julilili42/papers huggingface dataset:
Immunocytological and Preliminary Immunohistochemical Studies of Prothymosin α, a Human Cancer–associated Polypeptide, With a Well-characterized Polyclonal Antibody
2008-07-21

Prothymosin α (ProTα) is a nuclear polypeptide of great biological and, possibly clinical, importance, because its expression levels have been associated with early diagnosis/prognosis of human cancer. It is therefore interesting to raise easily available and cost-effective antibodies that would be applied to develop reliable ProTα immunodiagnostics. In this study, New Zealand white rabbits and laying hens were parallel immunized against intact ProTα or the synthetic fragments ProTα[1-28], ProTα[87-109], and ProTα[101-109], all conjugated to keyhole limpet hemocyanin (KLH). The corresponding antibodies G and Y were immunochemically evaluated in parallel with ELISA and Western blot systems and applied to fluorescence immunocytology experiments using various cancer cell lines and normal cells. The antibody G raised against ProTα[101-109]/KLH had excellent functional characteristics in the Western blot and immunocytology experiments, where the fluorescent signal was almost exclusively shown in the cell nucleus independently of the cells assayed. The above antibody has been applied to preliminary IHC staining of human cancer prostate tissues, leading to a high percentage of clearly and intensively stained nuclei in the adenocarcinoma tissue; this antibody can be further used in cancer tissue immunostaining and in research concerning the role of ProTa in tumorigenesis.
HEIGHT AND WEIGHT DIFFERENCES BETWEEN NORTH AND SOUTH KOREA
2008-07-23

Summary This paper investigates height and weight differences between the two Koreas by comparing national anthropometric data published by the South Korean Research Institute of Standard and Science with United Nations survey data collected inside North Korea in 2002. For socioeconomic reasons, pre-school children raised in the developing country of North Korea are up to 13 cm shorter and up to 7 kg lighter than children who were brought up in South Korea – an OECD member. North Korean women were also found to weigh up to 9 kg less than their Southern counterparts.
Tonotopic Variation in the Calcium Dependence of Neurotransmitter Release and Vesicle Pool Replenishment at Mammalian Auditory Ribbon Synapses
2008-07-23

The mammalian cochlea is specialized to recognize and process complex auditory signals with remarkable acuity and temporal precision over a wide frequency range. The quality of the information relayed to the auditory afferent fibers mainly depends on the transfer characteristics of inner hair cell (IHC) ribbon synapses. To investigate the biophysical properties of the synaptic machinery, we measured changes in membrane capacitance (Δ C m ) in low-frequency (apical region, ∼300 Hz) and high-frequency (basal, ∼30 kHz) gerbil IHCs maintained in near physiological conditions (1.3 m m extracellular Ca 2+ and body temperature). With maturation, the Ca 2+ efficiency of exocytosis improved in both apical and basal IHCs and was more pronounced in the latter. Prehearing IHCs showed a similar Ca 2+ cooperativity of exocytosis despite the smaller Δ C m in apical cells. After maturation, Δ C m in high-frequency IHCs increased linearly with the Ca 2+ current, whereas, somewhat surprisingly, the relationship was significantly more nonlinear in low-frequency cells. This tonotopic difference seemed to be correlated with ribbon synapse morphology (spherical in apical and ellipsoid in basal IHCs) but not with the expression level of the proposed Ca 2+ sensor otoferlin or the spatial coupling between Ca 2+ channels and active zones. Repetitive stimulation of adult IHCs showed that vesicle pool refilling could become rate limiting for vesicle release, with high-frequency IHCs able to sustain greater release rates. Together, our findings provide the first evidence for a tonotopic difference in the properties of the synaptic machinery in mammalian IHCs, which could be essential for fine-tuning their receptor characteristics during sound stimulation.
Staphylococcus Aureus Evasion of Innate Antimicrobial Defense
2008-07-23

Bacterial pathogens colonize human body surfaces soon after birth. In order to survive the constant threat of invasion and infection, the human innate immune system has evolved several efficient mechanisms to prevent harmful microorganisms from traversing epithelial barriers. These include cationic antimicrobial peptides (CAMPs) such as defensins and the cathelicidin LL-37, bacteriolytic enzymes such as lysozyme, antimicrobial fatty acids, toxic oxygen- or nitrogen-containing molecules, the bacteriolytic complement components and further mechanisms with indirect impacts on bacterial multiplication. Staphylococcus aureus is an important human commensal and pathogen. In order to successfully establish an infection, S. aureus has evolved several mechanisms to resist the innate immune system. In this review, we focus on the mechanisms employed by S. aureus to achieve protection against antimicrobial host defense molecules with special emphasis on CAMPs. Lessons from recent studies on antimicrobial host defense molecules and cognate bacterial resistance adaptation should help in the development of more sustainable anti-infective compounds.
BALLDock/SLICK: A New Method for Protein-Carbohydrate Docking
2008-07-23

Protein-ligand docking is an essential technique in computer-aided drug design. While generally available docking programs work well for most drug classes, carbohydrates and carbohydrate-like compounds are often problematic for docking. We present a new docking method specifically designed to handle docking of carbohydrate-like compounds. BALLDock/SLICK combines an evolutionary docking algorithm for flexible ligands and flexible receptor side chains with carbohydrate-specific scoring and energy functions. The scoring function has been designed to identify accurate ligand poses, while the energy function yields accurate estimates of the binding free energies of these poses. On a test set of known protein-sugar complexes we demonstrate the ability of the approach to generate correct poses for almost all of the structures and achieve very low mean errors for the predicted binding free energies.
A Stable Niche Supports Long-Term Maintenance of Human Epidermal Stem Cells in Organotypic Cultures
2008-07-24

Abstract Stem cells in human interfollicular epidermis are still difficult to identify, mainly because of a lack of definitive markers and the inability to label human beings for label-retaining cells (LRCs). Here, we report that LRCs could be identified and localized in organotypic cultures (OTCs) made with human cells. Labeling cultures for 2 weeks with iododeoxyuridine (IdU) and then chasing for 6–10 weeks left &amp;lt;1% of basal cells retaining IdU label. Whole mounts demonstrated that LRCs were individually dispersed in the epidermal basal layer. Some LRCs, but not all, colocalized with cells expressing melanoma chondroitin sulfate proteoglycan, a putative stem cell marker. Although we found LRCs in both collagen- and scaffold-based OTCs, only the scaffold-OTCs supported long-term survival and regeneration. LRCs' short survival in collagen-OTCs was not due to loss of appropriate growth factors from fibroblasts. Instead, it was due to expression of metalloproteinases, especially matrix metalloproteinase (MMP)-2 and MMP-14, which caused collagen fragmentation, matrix degradation, and dislocation of specific basement membrane components bound to epidermal integrins. Blocking MMP activation not only abrogated MMP-dependent matrix degradation but also increased longevity of the epidermis and the LRCs in these cultures. Such findings indicate that the stem cell niche, the microenvironment surrounding and influencing the stem cell, is essential for stem cell survival and function, including long-term tissue regeneration. Disclosure of potential conflicts of interest is found at the end of this article.
Use of a Halogenase of Hormaomycin Biosynthesis for Formation of New Clorobiocin Analogues with 5‐Chloropyrrole Moieties
2008-07-24

Abstract The depsipeptide antibiotic hormaomycin, which is produced by Streptomyces griseoflavus W‐384, contains a 5‐chloropyrrole moiety. In the producer strain we identified the gene hrmQ that shows sequence similarity to FADH 2 ‐dependent halogenases. This gene was cloned and heterologously expressed in Streptomyces roseochromogenes var. oscitans DS12.976, which is the producer of the aminocoumarin antibiotic clorobiocin, which contains a 5‐methylpyrrole moiety. For the present experiment, we used a mutant of this strain in which the respective pyrrole‐5‐methyltransferase had been inactivated. Expression of the halogenase hrmQ in this mutant strain led to the formation of two new clorobiocin derivatives that carried a 5‐chloropyrrole moiety. These compounds were isolated on a preparative scale, their structures were elucidated by 1 H NMR spectroscopy and mass spectrometry, and their antibacterial activity was determined. The substrate of HrmQ is likely to be a pyrrole‐2‐carboxyl‐ S ‐[acyl carrier protein] thioester. If this assumption is true, this study presents the first experiment in combinatorial biosynthesis that uses a halogenase that acts on an acyl carrier protein‐bound substrate.
Enzastaurin‐induced apoptosis in glioma cells is caspase‐dependent and inhibited by BCL‐XL
2008-07-24

Abstract The novel protein kinase C‐β inhibitor enzastaurin (ENZA) induced apoptosis in LNT‐229 and T98G cells whereas A172 cells were resistant. Further, ENZA reduced proliferation in glioblastoma‐initiating cells T 269 and T 323 but did not induce apoptosis. ENZA‐induced apoptosis involved cleavage of caspases 3, 8, and 9 and led to mitochondrial cytochrome c release and was strongly suppressed by the broad spectrum caspase inhibitor zVAD‐fmk but only slightly by the expression of the viral caspase 1/8 inhibitor cytokine response modifier‐A. ENZA did not reduce the phosphorylation of protein kinase B (Akt), but of p70 S6 kinase and of its substrate S6 protein in T98G cells. Inhibition of the phosphatidylinositol 3 kinase signaling pathway did not restore sensitivity of A172 cells towards ENZA, and constitutively active Akt did not protect LNT‐229 and T98G cells from ENZA‐induced apoptosis. Dephosphorylation of glycogen synthase kinase 3β, a biomarker of ENZA action, and cell death induction by ENZA were separately regulated. Inhibition or activation of Akt only weakly modulated ENZA‐induced dephosphorylation of glycogen synthase kinase 3β. In ENZA‐resistant A172 cells, apoptosis ligand 2 (Apo2L.0)‐induced cleavage of caspases 3, 8, and 9 was increased by ENZA, resulting in synergistic activity of ENZA and Apo2L.0.
Self‐regulation of regional cortical activity using real‐time fMRI: The right inferior frontal gyrus and linguistic processing
2008-07-25

Abstract Neurofeedback of functional magnetic resonance imaging (fMRI) can be used to acquire selective control over activation in circumscribed brain areas, potentially inducing behavioral changes, depending on the functional role of the targeted cortical sites. In the present study, we used fMRI‐neurofeedback to train subjects to enhance regional activation in the right inferior frontal gyrus (IFG) to influence speech processing and to modulate language‐related performance. Seven subjects underwent real‐time fMRI‐neurofeedback training and succeeded in achieving voluntary regulation of their right Brodmann's area (BA) 45. To examine short‐term behavioral impact, two linguistic tasks were carried out immediately before and after the training. A significant improvement of accuracy was observed for the identification of emotional prosodic intonations but not for syntactic processing. This evidence supports a role for the right IFG in the processing of emotional information and evaluation of affective salience. The present study confirms the efficacy of fMRI‐biofeedback for noninvasive self‐regulation of circumscribed brain activity. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Vascular signalling mediated by ZWILLE potentiates WUSCHEL function during shoot meristem stem cell development in theArabidopsisembryo
2008-07-25

Stem cells are maintained in an undifferentiated state by signals from their microenvironment, the stem cell niche. Despite its central role for organogenesis throughout the plant's life, little is known about how niche development is regulated in the Arabidopsis embryo. Here we show that, in the absence of functional ZWILLE (ZLL), which is a member of the ARGONAUTE (AGO) family, stem cell-specific expression of the signal peptide gene CLAVATA3 (CLV3) is not maintained despite increased levels of the homeodomain transcription factor WUSCHEL (WUS), which is expressed in the organising centre (OC) of the niche and normally promotes stem cell identity. Tissue-specific expression indicates that ZLLacts to maintain the stem cells from the neighbouring vascular primordium,providing direct evidence for a non-cell-autonomous mechanism. Furthermore,mutant and marker gene analyses suggest that during shoot meristem formation, ZLL functions in a similar manner but in a sequential order with its close homologue AGO1, which mediates RNA interference. Thus, WUS-dependent OC signalling to the stem cells is promoted by AGO1 and subsequently maintained by a provascular ZLL-dependent signalling pathway.
Autonomic dysfunction in different subtypes of multiple system atrophy
2008-07-25

Abstract Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA‐C) and the parkinsonian (MSA‐P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA‐C and 26 with MSA‐P in comparison with 27 age‐ and sex‐matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA‐P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA‐C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. © 2008 Movement Disorder Society
A Maltooctaose Derivative (“Acyclodextrin”) as a Chiral Stationary Phase for Enantioselective Gas Chromatography
2008-07-25

Abstract The enantiorecognition mechanism of several cyclodextrin derivatives is still not completely rationalized, and the application of acyclic selectors may aid to explain the role of the cavity (typical of the underivatized cyclic selectors) combined with the functional groups introduced by multistep synthesis. Octakis[(3‐ O ,‐4′′ O )‐butanoyl‐(1′‐ O ,2,6‐di‐ O )‐ n ‐pentyl]maltooctaose was applied as a chiral stationary phase for gas chromatographic enantioseparation. Selected racemic compounds were enantioseparated also on the acyclic phase. The promising results of this chiral selector [and its direct comparison with the cyclic counterpart octakis(2,6‐di‐ O ‐ n ‐pentyl‐3‐ O ‐butanoyl)‐γ‐cyclodextrin (Lipodex E)] suggest the application of other well‐known spectroscopic techniques (CD, NMR) to point out further details on the mechanism of enantiorecognition.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
SUCCESSFUL CADAVERIC RENAL TRANSPLANTATION IN A 3.9 KG INFANT
2008-07-27

1Pediatrics, University Hospital of Tuebingen, Germany, 2Pediatric Surgery, University Hospital of Tuebingen, Germany, 3General, Visceral and Transplant Surgery, University Hospital of Tuebingen, Germany
SUCCESSFUL THERAPY OF A DISSEMINATED CYTOMEGALOVIRUS (CMV) INFECTION WITH ORAL VALGANCICLOVIR IN A 4 YEAR-OLD BOY AFTER KIDNEY TRANSPLANTATION
2008-07-27

1Department of Pediatrics, University Hospital of Tuebingen, Germany, 2Department of Medical Virology, University Hospital of Tuebingen, Germany, 3Department of Pediatric Surgery, University Hospital of Tuebingen, Germany, 4Department of General, Visceral and Transplant Surgery, University Hospital of Tuebingen, Germany
Transferable Ageing Provisions in Individual Health Insurance Contracts
2008-07-29

Abstract We consider lifetime health insurance contracts in which ageing provisions are used to smooth the premium profile. The capital stock accumulated for each individual can be decomposed into two parts: a premium insurance and an annuitized life insurance, only the latter being transferable between insurers without triggering premium changes through risk segmentation. In a simulation based on German data, the transferable share declines in age and falls with an increasing age of entry into the contract. In spite of different benefit profiles, it is almost identical for women and men.
Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR KINASE Proteins Serve Brassinosteroid-Dependent and -Independent Signaling Pathways
2008-07-30

Abstract The Arabidopsis (Arabidopsis thaliana) SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK) genes belong to a small family of five plant receptor kinases that are involved in at least five different signaling pathways. One member of this family, BRASSINOSTEROID INSENSITIVE1 (BRI1)-ASSOCIATED KINASE1 (BAK1), also known as SERK3, is the coreceptor of the brassinolide (BR)-perceiving receptor BRI1, a function that is BR dependent and partially redundant with SERK1. BAK1 (SERK3) alone controls plant innate immunity, is also the coreceptor of the flagellin receptor FLS2, and, together with SERK4, can mediate cell death control, all three in a BR-independent fashion. SERK1 and SERK2 are essential for male microsporogenesis, again independent from BR. SERK5 does not appear to have any function under the conditions tested. Here, we show that the different SERK members are only redundant in pairs, whereas higher order mutant combinations only show additive phenotypes. Surprisingly, SERK members that are redundant within one are not redundant in another pathway. We also show that this evolution of functional pairs occurred by a change in protein function and not by differences in spatial expression. We propose that, in plants, closely related receptor kinases have a minimal homo- or heterodimeric configuration to achieve specificity.
Complementary Contributions of Prefrontal Neuron Classes in Abstract Numerical Categorization
2008-07-30

The primate prefrontal cortex (PFC) plays a cardinal role in forming abstract categories and concepts. However, it remains elusive how this is accomplished and to what extent the interaction of functionally distinct neuron classes underlies this representation. Here, we inferred the major cortical cell types, putative pyramidal cells, and interneurons by characterizing the waveforms of action potentials recorded in monkeys performing a cognitively demanding numerosity categorization task. Putative interneurons responded much faster than cells classified as pyramidal neurons and exhibited a higher reliability of category discrimination, whereas putative pyramidal cells showed a higher degree of category selectivity. An analysis of the numerosity tuning profiles and the temporal interactions of adjacent neurons indicated that inhibitory input by putative interneurons shapes the tuning to numerical categories of putative PFC pyramidal cells. These findings favor feedforward mechanisms subserving cognitive categorization and help to clarify cellular interactions in PFC microcircuits.
Audit of motor weakness and premature catheter dislodgement after epidural analgesia in major abdominal surgery
2008-07-30

Summary In a quality improvement audit on epidural analgesia in 300 patients after major abdominal surgery, we identified postoperative lower leg weakness and premature catheter dislodgement as the most frequent causes of premature discontinuation of postoperative epidural infusion. Lower limb motor weakness occurred in more than half of the patients with lumbar epidural analgesia. In a second period monitoring 177 patients, lumbar catheter insertion was abandoned in favour of exclusive thoracic placement for epidural catheters. Additionally, to prevent outward movement, the catheters were inserted deeper into the epidural space (mean (SD) 5.2 (1.5) cm in vs 4.6 (1.3) cm in ). Lower leg motor weakness declined from 14.7% to 5.1% (odds ratio 0.35; 95% confidence interval 0.16–0.74) between the two periods. Similarly, the frequency of premature catheter dislodgement was reduced from 14.5% to 5.7% (odds ratio 0.35; 95% confidence interval 0.17–0.72). With a stepwise logistic regression model we demonstrated that the odds of premature catheter dislodgement was reduced by 43% for each centimetre of additional catheter advancement in . We conclude that careful audit of specific complications can usefully guide changes in practice that improve success of epidural analgesia regimens.
Inactivation of the general transcription factor TnrA in Bacillus subtilis by proteolysis
2008-07-30

Under conditions of nitrogen limitation, the general transcription factor TnrA in Bacillus subtilis activates the expression of genes involved in assimilation of various nitrogen sources. Previously, TnrA activity has been shown to be controlled by protein-protein interaction with glutamine synthetase, the key enzyme of ammonia assimilation. Furthermore, depending on ATP and 2-oxoglutarate levels, TnrA can bind to the GlnK-AmtB complex. Here, we report that upon transfer of nitrate-grown cells to combined nitrogen-depleted medium, TnrA is rapidly eliminated from the cells by proteolysis. As long as TnrA is membrane-bound through GlnK-AmtB interaction it seems to be protected from degradation. Upon removal of nitrogen sources, the localization of TnrA becomes cytosolic and degradation occurs. The proteolytic activity against TnrA was detected in the cytosolic fraction but not in the membrane, and its presence does not depend on the nitrogen regime of cell growth. The proteolytic degradation of TnrA as a response to complete nitrogen starvation might represent a novel mechanism of TnrA control in B. subtilis.
Tumor-Associated MICA Is Shed by ADAM Proteases
2008-08-01

Abstract The immunoreceptor NKG2D promotes immunosurveillance of malignant cells and protects the host from tumor initiation by activating natural killer cells and costimulating CD8 T cells. NKG2D-mediated recognition of malignant cells by cytotoxic lymphocytes is enabled through the tumor-associated expression of NKG2D ligands (NKG2DL) resulting from cellular or genotoxic stress. Shedding of NKG2DL is thought to constitute a major countermechanism of tumor cells to subvert NKG2D-mediated immunosurveillance. Here, we report that the prototypical NKG2DL MICA is released by proteolytic cleavage in the stalk of the MICA ectodomain, where deletions, but not alanine substitutions, impede MICA shedding. Small compound-mediated stimulation and inhibition of MICA shedding adduced characteristics that indicated an involvement of members of the “a disintegrin and metalloproteinase” (ADAM) family. Accordingly, MICA shedding by tumor cells was inhibited by silencing of the related ADAM10 and ADAM17 proteases, which are known to promote tumor growth by releasing epidermal growth factor receptor ligands. Collectively, our data show that ADAM10 and ADAM17 are critically involved in the tumor-associated proteolytic release of soluble MICA facilitating tumor immune escape. Hence, therapeutic blockade of ADAM10 and ADAM17 seems promising for cancer treatment by targeting both growth and immune escape of tumors. [Cancer Res 2008;68(15):6368–76]