gebhart/patrepeval huggingface dataset:
The endocytic receptor protein LRP also mediates neuronal calcium signaling via N -methyl- d -aspartate receptors (2000)

The low density lipoprotein receptor-related protein (LRP) is an endocytic receptor that is a member of the low density lipoprotein receptor family. We report that the LRP ligand, activated alpha(2)-macroglobulin (alpha(2)M*), induces robust calcium influx in cultured primary neurons, but not in nonneuronal LRP-containing cells in the same culture. The calcium influx is mediated through N-methyl-d-aspartate receptor channels, which explains the neuron specificity of the response. Microapplication of alpha(2)M* leads to a localized response at the site of application that dissipates rapidly, suggesting that the calcium signal is temporally and spatially discrete. Calcium influx to alpha(2)M* is blocked by the physiological LRP inhibitor, receptor-associated protein. Bivalent antibodies to the extracellular domain of LRP, but not Fab fragments of the same antibody, cause calcium influx, indicating that the response is specific to LRP and may require dimerization of the receptor. Thus, LRP is an endocytic receptor with a novel signaling role.
Imidazole‐Quartet Water and Proton Dipolar Channels (2011)

Dipolar water wires stabilize quartets of ureido imidazole compounds (I-quartets) in a manner reminiscent of stabilization of guanine (G) quartets by cation templating (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Enlarging the Amino Acid Set of Escherichia coli by Infiltration of the Valine Coding Pathway (2001)

Aminoacyl transfer RNA (tRNA) synthetases establish the rules of the genetic code by catalyzing the aminoacylation of tRNAs. For some synthetases, accuracy depends critically on an editing function at a site distinct from the aminoacylation site. Mutants of Escherichia coli that incorrectly charge tRNA(Val) with cysteine were selected after random mutagenesis of the whole chromosome. All mutations obtained were located in the editing site of valyl-tRNA synthetase. More than 20% of the valine in cellular proteins from such an editing mutant organism could be replaced with the noncanonical aminobutyrate, sterically similar to cysteine. Thus, the editing function may have played a central role in restricting the genetic code to 20 amino acids. Disabling this editing function offers a powerful approach for diversifying the chemical composition of proteins and for emulating evolutionary stages of ambiguous translation.
Fully Printed Flexible Fingerprint-like Three-Axis Tactile and Slip Force and Temperature Sensors for Artificial Skin (2014)

A three-axis tactile force sensor that determines the touch and slip/friction force may advance artificial skin and robotic applications by fully imitating human skin. The ability to detect slip/friction and tactile forces simultaneously allows unknown objects to be held in robotic applications. However, the functionalities of flexible devices have been limited to a tactile force in one direction due to difficulties fabricating devices on flexible substrates. Here we demonstrate a fully printed fingerprint-like three-axis tactile force and temperature sensor for artificial skin applications. To achieve economic macroscale devices, these sensors are fabricated and integrated using only printing methods. Strain engineering enables the strain distribution to be detected upon applying a slip/friction force. By reading the strain difference at four integrated force sensors for a pixel, both the tactile and slip/friction forces can be analyzed simultaneously. As a proof of concept, the high sensitivity and selectivity for both force and temperature are demonstrated using a 3×3 array artificial skin that senses tactile, slip/friction, and temperature. Multifunctional sensing components for a flexible device are important advances for both practical applications and basic research in flexible electronics.
Controlling Mammalian Cell Interactions on Patterned Polyelectrolyte Multilayer Surfaces (2004)

A newly discovered class of cell resistant surfaces, specifically engineered polyelectrolyte multilayers, was patterned with varying densities of adhesion ligands to control attachment of mammalian cells and to study the effects of ligand density on cell activity. Cell adhesive patterns were created on cell resistant multilayer films composed of poly(acrylic acid) and polyacrylamide through polymer-on-polymer stamping of poly(allylamine hydrochloride) PAH and subsequent reaction of the amine functional groups with an adhesion ligand containing RGD (Arg-Gly-Asp). These cell patterns demonstrated great promise for long-term applications since they remained stable for over 1 month, unlike ethylene glycol functional surfaces. By changing the stamping conditions of PAH, it was possible to alter the number of available functional groups in the patterned regions, and as a result, control the ligand density. Cell spreading, morphology, and cytoskeletal organization were compared at four different RGD densities. The highest RGD density, approximately 152 000 molecules/microm2, was created by stamping PAH at a pH of 11.0. Lowering the stamping ink pH led to patterns with lower ligand surface densities (83 000 molecules/microm2 for pH 9.0, 53,000 molecules/ microm2 for pH 7.0, and 25 000 molecules/microm2 for pH 3.5). An increasing number of cells attached and spread as the RGD density of the patterns increased. In addition, more cells showed well-defined actin stress fibers and focal adhesions at higher levels of RGD density. Finally, we found that pattern geometry affected cytoskeletal protein organization. Well-formed focal adhesions and cell-spanning stress fibers were only found in cells on wider line patterns (at least 25 microm in width).
Cardiac disease and Rett syndrome (2006)

Rett syndrome (RS) is a neurodevelopmental disease,1 affecting approximately 1 in 10 000-15 000 females. Clinical severity of RS may vary with increasing age, following a four stage model.
Submerged Cultures in Australia (1988)

The gradual suppression of different cultures such as those of the Irish, Celts, Scots and other races in Australia, on their migration from Europe to Australia is discussed. Australia is described as a nation of submerged cultures, where a secular culture and way of life have been established over the years.
Expression of the yes proto-oncogene in cerebellar Purkinje cells. (1989)

To identify the kinds of cells in the brain that express the yes proto-oncogene, we examined chicken brains by using immunofluorescent staining and in situ hybridization. Both approaches showed that the highest level of the yes gene product was in cerebellar Purkinje cells. In addition, we analyzed Purkinje cell degeneration (pcd) mutant mice. The level of yes mRNA in cerebella of pcd mutants was four times lower than that found in cerebella of normal littermates. Our studies point to Purkinje cells as an attractive model for functional studies of the yes protein.
Effects of 830-nm Laser, Used in Two Doses, on Biomechanical Properties of Osteopenic Rat Femora (2006)

The results of the present study indicate that photoradiation had stimulatory effects on femora of osteopenic rats, mainly at the dose of 120 J/cm.(2) However, further studies are needed to investigate the effects of different parameters, wavelengths, and sessions of applications on ovariectomized rats.
IgG-Fc receptors and the clinical relevance of their polymorphisms. (2001)

Receptors for the Fc part of IgG form the bridge between immune complexes, antibodies and blood cells. Besides phagocytes, such as granulocytes and monocytes, also lymphocytes and platelets express members of the large family of IgG-Fc receptors or Fc gamma Rs. Three main classes of leukocyte Fc gamma Rs can be distinguished: Fc gamma RI, Fc gamma RII and Fc gamma RIII. Depending on the type of intracellular domain of the leukocyte Fc gamma Rs, interaction of a cell with an antibody-sensitized particle will induce either an activating signal (leading to phagocytosis, degranulation or toxic oxygen formation) or, in case of Fc gamma RIIb, an inhibiting signal. The inhibiting role of Fc gamma RIIb has long been thought to be only important for B-cell responses, however, recently it has been indicated that Fc gamma RIIb may have a much broader role in immune response, also regulating responses of phagocytes. In general, leukocyte Fc gamma Rs have high affinity for IgG1 and IgG3 subclasses. However, the affinity for the various IgG subclasses is influenced by receptor polymorphisms encoded by single nucleotide polymorphisms of the Fc gamma RIIa and Fc gamma RIIIa and Fc gamma RIIIb encoding genes. Because these subtle Fc gamma R changes determine the level of clearance of immune complexes, associations between Fc gamma R isoforms and disease risks have been investigated and also indicated as discussed in this review. Next to the leukocyte Fc gamma Rs, an IgG transport receptor, FcRn (neonatal Fc receptor) has been described. This receptor seems to be important for placental IgG transport and for IgG plasma level homeostasis. FcRn is expressed by endothelial cells and hepatocytes and functions in these cells as a receptor rescuing IgG from destruction, thereby increasing IgG half life. Also blood cells express FcRn and the exact role of FcRn in these cells is still to determined. Thus, although a lot is known, questions on the exact pattern of expression of the IgG receptors and their role in immune response still remain.
X-ray Photoelectron Spectroscopy Sulfur 2p Study of Organic Thiol and Disulfide Binding Interactions with Gold Surfaces (1996)

The presence of two sulfur species was detected in X-ray photoelectron spectroscopy (XPS) studies of thiol and disulfide molecules adsorbed onto gold surfaces. These species are assigned to bound thiolate (S2p3/2 binding energy of 162 eV) and unbound thiol/disulfide (S2p3/2 binding energy from 163.5 to 164 eV). These assignments are consistent with XPS data obtained from different thiols (C12, C16, C18, and C22 alkane thiols, a fluorinated thiol, and a cyclic polysiloxane thiol) and different adsorption conditions (solvent type, thiol concentration, temperature, and rinsing). In particular, the use of a poor solvent for thiol adsorption solutions (e.g., ethanol for long chain alkanethiols) and the lack of a rinsing step both resulted in unbound thiol molecules present at the surface of the bound thiolate monolayer. This has implications for recent studies asserting the presence of multiple binding sites for gold−thiolate species in organic monolayers.
Discovery and Mechanistic Study of a Small Molecule Inhibitor for Motor Protein KIFC1 (2013)

Centrosome amplification is observed in many human cancers and has been proposed to be a driver of both genetic instability and tumorigenesis. Cancer cells have evolved mechanisms to bundle multiple centrosomes into two spindle poles to avoid multipolar mitosis that can lead to chromosomal segregation defects and eventually cell death. KIFC1, a kinesin-14 family protein, plays an essential role in centrosomal bundling in cancer cells, but its function is not required for normal diploid cell division, suggesting that KIFC1 is an attractive therapeutic target for human cancers. To this end, we have identified the first reported small molecule inhibitor AZ82 for KIFC1. AZ82 bound specifically to the KIFC1/microtubule (MT) binary complex and inhibited the MT-stimulated KIFC1 enzymatic activity in an ATP-competitive and MT-noncompetitive manner with a Ki of 0.043 μM. AZ82 effectively engaged with the minus end-directed KIFC1 motor inside cells to reverse the monopolar spindle phenotype induced by the inhibition of the plus end-directed kinesin Eg5. Treatment with AZ82 caused centrosome declustering in BT-549 breast cancer cells with amplified centrosomes. Consistent with genetic studies, our data confirmed that KIFC1 inhibition by a small molecule holds promise for targeting cancer cells with amplified centrosomes and provided evidence that functional suppression of KIFC1 by inhibiting its enzymatic activity could be an effective means for developing cancer therapeutics.
Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography (2002)

We demonstrate that tissue structure, birefringence, and blood flow can be imaged simultaneously by use of techniques of polarization-sensitive optical coherence tomography and phase-resolved optical Doppler tomography. An efficient data-acquisition procedure is implemented that optimizes the concurrent processing and display of all three image types. Images of in vivo human skin acquired with a high-speed fiber-based system are presented.
Hybrid PGS-PCL microfibrous scaffolds with improved mechanical and biological properties (2010)

Poly(glycerol sebacate) (PGS) is a biodegradable elastomer that has generated great interest as a scaffold material due to its desirable mechanical properties. However, the use of PGS in tissue engineering is limited by difficulties in casting micro- and nanofibrous structures, due to high temperatures and vacuum required for its curing and limited solubility of the cured polymer. In this paper, we developed microfibrous scaffolds made from blends of PGS and poly(ε-caprolactone) (PCL) using a standard electrospinning set-up. At a given PGS:PCL ratio, higher voltage resulted in significantly smaller fibre diameters (reduced from ∼4 µm to 2.8 µm; p < 0.05). Further increase in voltage resulted in the fusion of fibres. Similarly, higher PGS concentrations in the polymer blend resulted in significantly increased fibre diameter (p < 0.01). We further compared the mechanical properties of electrospun PGS:PCL scaffolds with those made from PCL. Scaffolds with higher PGS concentrations showed higher elastic modulus (EM), ultimate tensile strength (UTS) and ultimate elongation (UE) (p < 0.01) without the need for thermal curing or photocrosslinking. Biological evaluation of these scaffolds showed significantly improved HUVEC attachment and proliferation compared to PCL-only scaffolds (p < 0.05). Thus, we have demonstrated that simple blends of PGS prepolymer with PCL can be used to fabricate microfibrous scaffolds with mechanical properties in the range of a human aortic valve leaflet.
ompT encodes the Escherichia coli outer membrane protease that cleaves T7 RNA polymerase during purification (1988)

Bacteriophage T7 RNA polymerase is stable in Escherichia coli but very susceptible to cleavage by at least one endoprotease after cell lysis. The major source of this endoprotease activity was found to be localized to the outer membrane of the cell. A rapid whole-cell assay was developed to screen different strains for the presence of this proteolytic activity. Using this assay, we identified some common laboratory strains that totally lack the protease. Genetic and Southern analyses of these null strains allowed us to conclude that the protease that cleaves T7 RNA polymerase is OmpT (formerly termed protein a), a known outer membrane endoprotease, and that the null phenotype results from deletion of the OmpT structural gene. A recombinant plasmid carrying the ompT gene enables these deletion strains to synthesize OmpT and converts them to a protease-positive phenotype. The plasmid led to overproduction of OmpT protein and protease activity in the E. coli K-12 and B strains we used, but only weak expression in the E. coli C strain, C1757. This strain-dependent difference in ompT expression was investigated with respect to the known influence of envZ on OmpT synthesis. A small deletion in the ompT region of the plasmid greatly diminishes the amount of OmpT protein and plasmid-encoded protease present in outer membranes. Use of ompT deletion strains for production of T7 RNA polymerase from the cloned gene has made purification of intact T7 RNA polymerase routine. Such strains may be useful for purification of other proteins expressed in E. coli.
Inhibitory effect of blocking TGF-beta/Smad signal on injury-induced fibrosis of corneal endothelium. (2008)

Inhibition of Smad and JNK signals do not affect corneal endothelium defect repair. Inhibition of Smad suppresses fibrogenic reaction via EnMT of corneal endothelium in vivo.
Cytokine Receptors and Signal Transduction (1992)

Cytokinesp lay a vital role in coordinating immune and inflammatory responses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrinsic tyrosine kinase activity. Based on their structure, cytokinere ceptors are classified into several groups. High affinity receptors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distinct subunits, α and β. The α subunits are primary cytokine binding proteins, and the β subunits are required for formation of high affinity binding sites as well as for signal transduction. The GM-CSF, IL-3, and IL-5 receptors appear to share the same β subunit in human, and therefore cross-talk among these cytokines may occur at the receptor level. High affinity receptors presumably are linked to various signal transduction pathways that lead to different cytokine functions. Differential expression of the cytokine receptors as well as reorganization of intracellular signalling pathways are critical for development of hemopoietic cells.
Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats (1997)

Following spinal cord contusion in the rat, apoptosis has been observed in the white matter for long distances remote from the center of the lesion and is primarily associated with degenerating fiber tracts. We have previously reported that many of the apoptotic cells are oligodendrocytes. Here we show that the oligodendrocyte death is maximal at 8 days postinjury and suggest that loss of oligodendrocytes may result in demyelination of axons that have survived the initial trauma. There are two mechanisms that may account for the observed oligodendrocyte apoptosis. The apoptotic cell death may result from the loss of trophic support after axonal degeneration or it may be the consequence of microglial activation. The hypothesis that oligodendrocyte apoptosis is secondary to microglial activation is supported by our observations of microglia with an activated morphology in the same regions as apoptosis and apparent contact between some of the apoptotic oligodendrocytes and microglial processes. In addition to oligodendrocyte apoptosis, a subpopulation of microglia appears to be susceptible to apoptotic cell death as well, as evidenced by the presence of apoptotic bodies in OX42 immunopositive profiles. Thus, the population of apoptotic cells following spinal cord contusion is comprised of oligodendrocytes and putative phagocytic microglia or macrophages. Given the delayed time course of oligodendrocyte death, the apoptotic death of oligodendrocytes may be amenable to pharmacological intervention with subsequent improvement in functional recovery.
Heat Shock Protein-Mediated Cross-Presentation of Exogenous HIV Antigen on HLA Class I and Class II (2004)

Strong CD4(+) and CD8(+) T cell responses are considered important immune components for controlling HIV infection, and their priming may be central to an effective HIV vaccine. We describe in this study an approach by which multiple CD4(+) and CD8(+) T cell epitopes are processed and presented from an exogenously added HIV-1 Gag-p24 peptide of 32 aa complexed to heat shock protein (HSP) gp96. CD8(+) T cell recognition of the HSP/peptide complex, but not the peptide alone, was inhibited by brefeldin A, suggesting an endoplasmic reticulum-dependent pathway. This is the first report to describe efficient processing and simultaneous presentation of overlapping class I- and class II-restricted epitopes from the same extracellularly added precursor peptide complexed to HSP. Given previous reports of the strong immunogenicity of HSP/peptide complexes, the present data suggest that HSP-complexed peptides containing multiple MHC class I- and class II-restricted epitopes represent potential vaccine candidates for HIV and other viral infections suitable to induce effective CTL memory by simultaneously providing CD4 T cell help.
Serotonin Reuptake Inhibitors: The Corner Stone in Treatment of Depression for Half a Century – A Medicinal Chemistry Survey (2006)

Inhibition of serotonin (5-HT) reuptake has been a central theme in the therapy of depression for half a century. Through the years these therapies have improved, particularly with regard to side effects, and today's selective serotonin reuptake inhibitors (SSRIs) constitute a reasonably effective offer for the patients. However, there is still room for major improvement and considering that almost 20% of the population in the western world will experience a depressive period in their lifetime, there is a large need for improved therapies. A large spectrum of targets and strategies are currently being pursued, but so far none of these new approaches have been successful, mainly due to lack of a deeper understanding of the disease biology. Since inhibition of 5-HT reuptake ensures a certain degree of antidepressant efficacy, there has been a large interest in various combinations with serotonin reuptake inhibitors (SRIs) in order to improve on the shortcomings of treatment with SSRIs. Some of these approaches have resulted in marketed antidepressants, eg combinations of SRI with norepinephrine (NE) reuptake inhibition, whereas other approaches are still at an experimental stage. This review attempts to present the current status of these add-on/combination approaches with particular focus on the medicinal chemistry aspects.
Physiology of Local Renin-Angiotensin Systems (2006)

Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the system is characterized by an increased complexity, as evidenced by the discovery of new functional components and pathways of the RAS. In recent years, the pathophysiological implications of the system have been the main focus of attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin (ANG) II receptor blockers have become important clinical tools in the treatment of cardiovascular and renal diseases such as hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue RAS also plays an important role in mediating diverse physiological functions. These focus not only on the classical actions of ANG on the cardiovascular system, namely, the maintenance of cardiovascular homeostasis, but also on other functions. Recently, the research efforts studying these noncardiovascular effects of the RAS have intensified, and a large body of data are now available to support the existence of numerous organ-based RAS exerting diverse physiological effects. ANG II has direct effects at the cellular level and can influence, for example, cell growth and differentiation, but also may play a role as a mediator of apoptosis. These universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli. Transgenic overexpression and knock-out strategies of RAS genes in animals have also shown a central functional role of the RAS in prenatal development. Taken together, these findings may become increasingly important in the study of organ physiology but also for a fresh look at the implications of these findings for organ pathophysiology.