Distant Branches Research Articles

Intraganglionic interactions between satellite cells and adult sensory neurons.

Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance.

The Blind Men and the Piwi Elephant—Opening a Can of Worms

The Blind Men and the Piwi Elephant—Opening a Can of Worms

Reunification by Y-Chromosome Lineage Analysis of an Ashkenazi Jewish Family with a Rare Surname who were Spatially and Temporally Separated

Y-chromosome lineage analysis is very useful for confirming a relationship between paternal relatives separated by various circumstances. In this study, we attempted to reconnect three paternal lineages who all share the same rare Ashkenazi Jewish surname Korenbaum or a derivative of that name. Even though some of the men tested from each of these three lineages were from different continents, they all shared an oral history of a male ancestor from the Bug River region in modern day Belarus and a strong reference to familial separation. Because the surname is exceedingly rare, it is believed that all Korenbaums are related. However, genealogical research has thus far been unable to connect several distant branches including a large branch living in Germany Today Korenbaums are spread around the world, with significant populations in the United States, Israel, France, Russia, Germany, England and other countries. The Y-DNA analysis was performed using four Y-chromosome biallelic markers and twelve YSTR markers to determine the haplogroup and haplotype for the various Korenbaum descendants. It was determined that all three Korenbaum lineages possessed the same rare haplotype belonging to the Near East Yhaplogroup E1b1b1b2a. This analysis supports that these lineages share a common paternal ancestor. Two of these lineages were confirmed by genealogical records to have a common male ancestor born in the mid-19th century. While the third lineage could not be directly connected though genealogical records, the rareness of the surname, their shared oral history, the age of Ashkenazi surnames and records of the oldest Korenbaum ancestor point to a likely common ancestor born in the late 18th century in modern-day Belarus. We conclude that Ychromosome analysis is a powerful tool in lineage confirmations of displaced peoples. However, its usefulness is greatly diminished if not used in conjunction with other investigative tools. Further work on the Korenbaum family may prove useful for understanding Y-lineage evolution rates and dating.

Additivity or cooperativity: which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?

Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data from several series of thermolysin inhibitors in which simultaneous structural modifications were investigated to determine whether they are cooperative or additive. Data revealed that, while additivity is at work in some cases, cooperativity is more commonly demonstrated. Cooperativity and additivity were then correlated with ligand descriptors, such as the spacing and the topological features of the modified groups, in a manner that may provide guidance as to when each model should be utilized. Cooperativity was particularly associated with contiguous groups and small unbranched hydrophobic side chain. Additivity, on the other hand, was associated with moderately distant hydrophobic group combinations and side chain branching. Such correlations can improve the predictability of SAR studies and can provide a starting point for additional investigations that may lead to further significant enhancements in the current scoring functions.

The molecular characterization and temporal–spatial expression of myocyte enhancer factor 2 genes in the goat and their association with myofiber traits

The myocyte enhancer factor-2 (MEF2) gene family in vertebrates includes MEF2A, MEF2B, MEF2C, and MEF2D, which have important functions in the regulation of muscular growth and development. To investigate their temporal–spatial expression and functions in the goat, these genes were cloned (accession nos. JN967621–24) and their expression patterns characterized at five postnatal stages (3, 30, 60, 90, and 120days). Association analysis was then applied regarding MEF2 expression levels and myofiber diameter and density. MEF2B was shown to be weakly homologous with other species, the distant branches with other members and the lowest expression levels, suggesting that it is distinct from other family members. Expression of the other three MEF2 genes was widely distributed, but this was largely accumulated in the skeletal muscle and myocardium compared with the viscera at all developmental stages. MEF2A and MEF2D expression levels were higher overall than MEF2B and MEF2C in six tissues, and were significantly positively correlated with the myofiber diameter of the longissimus dorsi. These findings suggest that goat MEF2 genes mainly function in the skeletal muscle and myocardium, and that MEF2A and MEF2D are likely to effectively promote muscular growth and development during postnatal stages. MEF2A expression was highest in the myocardium, where MEF2C expression increased with age, implying that both gene products are related to the growth and development of postnatal myocardium.

Cloning of a functional 25‐hydroxyvitamin D‐1α‐hydroxylase in zebrafish (Danio rerio)

Activation of precursor 25-hydroxyvitamin D3 (25D) to hormonal 1,25-dihydroxyvitamin D3 (1,25D) is a pivotal step in vitamin D physiology, catalysed by the enzyme 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase). To establish new models for assessing the physiological importance of the 1α-hydroxylase-25D-axis, we used Danio rerio (zebrafish) to characterize expression and biological activity of the gene for 1α-hydroxylase (cyp27b1). Treatment of day 5 zebrafish larvae with inactive 25D (5-150 nM) or active 1,25D (0.1-10 nM) induced dose responsive expression (15-95-fold) of the vitamin D-target gene cyp24a1 relative to larvae treated with vehicle, suggesting the presence of Cyp27b1 activity. A full-length zebrafish cyp27b1 cDNA was then generated using RACE and RT-PCR methods. Sequencing of the resulting clone revealed an open reading frame encoding a protein of 505 amino acids with 54% identity to human CYP27B1. Transfection of a cyp27b1 expression vector into HKC-8, a human kidney proximal tubular epithelial cell line, enhanced intracrine metabolism of 25D to 1,25D resulting in greater than twofold induction of CYP24A1 mRNA expression and a 25-fold increase in 1,25D production compared to empty vector. These data indicate that we have cloned a functional zebrafish CYP27B1, representing a phylogenetically distant branch from mammals of this key enzyme in vitamin D metabolism. Further analysis of cyp27b1 expression and activity in zebrafish may provide new perspectives on the biological importance of 25D metabolism.

Composite conserved promoter-terminator motifs (PeSLs) that mediate modular shuffling in the diverse T4-like myoviruses.

The diverse T4-like phages (Tquatrovirinae) infect a wide array of gram-negative bacterial hosts. The genome architecture of these phages is generally well conserved, most of the phylogenetically variable genes being grouped together in a series hyperplastic regions (HPRs) that are interspersed among large blocks of conserved core genes. Recent evidence from a pair of closely related T4-like phages has suggested that small, composite terminator/promoter sequences (promoterearly stem loop [PeSLs]) were implicated in mediating the high levels of genetic plasticity by indels occurring within the HPRs. Here, we present the genome sequence analysis of two T4-like phages, PST (168 kb, 272 open reading frames [ORFs]) and nt-1 (248 kb, 405 ORFs). These two phages were chosen for comparative sequence analysis because, although they are closely related to phages that have been previously sequenced (T4 and KVP40, respectively), they have different host ranges. In each case, one member of the pair infects a bacterial strain that is a human pathogen, whereas the other phage’s host is a nonpathogen. Despite belonging to phylogenetically distant branches of the T4-likes, these pairs of phage have diverged from each other in part by a mechanism apparently involving PeSL-mediated recombination. This analysis confirms a role of PeSL sequences in the generation of genomic diversity by serving as a point of genetic exchange between otherwise unrelated sequences within the HPRs. Finally, the palette of divergent genes swapped by PeSL-mediated homologous recombination is discussed in the context of the PeSLs’ potentially important role in facilitating phage adaption to new hosts and environments.

Bayesian modelling of compositional heterogeneity in molecular phylogenetics.

In molecular phylogenetics, standard models of sequence evolution generally assume that sequence composition remains constant over evolutionary time. However, this assumption is violated in many datasets which show substantial heterogeneity in sequence composition across taxa. We propose a model which allows compositional heterogeneity across branches, and formulate the model in a Bayesian framework. Specifically, the root and each branch of the tree is associated with its own composition vector whilst a global matrix of exchangeability parameters applies everywhere on the tree. We encourage borrowing of strength between branches by developing two possible priors for the composition vectors: one in which information can be exchanged equally amongst all branches of the tree and another in which more information is exchanged between neighbouring branches than between distant branches. We also propose a Markov chain Monte Carlo (MCMC) algorithm for posterior inference which uses data augmentation of substitutional histories to yield a simple complete data likelihood function that factorises over branches and allows Gibbs updates for most parameters. Standard phylogenetic models are not informative about the root position. Therefore a significant advantage of the proposed model is that it allows inference about rooted trees. The position of the root is fundamental to the biological interpretation of trees, both for polarising trait evolution and for establishing the order of divergence among lineages. Furthermore, unlike some other related models from the literature, inference in the model we propose can be carried out through a simple MCMC scheme which does not require problematic dimension-changing moves. We investigate the performance of the model and priors in analyses of two alignments for which there is strong biological opinion about the tree topology and root position.

Collateralization of Loans: Testing the Prediction of Theories

Using confidential data on a large sample of relationship lending, we analyze the determining factors of the collateralization of business loans from banks, distinguishing between firms with observable risk and firms with hidden information. We achieve three main results. First, we provide evidence that observably riskier borrowers are encouraged to give more collateral to banks to obtain a loan, whereas firms with hidden information are less risky borrowers, offering collateral to signal their quality. Second, we show that relationship banking has a direct impact on the use of collateral and produces moderating effects on the other determining factors. Finally, we observe that distant bank branches—i.e., branches that encounter greater difficulties collecting soft information and obtaining site-specific data from headquarters—are more likely to require collateral than local bank branches.

S100A7 in the Fallopian tube: a comparative study

The oviduct is a dynamic organ in which final gamete maturation, fertilization and early embryo development take place. It is considered to be a sterile site; however the mechanism for sterility maintenance is still unknown. S100A7 is an anti-microbial peptide that has been reported in human reproductive tissues such as prostate, testicle, ovary, normal cervical epithelium and sperm. The current work reports the presence of S100A7 in the Fallopian tube and its localization at the apical surface of epithelial cells. For comparison, porcine S100A7 was used for antibody development and search for peptide in reproductive tissues. Although present in boar seminal vesicles and seminal plasma, S100A7 was not detected on female porcine organs. Also, in contrast with the human protein, porcine S100A7 did not show anti-microbial activity under the conditions tested. Phylogenetic analyses showed high divergence of porcine S100A7 from human, primate, bovine, ovine and equine sequences, being the murine sequence at a most distant branch. The differences in sequence homology, Escherichia coli-cidal activity, detectable presence and localization of S100A7 from human and pig, suggest that there are possible different functions in each organism.

Genomic analysis of three sponge-associated Arthrobacter Antarctic strains, inhibiting the growth of Burkholderia cepacia complex bacteria by synthesizing volatile organic compounds

In this work we analyzed the ability of three Arthrobacter strains (namely TB23, TB26 and CAL618), which were isolated from the Antarctic sponges Haliclonissa verrucosa and Lyssodendrix nobilis, to specifically inhibit the growth of a panel of 40 Burkholderia cepacia complex strains, representing a major cause of infections in patients that are affected by Cystic Fibrosis. The inhibitory activity was due to the synthesis of antimicrobial compounds, very likely volatile organic compounds (VOCs), and was partially dependent on the growth media that were used for Antarctic strains growth. The phylogenetic analysis revealed that two of them (i.e. CAL 618 and TB23) were very close and very likely belonged to the same Arthrobacter species, whereas the strain TB26 was placed in a distant branch. The genome of the strains TB26 and CAL618 was also sequenced and compared with that of the strain TB23. The analysis revealed that TB23 and CAL618 shared more genomic properties (GC content, genome size, number of genes) than with TB26. Since the three strains exhibited very similar inhibition pattern vs Bcc strains, it is quite possible that genes involved in the biosynthesis of antimicrobial compounds very likely belong to the core genome.

Human races

Human races

Movement of intraretinal fluid from distant branch retinal vein occlusion to the submacular space

BackgroundExtramacular branch retinal vein occlusion (BRVO) occasionally causes serous macular detachment. We studied the movement of extravasated fluid from BRVO lesions to the submacular space.MethodsWe examined nine eyes from nine patients with serous retinal detachment caused by extramacular BRVO. In addition to a comprehensive ophthalmic examination, optical coherence tomography was performed in all nine eyes. Six of the patients also underwent fluorescein angiography.ResultsVisual acuity ranged from 0.03 to 0.9 (median 0.5). All nine eyes showed localized macular detachment and retinal edema which extended from the extramacular BRVO to the macula. Fluorescein angiography revealed dye leakage in the extramacular area but no macular leakage in the six eyes examined. Optical coherence tomography revealed serous retinal detachment in the macula and intraretinal swelling, with low reflectivity in the outer retina extending from the distant BRVO toward the detached macula in all nine eyes. Six eyes were treated with laser photocoagulation, covering the entire area of BRVO, and the other three eyes were treated with intravitreal bevacizumab. Serous retinal detachment and retinal swelling resolved within 3 months of treatment in all nine eyes.ConclusionDistant retinal vascular leakage appears to diffuse through the outer retina to the macula, then permeate into the subretinal space.

Broken degeneracies: the rotation curve and velocity anisotropy of the Milky Way halo

Abstract We use distant blue horizontal branch stars with Galactocentric distances 16 < r < 48 kpc as kinematic tracers of the Milky Way dark halo. We model the tracer density as an oblate, power law embedded within a spherical power-law potential. Using a distribution function method, we estimate the overall power-law potential and the velocity anisotropy of the halo tracers. We measure the slope of the potential to be γ∼ 0.4, and the overall mass within 50 kpc is ∼4 × 1011 M⊙. The tracer velocity anisotropy is radially biased with β∼ 0.5, which is in good agreement with local solar neighbourhood studies. Our results provide an accurate outer circular velocity profile for the Milky Way and suggest a relatively high-concentration dark matter halo (cvir∼ 20).

Efficient Selection of Branch-Specific Models of Sequence Evolution

The analysis of extant sequences shows that molecular evolution has been heterogeneous through time and among lineages. However, for a given sequence alignment, it is often difficult to uncover what factors caused this heterogeneity. In fact, identifying and characterizing heterogeneous patterns of molecular evolution along a phylogenetic tree is very challenging, for lack of appropriate methods. Users either have to a priori define groups of branches along which they believe molecular evolution has been similar or have to allow each branch to have its own pattern of molecular evolution. The first approach assumes prior knowledge that is seldom available, and the second requires estimating an unreasonably large number of parameters. Here we propose a convenient and reliable approach where branches get clustered by their pattern of molecular evolution alone, with no need for prior knowledge about the data set under study. Model selection is achieved in a statistical framework and therefore avoids overparameterization. We rely on substitution mapping for efficiency and present two clustering approaches, depending on whether or not we expect neighbouring branches to share more similar patterns of sequence evolution than distant branches. We validate our method on simulations and test it on four previously published data sets. We find that our method correctly groups branches sharing similar equilibrium GC contents in a data set of ribosomal RNAs and recovers expected footprints of selection through dN/dS. Importantly, it also uncovers a new pattern of relaxed selection in a phylogeny of Mantellid frogs, which we are able to correlate to life-history traits. This shows that our programs should be very useful to study patterns of molecular evolution and reveal new correlations between sequence and species evolution. Our programs can run on DNA, RNA, codon, or amino acid sequences with a large set of possible models of substitutions and are available at http://biopp.univ-montp2.fr/forge/testnh.

USEFULNESS OF INDOCYANINE GREEN ANGIOGRAPHY TO DEPICT THE DISTANT RETINAL VASCULAR ANOMALIES ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION CAUSING SEROUS MACULAR DETACHMENT

To report the usefulness of indocyanine green angiography (ICGA) to depict the retinal vascular anomalies associated with distant branch retinal vein occlusion resulting in serous retinal detachment at the macula. This was a retrospective, case series of 6 patients (6 eyes) with serous retinal detachments. Fluorescein angiography and ICGA showed that those 6 eyes had a distant branch retinal vein occlusion. The characteristics in ophthalmic examinations such as fundus appearance, fluorescein angiography, ICGA, optical coherence tomography, and clinical courses were evaluated. In addition to serous retinal detachments, five eyes exhibited hard exudates around the macula. Fluorescein angiography and ICGA clearly showed the vessel occlusion; however, no apparent abnormalities appeared in the macular area in any of the eyes. In four eyes, early-phase ICGA depicted the retinal vascular anomalies within the area of venous occlusion and those were seen as hyperfluorescent patches on late-phase ICGA. In two eyes, punctate hyperfluorescent spots were seen in the area of venous occlusion on late-phase ICGA. Optical coherence tomography depicted a serous retinal detachment at the macula and retinal swelling in the outer nuclear layer from the macula to the hyperfluorescent abnormalities on ICGA. The macular serous retinal detachments were resolved within 3 months after laser photocoagulation was applied to the hyperfluorescent areas on ICGA. Leakage from subsequent vascular anomalies after branch retinal vein occlusion can cause submacular fluid. Indocyanine green angiography is useful for detecting the causative vascular regions of the fluid.

Scientific Calculators and the Skill of Efficient Computation

Calculators are part and parcel of modern education. Involvement of science and engineering in different fields of knowledge is increasing with each bit of time is passed by, and they are playing a role in description and characterization of the delicate phenomena of nature arising day by day. These fields of knowledge and mathematics in particular, are influencing even those distant branches of knowledge, which were so far imagined to be free of mathematics. Even art is not free of mathematics and there exists mathematical art. Computations are getting lengthy and complex specially in design and analysis of engineering systems. Scientific calculators are handy tools. But an efficient computation is a skill that can be developed.Keywords: scientific calculators; calculator techniques; efficient computation; efficient use of calculators, computation skills; numerical techniquesDOI: http://dx.doi.org/10.3126/bibechana.v8i0.4702 BIBECHANA 8 (2012) 31-36

Autoregulated Splicing of muscleblind-like 1 (MBNL1) Pre-mRNA

Muscleblind-like 1 (MBNL1) is a splicing factor whose improper cellular localization is a central component of myotonic dystrophy. In myotonic dystrophy, the lack of properly localized MBNL1 leads to missplicing of many pre-mRNAs. One of these events is the aberrant inclusion of exon 5 within the MBNL1 pre-mRNA. The region of the MBNL1 gene that includes exon 5 and flanking intronic sequence is highly conserved in vertebrate genomes. The 3'-end of intron 4 is non-canonical in that it contains a predicted branch point that is 141 nucleotides from the 3'-splice site and an AAG 3'-splice site. Using a minigene that includes exon 4, intron 4, exon 5, intron 5, and exon 6 of MBNL1, we showed that MBNL1 regulates inclusion of exon 5. Mapping of the intron 4 branch point confirmed that branching occurs primarily at the predicted distant branch point. Structure probing and footprinting revealed that the highly conserved region between the branch point and 3'-splice site is primarily unstructured and that MBNL1 binds within this region of the pre-mRNA. Deletion of the MBNL1 response element eliminated MBNL1 splicing regulation and led to complete inclusion of exon 5, which is consistent with the suppressive effect of MBNL1 on splicing.

WHY ARE BANKS SO SCARCE IN DEVELOPING COUNTRIES? A REGULATORY AND INFRASTRUCTURE PERSPECTIVE

In developing countries, banks are simply not present where the majority of poor people live and work. This imposes burdensome access costs on customers who need to travel to distant branches, so the majority of the population opts out from the formal banking system. Banking services can be offered through everyday stores that exist in every community and by new technology, particularly mobile communications networks. Banking regulations, however, impede such possibilities in many developing countries.

Banking the Poor through Everyday Stores

require as many if not more financial transactions than average bank customers, since their income is less predictable, they are often paid more frequently (daily or weekly), and their daily financial circumstances may be more easily overwhelmed by health or other shocks. Yet active cash flow management may not translate into long-term financial accumulation, given the pressing consumption and investment needs poor people face. Thus, serving the poor presents two major challenges for retail banks: devising a viable revenue model that is consistent with customers’ cash flow needs and perceptions of value, and minimizing the infrastructure and operational burden of handling millions of small transactions. Concentrating low-value transactions at a limited number of branches is very costly for banks and their customers alike, especially if regulations mandate disproportionate investments at a branch relative to the volume of business conducted there. Banks have to invest large fixed costs in setting up and maintaining their branch network, and customers often expend significant time and money to travel to distant branches. As a result, banks often stay away from poor or rural communities, which they find too costly to serve, and poor people fall back on local, more informal options to manage their finances. Banking beyond branches is about shifting the bulk of low-value transactions to a much lower-cost and more ubiquitous retail channel, which makes for a significantly more compelling business case to serve the poor. The key is to leverage the corner shops that can be found in every village and in every neighborhood. Why shouldn’t banks be able to let these shops handle basic deposit and withdrawal transactions on their behalf? In much the same way the shops exchange their pre-purchased inventory of rice or cooking oil against cash, they can also exchange their own bank balance against cash, and vice versa. This can be done safely, as long