julilili42/papers huggingface dataset:
P2‐067: Significant elevation of plasma BACE in AD and MCI patients
2011-07-01

Beta-secretase (BACE1) isone of the two key enzymes in processing the amyloid precursor protein (APP) to produce Ab, which has long been considered the pathological hallmark of Alzheimer's disease (AD). We and others recently discovered that BACE1 activity was significantly increased in sporadic AD brains and that the concentrations of both CSF BACE1 enzymatic activity and protein were significantly increased in subjects with amnestic mild cognitive impairment (MCI). We have hypothesized that by using BACE1 as a biomarker candidate in CSF, it may aid in early detection and prediction of AD in the at-risk predementia MCI stage. Lumbar punctures, however, are considered an invasive procedure. It may be difficult to obtain the sample size necessary for biomarker validation studies, or for a broad clinical screening with a diagnostic indicator. Therefore, potential biomarkers from a more accessible source, such as blood plasma, are critical for advancement. In this study, we wanted to understand whether BACE in the blood from MCI and AD patients would be changed. There were at least 100 patients in each group. Clinically, the MCI subjects met Petersen criteria for amnestic MCI and the AD subjects met NINDS-ADRDA criteria for the diagnosis. Control group is composed by age-matched healthy individuals. We used BACE enzymatic activity assay, BACE ELISA, Ab1-x and sAPPb to measure BACE enzyme activity, expression levels and reaction product. Both BACE enzyme activity and expression levels are significantly changed in MCI and AD patients compared to healthy age-matched controls. To our knowledge, this is the first time blood from MCI and AD patients has been systematically examined for BACE1 functional proteins and enzyme activity, as well as the enzymatic product, sAPPb and total Ab1-x. Here, we report significant changes of BACE1 functional proteins in the blood among subjects with MCI or AD compared to age-matched cognitively normal controls. These finding are highly relevant for the improved hypothesis-driven generation of biomarkers for AD, regarding early detection and prediction, as well as for assessment of mechanisms for amyloid lowering compounds currently in phase II-III clinical trials.
P1‐365: Near‐infrared spectroscopy: a reliable tool to assess cortical changes in Alzheimer's disease and their progression over time
2011-07-01

The technique of Near-Infrared Spectroscopy (NIRS) is a non-invasive optical method allowing the in vivo measurement of brain activation via changes in the concentration of oxy- [O2Hb] and deoxygenated [HHb] haemoglobin in the cerebral cortex. Neuroimaging studies show widespread activation deficits in patients suffering from Alzheimer's disease (AD) during tasks targeting the visuo-spatial and executive domains located in prefrontal and parietal areas. Using NIRS the present study assessed changes in prefrontal and parietal oxygenation in AD patients and healthy controls and their progression over a one-year interval. 71 patients suffering from AD and 68 elderly healthy controls were measured during two versions of a verbal fluency task (VFT, letter and category) and a line orientation task (LO) using 44-channel (VFT) and 52-channel (LO) fNIRS. 14 patients and 49 controls completed a follow-up measurement after one year. During the letter version of the VFT and the LO AD-patients displayed a reduced activation pattern in the prefrontal (VFT) and the parietal cortex (LO) as compared to healthy controls. Increases in O2Hb in parietal regions correlated with prefrontal activity in AD-patients but remained independent in healthy controls. Prefrontal activation decreased significantly over the one year interval in AD-patients. Healthy controls showed no changes at follow up. Activation decreases in the prefrontal cortex were correlated with the decrease of the MMSE score, with greater decrease indicating lower MMSE score at the follow-up. fNIRS seems to be a well suited instrument to measure disease related changes in the cortex of AD patients and their progression over time. Considering the fact that we did not observe any changes in healthy controls without any cognitive decline fNIRS could be a promising device to be used in prospective studies of AD and other dementias.
P1‐364: Prefrontal lateralization during a verbal fluency task predicts neuropsychological changes in healthy elderly controls: a fNIRS study
2011-07-01

Near-Infrared Spectroscopy (NIRS) is a non-invasive optical method measuring brain activation by assessing changes in the concentration of oxy- [O2Hb] and deoxygenated [HHb] hemoglobin in the cerebral cortex. During a verbal fluency task (VFT) healthy controls display a typical pattern of activation in prefrontal regions with a distinct lateralization to the left dorso-lateral prefrontal cortex (DLPFC). This lateralization decreases with age indicating compensatory processes. We expected the amount of lateralization during the VFT to predict neuropsychological changes in healthy elderly controls over a one year interval. 44 elderly healthy controls (aged 55-82 years) were measured during two versions of a VFT (phonological and semantical) using 44-channel functional NIRS. MMST and DemTect were performed at the time of the fNIRS measurement and again after one year. During both versions of the VFT subjects displayed a typical activation pattern in the DLPFC with a distinct increase in O2Hb. Subjects’ lateralization did not correlate with age. The amount of lateralization during the letter version could account for a significant amount of the changes in MMST (16%) and DemTect (9%) after one year. Subjects displaying less distinct or no lateralization showed a decrease in neuropsychological performance whereas subjects with a clearly lateralized activation did not change in MMST or DemTect. fNIRS seems to be a suitable tool for the study of long term changes in elderly subjects when assessing brain activation and cognitive decline. As alternations in oxygenation probably occur even before atrophy in affected brain regions, fNIRS could add to the development of methods for the early detection of mild cognitive impairment or Alzheimer's disease.
Protein self-diffusion in crowded solutions
2011-07-05

Macromolecular crowding in biological media is an essential factor for cellular function. The interplay of intermolecular interactions at multiple time and length scales governs a fine-tuned system of reaction and transport processes, including particularly protein diffusion as a limiting or driving factor. Using quasielastic neutron backscattering, we probe the protein self-diffusion in crowded aqueous solutions of bovine serum albumin on nanosecond time and nanometer length scales employing the same protein as crowding agent. The measured diffusion coefficient D ( φ ) strongly decreases with increasing protein volume fraction φ explored within 7% ≤ φ ≤ 30%. With an ellipsoidal protein model and an analytical framework involving colloid diffusion theory, we separate the rotational D r ( φ ) and translational D t ( φ ) contributions to D ( φ ). The resulting D t ( φ ) is described by short-time self-diffusion of effective spheres. Protein self-diffusion at biological volume fractions is found to be slowed down to 20% of the dilute limit solely due to hydrodynamic interactions.
Electroproduction of the Roper resonance on the proton: The role of the three-quark core and the molecularNσcomponent
2011-07-05

The Roper resonance is considered as a mixed state of a three-quark core\\nconfiguration and a hadron molecular component N+sigma. Based on this ansatz we\\nstudy electroproduction of the Roper resonance. The strong and electromagnetic\\ncouplings induced by the quark core are calculated in the 3P0 model. The\\ncontribution of the vector meson cloud to the electromagnetic transition is\\ngiven in the framework of the VMD model. Results are compared with the recent\\nJLab electroproduction data.\\n
ETS‐1/RhoC signaling regulates the transcription factor c‐Jun in melanoma
2011-07-05

Abstract Recently, we discovered that the loss of E‐cadherin induces c‐Jun protein expression, which is a member of the AP‐1 transcription factor family and a key player in the processes of cell proliferation and tumor development and also found in elevated levels in melanomas. Notably, the mRNA level of c‐Jun was not affected, suggesting that c‐Jun is regulated at post‐transcriptional level. Here, we present data that suggest that the dynamic cytoskeletal network, linked to E‐cadherin, is involved in the regulation of the c‐Jun protein and transcriptional activity. In a signaling cascade, the loss of E‐cadherin activates the transcriptional regulator ETS‐1 and consequently leads to the induction of RhoC expression that stabilizes c‐Jun in melanoma. The link between RhoC and c‐Jun seems to be indirect via the cytoskeleton. We conclude that the loss of E‐cadherin mediated cell‐adhesion induces c‐Jun protein expression in a multistep process, offering several possibilities for therapeutic intervention.
Immunogenetics of ageing
2011-07-05

The ageing process is very complex. Human longevity is a multifactorial trait which is determined by genetic and environmental factors. Twin and family studies imply that up to 25% of human lifespan is heritable. The longevity gene candidates have generally fallen into the following categories: inflammatory and immune-related factors, stress response elements, mediators of glucose and lipid metabolism, components of DNA repair and cellular proliferation and mitochondrial DNA haplogroups. Because of the central role of HLA molecules in the development of protective immunity and the extraordinary degree of polymorphism of HLA genes, many studies have addressed the possible impact of these genes on human longevity. Most of the data available so far demonstrated a possible role of HLA class II specificities in human longevity but definitive evidence has remained elusive. Although the data are limited and controversial, it has been hypothesized that longevity could be associated with cytokine gene polymorphisms correlating with different levels of cytokine production, thereby modulating immune responses in health and disease. Because of the essential role of cytokines in immune responses, the regulation of cytokine gene expression and their polymorphic nature, the genetic variations of these loci with functional significance could be appropriate immunogenetic candidate markers implicated in the mechanism of successful ageing and longevity. In addition, several other genes such as Toll-like receptor genes, Cycloxygenases (COX)/Lipoxygenases (LOX), CCR5, NK receptor genes and MBL2 have been assessed as a possible biomarkers associated with ageing. This review will summarize the data on the role of these immune genes in human longevity.
Functional dissection of SiiE, a giant non-fimbrial adhesin of Salmonella enterica
2011-07-05

Salmonella enterica deploys the giant non-fimbrial adhesin SiiE to adhere to the apical side of polarized epithelial cells. The establishment of close contact is a prerequisite for subsequent invasion mediated by translocation of effector proteins of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type III secretion system (T3SS). Although SiiE is secreted into the culture medium, the adhesin is retained on the bacterial envelope in the phase of highest bacterial invasiveness. To dissect the structural requirements for secretion, retention and adhesive properties, comprehensive deletional and functional analyses of various domains of SiiE were performed. We observed that β-sheet and coiled-coil domains in the N-terminal moiety of SiiE are required for the control of SiiE retention on the surface and co-ordinated release. These results indicate a novel molecular mechanism for the control of surface display of a T1SS-secreted adhesin that acts cooperatively with the SPI1-T3SS.
Cone-rod dystrophy associated with amelogenesis imperfecta in a child with neurofibromatosis type 1
2011-07-05

Our case shows a unique combination of NF1 and Jalili syndrome. The random association of two diseases is unusual and deserves attention. This case highlights the importance not only of detailed clinical examination, but also of molecular genetic analysis, which together provide a precise diagnosis.
4U 0115 + 63: phase lags and cyclotron resonant scattering
2011-07-06

High mass X-ray binaries are among the brightest objects of our Galaxy in the\\nhigh energy domain (0.1-100 keV). Despite our relatively good knowledge of\\ntheir basic emission mechanisms, the complex problem of understanding their\\ntime and energy dependent X-ray emission is not completely solved. &lt;P&gt; In this\\npaper, we study the energy dependent pulse profiles of the high mass X-ray\\nbinary pulsar 4U 0115+63 to investigate how they are affected by cyclotron\\nresonant scattering. &lt;P&gt; We analyze archival BeppoSAX and RXTE observations\\nperformed during the giant outburst of the source which occurred in 1999. We\\nexploit a cross correlation technique to compare the pulse profiles in\\ndifferent energy ranges and develop a relativistic ray-tracing model to\\ninterpret our findings. We also study the phase dependency of the cyclotron\\nabsorption features by performing phase resolved spectroscopy. &lt;P&gt; The pulse\\nprofiles of 4U 0115+63 displayed clear "phase-lags" at energies close to those\\nof the cyclotron absorption features that characterize the X-ray emission of\\nthe source. We reproduce qualitatively this phenomenon by assuming an energy\\ndependent beaming of the emission from the column surface and verify that our\\nmodel is also compatible with the results of phase resolved spectral analysis.\\n&lt;P&gt; We showed that cyclotron resonant scattering affects the pulse profile\\nformation mechanisms in a complex way, which necessitates both improvements in\\nthe modeling and the study of other sources to be better understood.\\n
Human mesenchymal stromal cells express CD14 cross‐reactive epitopes
2011-07-06

Abstract Mesenchymal stromal cells (MSCs) do not express a unique definite epitope or marker gene. As such, minimal criteria were recently established for defining multipotent MSC. These criteria include expression of CD73, CD90, CD105, and a lack of hematopoietic marker expression. However, we detected binding of a CD14 antibody on bone marrow‐ and placenta‐derived MSC and investigated the staining of CD14 antibodies on these MSC in more detail. The MSC were isolated from human bone marrow and placenta tissue, expanded, characterized by quantitative RT‐PCR, flow cytometry, and immunocytochemistry and differentiated to generate osteoblasts, chondrocytes, and adipocytes. The CD14‐cross‐reactive MSCs were enriched by cell sorting. Human peripheral blood mononuclear cells, fibroblasts, and hematopoietic cell lines served as controls. Utilizing four different clones of CD14 monoclonal antibodies, we found that three CD14 reagents stained the MSC. Two CD14 antibodies (HCD14 and M5E2) clearly marked the CD90 + MSC population with distinct intensities, clone 134 620 generated a shift in flow cytometry histograms, but clone MΦP9 did not stain MSC. Transcripts encoding CD14 or the CD14 protein were not detected in MSC. We confirm that bone marrow‐ and placenta‐derived MSC do not express CD14 and that the CD14 antibody MΦP9 discriminates between monocytes and MSC more efficiently than the other antibodies employed here. This investigation does not contradict previous work but provides a more accurate characterization of MSC. © 2011 International Society for Advancement of Cytometry
The prognostic value of hematological and systemic inflammatory disorders in invasive bladder cancer
2011-07-06

The degree of systemic inflammation and hematological disorders in invasive bladder cancer is often associated with more aggressive disease. The incorporation of hemoglobin levels, serum C-reactive protein and platelet counts into current nomograms might improve significantly the predictive accuracy of standard clinicopathological risk factors and provide improved prognostication for counseling more selectively the use of chemotherapy in the neoadjuvant, adjuvant and metastatic setting.
Downregulation of Klotho expression by dehydration
2011-07-06

Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal tissue counteracts aging. Overexpression of Klotho substantially prolongs the life span. Klotho deficiency leads to excessive formation of 1,25(OH) 2 D 3 , growth deficit, accelerated aging, and early death. Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. The present study explored the possibility that dehydration influences Klotho expression. Klotho transcript levels were determined by RT-PCR, and Klotho protein abundance was detected by Western blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in human embryonic kidney (HEK293) cells. Dehydration was followed by a significant decline of renal Klotho transcript levels and protein abundance, accompanied by an increase in plasma osmolarity as well as plasma ADH, aldosterone, and 1,25(OH) 2 D 3 levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 μM) significantly decreased Klotho transcription and protein expression in HEK293 cells. In conclusion, the present observations disclose a powerful effect of dehydration on Klotho expression, an effect at least partially mediated by enhanced release of ADH and aldosterone.
Field reconnaissance geologic mapping of the Columbia Hills, Mars, based on Mars Exploration Rover Spirit and MRO HiRISE observations
2011-07-06

Chemical, mineralogic, and lithologic ground truth was acquired for the first time on Mars in terrain units mapped using orbital Mars Reconnaissance Orbiter's High Resolution Imaging Science Experiment (MRO HiRISE) image data. Examination of several dozen outcrops shows that Mars is geologically complex at meter length scales, the record of its geologic history is well exposed, stratigraphic units may be identified and correlated across significant areas on the ground, and outcrops and geologic relationships between materials may be analyzed with techniques commonly employed in terrestrial field geology. Despite their burial during the course of Martian geologic time by widespread epiclastic materials, mobile fines, and fall deposits, the selective exhumation of deep and well-preserved geologic units has exposed undisturbed outcrops, stratigraphic sections, and structural information much as they are preserved and exposed on Earth. A rich geologic record awaits skilled future field investigators on Mars. The correlation of ground observations and orbital images enables construction of a corresponding geologic reconnaissance map. Most of the outcrops visited are interpreted to be pyroclastic, impactite, and epiclastic deposits overlying an unexposed substrate, probably related to a modified Gusev crater central peak. Fluids have altered chemistry and mineralogy of these protoliths in degrees that vary substantially within the same map unit. Examination of the rocks exposed above and below the major unconformity between the plains lavas and the Columbia Hills directly confirms the general conclusion from remote sensing in previous studies over past years that the early history of Mars was a time of more intense deposition and modification of the surface. Although the availability of fluids and the chemical and mineral activity declined from this early period, significant later volcanism and fluid convection enabled additional, if localized, chemical activity.
4D Flexible Atom-Pairs: An efficient probabilistic conformational space comparison for ligand-based virtual screening
2011-07-06

Our 4D method yields a robust performance on 40 pharmaceutically relevant targets. The conformational space encoding enables an efficient comparison of the conformational space. Therefore, the weakness of the 3D-based approaches on single conformations is circumvented. With over 100,000 similarity calculations on a single desktop CPU, the utilization of the 4D flexible atom-pair in real-world applications is feasible.
GBA-associated PD presents with nonmotor characteristics
2011-07-07

To evaluate whether there exists distinct characteristics in glucocerebrosidase (GBA)-associated Parkinson disease (PD) with regard to motor and nonmotor symptoms as well as imaging characteristics assessed by transcranial sonography (TCS).Twenty patients with PD with heterozygous GBA mutations (N370S, L444P) (GBA-PD) in comparison to 20 patients with sporadic PD negative for GBA mutations (sPD) were included. We assessed motor impairment with the Unified Parkinson's Disease Rating Scale-III. Nonmotor symptoms were evaluated using the Montreal Cognitive Assessment, Neuropsychiatric Inventory, revised form of the Beck Depression Inventory, Parkinson Disease Sleep Scale, Sniffin' Sticks, and Unified Multiple System Atrophy Rating Scale items 9-12. TCS imaging was used to detect morphologic characteristics.Patients with GBA-PD more often had a variety of nonmotor symptoms, namely dementia, neuropsychiatric disturbances, and autonomic dysfunction, and had more severe cases, than patients with sPD. They also demonstrated a higher prevalence of a reduced echogenicity of the brainstem raphe assessed by TCS.Especially nonmotor symptoms seem to be very common in GBA-PD. Further studies are needed to validate these observations in order to better understand the pathogenesis of GBA-PD and develop specific therapeutic concepts.