On the comparison between differential vibrational spectroscopy spectra and theoretical data in the carboxyl region of photosystem II

Understanding the structural modification experienced by the Mn₄CaO₅ oxygen‐evolving complex of photosystem II along the Kok‐Joliot's cycle has been a challenge for both theory and experiments since many decades. In particular, differential infrared spectroscopy was extensively used to probe the surroundings of the reaction center, to catch spectral changes between different S‐states along the catalytic cycle. Because of the complexity of the signals, only a limited quantity of identified peaks have been assigned so far, also because of the difficulty of a direct comparison with theoretical calculations. In the present work, we critically reconsider the comparison between differential vibrational spectroscopy and theoretical calculations performed on the structural models of the photosystem II active site and an inorganic structural mimic. Several factors are currently limiting the reliability of a quantitative comparison, such as intrinsic errors associated to theoretical methods, and most of all, the uncertainty attributed to the lack of knowledge about the localization of the underlying structural changes. Critical points in this comparison are extensively discussed. Comparing several computational data of differential S₂/S₁ infrared spectroscopy, we have identified weak and strong points in their interpretation when compared with experimental spectra.     

Finger printing of acid lime varieties and clones having varied resistance to bacterial canker,using RAPD marker

Citrus is an important fruit crop having divergent genetic variation within the species. The germplasm identification and characterisation is an important link between the conservation and utilisation of genetic resources. Conventionally, variety/clone identification has relied on morphological characters such as growth habit, leaf, floral and fruit characters etc. Investigation through RAPD (random amplified polymorphic DNA) markers was carried out for determination of genetic variation among 12 acid lime clones having varied resistance to bacterial canker disease. DNA was extracted from the leaf of 12 acid lime clones and was subjected to PCR using 20 random primers (nine from OPM and 11 from OPA series) which yielded a total of 127 distinct DNA fragments, out of which 103 were polymorphic. Genetic similarity was evaluated based on the presence or absence of bands. The bands obtained were polymorphic, with sizes ranging from 750 bp to 2.5 kb. Cluster analysis using the similarity coefficient showed that the Balaji, RHRL-124 and PKM-1 formed one cluster and the remaining clones formed a second cluster, which in turn were divided into TAL 94-9, TAL 94-10, TAL 94-11 and TAL 94-12 which formed the first subcluster; the Nalgonda selection and local acid lime formed a second subcluster; TAL 94-8, RHRL-49 and RHRL-122 did not resemble any other clones. Among the 12 acid lime clones, Balaji, RHRL-124, RHRL-122 and PKM-1 were found to be moderately resistant to bacterial canker. Correlation of RAPD data with canker disease incidence in the moderately resistant acid lime clones viz., Balaji, RHRL-124 and PKM-1 were formed as one cluster, and all susceptible clones formed as a second cluster viz., except TAL-94-9, RHRL-122, which were found to be moderately resistant and did not form a cluster with any other acid lime clone.     

Glucagon releasing activity of a cyclic peptide related to somatostatin

A possible benefit of creating smaller and more rigid active analogs of somatostatin is the discovery of compounds which selectively inhibit the secretion of insulin, glucagon or growth hormone. A series of cyclic tetrapeptide analogs related to somatostatin was synthesized, and one member of this series was found to cause an unexpected stimulation of glucagon secretion while having little if any effect on either insulin or growth hormone secretion. A sustained increase in plasma glucose levels was also observed. Two possible modes of action are proposed.     

A super active cyclic hexapeptide analog of somatostatin

The cyclic hexapeptide, cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe), I, has been shown to have the biological properties of somatostatin. We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50–100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release. The hydroxyl group of tyrosine is seen to lend a 10-fold enhancement to the potency. Potency also is found to be correlated with hydrophobicity. II is found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The analog is found to be quite stable in the blood and in the gastrointestinal tract, but the bioavailability after oral administration is only 1–3%. The biological properties and long duration of II should allow clinical evaluation of the inhibition of glucagon release as an adjunct to insulin in the treatment of patients with diabetes.     

Characterisation of polymorphic microsatellite markers for skates (Elasmobranchii: Rajidae) from expressed sequence tags

Simple sequence repeat markers (SSRs, microsatellites) were characterised for skates (Elasmobranchii: Rajidae) from published expressed sequence tags (ESTs) of Leucoraja erinacea. These were tested in four European species (Raja clavata, Raja montagui, Dipturus batis, and Leucoraja naevus). Thirteen of the fourteen amplified loci were polymorphic in at least one species. Polymorphic loci possessed on average 4.5–5.9 alleles per species, and expected heterozygosity ranged from 0.05 to 0.88. Possible null alleles were detected at three loci, while one locus showed significant deviation from Hardy–Weinberg Equilibrium proportions. Three locus-pairs exhibited significant linkage disequilibrium in one or more species. This marker set will be valuable for population genetic analyses of the focal taxa, and may prove useful for studies of other skate species.     

Causes of Early Childhood Deaths in Urban Dhaka,Bangladesh

Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD±7.3). Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006–2007. The leading cause of under-five death was respiratory infections (22%). The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year) were similar (36 versus 32). The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years.     

Cell and tissue polarity in the intestinal tract during tumourigenesis: cells still know the right way up,but tissue organization is lost

Cell and tissue polarity are tightly coupled and are vital for normal tissue homeostasis. Changes in cellular and tissue organization are common to even early stages of disease, particularly cancer. The digestive tract is the site of the second most common cause of cancer deaths in the developed world. Tumours in this tissue arise in an epithelium that has a number of axes of cell and tissue polarity. Changes in cell and tissue polarity in response to genetic changes that are known to underpin disease progression provide clues about the link between molecular-, cellular- and tissue-based mechanisms that accompany cancer. Mutations in adenomatous polyposis coli (APC) are common to most colorectal cancers in humans and are sufficient to cause tumours in mouse intestine. Tissue organoids mimic many features of whole tissue and permit identifying changes at different times after inactivation of APC. Using gut organoids, we show that tissue polarity is lost very early during cancer progression, whereas cell polarity, at least apical–basal polarity, is maintained and changes only at later stages. These observations reflect the situation in tumours and validate tissue organoids as a useful system to investigate the relationship between cell polarity and tissue organization.     

The EphB4 Receptor Tyrosine Kinase Promotes Lung Cancer Growth: A Potential Novel Therapeutic Target

Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.     

Near-infrared laser delivery of nanoparticles to developing embryos: a study of efficacy and viability

Targeted delivery of materials to individual cells remains a challenge in nanoscience and nanomedicine. Near infrared (NIR) laser injection may be a promising alternative to manual injection (where the micropipet diameter limits targeting to small cells) or other laser techniques (such as picosecond green and UV lasers, which can be damaging to cells). However, the efficiency with which NIR pulses can deliver nanoparticles and any adverse effects on living cells needs thorough testing. Toward this end, we have determined the efficacy and toxicity of delivering quantum dots (QDs) into cells of Xenopus laevis embryos by NIR laser injection. Because this model system provides not only living cells but also a developing organism, we were able to assess relatively long-term effects of NIR pulses on embryonic development (through the tadpole stage). We developed parameters for NIR pulses that did not affect embryonic viability or morphology and delivered QDs as effectively as manual injection. Higher intensities of NIR pulses caused permanent damage to the targeted cells, and thus NIR pulses may also prove useful for ablation of specific cells within tissues.