PSMIX: an R package for population structure inference via maximum likelihood method

Background  

Inference of population stratification and individual admixture from genetic markers is an integrative part of a study in diverse situations, such as association mapping and evolutionary studies. Bayesian methods have been proposed for population stratification and admixture inference using multilocus genotypes and widely used in practice. However, these Bayesian methods demand intensive computation resources and may run into convergence problem in Markov Chain Monte Carlo based posterior samplings.     

Therapeutic Hypothermia Modifies Perinatal Asphyxia-Induced Changes of the Corpus Callosum and Outcome in Neonates

What Is Known about this Subject?

Diffusion-weighted MRI has demonstrated changes in the corpus callosum of term neonates with perinatal asphyxia. The severity of cerebral changes demonstrated using diffusion-weighted MRI is difficult to assess without measuring values of the Apparent Diffusion Coefficient (ADC).

What Is New?

ADC values of the anterior part of the corpus callosum are slightly higher than of the posterior part in full term infants with perinatal asphyxia. Low ADC values of the corpus callosum were associated with an adverse outcome in infants with perinatal asphyxia. In infants treated with hypothermia lower ADC values than with normothermia were associated with a poor outcome, supporting neuroprotective effects of hypothermia

Background

Using MRI, changes can be detected in the corpus callosum (CC) following perinatal asphyxia which are associated with later neurodevelopmental outcome.

Aim

To study the association between the apparent diffusion coefficient of water (ADC) in the CC on MRI in neonates with perinatal asphyxia and neurodevelopmental outcome at 18 months of age.

Subjects, Methods

Of 121 infants 32 (26%) died and 13 (11%) survived with an adverse neurological outcome. Sixty-five (54%) received therapeutic hypothermia. MRI was performed within 7 days after birth using a 1.5 T or 3.0 T system, and ADC values were measured in the anterior and posterior CC. The association between ADC and composite outcome (death or abnormal neurodevelopment) was analyzed for both normothermia and hypothermia cases using receiver operating characteristics.

Results

ADC values of the posterior CC were lower than of the anterior part (mean difference 0.050 x 10^-3 mm²/s, p<0.001). Field strength did not affect ADC values. ADC values of the posterior part of the CC were significantly lower in infants with basal ganglia/thalamus or near total brain injury (p<0.001). Lower ADC values were associated with an adverse outcome, but cut-off levels were lower after hypothermia (1.024 x 10^-3 mm²/s vs 0.969 x 10^-3 mm²/s)

Conclusion

Low ADC values of the posterior part of the corpus callosum are associated with an adverse outcome in term or near term neonates with perinatal asphyxia. Therapeutic hypothermia slightly modifies this association, showing that lower values were needed for an adverse outcome.     

Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: Case report

Background  

It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury.     

Structural genomics of human proteins – target selection and generation of a public catalogue of expression clones

Background  

The availability of suitable recombinant protein is still a major bottleneck in protein structure analysis. The Protein Structure Factory, part of the international structural genomics initiative, targets human proteins for structure determination. It has implemented high throughput procedures for all steps from cloning to structure calculation. This article describes the selection of human target proteins for structure analysis, our high throughput cloning strategy, and the expression of human proteins in Escherichia colihost cells.     

Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study

Background  

There is a growing interest in the role of the endothelium in migraine. Recently, our group showed differences in endothelial function between the anterior and posterior cerebral circulation in healthy subjects, reduced vasodilatatory capacity of the posterior cerebral circulation and unimpaired systemic endothelial function in migraine patients without comorbidities. However, the relationship between cerebral and systemic endothelial function and the anterior and posterior cerebral endothelial function in migraine patients is still not clear.     

Endometrial glands as a source of nutrients,growth factors and cytokines during the first trimester of human pregnancy: A morphological and immunohistochemical study

Background  

The maternal circulation to the human placenta is not fully established until 10–12 weeks of pregnancy. During the first trimester the intervillous space is filled by a clear fluid, in part derived from secretions from the endometrial glands via openings in the basal plate. The aim was to determine the activity of the glands throughout the first trimester, and to identify components of the secretions.     

Novel gene expression patterns along the proximo-distal axis of the mouse embryo before gastrulation

Background  

To date, the earliest stage at which the orientation of the anterior-posterior axis in the mouse embryo is distinguishable by asymmetric gene expression is shortly after E5.5. At E5.5, prospective anterior markers are expressed at the distal tip of the embryo, whereas prospective posterior markers are expressed more proximally, close to the boundary with the extraembryonic region.     

Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa

Background  

Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon.     

Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

Background

The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents.

Methodology

Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted.

Principal Findings

Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca''s area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance.

Conclusions

Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions.

Significance

Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.     

An image processing approach to computing distances between RNA secondary structures dot plots

Background  

In phylogenetic inference one is interested in obtaining samples from the posterior distribution over the tree space on the basis of some observed DNA sequence data. One of the simplest sampling methods is the rejection sampler due to von Neumann. Here we introduce an auto-validating version of the rejection sampler, via interval analysis, to rigorously draw samples from posterior distributions over small phylogenetic tree spaces.     

Unusual linkage patterns of ligands and their cognate receptors indicate a novel reason for non-random gene order in the human genome

Background  

Prior to the sequencing of the human genome it was typically assumed that, tandem duplication aside, gene order is for the most part random. Numerous observers, however, highlighted instances in which a ligand was linked to one of its cognate receptors, with some authors suggesting that this may be a general and/or functionally important pattern, possibly associated with recombination modification between epistatically interacting loci. Here we ask whether ligands are more closely linked to their receptors than expected by chance.     

A Clinical Approach to Brown Adipose Tissue in the Para-Aortic Area of the Human Thorax

Background

Human thoracic brown adipose tissue (BAT), composed of several subdivisions, is a well-known target organ of many clinical studies; however, the functional contribution of each part of human thoracic BAT remains unknown. The present study analyzed the significance of each part of human thoracic BAT in the association between regional distribution, cellularity, and factors involved in the functional regulation of thoracic BAT.

Methods

We analyzed 1550 healthy adults who underwent medical check-ups by positron-emission tomography and computed tomography (PET–CT) imaging, 8 cadavers, and 78 autopsy cases in an observational study. We first characterized the difference between the mediastinum and the supraclavicular areas using counts of BAT detection and conditions based on PET–CT outcomes. The measurable important area was then subjected to systematic anatomical and immunohistochemical analyses using anti-uncoupling protein 1 (UCP1) antibody to characterize the cellularity in association with age and sex.

Results

In PET–CT scanning, the main site of thoracic BAT was the mediastinum rather than the supraclavicular area (P < 0.05). Systemic macroanatomy revealed that the thumb-sized BAT in the posterior mediastinal descending para-aortic area (paBAT) had feeding vessels from the posterior intercostal arteries and veins and sympathetic/parasympathetic innervation from trunks of the sympathetic and vagus nerves, respectively. Immunohistochemical analysis indicated that the paBAT exhibited immunoreactivity for tyrosine hydroxylase and vesicular acetylcholine transporter located in the pericellular nervous fibers and intracellular UCP1. The brown adipose cells of paBAT showed age-dependent decreases in UCP1 expression (P < 0.05), accompanied by a significant increase in vacuole formation, indicating fat accumulation (P < 0.05), from 10 to 37 years of age (P < 0.01).

Conclusions

paBAT may be one of the essential sites for clinical application in BAT study because of its visible anatomy with feeding vessels and sympathetic/parasympathetic innervation functionally affected by outer condition and senescence.     

Growth patterns in Onychophora (velvet worms): lack of a localised posterior proliferation zone

Background  

During embryonic development of segmented animals, body segments are thought to arise from the so-called "posterior growth zone" and the occurrence of this "zone" has been used to support the homology of segmentation between arthropods, annelids, and vertebrates. However, the term "posterior growth zone" is used ambiguously in the literature, mostly referring to a region of increased proliferation at the posterior end of the embryo. To determine whether such a localised posterior proliferation zone is an ancestral feature of Panarthropoda (Onychophora + Tardigrada + Arthropoda), we examined cell division patterns in embryos of Onychophora.     

Peristalsis in the junction region of the <Emphasis Type="Italic">Drosophila</Emphasis> larval midgut is modulated by DH31 expressing enteroendocrine cells

Background  

The underlying cellular and molecular mechanisms that coordinate the physiological processes in digestion are complex, cryptic, and involve the integration of multiple cellular and organ systems. In all intestines, peristaltic action of the gut moves food through the various stages of digestion from the anterior end towards the posterior, with the rate of flow dependent on signals, both intrinsic and extrinsic to the gut itself.     

The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano

Background  

Macrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S-phase.     

Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin

Background  

Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA.     

Polylepis woodland dynamics during the last 20,000 years

Aim

To determine the palaeoecological influences of climate change and human land use on the spatial distribution patterns of Polylepis woodlands in the Andes.

Location

Tropical Andes above 2,900 m between 2°S and 18°S of latitude.

Methods

Pollen and charcoal data were gathered from 13 Andean lake sediment records and were rescaled by the maximum value in each site. The rescaled pollen data were used to estimate a mean abundance and coefficient of variation to show woodland expansions/contractions and woodland fragmentation over the last 20,000 years. The rescaled charcoal was displayed as a 200‐year moving median using 500‐year bins to infer the influence of fire on woodland dynamics at landscape scale. Pollen and charcoal were compared with speleothem, clastic flux and archaeological data to assess the influence of moisture balance, glacial activity and human impact on the spatial distribution of Polylepis woodlands.

Results

Woodland expansion and fire were correlated with precipitation changes and glacier dynamics from c. 20 to 6 kcal bp (thousands of calibrated years before present). Charcoal abundances between 20 and 12 kcal bp were less common than from 12 kcal bp to modern. However, human‐induced fires were unlikely to be the main cause of a woodland decline centred at 11 kcal bp , as woodlands recovered from 10.5 to 9.5 kcal bp (about twofold increase). Charcoal peaks analogous to those that induced the woodland decline at 11 kcal bp were commonplace post‐9.5 kcal bp but did not trigger an equivalent woodland contraction. An increase in the coefficient of variation after c. 5.5 kcal bp suggests enhanced fragmentation and coincided with the shift from logistic to exponential growth of human populations. Over the last 1,000 years, Polylepis became hyper‐fragmented with over half of sites losing Polylepis from the record and with coefficients of variation paralleling those of glacial times.

Main conclusions

Polylepis woodlands formed naturally patchy woodlands, rather than a continuous vegetation belt, prior to human occupation in the Andes. The main factors controlling pre‐human woodland dynamics were precipitation and landscape heterogeneity. Human activity led to hyper‐fragmentation during the last c. 1,000 years.     

Expression and cytosolic assembly of the S-layer fusion protein mSbsC-EGFP in eukaryotic cells

Background  

Native as well as recombinant bacterial cell surface layer (S-layer) protein of Geobacillus (G.) stearothermophilus ATCC 12980 assembles to supramolecular structures with an oblique symmetry. Upon expression in E. coli, S-layer self assembly products are formed in the cytosol. We tested the expression and assembly of a fusion protein, consisting of the mature part (aa 31–1099) of the S-layer protein and EGFP (enhanced green fluorescent protein), in eukaryotic host cells, the yeast Saccharomyces cerevisiae and human HeLa cells.