gebhart/patrepeval huggingface dataset:
Studies on Lactoferricin-derived Escherichia coli Membrane-active Peptides Reveal Differences in the Mechanism of N-Acylated Versus Nonacylated Peptides (2011)

To improve the low antimicrobial activity of LF11, an 11-mer peptide derived from human lactoferricin, mutant sequences were designed based on the defined structure of LF11 in the lipidic environment. Thus, deletion of noncharged polar residues and strengthening of the hydrophobic N-terminal part upon adding a bulky hydrophobic amino acid or N-acylation resulted in enhanced antimicrobial activity against Escherichia coli, which correlated with the peptides' degree of perturbation of bacterial membrane mimics. Nonacylated and N-acylated peptides exhibited different effects at a molecular level. Nonacylated peptides induced segregation of peptide-enriched and peptide-poor lipid domains in negatively charged bilayers, although N-acylated peptides formed small heterogeneous domains resulting in a higher degree of packing defects. Additionally, only N-acylated peptides perturbed the lateral packing of neutral lipids and exhibited increased permeability of E. coli lipid vesicles. The latter did not correlate with the extent of improvement of the antimicrobial activity, which could be explained by the fact that elevated binding of N-acylated peptides to lipopolysaccharides of the outer membrane of gram-negative bacteria seems to counteract the elevated membrane permeabilization, reflected in the respective minimal inhibitory concentration for E. coli. The antimicrobial activity of the peptides correlated with an increase of membrane curvature stress and hence bilayer instability. Transmission electron microscopy revealed that only the N-acylated peptides induced tubular protrusions from the outer membrane, whereas all peptides caused detachment of the outer and inner membrane of E. coli bacteria. Viability tests demonstrated that these bacteria were dead before onset of visible cell lysis.
Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability (2009)

Accordingly, our study indicates there are functionally relevant polymorphisms in ABCB11 which may be of potential relevance in the predisposition to acquired liver disorders such as drug-induced cholestasis.
Hemolysis-associated priapism in sickle cell disease (2005)

Abstract Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. Hemolysis decreases the availability of circulating nitric oxide, which plays an important role in erectile function.
Radiation Effects on Aqueous Thiourea Solutions (1957)

Thiourea and elemental sulfur (1), as well as other compounds containing sulfur in labile organic and inorganic linkage, play an important part in radiation chemical reactions in vitro and in vivo (2-5), owing to their protective action against radiation effects. The protective power of a substance in aqueous solution means its ability to decrease or abolish the effect of radiation on another solute, and this depends on the relative probabilities with which the two substances eliminate radicals formed from the solvent (water) by radiation. Very low concentrations of solute decrease the probability of collision between solute and radicals and therefore favor the recombination of radicals. At higher concentrations of solute this competing recombination gradually becomes negligible; i.e., the radiation yield increases. For some substances a constant yield is reached; for others the yield continuously increases with concentration. This variation in concentration dependence is not yet fully understood, as pointed out in previous communications (6-9). A possible explanation is that with good protectors, i.e., good acceptors of radicals, the recombination of radicals will become more negligible at lower concentrations than with inefficient ones, leading to a constant number of molecules changed per 100 ev (G). Other factors, e.g., molecular weight and shape of molecules, in particular in proteins, may be additional causes. It was observed in preliminary experiments that the amounts of sulfur liberated by ionizing radiations from thiourea increased with concentration without reaching a constant value, although this substance is a good protector. Because of this apparent contradiction in the yield/concentration relationship, it seemed of interest to investigate the radiation chemistry of thiourea in greater detail. The results obtained exceeded the initial purpose of the investigation and revealed various interesting and unusual features in the radiation reaction. Since the preliminary experiments were carried out with the crude technique of weighing very small amounts of sulfur, a more quantitative procedure was adopted 35
Platelets: Testing, Dosing and the Storage Lesion—Recent Advances (2006)

The demand for platelet transfusions continues to grow. Several complementary approaches that may help meet this demand in the future are reviewed. First, platelet bacterial testing is beginning to allow the extension of platelet storage beyond 5 days. Studies are also underway aimed at better preserving viability and function during ex vivo platelet storage: additive solutions and other approaches are being developed to try to negate the "platelet storage lesion." Finally, new approaches to dosing platelets may help extend the limited supply.
Down Regulation of Gene Expression by the Vaccinia Virus D10 Protein (1999)

Vaccinia virus genes are expressed in a sequential fashion, suggesting a role for negative as well as positive regulatory mechanisms. A potential down regulator of gene expression was mapped by transfection assays to vaccinia virus open reading frame D10, which encodes a protein with no previously known function. Inhibition was independent of the promoter type used for the reporter gene, indicating that the mechanism did not involve promoter sequence recognition. The inhibition was overcome, however, when the open reading frame of the reporter gene was preceded by the encephalomyocarditis virus internal ribosome entry site, which excludes the possibility of nonspecific metabolic or other antiviral effects and suggests that capped mRNAs or cap-dependent translation might be the target of the D10 product. The inducible overexpression of the D10 gene by a recombinant vaccinia virus severely inhibited viral protein synthesis, decreased the steady-state level of viral late mRNA, and blocked the formation of infectious virus.
Integration of DNA into bacterial chromosomes from plasmids without a counter-selection marker (2012)

Most bacteria can only be transformed with circular plasmids, so robust DNA integration methods for these rely upon selection of single-crossover clones followed by counter-selection of double-crossover clones. To overcome the limited availability of heterologous counter-selection markers, here we explore novel DNA integration strategies that do not employ them, and instead exploit (i) activation or inactivation of genes leading to a selectable phenotype, and (ii) asymmetrical regions of homology to control the order of recombination events. We focus here on the industrial biofuel-producing bacterium Clostridium acetobutylicum, which previously lacked robust integration tools, but the approach we have developed is broadly applicable. Large sequences can be delivered in a series of steps, as we demonstrate by inserting the chromosome of phage lambda (minus a region apparently unstable in Escherichia coli in our cloning context) into the chromosome of C. acetobutylicum in three steps. This work should open the way to reliable integration of DNA including large synthetic constructs in diverse microorganisms.
Quantitative assessment of impedance tomography for temperature measurements in microwave hyperthermia (1988)

The objective of this study is a non-invasive assessment of the thermal dose in microwave hyperthermia. We intend to monitor the induced temperature rise via the change in the resistivity of body tissue, and hence control the microwave power during treatment. An initial feasibility study using electrical impedance tomography in vivo has indicated that a microwave induced temperature difference of a suitable magnitude can be mapped from a knowledge of the temperature coefficient of conductivity for tissue (typically 2% per degrees C). The accuracy of the currently employed reconstruction algorithm is assessed from data simulated by finite element prediction methods. A circular arrangement of electrodes surrounding a conductive sheet is used to evaluate the voltage distribution on the boundary of the sheet. A range of regions inside the circular field are chosen and the conductivity is changed uniformly by steps of 1% up to 10%. Images of these changes are produced. It is noticed that the algorithm underestimates the values of resistivity change for the small areas and overestimates the change for the larger areas. We are studying results for a variety of shapes of surface regions of the body that undergo resistivity change with microwave heating applied. Further work is necessary to account for three-dimensional current paths. Preliminary results are also presented of experimental investigations of the microwave-induced temperature rise in layers of carbon-loaded paper sheet.
Twist Relates to Tubular Epithelial-Mesenchymal Transition and Interstitial Fibrogenesis in the Obstructed Kidney (2007)

Epithelial-mesenchymal transition (EMT) is a critical step in renal fibrosis. It has been recently reported that a transcription factor, Twist, plays a pivotal role in metastasis of breast tumors by inducing EMT. In this study, we examined whether Twist relates to renal fibrogenesis including EMT of tubular epithelia, evaluating Twist expression level in the unilateral ureteral obstruction (UUO) model. Kidneys of mice subjected to UUO were harvested 1, 3, 7, and 10 days after obstruction. Compared with control kidneys, Twist mRNA-level significantly increased 3 days after UUO (UUO day 3 kidney) and further augmented until 10 days after UUO. Twist expression increased in tubular epithelia of the dilated tubules and the expanded interstitial areas of UUO kidneys, where cell-proliferating appearances were frequently found in a time-dependent manner. Although a part of tubular cells in whole nephron segment were immunopositive for Twist in UUO day 7 kidneys, tubular epithelia downstream of nephron more frequently expressed Twist than upstream of nephron. In UUO day 7 kidneys, some tubular epithelia were confirmed to coexpress Twist and fibroblast-specific protein-1, a marker for EMT, indicating that Twist is involved in tubular EMT under pathological state. Twist was expressed also in a number of alpha-smooth muscle actin-positive myofibroblasts located in the expanded interstitial area of UUO kidneys. From these findings, the present investigation suggests that Twist is associated with tubular EMT, proliferation of myofibroblasts, and subsequent renal fibrosis in obstructed kidneys.
RGD peptide‐conjugated poly(dimethylsiloxane) promotes adhesion, proliferation, and collagen secretion of human fibroblasts (2006)

A novel technique for conjugating Arg-Gly-Asp (RGD) peptides to poly(dimethylsiloxane) (PDMS) surfaces as well as its application to cell culture is presented in this paper. This technique performs RGD conjugation to PDMS through photochemical immobilization of functional NHS groups to PDMS surface followed with linking RGD peptide to the surface via coupling reaction with NHS. A bifunctional photolinker, N-sulfosuccinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate (sulfo-SANPAH), was used to conjugate RGD peptide to the surface. Compared to existing methods for peptide conjugation to PDMS, this technique is convenient, efficient, and free of organic contamination to PDMS surfaces. It can also be used to conjugate other peptides or proteins to most polymeric materials. In addition, cell culture studies showed that the RGD-conjugated PDMS surfaces promoted the adhesion, proliferation, and collagen production of human skin fibroblasts (HSFs). Finally, the RGD-conjugated PDMS surfaces are resistant to autoclaving and UV irradiation, which enables them to be repeatedly used in cell culture studies.
Increased cd1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis (1998)

Cluster of differentiation 1 (CD1) is a family of four distinct nonpolymorphic major histocompatibility complex class I-like molecules that can present microbial nonpeptide lipid antigens to T cells. Among the CD1 gene family, CD1d is found in a wide range of tissues including the intestine and liver, and has been proposed to play an important role in mucosal immunity. Primary biliary cirrhosis (PBC) is an immune-mediated liver disease involving the intrahepatic small bile ducts, which also belong to the mucosal immune system. In this study, we studied the expression of CD1d in patients with PBC and compared the data with those of patients with hepatic sarcoidosis, primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), and normal liver as controls. CD1d was found to be expressed in hepatocytes in all cases examined, and in epithelioid granuloma cells in 19 of 22 PBC livers and in 4 of 4 livers with hepatic sarcoidosis. In addition, CD1d was focally expressed on epithelial cells of the small bile ducts in approximately 50% of the PBC patients but in no controls. Such bile duct epithelial staining of CD1d was seen in early-stage PBC and virtually absent in late-stage PBC. Moreover, there was no evidence of expression of CD1d in large bile duct epithelial cells of PBC. The CD1d on biliary epithelial cells in PBC may be involved in the antigen presentation of microbial lipid antigen(s) to surrounding T cells. Alternatively, modified endogenous lipidic compounds may share analogy with bacterial lipid antigens and explain CD1d expression, a possible epiphenomenon rather than a proof of bacterial involvement.
The monoclonal antibody MAC387 detects an epitope on the calcium-binding protein MRP14 (1994)

The present study was initiated to identify the antigen recognized by the monoclonal antibody (MAb) MAC387 which is widely used for phenotypical characterization of myelomonocytic cells in situ. MAC387 has been described to show a similar reaction pattern as antisera to a complex formed by the calcium-binding proteins MRP8 and MRP14. However, the exact nature of the molecule recognized by MAC387 has been controversial. Using Western blot analysis, MAC387 was found to detect a single protein band of 14 kDa in lysates of human monocytes and granulocytes. Transfection of embryonic lung fibroblasts L132 with either MRP8 or MRP14 cDNA revealed that MAC387 reacts with MRP14 but not MRP8. This finding was confirmed by dot blot analysis of recombinant MRP8 and MRP14. Our data thus provide unequivocal evidence that MAC387 is a monoclonal antibody directed against the calcium-binding protein MRP14.
Syntheses of [1-15N]-2′-Deoxyinosine, [4-15N]-2′-DeoxyAICAR, and [1-15N]-2′-Deoxyguanosine (1999)

A high-yield synthesis of [1-15N]-2′-deoxyinosine (5), [4-15N]-2′-deoxyAICAR (7), and [1-15N]-2′-deoxyguanosine (10) from 2′-deoxyinosine (1) using relatively low expensive 15NH3 as 15N source is described. The method exploits 2-C reactivity of 2′-deoxyinosine (1) to obtain its 15N-labelled counterpart, through [1-15N]-2′-deoxyinosine (5), and successively, [4-15N]-2′-deoxyAICAR (7). [1-15N]-2′-Deoxyguanosine (10) can be prepared as well, through an improved cyclization procedure. No protection of sugar hydroxyl groups is required at any stage.
The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors. (1996)

An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cytosine deaminase 'suicide' gene under the control of tissue-specific tyrosinase gene promoter directly into the murine melanoma B16(F10) tumor. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine melanoma B16(F10) tumor growth and, in some cases, rejection of the pre-established tumor. The inhibition of tumor growth expressed as the increased survival of mice is better seen in the case of using DNA-DDAB/DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5-fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), increased transfection efficiency of surviving cancer cells (in this case DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.
Random synaptic feedback weights support error backpropagation for deep learning (2016)

The brain processes information through multiple layers of neurons. This deep architecture is representationally powerful, but complicates learning because it is difficult to identify the responsible neurons when a mistake is made. In machine learning, the backpropagation algorithm assigns blame by multiplying error signals with all the synaptic weights on each neuron's axon and further downstream. However, this involves a precise, symmetric backward connectivity pattern, which is thought to be impossible in the brain. Here we demonstrate that this strong architectural constraint is not required for effective error propagation. We present a surprisingly simple mechanism that assigns blame by multiplying errors by even random synaptic weights. This mechanism can transmit teaching signals across multiple layers of neurons and performs as effectively as backpropagation on a variety of tasks. Our results help reopen questions about how the brain could use error signals and dispel long-held assumptions about algorithmic constraints on learning.
Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication (2011)

Non-coding Y RNAs are required for the initiation of chromosomal DNA replication in mammalian cells. It is unknown how they perform this function or if they associate with a nuclear structure during DNA replication. Here, we investigate the association of Y RNAs with chromatin and their interaction with replication proteins during DNA replication in a human cell-free system. Our results show that fluorescently labelled Y RNAs associate with unreplicated euchromatin in late G1 phase cell nuclei before the initiation of DNA replication. Following initiation, Y RNAs are displaced locally from nascent and replicated DNA present in replication foci. In intact human cells, a substantial fraction of endogenous Y RNAs are associated with G1 phase nuclei, but not with G2 phase nuclei. Y RNAs interact and colocalise with the origin recognition complex (ORC), the pre-replication complex (pre-RC) protein Cdt1, and other proteins implicated in the initiation of DNA replication. These data support a molecular 'catch and release' mechanism for Y RNA function during the initiation of chromosomal DNA replication, which is consistent with Y RNAs acting as replication licensing factors.
IL-10 interrupts memory B cell expansion in the germinal center by inducing differentiation into plasma cells (1998)

Germinal center (GC) B cells undergo proliferation, somatic hypermutation and isotype switching in the course of differentiation into plasma cells to produce high-affinity antibodies. To understand the molecular mechanism regulating the expansion of memory B cells and the termination of expansion by differentiation into plasma cells, we investigated the effect of interleukin-2 (IL-2), IL-4, IL-10 and CD40 ligand (CD40L) on the differentiation of GC B cells in the defined culture system containing a follicular dendritic cell (FDC)-like cell line. IL-2, IL-4 and CD40L are required for the optimum proliferation and differentiation of GC B cells. When IL-10 was added to this culture condition, CD20+ CD38+ GC B cells sequentially differentiated into CD20+ CD38- memory B cells and then CD20- CD38+ plasma cells. In the absence of IL-10, the resulting CD20+ CD38- memory B cells continued to proliferate and retained its phenotype. The proliferation of memory B cells was interrupted by addition of IL-10 which induced the differentiation into plasma cells. The expression of CD80 and CD86 was up-regulated in the memory B cells, compared to naive B cells and plasma cells. The identity of memory B cells generated in vitro from GC B cells was further substantiated since memory B cells generated in vivo displayed the identical pattern of proliferation and differentiation under the same culture condition. These results highlight the potent role of GCT helper cells in the expansion and differentiation of memory B cells by regulating different cytokine production.
Metabolic engineering of microorganisms for isoprenoid production (2008)

Isoprenoids are ubiquitous in nature and range from essential cell components to unique secondary metabolites. The two isoprenoid biosynthetic pathways have received much attention from a metabolic engineering standpoint, and significant advances have been made in increasing flux through these pathways. Engineering later steps in isoprenoid biosynthetic pathways, specifically those related to the functionalization of terpene backbones, is at an earlier stage of development, both in terms of gene discovery and heterologous expression. Here we review recent advances in the metabolic engineering of microbes for isoprenoid production as well as some novel approaches to gene discovery and expression.