gebhart/patrepeval huggingface dataset:
Chemical and biological properties of a growth factor from human‐cultured osteosarcoma cells: Resemblance with platelet‐derived growth factor (1980)

A human osteosarcoma cell line, U-2 OS, cultured under serum-free conditions, was shown to produce a growth factor (osteosarcoma-derived growth factor, ODGF) for human-cultured glial cells, fibroblasts, and other cells. ODGF, collected from the spent medium of 2 OS cultures, was purified by a sequence involving heparin-Sepharose chromatography, hydrophobic chromatography, gel chromatography, and preparative gel electrophresis in SDS. Purified ODGF, at a concentration of 3 ng/ml, elicited a mitogenic response in human glial cells equivalent to 50% of that afforded by human serum at a final concentration of 1%. The preparation was estimated to be > 50% pure. The biological activity of ODGF resided in a cationic, relatively heat-resistant, reduction-susceptible protein with a molecular weight of 30,000 (by gel chromatography and SDS-gel electrophoresis). The electrophoretic behaviour of radioiodinated ODGF suggested that the protein was composed of two different polypeptide chains (about 13,000-14,00 and 16,000-17,000 daltons, respectively) linked via disulphide bonds. The molecular makeup of ODGF was thus similar to that of platelet-derived growth factor. 125I-ODGF could be precipitated by an antibody to platelet-derived growth factor, indicating that the two factors were immunologically related. Resemblance with platelet-derived growth factor was also indicated by the finding that the latter (but not, e.g., fibroblast growth factor or epidermal growth factor) competed with 125I-ODGF for binding to human-cultured glial cells.
Identification of Domains in IL-16 Critical for Biological Activity (1999)

IL-16 is a proinflammatory cytokine implicated in the pathogenesis of asthma and other conditions characterized by recruitment of CD4+ T cells to sites of disease. It is postulated that CD4 is an IL-16 receptor, although other receptors or coreceptors may exist. Among several known functions, IL-16 is a chemoattractant factor for CD4+ T cells and it inhibits MLR. We previously reported that an oligopeptide corresponding to the 16 C-terminal residues of human IL-16 inhibits chemoattractant activity. To identify functional domains with greater precision, shorter oligonucleotides containing native or mutated C-terminal IL-16 sequences were tested for IL-16 inhibition. Within the 16 C-terminal residues, the minimal peptide RRKS (corresponding to Arg106 to Ser109) was shown to mediate inhibition of IL-16 chemoattractant activity. Inhibition was lost when either arginine was substituted with alanine. Point mutations in IL-16 revealed that Arg107 is critical for chemoattractant activity, but MLR inhibition was unaffected by mutation of Arg107 or even deletion of the C-terminal tail through Arg106. Deletion of 12 or 22 N-terminal residues of IL-16 had no impact on chemoattractant activity, but MLR inhibition was reduced. Deletion of 16 C-terminal plus 12 N-terminal residues abolished both chemoattractant and MLR-inhibitory activity of IL-16. These data indicate that receptor interactions with IL-16 that activate T cell migration are not identical with those required for MLR inhibition, and suggest that both N-terminal and C-terminal domains in IL-16 participate in receptor binding or activation.
Pro-tumorigenic Effects of miR-31 Loss in Mesothelioma (2010)

The human genome encodes several hundred microRNA (miRNA) genes that produce small (21-23n) single strand regulatory RNA molecules. Although abnormal expression of miRNAs has been linked to cancer progression, the mechanisms of this dysregulation are poorly understood. Malignant mesothelioma (MM) of pleura is an aggressive and highly lethal cancer resistant to conventional therapies. We and others previously linked loss of the 9p21.3 chromosome in MM with short time to tumor recurrence. In this study, we report that MM cell lines derived from patients with more aggressive disease fail to express miR-31, a microRNA recently linked with suppression of breast cancer metastases. We further demonstrate that this loss is due to homozygous deletion of the miR-31-encoding gene that resides in 9p21.3. Functional assessment of miR-31 activity revealed its ability to inhibit proliferation, migration, invasion, and clonogenicity of MM cells. Re-introduction of miR-31 suppressed the cell cycle and inhibited expression of multiple factors involved in cooperative maintenance of DNA replication and cell cycle progression, including pro-survival phosphatase PPP6C, which was previously associated with chemotherapy and radiation therapy resistance, and maintenance of chromosomal stability. PPP6C, whose mRNA is distinguished with three miR-31-binding sites in its 3'-untranslated region, was consistently down-regulated by miR-31 introduction and up-regulated in clinical MM specimens as compared with matched normal tissues. Taken together, our data suggest that tumor-suppressive propensity of miR-31 can be used for development of new therapies against mesothelioma and other cancers that show loss of the 9p21.3 chromosome.
Antibacterial and Antifungal Properties of Essential Oils (2003)

In recent years there has been an increasing interest in the use of natural substances, and some questions concerning the safety of synthetic compounds have encouraged more detailed studies of plant resources. Essential oils, odorous and volatile products of plant secondary metabolism, have a wide application in folk medicine, food flavouring and preservation as well as in fragrance industries. The antimicrobial properties of essential oils have been known for many centuries. In recent years (1987-2001), a large number of essential oils and their constituents have been investigated for their antimicrobial properties against some bacteria and fungi in more than 500 reports. This paper reviews the classical methods commonly used for the evaluation of essential oils antibacterial and antifungal activities. The agar diffusion method (paper disc and well) and the dilution method (agar and liquid broth) as well as turbidimetric and impedimetric monitoring of microorganism growth in the presence of tested essential oils are described. Factors influencing the in vitro antimicrobial activity of essential oils and the mechanisms of essential oils action on microorganisms are reported. This paper gives an overview on the susceptibility of human and food-borne bacteria and fungi towards different essential oils and their constituents. Essential oils of spices and herbs (thyme, origanum, mint, cinnamon, salvia and clove) were found to possess the strongest antimicrobial properties among many tested. Keywords: essential oils, monoterpenes, antibacterial activity, antifungal activity, dilution method
Identity certified authentication for ad-hoc networks (2003)

Ad-hoc networks face huge security lacks. In the most general case entities need to build up a well-defined security association without any pre-established secret or common security infrastructure. In previous work we presented a protocol which provides a weak form of authentication that we call zero common-knowledge (ZCK) authentication. The protocol is extremely efficient and only requires symmetric primitives but does not provide identification. In this work we extend this approach in such a way that our new protocol provides identification at the cost of external infrastructure and moderate computing power. Our new protocol can be used to authenticate messages, e.g., to exchange keys for the earlier ZCK authentication protocol. Compared to public-key schemes, our approach is still very efficient.
Auxin-induced changes in the patterns of protein synthesis in soybean hypocotyl (1980)

The patterns of protein synthesis in elongating and mature (basal) sections of soybean hypocotyl were examined after incubation in a medium containing auxin (auxin-treated) or a medium lacking auxin (untreated). The hypocotyl sections (1.2 cm) were labeled with [(35)S]methionine, and polypeptide patterns were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis. Auxin treatment altered the pattern of protein synthesis in both elongating and basal soybean hypocotyl sections. Excision of terminal segments from incubated sections was required to clearly observe auxin-induced changes in the synthesis of polypeptides. Polypeptides synthesized in terminal segments, possibly in response to wounding, can mask subtle changes in the spectrum of polypeptides synthesized in response to auxin. Cytokinin treatment caused a decrease in [(35)S]methionine incorporation into polypeptides and altered the pattern of protein synthesis in untreated and auxin-treated elongating hypocotyl sections.
Dysregulation of the Endocannabinoid System in Obesity (2008)

An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB(1) inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB(1) blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation.
[Protective effect of extract of Apocynum venetum on kidneys of streptozotocin-induced diabetic rats]. (2010)

The aim of this study is to investigate the effects and mechanism of extract of Apocynum venetum (AV) on kidneys of streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in rats by intraperitoneal injection of streptozotocin (STZ). The indexes of the blood glucose, renal function and oxidative stress were observed. The DM rats were administrated with the AV for 8 weeks, the above-mentioned indexes were detected. The blood glucose level, BUN, 24 h urine protein excretion, urine volume, renal index, renal cortex's MDA level in model groups all increased significantly. Renal cortex's SOD and GSH activities decreased significantly compared with the normal control group (P < 0.05). The above-mentioned indexes were significantly improved by the AV treatment (P < 0.05). AV have protective effects on renal function of kidneys of streptozotocin-induced diabetic rats, and maybe via inhibition of the renal oxidative stress.
DNA binding properties of two Arabidopsis MADS domain proteins: binding consensus and dimer formation. (1996)

MADS domain proteins are members of a highly conserved family found in all eukaryotes. Genetic studies clearly indicate that many plant MADS domain proteins have different regulatory functions in flower development, yet they share a highly conserved DNA binding domain and can bind to very similar sequences. How, then, can these MADS box genes confer their specific functions? Here, we describe results from DNA binding studies of AGL1 and AGL2 (for AGAMOUS-like), two Arabidopsis MADS domain proteins that are preferentially expressed in flowers. We demonstrate that both proteins are sequence-specific DNA binding proteins and show that each binding consensus has distinct features, suggestion a mechanism for specificity. In addition, we show that the proteins with more similar amino acid sequences have more similar binding sequences. We also found that AGL2 binds to DNA in vitro as a dimer and determined the region of AGL2 that is sufficient for DNA binding and dimerization. Finally, we show that several plant MADS domain proteins can bind to DNA either as homodimers or as heterodimers, suggesting that the number of different regulators could be much greater than the number of MADS box genes.
Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients (2008)

A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
Induction of Auto-reactive Regulatory T Cells by Stimulation with Immature Autologous Dendritic Cells (2007)

We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAb and TAp with similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL-4, IL-10, Foxp3, and differentially expressed TGFbeta. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were approximately two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAb and TAp were not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBL response to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact.
Nonproteinogenic α-Amino Acid Preparation Using Equilibrium Shifted Transamination (2002)

Microbial α-transaminases such as tyrosine aminotransferase (TAT) and branched chain aminotransferase (BCAT) of Escherichia coli, are useful as industrial biocatalysts to prepare nonproteinogenic l-amino acids from α-keto acids and an amino donor. However, they typically yield only 50% product when l-glutamic acid, the preferred amino donor, is used due to accumulated 2-ketoglutaric acid. Accordingly, methods have been sought to increase the reaction yield by the recycle or removal of the keto acid by-product. In this report, we have investigated the biocatalytic coupling of δ-transamination with α-transamination to recycle 2-ketoglutaric acid, and thereby increase the yield of aminotransferase reaction products. Ornithine δ-aminotransferase (OAT) catalyses the reversible transfer of the δ-amino group of l-ornithine to 2-ketoglutaric acid forming l-glutamic acid semialdehyde and l-glutamic acid. The cyclisation of l-glutamic acid semialdehyde to form Δ1-pyrroline-5-carboxylate under physiological conditions, favours the reaction in the direction of l-glutamic acid formation. The Bacillus subtilis rocD gene encoding OAT was cloned and produced at high levels in E. coli. Combined cell extracts of separate E. coli strains overproducing OAT and E. coli tyrosine aminotransferase enabled the synthesis of l-2-aminobutyrate from 2-ketobutyric acid to reach a yield of 92% compared to 50% achievable by TAT alone. Similarly, combined extracts of strains overproducing OAT and E. coli branched-chain amino acid aminotransferase synthesised l-tert-leucine from trimethylpyruvic acid with a 73% yield compared to 31% with BCAT alone. The use of OAT as a general biocatalytic tool to achieve high yields in aminotransferase reactions is discussed.
A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers (2013)

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing.
CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain (2011)

In light of the adverse side-effects of opioids, cannabinoid receptor agonists may provide an effective alternative for the treatment of cancer pain. This study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain. Intraplantar injection of the CB1 receptor agonist arachidonylcyclopropylamide (ED(50) of 18.4 μg) reduced tumor-related mechanical hyperalgesia by activation of peripheral CB1 but not CB2 receptors. Similar injection of the CB2 receptor agonist AM1241 (ED50 of 19.5 μg) reduced mechanical hyperalgesia by activation of peripheral CB2 but not CB1 receptors. Both agonists had an efficacy comparable with that of morphine (intraplantar), but their analgesic effects were independent of opioid receptors. Isobolographic analysis of the coinjection of arachidonylcyclopropylamide and AM1241 determined that the CB1 and CB2 receptor agonists interacted synergistically to reduce mechanical hyperalgesia in the tumor-bearing paw. These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.
Viruses Teaching Immunology: Role of LCMV Model and Human Viral Infections in Immunological Discoveries (2019)

Virology has played an essential role in deciphering many immunological phenomena, thus shaping our current understanding of the immune system. Animal models of viral infection and human viral infections were both important tools for immunological discoveries. This review discusses two immunological breakthroughs originally identified with the help of the lymphocytic choriomeningitis virus (LCMV) model; immunological restriction by major histocompatibility complex and immunotherapy using checkpoint blockade. In addition, we discuss related discoveries such as development of tetramers, viral escape mutation, and the phenomenon of T-cell exhaustion.
Involvement of the Multidrug Resistance Protein 3 in Drug Sensitivity and Its Expression in Human Glioma (2001)

The multidrug resistance protein (MRP) family belongs to the ATP-binding cassette superfamily (ABC) of transporters, which are involved in ATP-dependent transport of hydrophobic compounds. One of the MRP family, MRP1, is partially associated with the multidrug resistance phenotype in brain tumors. In this study, we asked whether another MRP family gene, MRP3, could affect drug sensitivity to anticancer agents in human glioma cell lines and clinical glioma specimens. We first produced two antisense transfectants by introduction of antisense MRP3 cDNA into the glioma cell line NHG2, which endogenously expresses MRP3. The two MRP3 antisense transfectants showed 2- to 5-fold increases in drug sensitivity to etoposide and cisplatin compared with NHG2 cells, but their sensitivity to vincristine or nitrosourea was not changed. Two MRP3 cDNA sense transfectants of pig kidney cell lines showed 4- to 6-fold drug resistance to etoposide, but only 1.4- to 1.5-fold to cisplatin. We next compared the mRNA levels of four ABC transporters, multidrug resistance 1 (MDR1), MRP1, MRP2 and MRP3 in clinical samples, including 34 patients with gliomas, by quantitative RT-PCR analysis. In some of the clinical samples, increased expression of MRP1 and MRP3 was apparent in malignant gliomas. In situ hybridization revealed that glioma cells were stained with MRP3 probe. MRP3 may modulate drug sensitivity to certain anticancer agents in human gliomas.
Augmentation of spontaneous cytotoxicity of human lymphocytes by RU 41.740, a glucoprotein extract of Klebsiella pneumoniae. (1987)

RU 41.740 (Biostim) is an extract of Klebsiella pneumoniae with immunomodulating properties. This substance was observed to augment spontaneous cytotoxicity of human blood lymphocytes provided that monocytes were present during Biostim treatment. Maximal augmentation was observed after 2 h of incubation. The F1 fraction, a glucoprotein which comprises approximately 20% of Biostim, and LPS from Klebsiella pneumoniae were also observed to augment spontaneous cytotoxicity of lymphocytes. Biostim treatment of K562 cells, which were used as target cells for killing, did not change their sensitivity to the lytic action of spontaneously cytotoxic cells.