gebhart/patrepeval huggingface dataset:
Direction-Dependent Control of Balance During Walking and Standing (2009)

Human walking has previously been described as "controlled falling." Some computational models, however, suggest that gait may also have self-stabilizing aspects requiring little CNS control. The fore-aft component of walking may even be passively stable from step to step, whereas lateral motion may be unstable and require motor control for balance, as through active foot placement. If this is the case, walking humans might rely less on integrative sensory feedback, such as vision, for anteroposterior (AP) than for mediolateral (ML) balance. We tested whether healthy humans (n=10) exhibit such direction-dependent control, by applying low-frequency perturbations to the visual field (a projected virtual hallway) and measuring foot placement during treadmill walking. We found step variability to be nearly 10 times more sensitive to ML than to AP perturbations, as quantified by the increase in root-mean-square step variability per unit change in perturbation amplitude. This is not simply due to poorer physiological sensitivity of vision in the AP direction: similar perturbations applied to quiet standing produced reversed direction dependence, with an AP sensitivity 2.3-fold greater than that of ML. Tandem (heel-to-toe) standing yielded ML sensitivity threefold greater than that of AP, suggesting that the base of support influences the stability of standing. Postural balance nevertheless appears to require continuous, integrative motor control for balance in all directions. In contrast, walking balance requires step-by-step, integrative control for balance, but mainly in the lateral direction. In the fore-aft direction, balance may be maintained through an "uncontrolled," yet passively stabilized, series of falls.
Sequential Biventricular Pacing: (2004)

The study evaluated the clinical safety, performance, and efficacy of sequential biventricular pacing in the InSync III (Model 8042) biventricular stimulator in a multicenter, prospective 3-month study and assessed the proper functioning of features aiming at improving biventricular AV therapy delivery. The system was successfully implanted in 189 (95.9%) of 198 patients with symptomatic systolic heart failure and a prolonged QRS complex duration. Patients significantly improved their 6-minute hall walk distance (baseline 339 +/- 92 vs 3-month 422 +/- 127 meter, P < 0.001) and NYHA class (baseline 3.1 +/- 0.5 vs 3-month 1.9 +/- 0.7, P < 0.001). Echocardiographic optimization of sequential biventricular pacing showed an improvement in stroke volume compared to simultaneous stimulation (sequential 68 +/- 24 mL vs simultaneous 56 +/- 23 mL, P < 0.001) at baseline and at 3 months. In 88% (30/34) of the patients these improvements were seen within a small range of V-V delays of +/-20 ms and in 94% (32/34) within V-V delays of +/-40 ms. In contrast, programming beyond this range reduced stroke volume below that during simultaneous biventricular pacing. The device functioned as expected. LV lead dislodgement was observed in 12 patients and phrenic nerve stimulation required lead repositioning in 2 patients. Eight patients died during the study. Patient survival at 3 and 6 months was 97 +/- 2% and 94 +/- 2%, respectively. Cause of death was cardiac (n = 7), heart failure related (n = 3), arrhythmia related (n = 2), and unknown (n = 2). In conclusion, this sequential biventricular pacemaker was safe and efficacious.
Total Synthesis of Marine Glycosphingolipid Vesparioside B (2016)

The first total synthesis of a major component of marine glycolipid vesparioside B ( Scheme 1 , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent [4 + 3] coupling strategy. Key steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel β-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the β-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.
Hog1 Mitogen-Activated Protein Kinase Phosphorylation Targets the Yeast Fps1 Aquaglyceroporin for Endocytosis, Thereby Rendering Cells Resistant to Acetic Acid (2007)

Aquaporins and aquaglyceroporins form the membrane channels that mediate fluxes of water and small solute molecules into and out of cells. Eukaryotes often use mitogen-activated protein kinase (MAPK) cascades for the intracellular signaling of stress. This study reveals an aquaglyceroporin being destabilized by direct MAPK phosphorylation and also a stress resistance being acquired through this channel loss. Hog1 MAPK is transiently activated in yeast exposed to high, toxic levels of acetic acid. This Hog1 then phosphorylates the plasma membrane aquaglyceroporin, Fps1, a phosphorylation that results in Fps1 becoming ubiquitinated and endocytosed and then degraded in the vacuole. As Fps1 is the membrane channel that facilitates passive diffusional flux of undissociated acetic acid into the cell, this loss downregulates such influx in low-pH cultures, where acetic acid (pKa, 4.75) is substantially undissociated. Consistent with this downregulation of the acid entry generating resistance, sensitivity to acetic acid is seen with diverse mutational defects that abolish endocytic removal of Fps1 from the plasma membrane (loss of Hog1, loss of the soluble domains of Fps1, a T231A S537A double mutation of Fps1 that prevents its in vivo phosphorylation, or mutations generating a general loss of endocytosis of cell surface proteins [doa4Delta and end3Delta]). Remarkably, targetting of Fps1 for degradation may be the major requirement for an active Hog1 in acetic acid resistance, since Hog1 is largely dispensable for such resistance when the cells lack Fps1. Evidence is presented that in unstressed cells, Hog1 exists in physical association with the N-terminal cytosolic domain of Fps1.
Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. (2008)

Copeptin is a novel marker of the individual stress level. It more subtly mirrors moderate stress as compared to cortisol values.
Role of arabidopsis MYC and MYB homologs in drought- and abscisic acid-regulated gene expression. (1997)

In Arabidopsis, the induction of a dehydration-responsive gene, rd22, is mediated by abscisic acid (ABA) and requires protein biosynthesis for ABA-dependent gene expression. Previous experiments established that a 67-bp DNA fragment of the rd22 promoter is sufficient for dehydration- and ABA-induced gene expression and that this DNA fragment contains two closely located putative recognition sites for the basic helix-loop-helix protein MYC and one putative recognition site for MYB. We have carefully analyzed the 67-bp region of the rd22 promoter in transgenic tobacco plants and found that both the first MYC site and the MYB recognition site function as cis-acting elements in the dehydration-induced expression of the rd22 gene. A cDNA encoding a MYC-related DNA binding protein was isolated by DNA-ligand binding screening, using the 67-bp region as a probe, and designated rd22BP1. The rd22BP1 cDNA encodes a 68-kD protein that has a typical DNA binding domain of a basic region helix-loop-helix leucine zipper motif in MYC-related transcription factors. The rd22BP1 protein binds specifically to the first MYC recognition site in the 67-bp fragment. RNA gel blot analysis revealed that transcription of the rd22BP1 gene is induced by dehydration stress and ABA treatment, and its induction precedes that of rd22. We have reported a drought- and ABA-inducible gene that encodes the MYB-related protein ATMYB2. In a transient transactivation experiment using Arabidopsis leaf protoplasts, we demonstrated that both the rd22BP1 and ATMYB2 proteins activate transcription of the rd22 promoter fused to the beta-glucuronidase reporter gene. These results indicate that both the rd22BP1 (MYC) and ATMYB2 (MYB) proteins function as transcriptional activators in the dehydration- and ABA-inducible expression of the rd22 gene.
Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts. (2002)

The bone and bone marrow are the most common sites of metastasis in breast cancer. Matrix metalloproteinases (MMPs), particularly MMP-2, produced by cancer cells or, more typically, induced in the adjacent normal stroma are necessary for the degradation of extracellular matrix essential for cancer metastasis. Here we describe a mechanism by which breast cancer cells can rapidly use MMP-2 produced by bone marrow fibroblasts (BMFs). MMP-2 is stored in an inactive conformation in association with the cell surface or extracellular matrix of BMFs. Cocultures of BMFs and the human breast cancer cell line MDA-MB-231 induce release of MMP-2 into the culture supernatant without up-regulation of MMP-2 synthesis in either cell. MMP-2 is present on the surface of BMFs and is displaced by MDA-MB-231 cells or by fibronectin or fragments of fibronectin containing the fibronectin type II modules. Moreover, when fibronectin is eluted from the surface of MDA-MB-231 cells, they lose the ability to induce the release of MMP-2 from BMFs. These data are consistent with the displacement of inactive MMP-2 bound to normal fibroblasts via its collagen-binding domain by fibronectin type II modules of cancer cell-associated fibronectin. Cancer cells can then use the proteinase to facilitate tissue invasion. Because an identical mechanism can be demonstrated using fibroblasts from different sources, it is likely to be important for the rapid movement of malignant cells into a variety of normal tissues.
Single Framework Recombinant Antibody Fragments Designed for Protein Chip Applications (2002)

High-throughput proteomics, based on the microarray platform, requires stable, highly functional components that will yield a highly sensitive read-out of low abundance proteins. Although antibodies are the best characterized binding molecules for this purpose, only a fraction of them appear to behave satisfactorily in the chip format. Therefore, high demands need to be placed on their molecular design. In the present study, we have focused on recombinant antibody design based on a single framework for protein chip applications, aiming at defining crucial molecular probe parameters. Our results show that engineered human recombinant scFv antibody fragments that displayed appropriate biophysical properties (molecular [functional] stability in particular) can be generated, making them prime candidates for high-density antibody arrays. In fact, a superior framework that displays both multifaceted adsorption properties and very high functional stability over several months on chips (stored in a dried-out state) was identified. Taken together, designed scFv fragments based on a single molecular scaffold, readily accessible in large phage display libraries, can undoubtedly meet the requirements of probe content in antibody microarrays, particularly for global proteome analysis.
Lipids of selected molds grown for production of n−3 and n−6 polyunsaturated fatty acids (1992)

The lipid classes and component fatty acids of seven fungi were examined. Three marine fungi, Thraustochytrium aureum, Thraustochytrium roseum and Schizochytrium aggregatum (grown at 30, 25 and 25 degrees C, respectively), produced less than 10% lipid but contained docosahexaenoic acid (DHA) up to 30% and eicosapentaenoic acid (EPA) up to 11% of the total fatty acids. Mortierella alpinapeyron produced 38% oil containing solely n-6 polyunsaturated fatty acids (PUFA) with arachidonic acid (AA) at 11% of the total fatty acids. Conidiobolus nanodes and Entomorphthora exitalis produced 25% oil and contained both n-3 and n-6 PUFA, with AA at 16% and 18%, respectively. Saprolegnia parasitica produced 10% oil and contained AA and EPA, respectively, at 19% and 18%. The triacylglycerol fraction always represented the major component at between 44% and 68% of the total lipid. Each fungus, except T. aureum, had the greatest degree of fatty acid unsaturation in the phospholipid fraction. The triacylglycerol fraction of T. aureum was the most unsaturated with DHA representing 29% (w/w) of all fatty acids present. The presence of the enzyme ATP:citrate lyase correlated with the ability of molds to accumulate more than 10% (w/w) lipid when the fungi were grown in nitrogen-limiting media. In those molds that failed to accumulate more than 10% lipid, the enzyme was absent.
Impaired expression of thrombospondin-1 in eyes with age related macular degeneration (2005)

These findings suggest that decreased TSP-1 in Bruch's membrane and choroidal vessels during AMD may permit the formation of CNV.
Purification and characterization of a novel low molecular weight form of single-chain urokinase-type plasminogen activator. (1986)

A low Mr form (Mr 32,000) of single-chain urokinase-type plasminogen activator (scu-PA) was isolated from conditioned culture medium of a human lung adenocarcinoma cell line, CALU-3 (ATCC, HTB-55). The purified material (scu-PA-32k) consists of a single polypeptide chain and is immunologically similar to Mr 33,000 urokinase. Its NH2-terminal sequence is identical to that beginning at Leu-144 of Mr 54,000 urokinase. Whereas low Mr urokinase is derived from mature Mr 54,000 scu-PA by limited hydrolysis by plasmin first of the Lys-158-Ile-159 peptide bond and then of the Lys-136-Lys-137, scu-PA-32k is generated by specific hydrolysis of the Glu-143-Leu-144 peptide bond by an unidentified protease. scu-PA-32k resembles its Mr 54,000 scu-PA counterpart by its very low activity on chromogenic substrates for urokinase, by plasminogen-dependent fibrinolytic activity on fibrin plates, and by the lack of specific binding to fibrin. It activates plasminogen directly with high affinity, Km = 0.9 microM, but low turnover number, kcat = 0.0028 s-1. It is converted to fully active two-chain urokinase by plasmin with Km = 12 microM and kcat = 0.3 s-1. Like Mr 54,000 scu-PA, it causes significant lysis of a 125I-labeled fibrin clot in human plasma with relatively less fibrinogen breakdown as compared to urokinase. scu-PA-32k, which also has conserved fibrin specificity, represents a molecular variant which may be more suitable for large scale production as a fibrin-specific thrombolytic agent by recombinant DNA technology.
Recognition and Delivery of Effector Proteins into Eukaryotic Cells by Bacterial Secretion Systems (2006)

The direct transport of virulence proteins from bacterium to host has emerged as a common strategy employed by Gram-negative pathogens to establish infections. Specialized secretion systems function to facilitate this process. The delivery of 'effector' proteins by these secretion systems is currently confined to two functionally similar but mechanistically distinct pathways, termed type III and type IV secretion. The type III secretion pathway is ancestrally related to the multiprotein complexes that assemble flagella, whereas the type IV mechanism probably emerged from the protein complexes that support conjugal transfer of DNA. Although both pathways serve to transport proteins from the bacterium to host, the recognition of the effector protein substrates and the secretion information contained in these proteins appear highly distinct. Here, we review the mechanisms involved in the selection of substrates by each of these transport systems and secretion signal information required for substrate transport.
Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis (2000)

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);-low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL(+/-)E(-/-)) was associated with increased TG and increased total cholesterol (TC) compared with LPL(+/+)E(-/-) sibs. However despite their dyslipidemia, LPL(+/-)E(-/-) mice had significantly reduced lesion areas compared to the LPL(+/+)E(-/-) mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL(+/+)E(-/-) mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis. Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic).
HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein (2003)

The HIV-1 Gag protein recruits the cellular factor Tsg101 to facilitate the final stages of virus budding. A conserved P(S/T)AP tetrapeptide motif within Gag (the "late domain") binds directly to the NH2-terminal ubiquitin E2 variant (UEV) domain of Tsg101. In the cell, Tsg101 is required for biogenesis of vesicles that bud into the lumen of late endosomal compartments called multivesicular bodies (MVBs). However, the mechanism by which Tsg101 is recruited from the cytoplasm onto the endosomal membrane has not been known. Now, we report that Tsg101 binds the COOH-terminal region of the endosomal protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs; residues 222-777). This interaction is mediated, in part, by binding of the Tsg101 UEV domain to the Hrs 348PSAP351 motif. Importantly, Hrs222-777 can recruit Tsg101 and rescue the budding of virus-like Gag particles that are missing native late domains. These observations indicate that Hrs normally functions to recruit Tsg101 to the endosomal membrane. HIV-1 Gag apparently mimics this Hrs activity, and thereby usurps Tsg101 and other components of the MVB vesicle fission machinery to facilitate viral budding.
Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein (2003)

AcrAB of Escherichia coli, an archetype among bacterial multidrug efflux pumps, exports an extremely wide range of substrates including solvents, dyes, detergents and antimicrobial agents. Its expression is regulated by three XylS/AraC family regulators, MarA, SoxS and Rob. Although MarA and SoxS regulation works by the alteration of their own expression levels, it was not known how Rob, which is constitutively expressed, exerts its regulatory action. We show here that the induction of the AcrAB efflux pump by decanoate and the more lipophilic unconjugated bile salts is mediated by Rob, and that the low-molecular-weight inducers specifically bind to the C-terminal, non-DNA-binding domain of Rob. Induction of Rob is not needed for induction of AcrAB, and we suggest that the inducers act by producing conformational alterations in pre-existing Rob, as was suggested recently (Rosner, Dangi, Gronenborn and Martin, J Bacteriol 184: 1407-1416, 2002). Decanoate and unconjugated bile salts, which are present in the normal habitat of E. coli, were further shown to make the bacteria more resistant to lipophilic antibiotics, at least in part because of the induction of the AcrAB efflux pump. Thus, it is likely that E. coli is protecting itself by the Rob-mediated upregulation of AcrAB against the harmful effects of bile salts and fatty acids in the intestinal tract.
lnhibitory Effect of Diarylheptanoids on Nitric Oxide Production in Activated Murine Macrophages. (1998)

Thirteen novel diarylheptanoids bearing a chalcone or a flavanone moiety (1-13), a new curcumin derivative, 1,2-dihydrobis(de-O-methyl)curcumin (14), and two known flavonoids (15 and 16) isolated from the seeds of Alpinia blepharocalyx K. Schum. were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccaride (LPS)-activated murine macrophages J774.1 in vitro. All the tested compounds inhibited NO production in a concentration-dependent manner (IC50=36-568 microM). Among the compounds examined, blepharocalyxin B (13) was the most potent inhibitor of NO production (IC50=36 microM). Analysis of the structure activity relationship among these novel diarylheptanoids led to the conclusion that the position of attachment of a chalcone or a flavanone to a diarylheptanoid does not affect their inhibitory potency although their presence in association causes a substantial enhancement of the inhibitory activity. Moreover, a conjugated double bond in a chalcone moiety potentiated the inhibitory activity. On the other hand, hexamethoxydeoxycalyxin A (17) and pentamethoxycalyxin B (18), a methylated product of calyxin A (1) and an epimeric mixture of calyxin B, showed greatly reduced activity suggesting that phenolic hydroxyl groups are involved in the inhibitory activity.