Focus: Addiction: Smoking Use and Cessation Among People with Serious Mental Illness

Smoking rates in people with serious mental illness (SMI) are disproportionately high compared to the general population. It is a leading contributor to the early mortality in this population. Smoking cessation rates are low in this group, though patients are motivated to quit. Unfortunately, health care providers do not always prioritize smoking cessation for this population. This review provides an overview of prevalence rates, biological effects that maintain smoking, and evidence-based treatments for smoking cessation in SMI. In addition, objective and qualitative data from a chart review of 78 patients with SMI prescribed smoking cessation treatment at one community mental health center are described. Of these, 30 (38.5 percent) were found to either quit (16/78) or reduce (14/78) smoking. Varenicline appeared to be particularly effective. Review of the literature and results of this study suggest that smoking cessation pharmacotherapies are effective for SMI patients and should be offered to those who smoke.     

A New Efficient Stereoselective Method for the Synthesis of (E)-5-Aminoallyl-Pyrimidine-5′-Triphosphates Using Palladium-Catalyzed Heck Reaction

An efficient overall two-step strategy for the synthesis of (E)-5-aminoallyl-pyrimidine-5′-triphoshate, starting from commercially available pyrimidine-5′-triphosphate is described. The method involves regioselective iodination of pyrimidine-5′-triphosphate, followed by the palladium-catalyzed Heck coupling with allylamine. The catalytic reaction is highly stereoselective and compatible with many functional groups present in the reactants.     

KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro

The inhibitory 2DL1 and activating 2DS1 killer Ig-like receptors (KIR) both have shared ligand specificity for codon sequences in the C2 group HLA-Cw Ags. In this study, we have investigated NK cell activation by allogeneic target cells expressing different combinations of the HLA-KIR ligand groups C1, C2, and Bw4. We demonstrate that fresh NK cells as well as IL-2-propagated NK cells from 2DS1-positive donors that are homozygous for the C1 ligand group are activated in vitro by B lymphoblastoid cell lines expressing the C2 group. This response is, in part, due to the absence of C1 group recognition mediated by the inhibitory receptor 2DL2/3. This "missing self" alloresponse to C2, however, is rarely observed in NK cells from donors lacking 2DS1. Even in presence of 2DS1, the NK alloresponse is dramatically reduced in donors that have C2 group as "self." Analysis of selected NK clones that express 2DS1 mRNA and lack mRNA for 2DL1 demonstrates that activation by the C2 ligand and mAb cross-linking of 2DS1 in these clones induces IFN-gamma. Furthermore, this C2 group-induced activation is inhibited by Abs to both HLA class I and the receptor. Collectively, these studies demonstrate that NK cells from 2DS1-positive donors are activated by target cells that express the C2 group as an alloantigen. This leads to increased IFN-gamma-positive fresh NK cells and induces NK allocytotoxicity in IL2-propagated polyclonal NK cells and NK clones. This study also provides support for the concept that incompatibility for the HLA-KIR ligand groups C1, C2, and Bw4 dominates NK alloactivation in vitro.     

In vivo packaging of brome mosaic virus RNA3, but not RNAs 1 and 2, is dependent on a cis-acting 3' tRNA-like structure

The four encapsidated RNAs of brome mosaic virus (BMV; B1, B2, B3, and B4) contain a highly conserved 3' 200-nucleotide (nt) region encompassing the tRNA-like structure (TLS) which is required for packaging in vitro (Y. G. Choi, T. W. Dreher, and A. L. N. Rao, Proc. Natl. Acad. Sci. USA 99:655-660, 2002). To validate these observations in vivo, we performed packaging assays using Agrobacterium-mediated transient expression of RNAs and coat protein (CP) (P. Annamalai and A. L. N. Rao, Virology 338:96-111, 2005). Coexpression of TLS-less constructs of B1 or B2 or B3 and CP mRNAs in Nicotiana benthamiana leaves resulted in packaging of TLS-less B1 and B2 but not B3, suggesting that packaging of B3 requires the TLS in cis. This conjecture was confirmed by the efficient packaging of a B3 chimera in which the viral TLS was replaced with a cellular tRNA(Tyr). When N. benthamiana leaves were infiltrated with a mixture of transformants containing wild-type B1 (wtB1) plus wtB2 plus a TLS-less B3 (wtB1+wtB2+TLS-lessB3), the 3' end of progeny B3 was restored by heterologous recombination with that of either B1 or B2. This intrinsic cis-requirement of TLS in promoting B3 packaging was further confirmed when a mixture containing agrotransformants of TLS-less B1+B2+B3 was supplemented with either wtB4 or a 3' 200-nt or 3' 336-nt untranslated region (UTR) of B3. Northern blot analysis followed by sequencing of B3 progeny revealed that replication of TLS-less B3, but not TLS-less B1 or B2, was fully restored due to recombination with TLS from transiently expressed wtB4 or the B3 3' UTR. Collectively, these observations suggested that the requirement of a cis-acting TLS is distinct for B3 compared with B1 or B2.     

Inhibition of Zn(II) Binding Type IA Topoisomerases by Organomercury Compounds and Hg(II)

Type IA topoisomerase activities are essential for resolving DNA topological barriers via an enzyme-mediated transient single strand DNA break. Accumulation of topoisomerase DNA cleavage product can lead to cell death or genomic rearrangement. Many antibacterial and anticancer drugs act as topoisomerase poison inhibitors that form stabilized ternary complexes with the topoisomerase covalent intermediate, so it is desirable to identify such inhibitors for type IA topoisomerases. Here we report that organomercury compounds were identified during a fluorescence based screening of the NIH diversity set of small molecules for topoisomerase inhibitors that can increase the DNA cleavage product of Yersinia pestis topoisomerase I. Inhibition of relaxation activity and accumulation of DNA cleavage product were confirmed for these organomercury compounds in gel based assays of Escherichia coli topoisomerase I. Hg(II), but not As(III), could also target the cysteines that form the multiple Zn(II) binding tetra-cysteine motifs found in the C-terminal domains of these bacterial topoisomerase I for relaxation activity inhibition. Mycobacterium tuberculosis topoisomerase I activity is not sensitive to Hg(II) or the organomercury compounds due to the absence of the Zn(II) binding cysteines. It is significant that the type IA topoisomerases with Zn(II) binding domains can still cleave DNA when interfered by Hg(II) or organomercury compounds. The Zn(II) binding domains found in human Top3α and Top3β may be potential targets of toxic metals and organometallic complexes, with potential consequence on genomic stability and development.     

Burrowing behavior and ecology of the crab-eating Indian snake eel Pisoodonophis boro

Synopsis The snake eel Pisoodonophis boro burrows, causing leaks in the embankments and damaging the paddy fields and salt pans near estuaries. Field observations and laboratory experiments were made to study this behavior. P. boro was burrowing to eat the fiddler crab Uca annulipes in the mud flats. The eel showed a patchy distribution within the Uca zone. Salinity and the physical nature of the deposits controlled the distribution of the eel. Eel population density was low when the estuary was completely filled with neritic waters during the summer and fresh water during the monsoon period. The region of greatest abundance contained a good mixture of sand, silt and clay. Eels were not found where medium and fine sand formed the bulk of the substratum. The laboratory experiments showed that P. boro preferred loam soil although it could invariably burrow into hard substratum like sand for protection. The eel adapted itself to the experimental substrates ranging from sand to fine clay. However, their natural distribution was determined by Uca distribution. As U. annulipes is not found either in salt pans or in paddy fields P. boro rarely occurs in these habitats.     

Biocomposites of cellulose reinforced starch: improvement of properties by photo-induced crosslinking

In the present study, the composite films have been prepared from the aqueous dispersions of starch with microcrystalline cellulose using glycerol as plasticizer and irradiated under ultraviolet (UV) light using sodium benzoate as photo-sensitizer. Photo-crosslinking was characterized by measuring the water absorption under 100% relative humidity, swelling degree and gel fraction in dimethylsulphoxide (DMSO), upon irradiation time. Both, the incorporation of cellulose and photo-irradiation were found to decrease the water absorption, swelling in DMSO and increase the gel fraction. Thermal transitions indicated the anti-plasticization of amylopectin chains at the fiber/matrix interface. With increasing content of cellulose and photo-irradiation time, the tensile modulus and strength were found to improve. It is summarized that the combination of cellulose reinforcement and photo-crosslinking of matrix has improved the physical and mechanical properties.     

Chemicals isolated from Justicia adhatoda Linn reduce fitness of the mosquito,Aedes aegypti L

Extracts from Justicia adhatoda L. (Acanthaceae) strongly reduced the fitness of the mosquito, Aedes aegypti Linn. The methanolic extracts inhibited several enzymes responsible for protecting insects from oxidative and other damage, including glutathione‐S‐transferase, superoxide dismutase, cytochrome P450, and α‐ and β‐esterases. They increased repellency (maximum repellency at 100 ppm) in host‐seeking adult females using the “arm‐in cage assay.” Histopathological examination showed the extracts led to serious midgut cell damage. Justicia adhatoda extracts led to reduced fecundity and oviposition of gravid females compared to controls. The extracts led to substantially reduced A. aegypti survival. We infer that the extracts have potential to reduce pathogen transmission by suppressing population growth of A. aegypti, and possibly other mosquito species.     

Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.     

Lignocellulosic biomass (LCB): a potential alternative biorefinery feedstock for polyhydroxyalkanoates production

Reviews in Environmental Science and Bio/Technology - Polyhydroxyalkanoates (PHAs) are one of the most promising, degradable and eco-friendly alternatives to fossil fuel-based plastic....