gebhart/patrepeval huggingface dataset:
Neuronal Models for Studying Tau Pathology (2010)

Alzheimer's disease (AD) is the most frequent neurodegenerative disorder leading to dementia in the aged human population. It is characterized by the presence of two main pathological hallmarks in the brain: senile plaques containing beta-amyloid peptide and neurofibrillary tangles (NFTs), consisting of fibrillar polymers of abnormally phosphorylated tau protein. Both of these histological characteristics of the disease have been simulated in genetically modified animals, which today include numerous mouse, fish, worm, and fly models of AD. The objective of this review is to present some of the main animal models that exist for reproducing symptoms of the disorder and their advantages and shortcomings as suitable models of the pathological processes. Moreover, we will discuss the results and conclusions which have been drawn from the use of these models so far and their contribution to the development of therapeutic applications for AD.
An Integrated Implantable Stimulator That is Fail-Safe Without Off-Chip Blocking-Capacitors (2008)

We present a neural stimulator chip with an output stage (electrode driving circuit) that is fail-safe under single-fault conditions without the need for off-chip blocking-capacitors. To miniaturize the stimulator output stage two novel techniques are introduced. The first technique is a new current generator circuit reducing to a single step the translation of the digital input bits into the stimulus current, thus minimizing silicon area and power consumption compared to previous works. The current generator uses voltage-controlled resistors implemented by MOS transistors in the deep triode region. The second technique is a new stimulator output stage circuit with blocking-capacitor safety protection using a high-frequency current-switching (HFCS) technique. Unlike conventional stimulator output stage circuits for implantable functional electrical stimulation (FES) systems which require blocking-capacitors in the microfarad range, our proposed approach allows capacitance reduction to the picofarad range, thus the blocking-capacitors can be integrated on-chip. The prototype four-channel neural stimulator chip was fabricated in XFAB's 1-mum silicon-on-insulator CMOS technology and can operate from a power supply between 5-18 V. The stimulus current is generated by active charging and passive discharging. We obtained recordings of action potentials and a strength-duration curve from the sciatic nerve of a frog with the stimulator chip which demonstrate the HFCS technique. The average power consumption for a typical 1-mA 20-Hz single-channel stimulation using a book electrode, is 200 muW from a 6 V power supply. The silicon area occupation is 0.38 mm(2) per channel.
Sterile Testis Complementation with Spermatogonial Lines Restores Fertility to DAZL-Deficient Rats and Maximizes Donor Germline Transmission (2009)

Despite remarkable advances in assisted reproductive capabilities approximately 4% of all couples remain involuntarily infertile. In almost half of these cases, a lack of conception can in some measure be attributed to the male partner, wherein de novo Y-chromosomal deletions of sperm-specific Deleted-in-Azoospermia (DAZ) genes are particularly prevalent. In the current study, long-term cultures of rat spermatogonial stem cells were evaluated after cryo-storage for their potential to restore fertility to rats deficient in the DAZ-like (DAZL) gene. Detailed histological analysis of DAZL-deficient rat testes revealed an apparently intact spermatogonial stem cell compartment, but clear failure to produce mature haploid gametes resulting in infertility. After proliferating >1 million-fold in cell number during culture post-thaw, as few as 50,000 donor spermatogonia transplanted into only a single testis/recipient effectively restored fecundity to DAZL-deficient rats, yielding 100% germline transmission to progeny by natural mating. Based on these results, the potency and efficacy of this donor stem cell line for restoring fertility to azoospermic rodents is currently unprecedented. Prospectively, similar successes in humans could be directly linked to the feasibility of obtaining enough fully functional spermatogonial stem cells from minimal testis biopsies to be therapeutically effective. Thus, regeneration of sperm production in this sterile recipient provides an advanced pre-clinical model for optimizing the efficacy of stem cell therapies to cure a paradoxically increasing number of azoospermic men. This includes males that are rendered infertile by cancer therapies, specific types of endocrine or developmental defects, and germline-specific de novo mutations; all of whom may harbor healthy sources of their own spermatogonial stem cells for treatment.
Truncated variants of hyaluronan-binding protein 1 bind hyaluronan and induce identical morphological aberrations in COS-1 cells (2004)

Hyaluronan (HA)-binding protein 1 (HABP1) is multifunctional in nature and exists as a trimer through coiled-coil interaction between alpha-helices at its N- and C-termini. To investigate the importance of trimeric assemblage and HA-binding ability of HABP1, we generated and overexpressed variants of HABP1 by truncating the alpha-helices at its termini. Subsequently, these variants were transiently expressed in COS-1 cells to examine the influence of these structural variations on normal cell morphology, as compared with those imparted by HABP1. Substantiating the centrality of coiled-coil interaction for maintaining the trimeric assembly of HABP1, we demonstrate that disruption of trimerization does not alter the affinity of variants towards its ligand HA. Transient expression of HABP1 altered the morphology of COS-1 cells by generating numerous cytoplasmic vacuoles along with disruption of the f-actin network. Interestingly, the truncated variants also imparted identical morphological changes. Characterization of the cytoplasmic vacuoles revealed that most of these vacuoles were autophagic in nature, resembling those generated under stress conditions. The identical morphological changes manifested in COS-1 cells on transient expression of HABP1 or its variants is attributed to their comparable HA-binding ability, which in concert with endogenous HABP1, may deplete the cellular HA pool. Such quenching of HA below a threshold level in the cellular milieu could generate a stress condition, manifested through cytoplasmic vacuoles and a disassembly of the f-actin network.
Review: Zoology: An Introduction to the Study of Animals, by Richard A. Boolootian (1980)

Book Review| November 01 1980 Review: Zoology: An Introduction to the Study of Animals, by Richard A. Boolootian Zoology: An Introduction to the Study of AnimalsRichard A. Boolootian G. M. Rosenthal G. M. Rosenthal Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (1980) 42 (8): 502–504. https://doi.org/10.2307/4447081 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation G. M. Rosenthal; Review: Zoology: An Introduction to the Study of Animals, by Richard A. Boolootian. The American Biology Teacher 1 November 1980; 42 (8): 502–504. doi: https://doi.org/10.2307/4447081 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe American Biology Teacher Search This content is only available via PDF. Copyright 1980 The National Association of Biology Teachers Article PDF first page preview Close Modal You do not currently have access to this content.
Property changes of UHMW polyethylene hip cup endoprostheses during implantation (1984)

In this study it is demonstrated that the combined chemical and mechanical influences of the implant situation cause property changes of ultra-high-molecular-weight polyethylene (UHMW PE) hip joint cups. Nearly 30 out of 48 loosened cups, retrieved 3 weeks to 11 years after implantation, were investigated. Density measurements show a density increase with implantation time and a dependence of these changes from implant position and loading conditions. The rate of extractable constituents also increases with course of time. An increased in vivo conditioned oxidation of the UHMW PE can be demonstrated by infrared (IR) spectrometry. The density increase can be explained by post-crystallization, which is the result of oxidative chain scission. This leads to a reduction of the average molecular weight of the PE and to an increased extractability of constituents. Since these changes have been recognized as the reasons for aging and failing of UHMW PE, the methods of material characterization used in this study for retrieved implants will help to develop suitable in vitro testing and simulating methods. They are the prerequisite for the necessary improvements of the material properties of UHMW PE.
Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family (2002)

We have cloned and characterized a human cDNA that belongs to the histone deacetylase family, which we designate as HDAC11. The predicted HDAC11 amino acid sequence reveals an open reading frame of 347 residues with a corresponding molecular mass of 39 kDa. Sequence analyses of the putative HDAC11 protein indicate that it contains conserved residues in the catalytic core regions shared by both class I and II mammalian HDAC enzymes. Putative orthologues of HDAC11 exist in primate, mouse, Drosophila, and plant. Epitope-tagged HDAC11 protein expressed in mammalian cells displays histone deacetylase activity in vitro. Furthermore, HDAC11's enzymatic activity is inhibited by trapoxin, a known histone deacetylase inhibitor. Multiple tissue Northern blot and real-time PCR experiments show that the high expression level of HDAC11 transcripts is limited to kidney, heart, brain, skeletal muscle, and testis. Epitope-tagged HDAC11 protein localizes predominantly to the cell nucleus. Co-immunoprecipitation experiments indicate that HDAC11 may be present in protein complexes that also contain HDAC6. These results indicate that HDAC11 is a novel and unique member of the histone deacetylase family and it may have distinct physiological roles from those of the known HDACs.
Detection, evaluation, and management of iron-restricted erythropoiesis (2010)

Progress in our understanding of iron-restricted erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted erythropoiesis.
Telomerase-independent Regulation of ATR by Human Telomerase RNA (2006)

The human telomerase RNA (hTR), together with the telomerase reverse transcriptase, hTERT, constitute the core components of telomerase that is essential for telomere maintenance. While hTR is ubiquitously expressed, hTERT is normally restricted to germ cells and certain stem cells, but both are often deregulated during tumorigenesis. Here, we investigated the effects of changes in hTR cellular levels. Surprisingly, while inhibition of hTR expression triggers a rapid, telomerase-independent, growth arrest associated with p53 and CHK1 activation, its increased expression neutralizes activation of these pathways in response to genotoxic stress. These hTR effects are mediated through ATR and are sufficiently strong to impair ATR-mediated DNA-damage checkpoint responses. Furthermore, in response to low UV radiation, which activates ATR, endogenous hTR levels increase irrespective of telomerase status. Thus, we uncovered a novel, telomerase-independent, function of hTR that restrains ATR activity and participates in the recovery of cells from UV radiation.
Slow-binding inhibition of NAD+ glycohydrolase by arabino analogues of beta-NAD. (1992)

Modifications at the 2'-position of the nicotinamide-ribosyl moiety influence dramatically the nature of the interactions of the modified beta-NAD+ with calf spleen NAD+ glycohydrolase (EC 3.2.2.6), an enzyme that cleaves the nicotinamide-ribose bound in NAD(P)+. Nicotinamide arabinoside adenine dinucleotide (ara-NAD+) and nicotinamide 2'-deoxy-2'-fluoroarabinoside adenine dinucleotide (araF-NAD+) are not hydrolyzed at measurable rates and are the first documented examples of reversible slow binding inhibitors of this class of enzyme. The kinetic data obtained are consistent with both slow kon and koff rate constants in the formation of an enzyme-inhibitor complex, i.e. the association rate constants are about 10(4) and 10(6) slower than diffusion rates, respectively, for araF-NAD+ and ara-NAD+, and the half-life of the complex is about 3-10 min for both analogues. The kinetic model does not account for a slow turnover of an ADP-ribosyl-enzyme intermediary complex. AraF-NAD+ is one of the most potent inhibitors described for NAD+ glycohydrolase.
Preparation and characteristics of pyroelectric infrared sensors made of c-axis oriented La-modified PbTi03 thin films (1987)

Highly c-axis oriented La-modified PbTiO3 (PLT) thin films were deposited on (100) oriented Pt thin film or (100) cleaved MgO single crystals by rf-magnetron sputtering. Figures of merit for infrared detector were studied on the PLT thin films. It was found that a composition Pb1−xLaxTi1−x/4O3 where x=0.10 (PL10) was the most suitable for the infrared detector. The films have the advantage of having pyroelectric effect and polarization with the same direction even without a poling treatment. The films have high figures of merit Fv(=γ/cvεr) of 0.83×10−10 (C cm/J) and Fm(=γ/cv(εr tan δ)1/2) of 1.2×10−8 (C cm/J) because of relative low-dielectric constant εr of 200 and high-pyroelectric coefficient γ of 5.3×10−8 C/cm2 K. Both the Fv and the Fm of the films are 3 times as large as those of PbTiO3 ceramics. High sensitive pyroelectric infrared sensors were fabricated by using the PL10 films. The thickness of the films is 2 μm, and the electrodes were vacuum evaporated Ni-Cr of approximate area 7×10−4 cm2. The MgO substrate under the sensing area is etched off by phosphoric acid. The sensors have a large voltage responsivity of 2400 (V/W) at 25 Hz. A high specific detectivity D*(500,25,1) of 5×108 (cm(Hz)1/2 /W) has been attained.
Preparation, characterization, and properties of polylactide (PLA)–poly(ethylene glycol) (PEG) copolymers: A potential drug carrier (1990)

Abstract Polylactide (PLA)‐poly(ethylene glycol) (PEG) copolymers were synthesized from polyethylene glycol and D , L ‐lactide using low toxic stannous octoate as catalyst at 180°C by bulk polymerization. The copolymers were characterized by GPC, IR, and 13 C‐NMR. A full assignment NMR spectrum is presented. The physical, drug release, and biodegradable properties in vitro of PLA–PEG copolymers were investigated. The result indicates that the rates of drug release and biodegradation could be tailored by adjusting polymer composition. This amorphous material might be used as a drug carrier in medical applications.
Statistical Methods in Genetic Mapping (1994)

This report describes the proceedings from the second Workshop on Statistical Methods in Genetic Mapping, held in Tarrytown, NY on November 13-15, 1995. The workshop was supported by a grant from the National Center for Human Genome Research and covered a wide variety of topics pertaining to genetic mapping methods, integration and concerns. 25 refs.
The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine (1989)

The potent reinforcing properties of psychoactive drugs have been attributed to the activation of motivational processes localized to the limbic system. We investigated the role of 2 specific outputs of the forebrain limbic system, the tegmental pedunculopontine nucleus (TPP) and the periacqueductal gray (PAG) of the pons-midbrain, in the positive motivational effects of morphine and amphetamine. We now report that the TPP, but not the PAG nor other nearby regions, is a critical site in the neural system subserving the rewarding effects of both opiates and stimulants. Bilateral ibotenic acid lesions of the TPP blocked the positive reinforcing effects of both morphine and amphetamine in naive rats as measured in a conditioned place preference paradigm. However, TPP lesioned animals were still capable of acquiring a conditioned place preference to an environment paired with the peripheral opiate antagonist methylnaltrexone. This suggested that TPP lesions did not cause nonspecific deficits in the basic learning mechanisms underlying conditioned place preferences. Furthermore, while the TPP was critical for the acquisition of a conditioned preference to an environment paired with morphine in naive rats, rats that had acquired a morphine conditioned place preference prior to the lesions were capable of retaining and demonstrating these place preferences after lesions of the TPP. This again demonstrates that TPP lesions are producing an unconditioned deficit in motivation rather than a deficit in learning or memory. Finally, direct comparisons of the place preference data of individual animals with their correspondent TPP lesion sites indicated that the most effective lesions overlapped to a greater degree TPP perikarya with descending, rather than ascending, axons. This suggests that motivational information generated by drug stimuli acting at "upstream" neural structures flows in a descending direction through the TPP region of the brain stem. These results suggest that opiates and stimulants must ultimately activate a single brain-stem substrate in order to have a positive motivational impact. It is hypothesized that the neural circuits mediating the rewarding effects of drug stimuli acting at forebrain sites exit the limbic system in the TPP region of the brain stem, where motivation may ultimately influence or be isomorphic with the elicitation of motor responses subserving approach and exploration.
Fluorescein Binding to Normal Human Serum Proteins Demonstrated by Equilibrium Dialysis (1982)

The binding of fluorescein to normal human serum proteins in a physiologic solvent at 37 degree C was measured by equilibrium dialysis. Human serum contained 3.28 X 10(-3)M concentration fluorescein-binding sites, with an average association constant at 37 degree C of 0.54 X 10(4)M(-1). The percentage of total fluorescein bound by human serum proteins ranged from 83% to 53% when the total fluorescein concentration ranged from 6.9 X 10(-5) to 6.2 X 10(-3)M.
Real‐time diagnostic imaging of tumors and metastases by use of a replication‐competent herpes vector to facilitate minimally invasive oncological surgery (2006)

Current efforts on expanding minimally invasive techniques into the realm of oncological surgery are hindered by lack of accurate visualization of tumor margins and failure to detect micro metastases in real time. We used a systemic delivery of a herpes viral vector with cancer-selective infection and replication to precisely differentiate between normal and malignant tissue. NV1066 is a genetically modified, replication-competent herpes simplex virus carrying a transgene for enhanced green fluorescent protein (GFP). We tested the potential of NV1066 in delineating tumor tissue in vitro and in vivo in a wide range of cancers and whether NV1066-induced GFP expression can detect small foci of tumors and metastases in in vivo models using an operating endoscope with fluorescent filters. Our findings indicate that NV1066 can be used for real-time intraoperative imaging and enhanced detection of early cancers and metastases. We demonstrate that a single dose of NV1066, administered either locally (intratumoral or intracavitary) or systemically, will detect loco-regional and distant disease throughout the body. Such cancer selectivity is confirmed in 110 types of cancer cells from 16 different primary organs. Fluorescence-aided minimally invasive endoscopy revealed microscopic tumor deposits unrecognized by conventional laparoscopy/thoracoscopy. Furthermore, NV1066 ability to transit and infect tumor and metastases is proven in syngenic and transplanted tumors in different animal models, both immunocompetent and immunodeficient. Cancer-selective GFP expression is confirmed by histology, immunohistochemistry, and qRT-PCR. These studies form the basis for real-time, intraoperative diagnostic imaging of tumor and metastases by minimally invasive endoscopic technology.
Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity (2011)

IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5-producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5-producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5-producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5-producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5-producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer.