Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ): Molecular Effects and Its Importance as a Novel Therapeutic Target for Cerebral Ischemic Injury

Neurochemical Research - Cerebral ischemic injury is a leading cause of death and long-term disability throughout the world. Peroxisome proliferator-activated receptor gamma (PPAR-?) is a...     

Energy and cost trade-off for computational tasks offloading in mobile multi-tenant clouds

Cluster Computing - Mobile cloud computing augments smart-phones with computation capabilities by offloading computations to the cloud. Recent works only consider the energy savings of mobile...     

Truthful online double auction based dynamic resource provisioning for multi-objective trade-offs in IaaS clouds

Auction designs have recently been adopted for static and dynamic resource provisioning in IaaS clouds, such as Microsoft Azure and Amazon EC2. However, the existing mechanisms are mostly restricted to simple auctions, single-objective, offline setting, one-sided interactions either among cloud users or cloud service providers (CSPs), and possible misreports of cloud user’s private information. This paper proposes a more realistic scenario of online auctioning for IaaS clouds, with the unique characteristics of elasticity for time-varying arrival of cloud user requests under the time-based server maintenance in cloud data centers. We propose an online truthful double auction technique for balancing the multi-objective trade-offs between energy, revenue, and performance in IaaS clouds, consisting of a weighted bipartite matching based winning-bid determination algorithm for resource allocation and a Vickrey–Clarke–Groves (VCG) driven algorithm for payment calculation of winning bids. Through rigorous theoretical analysis and extensive trace-driven simulation studies exploiting Google cluster workload traces, we demonstrate that our mechanism significantly improves the performance while promising truthfulness, heterogeneity, economic efficiency, individual rationality, and has a polynomial-time computational complexity.

     

DNA Polymerases that Propagate the Eukaryotic DNA Replication Fork

Abstract

Three DNA polymerases are thought to function at the eukaryotic DNA replication fork. Currently, a coherent model has been derived for the composition and activities of the lagging strand machinery. RNA-DNA primers are initiated by DNA polymerase α -primase. Loading of the proliferating cell nuclear antigen, PCNA, dissociates DNA polymerase α and recruits DNA polymerase δ and the flap endonuclease FEN1 for elongation and in preparation for its requirement during maturation, respectively. Nick translation by the strand displacement action of DNA polymerase δ, coupled with the nuclease action of FEN1, results in processive RNA degradation until a proper DNA nick is reached for closure by DNA ligase I. In the event of excessive strand displacement synthesis, other factors, such as the Dna2 nuclease/helicase, are required to trim excess flaps. Paradoxically, the composition and activity of the much simpler leading strand machinery has not been clearly established. The burden of evidence suggests that DNA polymerase ε normally replicates this strand, but under conditions of dysfunction, DNA polymerase δ may substitute.     

Chromium Removal from Aqueous System and Industrial Wastewater by Agricultural Wastes

This study involved the development of formaldehyde-treated, deseeded sunflower head waste–based biosorbent (FSH) for the biosorption of Cr(VI) from aqueous solution and industrial wastewater. Batch-mode experiments were conducted to determine the kinetics, sorption isotherms, effect of pH, initial Cr(VI) concentration, biosorbent dose, and contact time. The results demonstrated that FSH can sequester Cr(VI) from the aqueous solution. The maximum sorption occurred at pH = 2.0, biosorbent dose = 4.0 g/L, concentration of 100 mg/L at 25°C at 180 rpm after 2 h contact time. The FSH had an adsorption capacity of 7.85 mg/g for Cr(VI) removal at pH 2.0. The rate of adsorption was rapid, and equilibrium was attained within 2 h. The equilibrium sorption data fitted the Langmuir isotherm model, which was further confirmed by the chi-square test.     

A new subspecies of Pedicularis zeylanica (Scrophulariaceae) from the Western Ghats of south India

Pedicularis zeylanica subsp. anamallyensis T. Husain & A. Garg, a new subspecies of Nilgiri lousewort from the Western Ghats of south India, is described and illustrated.     

Synthesis of a Smart Gold Nano‐vehicle for Liver Specific Drug Delivery

Targeting drug formulations to specific tissues and releasing the bioactive content in response to a certain stimuli remains a significant challenge in the field of biomedical science. We have developed a nanovehicle that can be used to deliver “drugs” to “specific” tissues. For this, we have simultaneously modified the surface of the nanovehicle with “drugs” and “tissue-specific ligands”. The “tissue-specific ligands” will target the nanovehicle to the correct tissue and release the “drug” of interest in response to specific stimuli. We have synthesised a “lactose surface-modified gold nanovehicle” to target liver cells and release the model fluorescent drug (coumarin derivative) in response to the differential glutathione concentration (between blood plasma and liver cells). Lactose is used as the liver-specific targeting ligand given the abundance of l-galactose receptors in hepatic cells. The coumarin derivative is used as a fluorescent tag as well as a linker for the attachment of various biologically relevant molecules. The model delivery system is compatible with a host of different ligands and hence could be used to target other tissues as well in future. The synthesised nanovehicle was found to be non-toxic to cultured human cell lines even at elevated non-physiological concentrations as high as 100 μg/mL. We discover that the synthesised gold-based nanovehicle shows considerable stability at low extracellular glutathione concentrations; however coumarin is selectively released at high hepatic glutathione concentration.     

Role of N-Cadherin cis and trans Interfaces in?the Dynamics of Adherens Junctions in Living Cells

Cadherins, Ca²⁺-dependent adhesion molecules, are crucial for cell-cell junctions and remodeling. Cadherins form inter-junctional lattices by the formation of both cis and trans dimers. Here, we directly visualize and quantify the spatiotemporal dynamics of wild-type and dimer mutant N-cadherin interactions using time-lapse imaging of junction assembly, disassembly and a FRET reporter to assess Ca²⁺-dependent interactions. A trans dimer mutant (W2A) and a cis mutant (V81D/V174D) exhibited an increased Ca²⁺-sensitivity for the disassembly of trans dimers compared to the WT, while another mutant (R14E) was insensitive to Ca²⁺-chelation. Time-lapse imaging of junction assembly and disassembly, monitored in 2D and 3D (using cellular spheroids), revealed kinetic differences in the different mutants as well as different behaviors in the 2D and 3D environment. Taken together, these data provide new insights into the role that the cis and trans dimers play in the dynamic interactions of cadherins.     

The Impact of Motor Axon Misdirection and Attrition on Behavioral Deficit Following Experimental Nerve Injuries

Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomical substrates that underlie the poor functional recovery associated with these devastating injuries. Yet, functional deficits associated with axonal misdirection in experimental neuroma-in-continuity injuries have not yet been studied. We hypothesized that experimental neuroma-in-continuity injuries would result in motor axon misdirection and attrition with proportional persistent functional deficits. The femoral nerve misdirection model was exploited to assess major motor pathway misdirection and axonal attrition over a spectrum of experimental nerve injuries, with neuroma-in-continuity injuries simulated by the combination of compression and traction forces in 42 male rats. Sciatic nerve injuries were employed in an additional 42 rats, to evaluate the contribution of axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks. Retrograde motor neuron labeling techniques were utilized to determine the degree of axonal misdirection and attrition. Characteristic histological neuroma-in-continuity features were demonstrated in the neuroma-in-continuity groups and poor functional recovery was seen despite successful nerve regeneration and muscle reinnervation. Good positive and negative correlations were observed respectively between axonal misdirection (p<.0001, r²=.67), motor neuron counts (attrition) (p<.0001, r²=.69) and final functional deficits. We demonstrate prominent motor axon misdirection and attrition in neuroma-in-continuity and transection injuries of mixed motor nerves that contribute to the long-term functional deficits. Although widely accepted in theory, to our knowledge, this is the first experimental evidence to convincingly demonstrate these correlations with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes the need to focus on strategies that promote both robust and accurate nerve regeneration to optimize functional recovery. It also demonstrates that clinically relevant neuroma-in-continuity injuries can now also be subjected to experimental investigation.