Synthesis of enantiopure trans-N-Boc-3-aminobicyclo[2.2.2]octane-2-carboxylic acids and their bicyclic 1,3-amino alcohol derivatives via the [4+2] cycloaddition of 1,3-cyclohexadiene to a chiral β-nitroacrylate

The chiral β-nitroacrylate 2 derived from the (R)- or (S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl) benzoic acid 1 acts as a reactive dienophile in a diastereoselective Diels-Alder reaction with 1,3-cyclohexadiene. The major cycloadducts have been isolated and transformed into enantiopure trans(2S,3S)- or (2R,3R)-N-Boc-3-aminobicyclic[2,2,2]octane-2-carboxylic acids 5. The trans-(2S,3S)- or (2R,3R)-N-Boc 3-(hydoxymethyl)-2-aminobicyclic[2,2,2]octane 6 derivatives were also obtained.     

Utilization of human DC-SIGN and L-SIGN for entry and infection of host cells by the New World arenavirus,Junín virus

The target cell tropism of enveloped viruses is regulated by interactions between viral proteins and cellular receptors determining susceptibility at a host cell, tissue or species level. However, a number of additional cell-surface moieties can also bind viral envelope glycoproteins and could act as capture receptors, serving as attachment factors to concentrate virus particles on the cell surface, or to disseminate the virus infection to target organs or susceptible cells within the host. Here, we used Junín virus (JUNV) or JUNV glycoprotein complex (GPC)-pseudotyped particles to study their ability to be internalized by the human C-type lectins hDC- or hL-SIGN. Our results provide evidence that hDC- and hL-SIGN can mediate the entry of Junín virus into cells, and may play an important role in virus infection and dissemination in the host.     

Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme

Human ACE is a central component of the renin–angiotensin system and a major therapeutic target for cardiovascular diseases. The somatic form of the enzyme (sACE) comprises two homologous metallopeptidase domains (N and C), each bearing a zinc active site with similar but distinct substrate and inhibitor specificities. In this study, we present the biological activity of silacaptopril, a silylated analogue of captopril, and its binding affinity towards ACE. Based on the recently determined crystal structures of both the ACE domains, a series of docking calculations were carried out in order to study the structural characteristics and the binding properties of silacaptopril and its analogues with ACE. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Sampling Bias in Roadsides: The Case of Galling Aphids on Pistacia Trees

Sampling along roadsides is convenient and is widely practiced in insect population researches. Ecological conditions in road verges are very different than those prevailing in natural habitats and they affect the annual growth of plants in semi-arid and arid regions. This in turn may improve development, survival and abundance of insects feeding on plants growing in roadsides. These trends may bias the results of sampling. To verify this assertion, we quantified the effects of growing in roadside on annual growth of Pistacia atlantica trees and Pistacia palaestina shrubs and compare two demographic indexes of nine gall-inducing aphid species on trees growing along roads with trees in the open landscape, in Israel. The annual growth of the two host plants was significantly more vigorous in roadsides than away from roads. Tests of Combined Probabilities showed that the likelihood of P. atlantica and P. palaestina to be parasitized by more galls of Fordini species is higher in roadsides than away from roads. Moreover, in the semi-dry regions of Israel, three aphid species on P. atlantica and five species on P. palaestina induced more galls in plants growing along roads than away from roads, while in the rainy Northern region, the difference was not significant between the two habitats. These results indicate a biased evaluation of population size in roadside habitat, which has to be accounted in insect–plant relation researches.     

Bovine skeletal muscle adenosine deaminase. Purification and some properties

A low molecular weight form of adenosine deaminase from bovine skeletal muscle was purified about 930-fold. The enzyme had a mol. wt of 31,000, a Km value for adenosine of 2.37 X 10(-5) M and a pH optimum at 7.0. This enzyme is very resistant to heat inactivation and does not require metal activators or other dialysable cofactors. A possible role in the post-mortem metabolism of adenine nucleotide in skeletal muscle is discussed.     

Surface chemistry and reactivity of bacteriogenic iron oxides from Axial Volcano, Juan de Fuca Ridge, north-east Pacific Ocean

Iron oxides were collected from the caldera of Axial Volcano, a site of hydrothermal vent activity along the Juan de Fuca Ridge. Mineralogical inspection using X‐ray diffraction (XRD) revealed the majority of samples to be 2‐line ferrihydrite, with one of the samples corresponding to poorly ordered goethite. Examination using environmental scanning electron microscopy (ESEM) found the constituents of the iron oxides to consist predominantly of bacterial‐like structures that resembled the iron oxidizing bacteria Leptothrix ochracea, Gallionella ferruginea and a novel PV‐1 strain. X‐ray photoelectron spectroscopy (XPS) detected the presence of Fe, O, C, N, Ca, Si and P on all the samples with the exception of poorly ordered goethite, where Ca and P were absent, in addition to a weak N peak. Binding energy shifts of the Fe 2p and O 1s peaks were indicative of ferrihydrite and hydroxyl functional groups, while the presence and speciation of the C 1s peak was attributed to the presence of bacteria. Use of acid‐base titration data modelling in conjunction with a linear programming regression method (LPM) indicated that the iron oxides are composed of heterogeneous surface functional groups. Differences in iron oxide reactivity values correlated with differences in the bacterial and mineral fabric of the samples. The diverse surface chemistry and high reactivity of these iron oxides may be important in the global cycling of various elements throughout the oceans due to their presence along widespread mid‐ocean ridges.     

Organization and expression of mouse Hox3 cluster genes

Summary The three yolk protein genes (yp) of Drosophila melanogaster are transcribed in a sex- and tissue-limited fashion. We have searched for cis-regulatory sequences in regions flanking yp1 and yp2 to identify the elements that confer female-specific expression in the fat body. One such 127 by element has previously been identified in this region. We show here the existence of two additional regions which confer female fat body-specific expression on an Adh reporter gene and on the native yp2 gene, respectively. This suggests some redundancy in the regulation of expression of the yp genes. Computer searches for putative binding sites for the DSX protein, which regulates sex-specific expression of the yp genes, revealed several such sites in our constructs. However, the significance of these is unclear since many such sites also occur in genes which one would not expect to be regulated in a sex-specific manner (e.g. Adh, Actin 5C). We suggest that DSX acts in concert with other proteins to mediate sex- and tissue-specific expression of the yp genes.     

Cognitive Dysfunction Precedes the Onset of Motor Symptoms in the MitoPark Mouse Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by progressive loss of dopamine neurons, leading to loss of motor coordination. However, PD is associated with a high rate of non-motor neuropsychiatric comorbities that often develop before the onset of movement symptoms. The MitoPark transgenic mouse model is the first to recapitulate the cardinal clinical features, namely progressive neurodegeneration and death of neurons, loss of motor function and therapeutic response to L-DOPA. To investigate whether MitoPark mice exhibit early onset of cognitive impairment, a non-motor neuropsychiatric comorbidity, we measured performance on a spatial learning and memory task before (∼8 weeks) or after (∼20 weeks) the onset of locomotor decline in MitoPark mice or in littermate controls. Consistent with previous studies, we established that a progressive loss of spontaneous locomotor activity began at 12 weeks of age, which was followed by progressive loss of body weight beginning at 16–20 weeks. Spatial learning and memory was measured using the Barnes Maze. By 20 weeks of age, MitoPark mice displayed a substantial reduction in overall locomotor activity that impaired their ability to perform the task. However, in the 8-week-old mice, locomotor activity was no different between genotypes, yet MitoPark mice took longer, traveled further and committed more errors than same age control mice, while learning to successfully navigate the maze. The modest between-day learning deficit of MitoPark mice was characterized by impaired within-day learning during the first two days of testing. No difference was observed between genotypes during probe trials conducted one or twelve days after the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited impaired novel object recognition when compared to control mice. Together, these data establish that mild cognitive impairment precedes the loss of motor function in a novel rodent model of PD, which may provide unique opportunities for therapeutic development.