Arabidopsis RecQl4A suppresses homologous recombination and modulates DNA damage responses

The DNA damage response and DNA recombination are two interrelated mechanisms involved in maintaining the integrity of the genome, but in plants they are poorly understood. RecQ is a family of genes with conserved roles in the regulation of DNA recombination in eukaryotes; there are seven members in Arabidopsis. Here we report on the functional analysis of the Arabidopsis RecQl4A gene. Ectopic expression of Arabidopsis RecQl4A in yeast RecQ-deficient cells suppressed their hypersensitivity to the DNA-damaging drug methyl methanesulfonate (MMS) and enhanced their rate of homologous recombination (HR). Analysis of three recQl4A mutant alleles revealed no obvious developmental defects or telomere deregulation in plants grown under standard growth conditions. Compared with wild-type Arabidopsis, the recQl4A mutant seedlings were found to be hypersensitive to UV light and MMS, and more resistant to mitomycin C. The average frequency of intrachromosomal HR in recQl4A mutant plants was increased 7.5-fold over that observed in wild-type plants. The data reveal roles for Arabidopsis RecQl4A in maintenance of genome stability by modulation of the DNA damage response and suppression of HR.

Promotion of oxygen reduction by a bio-inspired tethered iron phthalocyanine carbon nanotube-based catalyst

Electrocatalysts for oxygen reduction are a critical component that may dramatically enhance the performance of fuel cells and metal-air batteries, which may provide the power for future electric vehicles. Here we report a novel bio-inspired composite electrocatalyst, iron phthalocyanine with an axial ligand anchored on single-walled carbon nanotubes, demonstrating higher electrocatalytic activity for oxygen reduction than the state-of-the-art Pt/C catalyst as well as exceptional durability during cycling in alkaline media. Theoretical calculations suggest that the rehybridization of Fe 3d orbitals with the ligand orbitals coordinated from the axial direction results in a significant change in electronic and geometric structure, which greatly increases the rate of oxygen reduction reaction. Our results demonstrate a new strategy to rationally design inexpensive and durable electrochemical oxygen reduction catalysts for metal-air batteries and fuel cells.close34

Models and algorithms for energy-efficient scheduling with immediate start of jobs

We study a scheduling model with speed scaling for machines and the immediate start requirement for jobs. Speed scaling improves the system performance, but incurs the energy cost. The immediate start condition implies that each job should be started exactly at its release time. Such a condition is typical for modern Cloud computing systems with abundant resources. We consider two cost functions, one that represents the quality of service and the other that corresponds to the cost of running. We demonstrate that the basic scheduling model to minimize the aggregated cost function with n jobs is solvable in O(nlogn) time in the single-machine case and in O(n²m) time in the case of m parallel machines. We also address additional features, e.g., the cost of job rejection or the cost of initiating a machine. In the case of a single machine, we present algorithms for minimizing one of the cost functions subject to an upper bound on the value of the other, as well as for finding a Pareto-optimal solution

Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200

Photoluminescence lifetime engineering via organic resonant films with molecular aggregates

Manipulating the spontaneous emission rate of fluorophores is vital in creating bright incoherent illumination for optical sensing and imaging, as well as fast single-photon sources for quantum technology applications. This can be done via increasing the Purcell effect by using non-monolithic optical nanocavities; however, achieving the desired performance is challenging due to difficulties in fabrication, precise positioning, and frequency tuning of cavity-emitter coupling. Here, we demonstrate a simple approach to achieve a wavelength-dependent photoluminescence (PL) lifetime modification using monolithic organic molecular aggregates films. These single monolithic organic films are designed to have a Lorentzian dispersion, including epsilon-near-zero (ENZ) and epsilon-near-pole (ENP) spectral regions with increased and decreased photonic density of states, respectively. This dispersion leads to enhanced and depressed PL decay rates at different wavelengths. Both time-resolved photoluminescence (TRPL) and fluorescence lifetime imaging microscopy (FLIM) measurements are implemented to verify the validity of this approach. This approach offers a promising way to design dual-functional optical sources for a variety of applications, including bioimaging, sensing, data communications, and quantum photonics applications.journal articl

A review of combined advanced oxidation technologies for the removal of organic pollutants from water

Water pollution through natural and anthropogenic activities has become a global problem causing short-and long-term impact on human and ecosystems. Substantial quantity of individual or mixtures of organic pollutants enter the surface water via point and nonpoint sources and thus affect the quality of freshwater. These pollutants are known to be toxic and difficult to remove by mere biological treatment. To date, most researches on the removal of organic pollutants from wastewater were based on the exploitation of individual treatment process. This single-treatment technology has inherent challenges and shortcomings with respect to efficiency and economics. Thus, application of two advanced treatment technologies characterized with high efficiency with respect to removal of primary and disinfection by-products in wastewater is desirable. This review article focuses on the application of integrated technologies such as electrohydraulic discharge with heterogeneous photocatalysts or sonophotocatalysis to remove target pollutants. The information gathered from more than 100 published articles, mostly laboratories studies, shows that process integration effectively remove and degrade recalcitrant toxic contaminants in wastewater better than single-technology processing. This review recommends an improvement on this technology (integrated electrohydraulic discharge with heterogeneous photocatalysts) viz-a-vis cost reduction in order to make it accessible and available in the rural and semi-urban settlement. Further recommendation includes development of an economic model to establish the cost implications of the combined technology. Proper monitoring, enforcement of the existing environmental regulations, and upgrading of current wastewater treatment plants with additional treatment steps such as photocatalysis and ozonation will greatly assist in the removal of environmental toxicants

Generation of shRNAs from randomized oligonucleotides

Suppression of gene expression by small interfering RNA (siRNA) has proved to be a gene-specific and cost effective alternative to other gene suppression technologies. Short hairpin RNAs (shRNAs) generated from the vector-based expression are believed to be processed into functional siRNAs in vivo, leading to gene silencing. Since an shRNA library carries a large pool of potential siRNAs, such a library makes it possible to knock down gene expression at the genome wide scale. Although much of research has been focused on generating shRNA libraries from either individually made gene specific sequences or cDNA libraries, there is no report on constructing randomized shRNA libraries, which could provide a good alternative to these existing libraries. We have developed a method of constructing shRNAs from randomized oligonucleotides. Through this method, one can generate a partially or fully randomized shRNA library for various functional analyses. We validated this procedure by constructing a p53-specific shRNA. Western blot revealed that the p53-shRNA successfully suppressed expression of the endogenous p53 in MCF-7 cells. We then made a partially randomized shRNA library. Sequencing of 15 randomly picked cloned confirmed the randomness of the library. Therefore, the library can be used for various functional assays, such as target validation when a suitable screening or selection method is available