Molecular and serological studies on the recent seal virus epizootics in Europe and Siberia

The virus epizootics which occurred in seals in both Europe and Siberia during 1987/1988 were caused by two different morbillivirus, referred to as phocid distemper virus (PDV) 1 and 2, respectively. Molecular and serological studies have shown that the European virus is quite distinct from canine distemper virus (CDV), its closest relative in the morbillivirus group. Analysis of tissues obtained from infected seals from a wide geographical distrubution over Northern Europe showed that the infectious agent (PDV 1) was identical in all cases. Nucleotide sequence analysis of one of the virus genes suggested that this virus has evolved away from CDV over a long time period and is most probably an enzootic virus of marine mammals. In contrast, the virus (PDV 2) which caused the deaths of many Siberian seals was indistinguishable, both serologically and at the molecular level, from CDV and must have originated from a land source.

The Asian elephants Elephas maximus of Cat Tien National Park, Vietnam: status and conservation of a vanishing population

This study updates the status and conservation of the Endangered Asian elephant Elephas maximus in Cat Tien National Park, Vietnam. Line transect indirect surveys, block surveys for elephant signs, village surveys of elephant-human conflict incidents, guard-post surveys for records of sightings, and surveys of elephant food plants were undertaken during the dry and wet seasons of 2001. A minimum of 11 elephants and a maximum of 15-17 elephants was estimated for c. 500 km2 of the Park and its vicinity. The elephants are largely confined to the southern boundary of the Park and make extensive use of the adjoining La Nga State Forest Enterprises. During the dry season the elephants depend on at least 26 species of wild and cultivated plants, chiefly the fruits of cashew. Most of the villages surveyed reported some elephant-human conflict. Two adult male elephants seem to cover a large area to raid crops, whereas the family groups restrict themselves to a few villages; overall, the conflict is not serious. Since 2001 there have been no reports of any deaths or births of elephants in the Park. We make recommendations for habitat protection and management, increasing the viability of the small population, reducing elephant-human conflicts, and improving the chances of survival of the declining elephants of this Park. The Government has now approved an Action Plan for Urgent Conservation Areas in Vietnam that calls for the establishment of three elephant conservation areas in the country, including Cat Tien National Park.

Artemisinin-based combination with curcumin adds a new dimension to malaria therapy

Malaria afflicts 300 million people worldwide, with over a million deaths every year. With no immediate prospect of a vaccine against the disease, drugs are the only choice to treat it. Unfortunately, the parasite has become resistant to most antimalarials, restricting the option to use artemisinins (ARTs) for effective cure. With the use of ARTs as the front-line antimalarials, reports are already available on the possible resistance development to these drugs as well. Therefore, it has become necessary to use ART-based combination therapies to delay emergence of resistance. It is also necessary to discover new pharmacophores to eventually replace ART. Studies in our laboratory have shown that curcumin not only synergizes with ART as an antimalarial to kill the parasite, but is also uniquely able to prime the immune system to protect against parasite recrudescence in the animal model. The results indicate a potential for the use of ART curcumin combination against recrudescence/relapse in falciparum and vivax malaria. In addition, studies have also suggested the use of curcumin as an adjunct therapy against cerebral malaria. In this review we have attempted to highlight these aspects as well as the studies directed to discover new pharmacophores as potential replacements for ART.

DNA targeting polyaza macrobicyclic dizinc(II) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

A series of macrobicyclic dizinc(II) complexes Zn2L1-2B](ClO4)(4) (1-6) have been synthesized and characterized (L1-2 are polyaza macrobicyclic binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding, DNA hydrolysis and anticancer activity of these complexes were investigated. The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence and CD spectroscopy. The DNA binding constant values of the complexes were found to range from 2.80 x 10(5) to 5.25 x 10(5) M-1, and the binding affinities are in the following order: 3 > 6 > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1-6 are found to effectively promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under physiological conditions give observed rate constants (k(obs)) of 5.56 +/- 0.1 and 5.12 +/- 0.2 h(-1), respectively, showing a 10(7)-fold rate acceleration over the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II) complexes 1-6 bind and cleave bovine serum albumin (BSA), and effectively promote the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The cytotoxicity of the complexes was further confirmed by lactate dehydrogenase enzyme levels in cancer cell lysate and content media.

A Novel Anticancer Agent, 8-Methoxypyrimido4 `,5 `: 4,5]thieno(2,3-b) Quinoline-4(3H)-One Induces Neuro 2a Neuroblastoma Cell Death through p53-Dependent, Caspase-Dependent and Independent Apoptotic Pathways

Neuroblastoma is the most common cancer in infants and fourth most common cancer in children. Despite recent advances in cancer treatments, the prognosis of stage-IV neuroblastoma patients continues to be dismal which warrant new pharmacotherapy. A novel tetracyclic condensed quinoline compound, 8-methoxypyrimido 4 `,5 `: 4,5] thieno(2,3-b) quinoline-4(3H)-one (MPTQ) is a structural analogue of an anticancer drug ellipticine and has been reported to posses anticancer property. Study on MPTQ on neuroblastoma cells is very limited and mechanisms related to its cytotoxicity on neuroblastoma cells are completely unknown. Here, we evaluated the anticancer property of MPTQ on mouse neuro 2a and human SH-SY5Y neuroblastoma cells and investigated the mechanisms underlying MPTQ-mediated neuro 2a cell death. MPTQ-mediated neuro 2a and SH-SY5Y cell deaths were found to be dose and time dependent. Moreover, MPTQ induced cell death reached approximately 99.8% and 90% in neuro 2a and SH-SY5Y cells respectively. Nuclear oligonucleosomal DNA fragmentation and Terminal dUTP Nick End Labelling assays indicated MPTQ-mediated neuro 2a cell death involved apoptosis. MPTQ-mediated apoptosis is associated with increased phosphorylation of p53 at Ser15 and Ser20 which correlates with the hyperphosphorylation of Ataxia-Telangiectasia mutated protein (ATM). Immunocytochemical analysis demonstrated the increased level of Bax protein in MPTQ treated neuro 2a cells. MPTQ-mediated apoptosis is also associated with increased activation of caspase-9, -3 and -7 but not caspase-2 and -8. Furthermore, increased level of caspase-3 and cleaved Poly ( ADP Ribose) polymerase were observed in the nucleus of MPTQ treated neuro 2a cells, suggesting the involvement of caspase-dependent intrinsic but not extrinsic apoptotic pathway. Increased nuclear translocation of apoptosis inducing factor suggests additional involvement of caspase-independent apoptosis pathway in MPTQ treated neuro 2a cells. Collectively, MPTQ-induced neuro 2a cell death is mediated by ATM and p53 activation, and Bax-mediated activation of caspase-dependent and caspase-independent mitochondrial apoptosis pathways.

Maximizing transported data in a wireless sensor network: how much can the network transport before partition?

We consider a scenario where the communication nodes in a sensor network have limited energy, and the objective is to maximize the aggregate bits transported from sources to respective destinations before network partition due to node deaths. This performance metric is novel, and captures the useful information that a network can provide over its lifetime. The optimization problem that results from our approach is nonlinear; however, we show that it can be converted to a Multicommodity Flow (MCF) problem that yields the optimal value of the metric. Subsequently, we compare the performance of a practical routing strategy, based on Node Disjoint Paths (NDPs), with the ideal corresponding to the MCF formulation. Our results indicate that the performance of NDP-based routing is within 7.5% of the optimal.

Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation

Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.

Haemophilus influenzae Genome Database (HIGDB): A single point web resource for Haemophilus influenzae

Background: Haemophilus influenzae (H. Influenzae) is the causative agent of pneumonia, bacteraemia and meningitis. The organism is responsible for large number of deaths in both developed and developing countries. Even-though the first bacterial genome to be sequenced was that of H. Influenzae, there is no exclusive database dedicated for H. Influenzae. This prompted us to develop the Haemophilus influenzae Genome Database (HIGDB). Methods: All data of HIGDB are stored and managed in MySQL database. The HIGDB is hosted on Solaris server and developed using PERL modules. Ajax and JavaScript are used for the interface development. Results: The HIGDB contains detailed information on 42,741 proteins, 18,077 genes including 10 whole genome sequences and also 284 three dimensional structures of proteins of H. influenzae. In addition, the database provides ``Motif search'' and ``GBrowse''. The HIGDB is freely accessible through the URL:http://bioserverl.physicslisc.ernetin/HIGDB/. Discussion: The HIGDB will be a single point access for bacteriological, clinical, genomic and proteomic information of H. influenzae. The database can also be used to identify DNA motifs within H. influenzae genomes and to compare gene or protein sequences of a particular strain with other strains of H. influenzae. (C) 2014 Elsevier Ltd. All rights reserved.

Lesion Detection in Breast Ultrasound Images Using Tissue Transition Analysis

Breast cancer is one of the leading cause of cancer related deaths in women and early detection is crucial for reducing mortality rates. In this paper, we present a novel and fully automated approach based on tissue transition analysis for lesion detection in breast ultrasound images. Every candidate pixel is classified as belonging to the lesion boundary, lesion interior or normal tissue based on its descriptor value. The tissue transitions are modeled using a Markov chain to estimate the likelihood of a candidate lesion region. Experimental evaluation on a clinical dataset of 135 images show that the proposed approach can achieve high sensitivity (95 %) with modest (3) false positives per image. The approach achieves very similar results (94 % for 3 false positives) on a completely different clinical dataset of 159 images without retraining, highlighting the robustness of the approach.