Emergence of novel domains in proteins

Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently.

Analysing Google rankings through search engine optimization data

Purpose - The purpose of this paper is to identify the most popular techniques used to rank a web page highly in Google. Design/methodology/approach - The paper presents the results of a study into 50 highly optimized web pages that were created as part of a Search Engine Optimization competition. The study focuses on the most popular techniques that were used to rank highest in this competition, and includes an analysis on the use of PageRank, number of pages, number of in-links, domain age and the use of third party sites such as directories and social bookmarking sites. A separate study was made into 50 non-optimized web pages for comparison. Findings - The paper provides insight into the techniques that successful Search Engine Optimizers use to ensure a page ranks highly in Google. Recognizes the importance of PageRank and links as well as directories and social bookmarking sites. Research limitations/implications - Only the top 50 web sites for a specific query were analyzed. Analysing more web sites and comparing with similar studies in different competition would provide more concrete results. Practical implications - The paper offers a revealing insight into the techniques used by industry experts to rank highly in Google, and the success or other-wise of those techniques. Originality/value - This paper fulfils an identified need for web sites and e-commerce sites keen to attract a wider web audience.

Variscan lamprophyres in the Lower Penninic domain (Central Alps): age and tectonic significance

Lamprophyre dykes have been recently discovered in blocks of gneiss embedded in a calcschist formation of wildflysch type that forms the top of the Mesozoic-Tertiary metasedimentary cover of the Antigorio nappe (the Teggiolo zone) in the Val Bavona (Lower Penninic, NW Ticino, Switzerland). The presence of the lamprophyres gives a clue to the possible source of these blocks. Similar dykes occur in the N part of the Maggia nappe where they are intruded into the Matorello granite and the surrounding gneisses. We studied these lamprophyres at two localities in the Teggiolo zone (Tamierpass and Lago del Zott) and at one locality in the Maggia nappe (Laghetti). Detailed mineralogical and geochemical investigations confirm their great similarity, particularly between the Tamier and Laghetti dykes. They all recrystallized during Alpine metamorphism under amphibolite facies conditions and lost their primary mineral assemblages and textures. The chemistry reveals a calc-alkaline affinity, a limited differentiation range, features of mineral accumulation and intense remobilization in some cases. The lamprophyres are characterized by a high mg# and relatively low contents in REE and other incompatible elements. In situ SHRIMP and LA-ICPMS U-Pb zircon dating yielded ages of 284.8 +/- 1.7 Ma (Tamier), 290.0 +/- 1.3 Ma (Zott) and 290.5 +/- 3.7 Ma (Laghetti). These ages are compatible with the general late- to post-Variscan magmatic evolution of the Helvetic and Lower Penninic domains. The lamprophyres are considered as melts derived from the lithospheric Variscan mantle, variously hybridized and differentiated at the contact with crustal material during late- to post-orogenic extension. These lamprophyres are chemically distinct from earlier lamprophyres of Visean age, emplaced together with their associated granites in transcurrent fault zones during the Variscan orogenic compression. The similarity of these different dykes suggests that the front of the Maggia nappe is a likely source of the gneissic blocks embedded in the calcschists at the top of the Teggiolo zone. They would have been provided by the advancing Maggia nappe during its thrusting over the Antigorio nappe and simultaneous closure of the Teggiolo sedimentary basin.

Radiometric age constraints on mineral growth, metamorphism, and tectonism of the Gummfluh klippe, Brianconnais domain of the Prealpes, Switzerland

A combined Ar-40/Ar-39, K/Ar, Rb/Sr and stable isotope study has been made of white micas from the Gummfluh klippe (Brianconnais domain of the Prealpes), Switzerland. The klippe consists mainly of Mesozoic to early Tertiary carbonate rocks metamorphosed from anchizonal to epizonal conditions. At the base of the klippe is a 10-50 m thick, ductilely deformed marble mylonite containing deformed authigenic quartz segregations. Stable isotope measurements of the coexisting calcite (deltaO-18SMOW=24.5) and quartz (deltaO-18SMOW=28.4) from the mylonite indicate relatively low temperatures (< 300-degreesC) during mylonitization. Analyses of white mica separates of varying size fractions from the mylonitic rocks by K/Ar and Rb/Sr techniques yield ages between 57 and 103 Ma. This variation is correlated with two parameters, the size of the mineral fraction, and the proportion of 2M1 (more phengitic) to 1M (more muscovitic) polytype in the sample. The K/Ar and Rb/Sr ages are generally younger in the smaller size fractions, which also containless 2M1 phengite. High precision Ar-40/Ar-39 age spectra from different size fractions of these micas record three distinct components, a small Hercynian component (ca. 200-300 Ma), a significant Eoalpine component (64-80 Ma) forming Ar-40/Ar-39 age plateaus, and a very minor Tertiary component (ca. 20-40 Ma). Characterization of the samples by SEM indicates the presence of two white mica populations, a coarser grained, deformed, detrital mica that probably corresponds to the 2M1 phengite and a finer grained neoformed 1M mica. Collectively these observations suggest that the Gummfluh samples contain a mixture of detrital phengites of Hercynian age together with neocrystallized muscovites grown during the late Eoalpine metamorphic event followed by minor argon loss during the Tertiary. The main geologic episode recorded in the Ar-40/Ar-39 age spectra of white micas in the mylonite is of Late Cretaceous/Early Tertiary age (64-80 Ma), representing the first reliable Eoalpine ages ever to be reported from the Prealpes. Contrary to tectonic models, the marble mylonite at the base of the Gummfluh klippe appears to be a Cretaceous thrust plane and not the thrust surface formed during transport of the klippe into its present position from the Penninic Alps during the Tertiary. The late Cretaceous thrust developed during marine sedimentation at a depth of 800 m below the seafloor at temperatures of approximately 280-degrees-C, facilitated by warm fluids along the tectonic discontinuity.

Reproducibility of retinal thickness measurements in patients with age-related macular degeneration using 3D Fourier-domain optical coherence tomography (OCT) (Topcon 3D-OCT 1000)

Conventional time-domain optical coherence tomography (OCT) has become an important tool for following dry or exudative age-related macular degeneration (AMD). Fourier-domain three-dimensional (3D) OCT was recently introduced. This study tested the reproducibility of 3D-OCT retinal thickness measurements in patients with dry and exudative AMD.

Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration

To observe detailed changes in neurosensory retinal structure after anti-VEGF upload in age-related macular degeneration (AMD), by using spectral domain optical coherence tomography (SD-OCT).

Applications Of Visual Evoked Potentials And Fourier-domain Optical Coherence Tomography In Parkinson's Disease: A Controlled Study.

The goal of this cross-sectional observational study was to quantify the pattern-shift visual evoked potentials (VEP) and the thickness as well as the volume of retinal layers using optical coherence tomography (OCT) across a cohort of Parkinson's disease (PD) patients and age-matched controls. Forty-three PD patients and 38 controls were enrolled. All participants underwent a detailed neurological and ophthalmologic evaluation. Idiopathic PD cases were included. Cases with glaucoma or increased intra-ocular pressure were excluded. Patients were assessed by VEP and high-resolution Fourier-domain OCT, which quantified the inner and outer thicknesses of the retinal layers. VEP latencies and the thicknesses of the retinal layers were the main outcome measures. The mean age, with standard deviation (SD), of the PD patients and controls were 63.1 (7.5) and 62.4 (7.2) years, respectively. The patients were predominantly in the initial Hoehn-Yahr (HY) disease stages (34.8% in stage 1 or 1.5, and 55.8 % in stage 2). The VEP latencies and the thicknesses as well as the volumes of the retinal inner and outer layers of the groups were similar. A negative correlation between the retinal thickness and the age was noted in both groups. The thickness of the retinal nerve fibre layer (RNFL) was 102.7 μm in PD patients vs. 104.2 μm in controls. The thicknesses of retinal layers, VEP, and RNFL of PD patients were similar to those of the controls. Despite the use of a representative cohort of PD patients and high-resolution OCT in this study, further studies are required to establish the validity of using OCT and VEP measurements as the anatomic and functional biomarkers for the evaluation of retinal and visual pathways in PD patients.

Human Mitochondrial Hsp70 (mortalin): Shedding Light On Atpase Activity, Interaction With Adenosine Nucleotides, Solution Structure And Domain Organization.

The human mitochondrial Hsp70, also called mortalin, is of considerable importance for mitochondria biogenesis and the correct functioning of the cell machinery. In the mitochondrial matrix, mortalin acts in the importing and folding process of nucleus-encoded proteins. The in vivo deregulation of mortalin expression and/or function has been correlated with age-related diseases and certain cancers due to its interaction with the p53 protein. In spite of its critical biological roles, structural and functional studies on mortalin are limited by its insoluble recombinant production. This study provides the first report of the production of folded and soluble recombinant mortalin when co-expressed with the human Hsp70-escort protein 1, but it is still likely prone to self-association. The monomeric fraction of mortalin presented a slightly elongated shape and basal ATPase activity that is higher than that of its cytoplasmic counterpart Hsp70-1A, suggesting that it was obtained in the functional state. Through small angle X-ray scattering, we assessed the low-resolution structural model of monomeric mortalin that is characterized by an elongated shape. This model adequately accommodated high resolution structures of Hsp70 domains indicating its quality. We also observed that mortalin interacts with adenosine nucleotides with high affinity. Thermally induced unfolding experiments indicated that mortalin is formed by at least two domains and that the transition is sensitive to the presence of adenosine nucleotides and that this process is dependent on the presence of Mg2+ ions. Interestingly, the thermal-induced unfolding assays of mortalin suggested the presence of an aggregation/association event, which was not observed for human Hsp70-1A, and this finding may explain its natural tendency for in vivo aggregation. Our study may contribute to the structural understanding of mortalin as well as to contribute for its recombinant production for antitumor compound screenings.

A computerized tomography scan method for calculating the hernia sac and abdominal cavity volume in complex large incisional hernia with loss of domain

Preoperative progressive pneumoperitoneum (PPP) is a safe and effective procedure in the treatment of large incisional hernia (size > 10 cm in width or length) with loss of domain (LIHLD). There is no consensus in the literature on the amount of gas that must be insufflated in a PPP program or even how long it should be maintained. We describe a technique for calculating the hernia sac volume (HSV) and abdominal cavity volume (ACV) based on abdominal computerized tomography (ACT) scanning that eliminates the need for subjective criteria for inclusion in a PPP program and shows the amount of gas that must be insufflated into the abdominal cavity in the PPP program. Our technique is indicated for all patients with large or recurrent incisional hernias evaluated by a senior surgeon with suspected LIHLD. We reviewed our experience from 2001 to 2008 of 23 consecutive hernia surgical procedures of LIHLD undergoing preoperative evaluation with CT scanning and PPP. An ACT was required in all patients with suspected LIHLD in order to determine HSV and ACV. The PPP was performed only if the volume ratio HSV/ACV (VR = HSV/ACV) was a parts per thousand yen25% (VR a parts per thousand yen 25%). We have performed this procedure on 23 patients, with a mean age of 55.6 years (range 31-83). There were 16 women and 7 men with an average age of 55.6 years (range 31-83), and a mean BMI of 38.5 kg/m(2) (range 23-55.2). Almost all patients (21 of 23 patients-91.30%) were overweight; 43.5% (10 patients) were severely obese (obese class III). The mean calculated volumes for ACV and HSV were 9,410 ml (range 6,060-19,230 ml) and 4,500 ml (range 1,850-6,600 ml), respectively. The PPP is performed by permanent catheter placed in a minor surgical procedure. The total amount of CO(2) insufflated ranged from 2,000 to 7,000 ml (mean 4,000 ml). Patients required a mean of 10 PPP sessions (range 4-18) to achieve the desired volume of gas (that is the same volume that was calculated for the hernia sac). Since PPP sessions were performed once a day, 4-18 days were needed for preoperative preparation with PPP. The mean VR was 36% (ranged from 26 to 73%). We conclude that ACT provides objective data for volume calculation of both hernia sac and abdominal cavity and also for estimation of the volume of gas that should be insufflated into the abdominal cavity in PPP.

Gastric Bypass and Cardiac Autonomic Activity: Influence of Gender and Age

Obesity is associated with increased sympathetic activity and higher mortality. Treatment of this condition is often frustrating. Roux-en-Y gastric bypass is the most effective technique nowadays for treatment of obesity. The aim of the present study is to assess the effects of this surgery on the cardiac autonomic activity, including the influence of gender and age, through heart rate variability (HRV) analysis. The study group consisted of 71 obese patients undergoing gastric bypass. Time domain measures of HRV, obtained from 24-h Holter recordings, were evaluated before and 6 months after surgery, and the results were compared. Percentage of interval differences of successive normal sinus beats greater than 50 ms (pNN50) and square root of the mean squared differences of successive normal sinus beat intervals (rMSSD) was used to estimate the short-term components of HRV, related to the parasympathetic activity. Standard deviation of intervals between all normal sinus beats (SDNN) was related to overall HRV. SDNN, pNN50, and rMSSD showed significant increase 6 months after surgery (p < 0.001, p = 0.001 and p = 0.002, respectively). Men presented a greater increase of SDNN than women (p = 0.006) during the follow-up. There was a difference in rMSSD evolution for age groups (p = 0.002). Only younger patients presented significant increase of rMSSD. Overall HRV increased 6 months after surgery; this increase was more evident in men. Cardiac parasympathetic activity increased also, but in younger patients only.

Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene

We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene. ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis. The patient presented with a history of splenomegaly since 4 months of age, associated with cervical lymphadenopathy, which improved with oral corticosteroid treatment. Relevant laboratory findings were the presence of anemia, thrombocytopenia, and positive direct and indirect Coombs tests. He was not an offspring of consanguineous parents. Two cervical lymph node biopsies were performed, at 4 years and at 6 years of age. In both lymph nodes, there was marked paracortical expansion by lymphocytes in variable stages of immunoblastic transformation and a very high cell proliferating index. Some clear cells were also present, raising the suspicion of malignant lymphoma. In one of the lymph nodes, there was also a focus rich in large histiocytes with round nuclei and emperipolesis, consistent with focal Rosai-Dorfman disease. Immunostaining showed numerous CD3+ cells, many of which were double-negative (CD4- CD8-) and expressed CD57, especially around the follicles. Molecular studies of the lymph node biopsy showed a point deletion (4-base pair deletion) in exon 9 of the FAS gene (930del TGCT), which results in 3 missense amino acids. (c) 2008 Elsevier Inc. All rights reserved.

The viking age: the early history, manners, and customs of the ancestors of the English speaking nations ... by Paul B. Du Chaillu ...

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The viking age: the early history, manners, and customs of the ancestors of the English speaking nations ... by Paul B. Du Chaillu ...

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Validation of the French version of the Hierarchical Personality Inventory for Children (HiPIC): Influence of gender and age on personality traits from 8 to 12 years

The study was designed to investigate the psychometric properties of the French version and the cross-language replicability of the Hierarchical Personality Inventory for Children (HiPIC). The HiPIC is an instrument aimed at assessing the five dimensions of the Five-Factor Model for Children. Subjects were 552 children aged between 8 and 12 years, rated by one or both parents. At the domain level, reliability ranged from .83 to .93 and at the facet level, reliability ranged from .69 to .89. Differences between genders were congruent with those found in the Dutch sample. Girls scored higher on Benevolence and Conscientiousness. Age was negatively correlated with Extraversion and Imagination. For girls, we also observed a decrease of Emotional Stability. A series of exploratory factor analyses confirmed the overall five-factor structure for girls and boys. Targeted factor analyses and congruence coefficients revealed high cross-language replicability at the domain and at the facet levels. The results showed that the French version of the HiPIC is a reliable and valid instrument for assessing personality with children and has a particularly high cross-language replicability.