Miracle-dz/UniFAR-FTUs huggingface dataset:
More Hydrogen Bonds for the (structural) Biologist

TNF-α inhibits flow and insulin signaling leading to NO production in aortic endothelial cells. Am. The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. Sphingosine 1-phosphate and activation of endothelial nitric-oxide synthase. Differential regulation of Akt and MAP kinase pathways by EDG and bradykinin receptors in vascular endothelial cells.modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. RNA diversity has profound effects on the translation of neuronal nitric oxide synthase. Why does a given protein structure form and why is this structure stable? These fundamental biochemical questions remain fascinating and challenging problems because the physical bases of the forces that govern protein structure, stability and folding are still not well understood. Now, a general concept of hydrogen bonding in proteins is emerging. This concept involves not only N–H and O–H donor groups, but also C–H, and not only N and O as acceptor groups, but also π π-systems. We postulate that the incorporation of the entirety of these interactions leads to a more complete description of the problem, and that this could provide new perspectives and possibly new answers. The world of proteins used to be simple. Hydrogen atoms bound to nitrogen and oxygen atoms formed hydrogen bonds with lone electron pairs on other oxygen and nitrogen atoms. These 'classical' hydrogen bonds 1,2 (Fig. 1a) have been held responsible for the formation of secondary structural elements such as α helices and β sheets and, along with van der Waals and hydrophobic forces, they constitute one of the main pillars of overall protein stability and a principal determinant of protein conformation. However, this seemingly simple picture is not able to provide more than a qualitative explanation of protein structure, folding and stability. A quantitative description that would allow the calculation and prediction of the energetics of these phenomena needs to be more elaborate and, indeed, the 'classical' view on hydrogen bonds has evolved considerably over the years. In 1982, Taylor and Kennard presented unequivocal evidence for the existence of hydrogen bonds between C–H donor groups and oxygen acceptors 3 , and in the 1990s these hydrogen bonds were discovered for proteins at first 4 and then for other biological macromolecules 5 (Fig. 1b). Early this year, two papers dealing with even more …
BICGSTAB( L ) FOR LINEAR EQUATIONS INVOLVING UNSYMMETRIC MATRICES WITH COMPLEX

For a number of linear systems of equations arising from realistic problems, using the Bi-CGSTAB algorithm of van der Vorst [17] to solve these equations is very attractive. Unfortunately, for a large class of equations, where, for instance, Bi-CG performs well, the convergence of Bi-CGSTAB stagnates. This was observed speci(cid:12)cally in case of discretized advection dominated PDE’s. The stagnation is due to the fact that for this type of equations the matrix has almost pure imaginary eigenvalues. With his BiCGStab2 algorithm Gutknecht [5] attempted to avoid this stagnation. Here, we generalize the Bi-CGSTAB algorithm further, and overcome some shortcomings of BiCGStab2. In some sense, the new algorithm combines GMRES( l ) and Bi-CG and pro(cid:12)ts from both.
Merkel cells, a new localization of prepro‐orexin and orexin receptors

Orexins (OXA and OXB) are peptides derived from a common precursor called prepro‐orexin. They act through G‐protein receptors named orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). Orexins were first demonstrated in neurons of the lateral hypothalamus and found to be related to the control of food intake. However, it has been shown that they are widely distributed in both the nervous system and peripheral tissues, including endocrine organs such as the pituitary and adrenal glands. Merkel cells are neuroendocrine cells situated in the epidermis, tactile hairs and oral mucosa, and act as mechanoreceptors. Up to the present, various neuropeptides have been detected in these cells. The aim of the present study was to detect the presence of prepro‐orexin and orexin receptors (OX1R and OX2R) in porcine Merkel cells using immunohistochemistry. Prepro‐orexin was expressed in the cytoplasm of Merkel cells in the skin of the pig snout. Immunoreactivity for prepro‐orexin was more intense in the mature side of the cell, where the dense‐cored granules are accumulated. Epidermal nerve terminals associated with Merkel cells and dermal nerve fibres showed no immunostaining. Both orexin receptors (OX1R and OX2R) were also demonstrated in the cytoplasm of Merkel cells of pig snout skin. The finding of orexins and their receptors in Merkel cells suggests that they have an autocrine function. Further studies are needed to ascertain the significance of this function.
Neuroimaging of love: fMRI meta-analysis evidence toward new perspectives in sexual medicine.

INTRODUCTION Brain imaging is becoming a powerful tool in the study of human cerebral functions related to close personal relationships. Outside of subcortical structures traditionally thought to be involved in reward-related systems, a wide range of neuroimaging studies in relationship science indicate a prominent role for different cortical networks and cognitive factors. Thus, the field needs a better anatomical/network/whole-brain model to help translate scientific knowledge from lab bench to clinical models and ultimately to the patients suffering from disorders associated with love and couple relationships. AIM The aim of the present review is to provide a review across wide range of functional magnetic resonance imaging (fMRI) studies to critically identify the cortical networks associated with passionate love, and to compare and contrast it with other types of love (such as maternal love and unconditional love for persons with intellectual disabilities). METHODS Retrospective review of pertinent neuroimaging literature. MAIN OUTCOME MEASURES Review of published literature on fMRI studies of love illustrating brain regions associated with different forms of love. RESULTS Although all fMRI studies of love point to the subcortical dopaminergic reward-related brain systems (involving dopamine and oxytocin receptors) for motivating individuals in pair-bonding, the present meta-analysis newly demonstrated that different types of love involve distinct cerebral networks, including those for higher cognitive functions such as social cognition and bodily self-representation. CONCLUSIONS These metaresults provide the first stages of a global neuroanatomical model of cortical networks involved in emotions related to different aspects of love. Developing this model in future studies should be helpful for advancing clinical approaches helpful in sexual medicine and couple therapy.
Central Nervous System Vasculitis: Still More Questions than Answers

The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu’s disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu’s disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role.
Comparison of dopamine and norepinephrine in the treatment of shock.

BACKGROUND Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)
Evaluation of a Method for Finding Diffraction Points on Two Edges with Arbitrary Angle and Its Diffracted Fields

Estimation of the scattering of electromagnetic waves by buildings and other obstacles is very important for wireless communications in urban area. In our previous work, we have examined the diffracted fields by two horizontal edges with an arbitrary angle. In this paper, we consider the diffracted fields by two edges with an arbitrary angle which change in both horizontal and vertical directions. The numerical evaluation are carried out for two wedges and we compare the diffracted fields between parallel and arbitrary angle of edges. The results show that when the angle between two edges increases, relatively strong orthogonal polarized wave components appear, but the principal components are almost the same as the incident wave, and the effect of edge slant in vertical direction is smaller than horizontal one.
Regulation of protein stability by GSK3 mediated phosphorylation

Glycogen synthase kinase-3 (GSK3) plays important roles in numerous signaling pathways that regulate a variety of cellular processes including cell proliferation, differentiation, apoptosis and embryonic development. In the canonical Wnt signaling pathway, GSK3 phosphorylation mediates proteasomal targeting and degradation of β-catenin via the destruction complex. We recently reported a biochemical screen that discovered multiple additional protein substrates whose stability is regulated by Wnt signaling and/or GSK3 and these have important implications for Wnt/GSK3 regulation of different cellular processes.1 In this article, we also present a bio-informatics based screen for proteins whose stability may be controlled by GSK3 and β-Trcp, the SCF E3 ubiquitin ligase that is responsible for β-catenin degradation in the Wnt signaling pathway. Furthermore, we review various GSK3 regulated proteolysis substrates described in the literature. We propose that GSK3 phosphorylation dependent proteolysis is a widespread mechanism that the cell employs to regulate a variety of cell processes in response to signals.
NGF Is Essential for Hippocampal Plasticity and Learning

Nerve growth factor (NGF) is produced in the hippocampus throughout life and is retrogradely trafficked to septal cholinergic neurons, providing a potential mechanism for modulating cholinergic inputs and, thereby, hippocampal plasticity. To explore NGF modulation of hippocampal plasticity and function, NGF levels were augmented or blocked in intact adult rats, and subsequent in vivo effects on cholinergic neurons, hippocampal long-term potentiation (LTP), and learning were examined. NGF augmentation significantly enhanced cholinergic neuronal markers and facilitated induction of hippocampal LTP. Blockade of endogenous NGF significantly reduced hippocampal LTP and impaired retention of spatial memory. These findings reveal an essential role for NGF in regulating biological mechanisms related to plasticity and memory in the intact adult brain.
Agents for Integrating Distributed Data for Complex Computations

Algorithms for many complex computations assume that all the relevant data are available on a single node of a computer network. In the emerging distributed and networked knowledge environments, databases relevant for computations may reside on a number of nodes connected by a communication network. These data resources cannot be moved to other network sites due to privacy, security, and size considerations. The desired global computation must be decomposed into local computations to match the distribution of data across the network. The capability to decompose computations must be general enough to handle dierent distributions of data and dierent participating nodes in each instance of the global computation. In this paper, we present a methodology wherein each distributed data source is represented by an agent. Each such agent has the capability to decompose global computations into local parts, for itself and for agents at other sites. The global computation is then performed by the agent either exchanging some minimal summaries with other agents or travelling to all the sites and performing local tasks that can be done at each local site. The objective is to perform global tasks with a minimum of communication or travel by participating agents across the network.
Melanocyte Pygmentation – Friend or Foe on the Route to Melanoma

The epidermis forms the top protective covering of normal human skin and is itself composed of multiple layers from the stratum corneum at the top, to proliferating cells in the deep/basal layer (Liu & Fisher, 2010). The epidermal cell population is mainly constituted of two cell types: keratinocytes and melanocytes. Keratinocytes constitute the majority of the epidermis; they have a “supporting” and regulatory role for the melanocytes. Keratinocytes are linked through tight desmosomal intercellular junctions and also anchored into the basal membrane through hemidesmosomes, but melanocytes remain as singly scattered, unattached cells. Each single, well-differentiated, melanocyte interacts with 36 viable keratinocytes at various stages of progression to the upper cornified layer of the epidermis (Fitzpatrick & Breathnach, 1963) to form epidermal units. These structural and functional cellular units exhibit complex, life-long, cellular interactions originally laid down during embryonic life. There are considerable interindividual and intraindividual variations in melanocyte population densities, with more than twice as many melanocytes located in head and forearm skin compared with elsewhere on the body, as well as darker skin in the folded areas of axillae and perineum, traits that remain remarkably consistent between races (Szabo, 1967). Despite significant variation in skin pigmentation, the density of melanocytes at the epidermal-dermal junction is very similar across different skin types (Yamaguchi & Hearing, 2009). Thus the main contributor to racial differences in skin pigmentation is cellular activity rather than absolute melanocyte numbers (Szabo, 1967). Melanocytes play a central role in the response of skin to sunlight exposure. They are directly involved in UV-induced pigmentation as a defense mechanism. People with different skin color possess varied sensitivity to ultraviolet (UV) exposure, with darker skinned individuals being less susceptible to sun-induced skin alterations, including cancer, than fair skinned ones (Elwood & Diffey 1993). Such a difference can be explained in terms of protective UV filtering by epidermal pigmentation, because the skin color is also related to the type of melanin, the number, size, type, distribution and degradation of melanosomes, and the tyrosinase activity of melanocytes (Nordlund & Ortonne 1998, Yamaguchi & Hearing 2009). The decreased photocarcinogenesis seen in individuals with darker skin may also be attributed to the more efficient removal of UV-damaged cells (Yamaguchi & Hearing 2009, Alonso & Fuchs, 2003, Fuchs, 2008).
Plasmacytomagenesis in mice: model of neoplastic development dependent upon chromosomal translocations.

Three model systems of plasmacytomagenesis that are associated with mutations that affect c-myc transcription were discussed. Plasmacytoma induction by chronic peritoneal irritation induced by non-metabolized paraffin oils or plastic objects is strongly influenced by the immune status of the host. BALB/cAn mice must be exposed to natural environmental antigens to develop a high incidence of plasmacytomas. This may be related to T-cell priming. BALB/cAn mice raised under strict SPF conditions are refractory to plasmacytoma induction by pristane. The genotype of the mouse plays an important role in the chronic peritoneal irritation model of plasmacytomagenesis in mice. Only a few of the standard inbred strains are susceptible, notably BALB/cAn and NZB/B1. The genetic basis of susceptibility and resistance has been studied in crosses and congenic strains involving the susceptible BALB/cAn and resistant DBA/2 strains. While several genes play a role in determining resistance at least one resistance gene located on the distal end of Chr 4 reduces the incidence by at least 50% as determined in the BALB/cAn.DBA/2 Fv-1n/n congenic strain. The action of susceptibility and resistance genes is not known; hypothetically these genes could play a role in plasmacytomagenesis by increasing the probabilities of illegitimate exchanges between genes or by influencing the formation of mutations in genes that regulate mitotic cycling. Plasmacytomas appear to develop in the chronic inflammatory tissues induced by these agents. Fundamental unanswered questions are whether these inflammatory tissues provide products such as oxidants in vivo that damage DNA and promote mutagenesis. In the mouse there is a resident self-renewing B cell population that is CD5+. These B cells, which are known to be precursors of normal lamina propria IgA-secreting plasma cells, are directly in contact with the chronic inflammatory process induced by pristane; they may be targets in plasmacytomagenesis. The plasmacytomas that develop by the peritoneal mode of induction all have chromosomal translocations that directly or indirectly activate c-myc. The predominant MACTR found in 90% of these tumors is T(12;15) in which a heavy-chain switch region sequence is joined to the 5' region of c-myc. The evidence strongly suggests that the translocation develops in a late mature B cell that is in the process of isotype switching. An unanswered question is whether the switching associated T(12;15) takes place in a B cell that is exposed to the inflammatory microenvironment. (ABSTRACT TRUNCATED AT 400 WORDS)
Draft Genome Sequence of Lactobacillus paracasei DmW181, a Bacterium Isolated from Wild Drosophila

ABSTRACT The draft genome sequence of Lactobacillus paracasei DmW181, an anaerobic bacterium isolate from wild Drosophila flies, is reported here. Strain DmW181 possesses genes for sialic acid and mannose metabolism. The assembled genome is 3,201,429 bp, with 3,454 predicted genes.
Discrete exterior calculus for variational problems in computer vision and graphics

The paper demonstrates how discrete exterior calculus (DEC) tools may be useful in computer vision and graphics. A variational approach provides a link with mechanics. Our development of DEC includes discrete differential forms, discrete vector fields and the operators acting on these. This development of a discrete calculus, when combined with the methods of discrete mechanics and other recent work is likely to have promising applications in a field like computer vision which offers such a rich variety of challenging variational problems to be solved computationally. As a specific example we consider the problem of template matching and show how numerical methods derived from a discrete exterior calculus are starting to play an important role in solving the equations of averaged template matching. We also show some example applications using variational problems from computer graphics and mechanics to demonstrate that formulating the problem discretely and using discrete methods for solution can lead to efficient algorithms.
Grit-blasted titanium femoral stem in cementless primary total hip arthroplasty: a 5- to 10-year multicenter study.

A total of 133 cementless primary total hip arthroplasties using the Zweymuller-Alloclassic grit-blasted titanium tapered stem were performed in 3 institutions. The patient cohort was divided into 2 subgroups, nonselected and selected, on the basis of excellent bone stock and age (<65 years old at surgery). Acetabular components were all cementless, and bearing surfaces were all alumina-ceramic on polyethylene. After a 7.3-year average follow-up period (range, 5-10 years), 118 primary femoral replacements in 109 patients could be reviewed fully. Mean age at surgery was 55.7 years (range, 27-84 years). According to the Merle d'Aubigne and Charnley rating system, clinical results were graded excellent and good in 89% of hips and fair in 11%. Radiologically, early subsidence >2 mm could be detected in 4 hips (3.4%). Calcar atrophy and spot welds were noted in 77% and 82% of hips. Femoral osteolysis granuloma was noted in 4 hips (3.4%). There has been no stem fracture and no ceramic head breakage. The survivorship at 10 years with definite femoral aseptic loosening (radiographic failure) as the endpoint was 100% (95% Wilson confidence interval, 78.4%-100%; worst scenario, 95.4%). A significant difference between the nonselected and selected patient subgroups was observed only for early reoperation (P =.03) and proximal stress shielding (P =.01). Press-fitting but not filling the femoral canal with a rough titanium, straight, tapered femoral component represents, at intermediate follow-up, a promising cementless option in primary total hip arthroplasty.