineal clans. This work shows that these different dimensions of the organisation of the Xerente society can only be understood when considering together a group of villages: in this case, the village is not a functional unit.     

Molecular dynamics simulation approach for the prediction of transmembrane helix–helix heterodimers assembly

Computational methods are useful to identify favorable structures of transmembrane (TM) helix oligomers when experimental data are not available or when they cannot help to interpret helix-helix association. We report here a global search method using molecular dynamics (MD) simulations to predict the structures of transmembrane homo and heterodimers. The present approach is based only on sequence information without any experimental data and is first applied to glycophorin A to validate the protocol and to the HER2-HER3 heterodimer receptor. The method successfully reproduces the experimental structures of the TM domain of glycophorin A (GpA(TM)) with a root mean square deviation of 1.5 A. The search protocol identifies three energetically stable models of the TM domain of HER2-HER3 receptor with favorable helix-helix arrangement, including right-handed and left-handed coiled-coils. The predicted TM structures exhibit the GxxxG-like motif at the dimer interface which is presumed to drive receptor oligomerization. We demonstrate that native structures of TM domain can be predicted without quantitative experimental data. This search protocol could help to predict structures of the TM domain of HER heterodimer family.     

Animal board invited review: An update on the methods for semen quality evaluation in swine – from farm to the lab

Pig breeding is mainly conducted through artificial insemination with liquid-stored semen. It is, therefore, crucial to ensure that sperm quality is over the standard thresholds, as reduced sperm motility, morphology or plasma membrane integrity are associated with reduced farrowing rates and litter sizes. This work aims to summarise the methods utilised in farms and research laboratories to evaluate sperm quality in pigs. The conventional spermiogram consists in the assessment of sperm concentration, motility and morphology, which are the most estimated variables in farms. Yet, while the determination of these sperm parameters is enough for farms to prepare seminal doses, other tests, usually carried out in specialised laboratories, may be required when boar studs exhibit a decreased reproductive performance. These methods include the evaluation of functional sperm parameters, such as plasma membrane integrity and fluidity, intracellular levels of calcium and reactive oxygen species, mitochondrial activity, and acrosome integrity, using fluorescent probes and flow cytometry. Furthermore, sperm chromatin condensation and DNA integrity, despite not being routinely assessed, may also help determine the causes of reduced fertilising capacity. Sperm DNA integrity can be evaluated through direct (Comet, transferase deoxynucleotide nick end labelling (TUNEL) and its in situ nick variant) or indirect tests (Sperm Chromatin Structure Assay, Sperm Chromatin Dispersion Test), whereas chromatin condensation can be determined with Chromomycin A3. Considering the high degree of chromatin packaging in pig sperm, which only have protamine 1, growing evidence suggests that complete decondensation of that chromatin is needed before DNA fragmentation through TUNEL or Comet can be examined.     

An integrative approach to understanding host–parasitoid population dynamics in real landscapes

Many of our advances regarding the spatial ecology of predators and prey have been attributed to research with insect parasitoids and their hosts. Host–parasitoid systems are ideal for spatial-ecological studies because of the small size of the organisms, the often discrete distribution of their resources, and the relative ease with which host mortality from parasitoids can be determined. We outline an integrated approach to studying host–parasitoid interactions in heterogeneous natural landscapes. This approach involves conducting experiments to obtain critically important information on dispersal and boundary behavior of the host and parasitoid, large-scale manipulations of landscape structure to reveal the impacts of landscape change on host–parasitoid interactions and temporal population dynamics, and the development of spatially realistic, behavior-based landscape models. The dividends from such an integrative approach are far reaching, as is illustrated in our research on the prairie planthopper Prokelisia crocea and its egg parasitoid Anagrus columbi that occurs in the tall-grass prairies of North America. Here, we describe the population structure of this system which is based on a long-term survey of planthoppers and parasitoids among host–plant patches. We also outline novel approaches to experimentally quantify and model the movement and boundary behavior of animals in general. The value of this information is revealed in a landscape-level field experiment that was designed to test predictions about how landscape change affects the spatial and temporal population dynamics of the host and parasitoid. Finally, with these empirical data as the foundation, we describe novel simulation models that are spatially realistic and behavior based. Drawing from this integrated approach and case study, we identify key research questions for the future.     

Investigation on the role of nsSNPs in HNPCC genes – a bioinformatics approach

Background  

A central focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations not only provides insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. Missense mutations are nucleotide substitutions that change an amino acid in a protein, the deleterious effects of these mutations are commonly attributed to their impact on primary amino acid sequence and protein structure.     

Structure of respiratory complex I – An emerging blueprint for the mechanism

Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I.     

Modeling the spatial–temporal dynamics of water use efficiency in Yangtze River Basin using IBIS model

Climate change alters regional water and carbon cycling, which has been a hot study point in the filed of climatology and ecology. As a traditionally “water-rich” region of China, Yangtze River Basin plays an important role in regional economic development and ecosystem productivity. However, the mechanism of the influence of climate change on water and carbon cycling has been received little attention. As a coupling indicator for carbon and water, the water use efficiency (WUE) is widely used, which indicates the water consumption for carbon sequestration in watershed and regional scale. A lot of studies showed that climate change has significantly affected the water resource and production of the ecosystems in Yangtze River Basin during the period of 1956–2006, when great climate variations were occurred. To better understand the alternation pattern for the relationship between water and carbon cycling under climate change at regional scale, the WUE and the spatiotemporal variations patterns were simulated in the study area from 1956 to 2006 by using the Integrated Biosphere Simulator (IBIS). The results showed that the WUE spatial pattern had the annual and seasonal variations. In general, the average annual WUE value per square meter was about 0.58 g C/kg H₂O in Yangtze River Basin. The high WUE levels were mainly distributed in the eastern area of Sichuan, western area of Jiangxi and Hunan, and the highest value reached 0.88 g C/kg H₂O. The lowest WUE’s were mainly located in the western area of Sichuan and Qinghai with the lowest values reaching to 0.36 g C/kg H₂O. The WUE in other regions mostly ranged from 0.5 to 0.6 g C/kg H₂O. For the whole study area, the annual WUE slowly increased from 1956 to 2006. The WUE in the upper reaches of Yangtze River increased based on the simulated temporal trends, which mainly located in the western area of the Sichuan Basin; the WUE of the middle reaches of Yangtze River had increased slightly from 1987 to 1996, and then decreased from 1996 to 2006; the lower reaches of Yangtze River always had smaller WUE’s than the average from 1956 to 2006. The spatiotemporal variability of the WUE in the vegetation types was obvious in the Yangtze River Basin, and it was depended on the climate and soil conditions, and as well the disturbance in its distribution areas. The temporal variations of WUE among different vegetation types had similar trends but different in values. The forest type had higher WUE than any other vegetation types ranging from 0.65 to 0.8 g C/kg H₂O. The WUE of shrubland ranged from 0.45 to 0.6 g C/kg H₂O. The WUE of tundra was the lowest, indicating the differences in plant physiology. The consistence of the spatial pattern of WUE with the NPP indicated that the regional production of Yangtze River Basin increased based on the water resources prompted and vegetation restoration. We found the drought climate was one of critical factor that impacts the alteration of WUE in Yangtze River Basin in the simulation.     

Modeling the spatial–temporal dynamics of water use efficiency in Yangtze River Basin using IBIS model

Climate change alters regional water and carbon cycling, which has been a hot study point in the filed of climatology and ecology. As a traditionally “water-rich” region of China, Yangtze River Basin plays an important role in regional economic development and ecosystem productivity. However, the mechanism of the influence of climate change on water and carbon cycling has been received little attention. As a coupling indicator for carbon and water, the water use efficiency (WUE) is widely used, which indicates the water consumption for carbon sequestration in watershed and regional scale. A lot of studies showed that climate change has significantly affected the water resource and production of the ecosystems in Yangtze River Basin during the period of 1956–2006, when great climate variations were occurred. To better understand the alternation pattern for the relationship between water and carbon cycling under climate change at regional scale, the WUE and the spatiotemporal variations patterns were simulated in the study area from 1956 to 2006 by using the Integrated Biosphere Simulator (IBIS). The results showed that the WUE spatial pattern had the annual and seasonal variations. In general, the average annual WUE value per square meter was about 0.58 g C/kg H₂O in Yangtze River Basin. The high WUE levels were mainly distributed in the eastern area of Sichuan, western area of Jiangxi and Hunan, and the highest value reached 0.88 g C/kg H₂O. The lowest WUE’s were mainly located in the western area of Sichuan and Qinghai with the lowest values reaching to 0.36 g C/kg H₂O. The WUE in other regions mostly ranged from 0.5 to 0.6 g C/kg H₂O. For the whole study area, the annual WUE slowly increased from 1956 to 2006. The WUE in the upper reaches of Yangtze River increased based on the simulated temporal trends, which mainly located in the western area of the Sichuan Basin; the WUE of the middle reaches of Yangtze River had increased slightly from 1987 to 1996, and then decreased from 1996 to 2006; the lower reaches of Yangtze River always had smaller WUE’s than the average from 1956 to 2006. The spatiotemporal variability of the WUE in the vegetation types was obvious in the Yangtze River Basin, and it was depended on the climate and soil conditions, and as well the disturbance in its distribution areas. The temporal variations of WUE among different vegetation types had similar trends but different in values. The forest type had higher WUE than any other vegetation types ranging from 0.65 to 0.8 g C/kg H₂O. The WUE of shrubland ranged from 0.45 to 0.6 g C/kg H₂O. The WUE of tundra was the lowest, indicating the differences in plant physiology. The consistence of the spatial pattern of WUE with the NPP indicated that the regional production of Yangtze River Basin increased based on the water resources prompted and vegetation restoration. We found the drought climate was one of critical factor that impacts the alteration of WUE in Yangtze River Basin in the simulation.     

An 800 year record of mangrove dynamics and human activities in the upper Gulf of Thailand

A multiproxy record comprising pollen, charcoal, loss on ignition and particle size analyses from two radiocarbon dated sediment cores from Klong Kone subdistrict on the western coast of the Gulf of Thailand provides insights on mangrove dynamics, environmental changes and human activities during the last 800 years. The mangroves were dominated by Rhizophora which indicates that the area has been influenced by the sea level from at least 820 cal bp until 720 cal bp. An intertidal area may have formed that supported mangrove development as part of an old shoreline during 820–720 cal bp. After 720 cal bp, mangroves decreased and were replaced by grasses, suggesting that a lower sea level caused the mangroves to grow closer to the sea until around 140 cal bp. Cereal pollen increased from 720 cal bp suggesting probable use of the shoreline for intensive cultivation. The mangroves were characterised by Avicennia, which increased toward the top of the 2 cores, suggesting that the mangroves then grew further inland, probably due to recent sea-level rise. Intensive human activity is recorded during the 20th century, as indicated by increased particle size, charcoal and carbonate content. At present, human activity in the area includes dams and construction as well as aquaculture.     

An evaluation of the phytochemical composition,antioxidant and cytotoxicity of the leaves of Litsea elliptica Blume – An ethnomedicinal plant from Brunei Darussalam

Litsea elliptica is traditionally believed to prevent and treat stomach ulcers, cancer, fever and headaches. This study investigates the phytochemical composition, antioxidant and cytotoxic effects of L. elliptica leaf extracts. The phytochemical content was determined via GCMS analysis and total phenolic content (TPC) and total flavonoid content (TFC) were analysed using the Folin-Ciocalteu and aluminium-chloride assays. Antioxidant activities were determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging and ferric-ion reducing antioxidant power (FRAP) assays, whereas cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and calcein/ethidium viability assays. The mechanism of cytotoxicity was investigated using Annexin V/propidium iodide. Modifications in the mitochondria were investigated using MitoTracker Red CMXRos. Ten and twenty-six compounds were characterized in the young-leaf and mixed-leaves extracts, respectively. The young-leaf methanolic extract demonstrated the highest antioxidant capacity of at least four-folds greater than the mixed-leaves and ethanolic extracts. The methanolic extract also had higher TPC and TFC values compared to the ethanolic extract. Although the mixed L. elliptica leaves had lower antioxidant capacities compared to the young leaves, the mixed leaves extract has demonstrated greater cytotoxicity against the A549 cancer cell line. Further investigation revealed that the L. elliptica leaves-induced cytotoxicity on A549 cells was possibly via the non-inflammatory mitochondria-mediated apoptotic pathway. Overall, our results showed the potential of the L. elliptica leaves possessing cytotoxic activities against carcinoma cells where the compounds present can be further investigated for its therapeutic application.