1,031 research outputs found

    Paradoxical signaling regulates structural plasticity in dendritic spines

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    Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics

    Investigating the evolution of apoptosis in malaria parasites: the importance of ecology

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    Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention. However, it is important to understand when and why parasites employ an apoptosis strategy before the likely long-and short-term success of such an intervention can be evaluated. The occurrence of apoptosis in unicellular parasites provides a challenge for evolutionary theory to explain as organisms are expected to have evolved to maximise their own proliferation, not death. One possible explanation is that protozoan parasites undergo apoptosis in order to gain a group benefit from controlling their density as this prevents premature vector mortality. However, experimental manipulations to examine the ultimate causes behind apoptosis in parasites are lacking. In this review, we focus on malaria parasites to outline how an evolutionary framework can help make predictions about the ecological circumstances under which apoptosis could evolve. We then highlight the ecological considerations that should be taken into account when designing evolutionary experiments involving markers of cell death, and we call for collaboration between researchers in different fields to identify and develop appropriate markers in reference to parasite ecology and to resolve debates on terminology.Host-parasite interactio

    Novel heuristic for low-batch manufacturing process scheduling optimisation with reference to process engineering

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    YesScheduling is an important element that has a major impact on the efficiency of all manufacturing processes. It plays an important role in optimising the manufacturing times and costs resulting in energy efficient processes. It has been estimated that more than 75% of manufacturing processes occur in small batches. In such environments, processes must be able to perform a variety of operations on a mix of different batches. Batch-job scheduling optimisation is the response to such low batch manufacturing problems. The optimisation of batch-job process scheduling problem is still a challenge to researchers and is far from being completely solved due to its combinatorial nature. In this paper, a novel hybrid heuristic (HybH) solution approach for batch-job scheduling problem is presented with the objective of optimising the overall Makespan (Cmax). The proposed HybH is the combination of Index Based Heuristic (IBH) and the Finished Batch-Job (FBJ) process schedule. The heuristic assigns the first operation to a batch-job using IBH and the remaining operations on the basis FBJ process schedule. The FBJ process schedule gives priority to the batch-job with early finished operations, without violating the constraints of process order. The proposed HybH is explained with the help of a detailed example. Several benchmark problems are solved from the literature to check the validity and effectiveness of the proposed heuristic. The presented HybH has achieved batch-job process schedules which have outperformed the traditional heuristics. The results are encouraging and show that the proposed heuristic is a valid methodology for batch process scheduling optimisation

    Prevalent phenotypes and antibiotic resistance in Escherichia coli and Klebsiella pneumoniae at an Indian tertiary care hospital: plasmid-mediated cefoxitin resistance

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    SummaryBackgroundThe β-lactam antibiotics, in combination with aminoglycosides, are among the most widely prescribed antibiotics. However, because of extensive and unnecessary use, resistance to these drugs continues to increase. In recent years, resistance in the Indian bacterial population has increased markedly, the majority showing complex mechanisms. Due to increased transcontinental movement of the human population, it would be wise to know the prevalence and resistance complexity of these strains, well in advance, in order to formulate a policy for empirical therapy.MethodsOne hundred and eighty-one isolates of Escherichia coli and 61 isolates of Klebsiella pneumoniae obtained from 2655 non-repeat samples of pus (912) and urine (1743) were studied, and their resistance rates and patterns were noted. The isolates were analyzed for prevalent aminoglycoside and cephalosporin resistance phenotypes and for the presence of extended spectrum β-lactamase (ESBL) and AmpC enzymes by spot-inoculation and modified three-dimensional tests developed in our laboratory. Fourteen isolates of E. coli and six of K. pneumoniae, resistant to all of the antibiotics tested, were selected for plasmid screening, curing, and transconjugation experiments, and for comparative evaluation of the double disk synergy test (DDST) and modified three-dimensional test (TDT) for detection of β-lactamases.ResultsUrinary E. coli isolates showed maximum susceptibility to amikacin (57.1%), followed by tobramycin (38.5%) and gentamicin (31.9%). Eighteen (19.8%) isolates were susceptible to cefotaxime, whereas 11 (12.1%) were susceptible to ceftriaxone. The K. pneumoniae isolates from urine samples showed maximum susceptibility to tobramycin (63.6%) followed by amikacin (54.5%). Of the K. pneumoniae isolates, 31.8% were susceptible to cefotaxime and 13.6% were susceptible to ceftriaxone. A more or less similar trend of antibiotic susceptibility was noted in E. coli and K. pneumoniae isolates from pus samples. Twenty-six (14.4%) E. coli and 15 (24.6%) K. pneumoniae isolates were found to be ESBL-producers by NCCLS-ESBL phenotypic confirmatory test. Eighteen (9.9%) E. coli and 19 (31.1%) K. pneumoniae isolates were found to be AmpC enzyme-producers by our modified TDT. The simultaneous occurrence of ESBL and AmpC enzymes was noted in 7.7% and 9.8% isolates of E. coli and K. pneumoniae, respectively.ConclusionsThe prevalence of multidrug-resistant bacterial isolates is quite high in our bacterial population. On comparative evaluation of DDST and TDT in resistant isolates, TDT was found to be the better method, detecting ESBLs in 80% of isolates compared to 15% with DDST. A 19.9-kb plasmid was consistently present in all the screened isolates of E. coli and K. pneumoniae, and was inferred to encode cefoxitin and tetracycline resistance based on curing and transconjugation experiments

    Protective Effects of Salivary Factors in Dental Caries in Diabetic Patients of Pakistan

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    Salivary factors have been studied for their effects on the process of dental caries in patients of diabetes mellitus type 2. In this study, protective role of salivary pH, salivary flow rate, and salivary calcium is assessed in the patients of diabetes mellitus type 2 with dental caries. The samples of saliva were collected from 400 patients of diabetes mellitus type 2 and 300 age- and sex- matched controls after getting informed consent. All the subjects were classified into four groups according to age. The severity of dental caries was counted by decayed, missed, and filled teeth (DMFT) score. The salivary pH, flow rate, and calcium levels were found to be low in patients as compared to controls. The levels of fasting blood sugar, HbA1c, and DMFT score were found to be significantly high in patients than controls. The glycemic factors were significantly correlated with salivary factors indicating their influence on progression of caries in diabetes. On the basis of findings, it is concluded that the suitable salivary pH and flow rate may be regarded as main protective factors against dental caries in diabetes. Optimum level of salivary calcium may be responsible for continuous supply of calcium to arrest the demineralization and help reduce the occurrence of dental caries

    Performance Enhancement of Wearable Antenna Using High Impedance Surfaces

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    This paper presents a novel textile wearable antenna that has been designed to operate at Wi-Fi bands of 2.4GHz & 5.8GHz. Antenna performance in free space environment showed Gain of 1.8dBi at 2.4GHz and 4.5dBi at 5.8GHz. However, performance deteriorated when antenna was operated near human body which is lossy and complex in nature. For mitigating the human body effect on antenna performance, high impedance surface (HIS) was designed and integrated with this textile antenna. Due to shielding effect of HIS, antenna Gain increased to 8dBi at 2.4GHz and 9dBi at 5.8GHz. The SAR values were also reduced to 0.682W/Kg at 2.4GHz and 0.0692W/Kg at 5.8GHz for 10g tissue. The proposed antenna was also tested under bending and crumpling conditions. It was observed that antenna performance was not significantly deteriorated. The proposed textile antenna can have exciting applications in emerging wearable technologies