Special Issue on ‘‘Ribogenomics-the study of RNA-centric molecular mechanisms and cellular processes’’

The journal Genomics Proteomics&Bioinformatics(GPB)is now inviting submissions for a special issue(to be published in spring of 2014)on the topic of‘‘The Ribogenomics of Life’’.Life was born of the RNA world.The RNA world was governed by RNA-centric mechanisms and processes in single cells.These operationally defined cells became more complex and heterogeneous:some were robust against changes but lost potential for diversity and others became complex but more opportunistic.Proteins w     

Is there a ‘plenhaptic’ function?

One approach to gauge the complexity of the computational problem underlying haptic perception is to determine the number of dimensions needed to describe it. In vision, the number of dimensions can be estimated to be seven. This observation raises the question of what is the number of dimensions needed to describe touch. Only with certain simplified representations of mechanical interactions can this number be estimated, because it is in general infinite. Organisms must be sensitive to considerably reduced subsets of all possible measurements. These reductions are discussed by considering the sensing apparatuses of some animals and the underlying mechanisms of two haptic illusions.     

‘Conservative’ and ‘variable’ clusters of Alu-family DNA repeats in human chromosomes

The distribution of Alu-family DNA repeats (AFRs) in chromosomes of phytohaemagglutinin-stimulated peripheral blood lymphocytes of four normal donors and non-stimulated bone marrow cells of four patients with acute leukemia (ALL and ANLL) was studied by in situ hybridization using DNA of recombinant phage lambda containing multiple inserts of AFR as a probe. Over some chromosome bands (14cen, 16p13, 16cen) from normal donors and from leukemic patients clusters of silver grains were detected. Over other three bands (3q26, 8p11-p12 and 14q24) the clusters were found only in chromosomes from the four acute leukemia patients, and were absent from chromosomes of healthy donors. The results suggest non-random long-range distribution of AFRs in human chromosomes, and somatic variations in the distribution of the repeats.     

‘Minority’ as a sociological concept

This article considers how a Muslim cultural discourse of ‘propriety’ has influenced Muslim Arab Sudanese ethnic identity in two locations and time periods in an expanding diaspora. Focusing in particular on women and their embodied practices of whitening and propriety in Egypt in the nineties and the United Kingdom a decade later, I argue that the recent turn towards Muslim expressions of Sudaneseness is a form of resistance to racial labelling. While Sudanese have rejected being labelled ‘black’ in Egypt and in the UK, their renegotiation of a Muslim religious identity in the diaspora nevertheless confirms a racialized Sudanese ethnicity. This study contributes to the rethinking of ethnicity in a transnational space where ethnic nationalism and globalized Islamic discourse intersect with local histories and hierarchies of race and gender.     

Reading Wacquant as both ‘lumper’ and ‘splitter’

In this short response to Loïc Wacquant's ‘Marginality, Ethnicity and Penality in the Neo-liberal City’, I outline two intellectual conversations that emerge from the author's work. The first develops out of the connections that the author draws between systems of criminal justice and welfare. The second grows out of the disassociation he urges us to see between the logics and trajectories of crime, on the one hand, and criminal justice on the other. I then briefly describe how my own work has been influenced by and contributes to these two ongoing streams of research.     

Critique of ‘Australopithecus afarensis’ as a single species based on dental metrics and morphology

Leonard andHegmon (1987) compare a series of dental metrics of ‘Australopithecus afarensis Johanson, White, andCoppens, 1978’ with criteria for modern apes, to test the hypothesis that ‘A. afarensis’ represents a single species. They also compare the morphology of the lower third premolar. The dental breadth of ‘A. afarensis’ shows a wide range of variation, particularly in the lower third premolar morphology which displays greater variation than in modern apes—yet the study concludes that the single species hypothesis cannot be rejected. The study is flawed by applying criteria for pongids inappropriate for a hominid. When ‘A. afarensis’ is compared with criteria for hominids, the range of variation in dental size, breadth, and third premolar morphology is greater than that in any hominid species. The single species hypothesis is, therefore, once again rejected. Moreover, the name ‘A. afarensis’ is preoccupied byPraeanthropus africanus (Weinert) and must be dropped.     

Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins

A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.     

Casares’ map function: no need for a ‘corrected’ Haldane’s map function

A genetic map function M(d) = RF provides a mapping from the additive genetic distance d to the non-additive recombination fraction RF between a given pair of loci, where the recombination fraction is the proportion of gametes that are recombinant between the two loci. Genetic map functions are needed because in most experiments all we can directly observe are the recombination events. However, since a recombination event is only observed if there are an odd number of crossovers between the two loci, recombination fractions are not additive. One of the most widely used map functions is Haldane’s map function, which is derived under the assumptions of no chiasma and no chromatid interference, and has been in widespread use since 1919. However, Casares recently proposed a ‘corrected’ Haldane’s map function – we show here that this ‘corrected’ map function is not correct due to faulty assumptions and mistakes in its derivation.     

The Green’s function formalism as a bridge between single- and multi-compartmental modeling

Neurons are spatially extended structures that receive and process inputs on their dendrites. It is generally accepted that neuronal computations arise from the active integration of synaptic inputs along a dendrite between the input location and the location of spike generation in the axon initial segment. However, many application such as simulations of brain networks use point-neurons—neurons without a morphological component—as computational units to keep the conceptual complexity and computational costs low. Inevitably, these applications thus omit a fundamental property of neuronal computation. In this work, we present an approach to model an artificial synapse that mimics dendritic processing without the need to explicitly simulate dendritic dynamics. The model synapse employs an analytic solution for the cable equation to compute the neuron’s membrane potential following dendritic inputs. Green’s function formalism is used to derive the closed version of the cable equation. We show that by using this synapse model, point-neurons can achieve results that were previously limited to the realms of multi-compartmental models. Moreover, a computational advantage is achieved when only a small number of simulated synapses impinge on a morphologically elaborate neuron. Opportunities and limitations are discussed.     

Genes for the ‘H’ subunit of human ferritin are present on a number of human chromosomes

Summary DNa has been extracted from hamster-human and mouse-human hybrid cell lines, restricted with EcoRI, and hybridised to a probe for the H subunit of human ferritin, pDBR2. Sequences highly homologous to this probe have been found on at least eight human chromosomes: 1, 2, 3, 6p216cen, 11, 14, 20, and Xq23–25Xqter. Only the gene on chromosome 11 appears to be expressed in these hybrids Southern blotting of DNA from somatic cell hybrids containing different subsets of human chromosomes. The study shows that H subunit sequences are found on at least nine different chromosomes.     

Differential effects of foods traditionally regarded as ‘heating’ and ‘cooling’ on prostaglandin E2 production by a macrophage cell line

Some components of natural foods may enhance or inhibit prostaglandin formation and potentially affect the inflammation condition. A macrophage cell line, RAW264.7, was employed to examine the effects of foods traditionally regarded as heating or cooling on the production of PGE₂, a well-known proinflammatory mediator. Foods traditionally regarded as heating (litchi, longan, and dried longan) or cooling (chrysanthemum flower, bitter gourd, and lotus seed plumule) were extracted sequentially with water and ethyl acetate. The water extracts (WE) and ethyl acetate extracts (EAE) were applied to RAW264.7 macrophages in the presence or absence of LPS (lipopolysaccharide). In the absence of LPS, the WEs from the heating foods, litchi, longan, or dried longan had a dose-dependent enhancing effect on PGE₂ production, with respective EC₅₀s of 8.4, 16, and 11 mg/ml. This effect was accompanied by significant induction of COX-2 protein expression, as shown by Western blot analysis. In contrast, LPS-induced PGE₂ production was inhibited in a dose-dependent manner by the WEs of the cooling foods, chrysanthemum flower, bitter gourd, and lotus seed plumule, with respective IC₅₀s of 0.6, 0.13, and 0.08 mg/ml. At the concentrations tested, none of the EAEs had any effect on basal PGE₂ production, while LPS-induced PGE₂ production was inhibited or increased by the EAE from bitter gourd and longan, respectively. Water-soluble extracts of foods traditionally regarded as heating enhanced basal PGE₂ production, while those from cooling foods significantly inhibited LPS-induced PGE₂ production by the macrophage cell line. This subject merits further study to determine whether appropriate food selection may help patients suffering from chronic inflammatory conditions.     

An ‘axis-like’ material in the centromeric region of metaphase-I chromosomes from mouse spermatocytes

This study reports the persistence of axis-like structures in the centromeric region of both homologues during the metaphase-I and anaphase-I stages of meiotic division of mouse spermatocytes. A novel type of silver argentaffin technique (NH₄–Ag) is employed. This technique includes the treatment of glutaraldehyde-fixed tissues with dilute ammonium hydroxide followed by a reduction of aldehyde groups with sodium borohydride. Staining is accomplished with ammoniacal silver nitrate in darkness followed by sulfite washing. The lateral elements of synaptonemal complexes and the single chromosomal axes of diplotene spermatocytes show a prominent reactivity with this technique. The pattern of very small grains over condensed chromatin is uniform and gives only a light opacity to the electron beam. The presence of an axis-like structure is seen in every centromeric end of meiotic chromosomes at metaphase I and anaphase I. The chromatin (heterochromatin) that surrounds the centromeric filament and some material distributed in irregular linear arrays along some of the homologues also showed a higher electron opacity than the bulk of deoxyribonucleoprotein. While the former is related to C+ heterochromatin, the latter could represent dispersed material of diplotene axes. It is suggested that the disposal of axial material is differentially delayed at the centromeric regions. The present evidence supports the hypothesis that axial fragments or lateral-element segments persisting at these regions contribute to the cohesiveness of centromeres of sister chromatids during normal disjunction.     

Interaction of meropenem with ‘N’ and ‘B’ isoforms of human serum albumin: a spectroscopic and molecular docking study

Carbapenems are used to control the outbreak of β-lactamases expressing bacteria. The effectiveness of drugs is influenced by its interaction with human serum albumin (HSA). Strong binding of carbapenems to HSA may lead to decreased bioavailability of the drug. The non-optimal drug dosage will provide a positive selection pressure on bacteria to develop resistance. Here, we investigated the interaction between meropenem and HSA at physiological pH 7.5 (N-isoform HSA) and non-physiological pH 9.2 (B-isoform HSA). Results showed that meropenem quenches the fluorescence of both ‘N’ and ‘B’ isoforms of HSA (ΔG < 0 and binding constant ~10⁴ M^?1). Electrostatic interactions and van der Waal interactions along with H-bonds stabilized the complex of meropenem with ‘N’ and ‘B’ isoforms of HSA, respectively. Molecular docking results revealed that meropenem binds to HSA near Sudlow’s site II (subdomain IIIA) close to Trp-214 with a contribution of a few residues of subdomain IIA. CD spectroscopy showed a change in the conformation of both the isoforms of HSA upon meropenem binding. The catalytic efficiency of HSA (only N-isoform) on p-nitrophenyl acetate was increased primarily due to a decrease in K_m and an increase in k_cat values. This study provides an insight into the molecular basis of interaction between meropenem and HSA.     

‘Nucleolar dominance’ as observed in barley translocation lines with specifically reconstructed SAT chromosomes

Summary Diploid homo- and heterokaryotypes of barley translocation lines with only one satellite chromosome pair containing two nucleolus organizer regions (NORs) in opposite arms were found to show repressed nucleolus formation by the transposed NOR as evident from the formation of only micronucleoli. The same was true for auto-tetraploid homokaryotypes and for translocation lines with all NORs tandemly arranged into the same chromosome arm. When NORs were transposed to chromosomes without NOR in the standard karyotype, the normal pattern of nucleolus formation remained unaffected. The modified mode of nucleolus formation after the combination of all NORs in one chromosome pair is interpreted to be due to intrachromosomal nucleolar dominance analogous to interchromosomal nucleolar dominance observed in certain interspecific hybrids.     

Study of morphological and phenological diversity in chestnut trees (‘Judia’ variety) as a function of temperature sum

Morphological and histological adaptation of chestnut leaves at the different altitudes and edaphoclimate conditions were shown. The study was carried out on Castanea sativa Mill. var. ‘Judia’. The growth range altitudes of ‘Judia’ were between 709 m a.s.l. and 860 m a.s.l. (above sea level), corresponding to a variation in the sum of temperatures (expressed in degree-day values – °D) of 2751 °D to 2316 °D in 2006 and 2338 °D to 1700 °D in 2007, between May and October. In 2007 the thickest leaves (319.9 μm), the highest stomata density (469.1 stomata mm⁻²), one of the largest leaf areas (69.2 cm²) and the highest fruit size (71.7 fruit kg⁻¹) were observed in Alfândega da Fé (759 m a.s.l., 2186 °D, during the May–October period) whereas in 2006 the highest fruit size (86.8 fruit kg⁻¹) was observed in Valpaços (860 m a.s.l., 2316 °D, during the same period).Additionally, the leaves of the trees grown in this locality (Valpaços) displayed one of the largest areas (57.0 cm²). Overall results suggest that annual climate conditions do significantly influence both fruit and leaf biometric characteristics, and that the range of temperatures from 2100 °D to 2300 °D (between May and October) correspond to the optimal temperature sum, which can be ascribed to different places, depending on the year in question. Concerning the molecular characterisation using nuclear microsatellites, the individuals more distant are those from Macedo de Cavaleiros and Alfândega da Fé (genetic distance = 0.227), while the ecotypes with closer similarities were those collected in Murça and Vinhais (genetic identity = 1.171). The current results suggest that the morphological and phenological differences among ecotypes are not related to the small genetic differences, but are simply phenotypic adaptations to diffent climatic conditions.     

Crystallin αB acts as a molecular guard in mouse decidualization: Regulation and function during early pregnancy

Although decidualization is crucial for the establishment of successful pregnancy, the molecular mechanism underlying decidualization remains poorly understood. Crystallin αB (CryAB), a small heat shock protein (sHSP), is up-regulated and phosphorylated in mouse decidua. In mouse primary endometrial stromal cells, CryAB is induced upon progesterone treatment via HIF1α. In addition, CryAB is strongly phosphorylated through the p38-MAPK pathway under stress or during in vitro decidualization. Knockdown of CryAB results in the increase of apoptosis of stromal cells and inhibits decidualization under oxidative or inflammatory stress. Our data indicate that CryAB protects decidualization against stress conditions.     

Gap junction and hemichannel-independent actions of connexins on cell and tissue functions – An update

Connexins, a family of transmembrane proteins, are components of both gap junction channels and hemichannels, which mediate the exchange of ions and small molecules between adjacent cells, and between the inside and outside of the cell, respectively. Substantial advancements have been made in the comprehension of the role of gap junctions and hemichannels in coordinating cellular events. In recent years, a plethora of studies demonstrate a role of connexin proteins in the regulation of tissue homeostasis that occurs independently of their channel activities. This is shown in the context of cell growth, adhesion, migration, apoptosis, and signaling. The major mechanisms of these channel-independent activities still remain to be discovered. In this review, we provide an updated overview on the current knowledge of gap junction- and hemichannel-independent functions of connexins, in particular, their effects on tumorigenesis, neurogenesis and disease development.     

Genetic and biochemical studies on perchloroethylene ‘in vitro’ and ‘in vivo’

Perchloroethylene (PCE) was tested in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension tests with and without a mammalian microsomal activation system (S9) and ‘in vivo’ by the intrasanguineous host-mediated assay. In addition, enzyme alteration studies were performed in mice non-pretreated or pretreated with phenobarbital + β-naphthoflavone. PCE did not induce any genetic effect either ‘in vitro’ or ‘in vivo’. In the suspension test, PCE was more toxic without metabolic activation and less toxic with mammalian microsomal activation. The enzymatic determinations showed an increase of the aminopyrine demethylase activity and of the level of cytochrome P-450.