gebhart/patrepeval huggingface dataset:
GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. (1997)

Previous studies have suggested that the GATA4 transcription factor plays an important role in regulating mammalian cardiac development. In the studies described in this report we have used gene targeting to produce GATA4-deficient mice. Homozygous GATA4-deficient (GATA4-/-) mice died between 8.5 and 10.5 days post coitum (dpc). GATA4-/- embryos displayed severe defects in both rostral-to-caudal and lateral-to-ventral folding, which were reflected in a generalized disruption of the ventral body pattern. This resulted in the defective formation of an organized foregut and anterior intestinal pore, the failure to close both the amniotic cavity and yolk sac, and the uniform lack of a ventral pericardial cavity and heart tube. Analysis of cardiac development in the GATA4-/- mice demonstrated that these embryos developed splanchnic mesoderm, which differentiated into primitive cardiac myocytes that expressed contractile proteins. However, consistent with the observed defect in ventral morphogenesis, these GATA4-/- procardiomyocytes failed to migrate to the ventral midline to form a linear heart tube and instead formed aberrant cardiac structures in the anterior and dorsolateral regions of the embryo. The defect in ventral migration of the GATA4-/- procardiomyocytes was not cell intrinsic because GATA4-/- cardiac myocytes and endocardial cells populated the hearts of GATA4-/- -C57BL/6 chimeric mice. Taken together, these results demonstrated that GATA4 is not essential for the specification of the cardiac cell lineages. However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis.
[Implantation of embryonic pancreas into the anterior chamber of healthy and diabetic rats]. (1988)

The possibility of pancreatic-islet embryonic implantation into the frontal chamber of the eye in Wistar rats has been demonstrated. The implantation was followed by the induction of alloxan diabetes. Clinical diabetic compensation has been shown in a number of experimental animals (maximum time of experiments--45 days). The formation of islet-like structures in the frontal chamber of the eye was confirmed microscopically. The structures contained B cells in their cytoplasm. Cellular differentiation leading to the appearance of functionally active endocrine cells has been noted in the implants.
The oxygen status of the developing seed (2009)

Recent applications of oxygen-sensitive microsensors have demonstrated steep oxygen gradients in developing seeds of various crops. Here, we present an overview on oxygen distribution, major determinants of the oxygen status in the developing seed and implications for seed physiology. The steady-state oxygen concentration in different seed tissues depends on developmental parameters, and is determined to a large extent by environmental factors. Photosynthetic activity of the seed significantly diminishes hypoxic constraints, and can even cause transient, local hyperoxia. Changes in oxygen availability cause rapid adjustments in mitochondrial respiration and global metabolism. We argue that nitric oxide (NO) is a key player in the oxygen balancing process in seeds, avoiding fermentation and anoxia in vivo. Molecular approaches aiming to increase oxygen availability within the seed are discussed.
Probiotics Have a Different Immunomodulatory Potential in vitro versus ex vivo upon Oral Administration in Children with Food Allergy (2007)

Probiotics enhanced the production of Th1 and regulatory cytokines in vitro. Oral administration of probiotics resulted in a slightly decreased ex vivo production of IL-10, TNF-alpha and IL-6. This indicates that probiotics have a different potential to modulate the immune response in vitro versus ex vivo.
Crystal Structure of the Cysteine-rich Secretory Protein Stecrisp Reveals That the Cysteine-rich Domain Has a K+ Channel Inhibitor-like Fold (2005)

Stecrisp from Trimeresurus stejnegeri snake venom belongs to a family of cysteine-rich secretory proteins (CRISP) that have various functions related to sperm-egg fusion, innate host defense, and the blockage of ion channels. Here we present the crystal structure of stecrisp refined to 1.6-angstrom resolution. It shows that stecrisp contains three regions, namely a PR-1 (pathogenesis-related proteins of group1) domain, a hinge, and a cysteine-rich domain (CRD). A conformation of solvent-exposed and -conserved residues (His60, Glu75, Glu96, and His115) in the PR-1 domain similar to that of their counterparts in homologous structures suggests they may share some molecular mechanism. Three flexible loops of hypervariable sequence surrounding the possible substrate binding site in the PR-1 domain show an evident difference in homologous structures, implying that a great diversity of species- and substrate-specific interactions may be involved in recognition and catalysis. The hinge is fixed by two crossed disulfide bonds formed by four of ten characteristic cysteines in the carboxyl-terminal region and is important for stabilizing the N-terminal PR-1 domain. Spatially separated from the PR-1 domain, CRD possesses a similar fold with two K+ channel inhibitors (Bgk and Shk). Several candidates for the possible functional sites of ion channel blocking are located in a solvent-exposed loop in the CRD. The structure of stecrisp will provide a prototypic architecture for a structural and functional exploration of the diverse members of the CRISP family.
IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells (1997)

We studied to what extent the presence of an inflammatory mediator PGE2, during the development of dendritic cells (DC) affects their subsequent ability to induce Th1- and Th2-type cytokines in maturing naive Th cells. PGE2 (10(-9)-10(-6) M) did not alter the morphology or the expression of class II MHC and costimulatory molecules on DC obtained from monocytes in the presence of granulocyte-macrophage CSF and IL-4, although at concentrations above 10(-8) M, PGE2 prevented the acquisition of CD1a marker. Both control DC and DC maturing in the presence of PGE2 (PGE2-DC) were potent stimulators of naive Th cells. In contrast to control DC, which produced high amounts of IL-12 and trace amounts of IL-10, PGE2-DC produced no IL-12 and high amounts of IL-10 when stimulated in the absence of PGE2. This distinct cytokine profile of PGE2-DC was stable for at least 48 h of additional culture in the absence of PGE2. Control DC induced the development of Th0-like cells from superantigen-activated naive Th cells, whereas PGE2-DC promoted the development of Th cells that produced high amounts of IL-4 and IL-5. Experiments using IL-12-neutralizing Abs or rIL-12 indicated a crucial role of IL-12 deficiency in the induction of type 2 cytokine profiles. These findings suggest that elevated levels of PGE2 promote type 2 Th responses by stably impairing the ability of maturing DC to produce IL-12. Since type 2 Th responses are protective in several Th1-related autoimmune disorders, PGE2-DC may be considered for use in immunotherapy.
Effect of Proteolytic Enzymes on Bacterial Flagella (1972)

Sheared flagella of Salmonella typhimurium strains SL 870 (Nml(+)Fla(+)) and SL 871 (Nml(-)Fla(+)) were found to be susceptible to proteolytic digestion by trypsin, chymotrypsin, and Pronase. The rate of tryptic digestion was similar for the epsilon-N-methyllysine-containing and the nonmethylated flagella. Thin fibers, which appeared to originate from only one end of the flagellar filament, were formed upon trypsin digestion. The fibers were not dissociated at extremes of pH or upon heating. The amino acid composition of the purified fibers was very different from that of intact Salmonella flagellin, and the fibers did not cross-react with antiflagellin or antiflagellar antiserum. The possible significance of these findings is discussed in relation to the flagellar structure.
Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells (2010)

Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor-mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient-derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells.
High Quality GaN Layers on Si(111) Substrates: AlN Buffer Layer Optimisation and Insertion of a SiN Intermediate Layer (2001)

We present a study on the material properties of GaN films grown on (111) silicon substrates by low-pressure metalorganic chemical vapour deposition using AlN buffer layers. This buffer layer is optimised with respect to growth temperature and time for the optical and structural properties of the GaN epilayers. The insertion of a SixNy intermediate layer significantly increases the optical and structural properties. It results in a reduction of the D0X FWHM to 10 meV and in a 2.5-fold increase of its luminescence intensity. The FWHM of symmetric and asymmetric ω-scans are reduced from 832 to 669 arcsec and from 702 to 547 arcsec, respectively.
An Armamentarium of Wart Treatments (2006)

Patients and clinicians experience the frustration of cutaneous viral warts caused by infection with the human papilloma virus (HPV).Warts appear in various forms on different sites of the body and include common warts (verruca vulgaris), plane or flat warts, myrmecia, plantar warts, coalesced mosaic warts, filiform warts, periungual warts, anogenital warts (venereal or condyloma acuminata), oral warts and respiratory papillomas. Cervical infection with HPV is now known to cause cervical cancer if untreated. A review of the medical literature reveals a huge armamentarium of wart monotherapies and combination therapies. Official evidence-based guidelines exist for the treatment of warts, but very few of the reported treatments have been tested by rigorous blinded, randomized controlled trials.Therefore, official recommendations do not often include treatments with reportedly high success rates, but they should not be ignored when considering treatment options. It is the purpose of this review to provide a comprehensive overview of the wart treatment literature to expand awareness of the options available to practitioners faced with patients presenting with problematic warts.
Post-Thaw Viability and Functionality of Cryopreserved Rat Fetal Brain Cells Cocultured with Sertoli Cells (1997)

Testis-derived Sertoli cells have been used to create an immune “privileged” site outside of the testis to facilitate cell transplantation protocols for diabetes and neurodegenerative diseases. In addition to secreting immunoprotective factors, Sertoli cells also secrete growth and trophic factors that appear to enhance the posttransplantation viability of isolated cells and, likewise, the postthaw viability of isolated, cryopreserved cells (26). It would be beneficial if Sertoli cells could be cryopreserved with the transplantable cell type without deleterious effects on the cells. This report describes a protocol for the cocryopreservation of rat Sertoli cells with rat ventral mesencephalic neurons, neurons from the lateral and medial ganglionic eminences and the hNT neuron cell line, and reports on the effects of Sertoli cells on the the postthaw viability of these neurons. Results of trypan blue exclusion analysis indicated that the presence of Sertoli cells did not deleteriously effect cryopreserved neurons and may improve their postthaw recoverability and viability in general. Specifically, results of the tyrosine hydroxylase immunostaining showed that Sertoli cells significantly enhance the postthaw viability of ventral mesencephalic dopaminergic cells in vitro.
Ring closure reactions of cyclic 2‐arylaminomethylene‐1,3‐diones (1996)

Abstract 5‐Arylaminomethylene compounds such as 5‐arylaminomethylenepyrimidine‐2,4,6‐triones 2 or 2‐phenylaminomethylenephenalene‐1,3‐dione 13 cyclize by thermolysis via migration of the arylamino group to pyrimido[4,5‐ b ]quinoline‐2,4‐diones 6 or 7‐oxo‐7 H ‐naphtho[1,8‐ bc ]acridine 15 , respectively. 2‐Phenylaminomethylenecyclohexane‐1,3‐dione 8 cyclizes to 9,9‐dimethyl‐9,10‐dihydrophenanthridin‐7(8 H )‐one 11 without rearrangement.
Angiogenesis: state of the art. (1999)

Considerable progress has been made recently in understanding the molecular mechanisms of angiogenesis, the formation of new blood vessels by a process of sprouting from preexisting vessels. Angiogenesis is fundamental to a number of physiological processes, including embryonic development, the normal menstrual cycle, and tissue or organ regeneration in which growth of new capillaries is tightly controlled by a finely tuned balance between positive and negative mediators of endothelial cell growth. When blood vessels grow unabated or out of control, angiogenesis becomes pathologic and plays a key role in the development of many neoplastic and non-neoplastic diseases. Presently, abundant results from laboratory experiments and clinical trials have greatly improved our understanding of the molecular basis underlying angiogenic events and paved a new way to the diagnosis and treatment of diseases that depend on angiogenesis. This review focuses on the current advances in the regulation and clinical application of angiogenesis.
An “Exacerbate-reverse” Strategy in Yeast Identifies Histone Deacetylase Inhibition as a Correction for Cholesterol and Sphingolipid Transport Defects in Human Niemann-Pick Type C Disease (2011)

Niemann-Pick type C (NP-C) disease is a fatal lysosomal lipid storage disorder for which no effective therapy exists. A genome-wide, conditional synthetic lethality screen was performed using the yeast model of NP-C disease during anaerobiosis, an auxotrophic condition that requires yeast to utilize exogenous sterol. We identified 12 pathways and 13 genes as modifiers of the absence of the yeast NPC1 ortholog (NCR1) and quantified the impact of loss of these genes on sterol metabolism in ncr1Δ strains grown under viable aerobic conditions. Deletion of components of the yeast NuA4 histone acetyltransferase complex in ncr1Δ strains conferred anaerobic inviability and accumulation of multiple sterol intermediates. Thus, we hypothesize an imbalance in histone acetylation in human NP-C disease. Accordingly, we show that the majority of the 11 histone deacetylase (HDAC) genes are transcriptionally up-regulated in three genetically distinct fibroblast lines derived from patients with NP-C disease. A clinically approved HDAC inhibitor (suberoylanilide hydroxamic acid) reverses the dysregulation of the majority of the HDAC genes. Consequently, three key cellular diagnostic criteria of NP-C disease are dramatically ameliorated as follows: lysosomal accumulation of both cholesterol and sphingolipids and defective esterification of LDL-derived cholesterol. These data suggest HDAC inhibition as a candidate therapy for NP-C disease. We conclude that pathways that exacerbate lethality in a model organism can be reversed in human cells as a novel therapeutic strategy. This "exacerbate-reverse" approach can potentially be utilized in any model organism for any disease.
IRTAs: a new family of immunoglobulinlike receptors differentially expressed in B cells (2002)

The IRTA1 and IRTA2 genes encode immunoglobulinlike cell surface receptors expressed in B cells and involved in chromosome 1q21 translocations in B-cell malignancy. We have now characterized and comparatively analyzed the structure and expression pattern of the entire family of IRTA genes, which includes 5 members contiguously located on chromosome 1q21. The IRTA messenger RNAs are expressed predominantly in the B-cell lineage within discrete B-cell compartments: IRTA1 is specific to the marginal zone, IRTA2 and IRTA3 are found in the germinal center light zone and in intraepithelial and interfollicular regions, and IRTA4 and IRTA5 are expressed predominantly in the mantle zone. All IRTA genes code for transmembrane receptors that are closely related to Fc receptors in their most amino-terminal extracellular domains and that possess cytoplasmic domains containing ITIM (immunotyrosine inhibition motifs)- and, possibly, ITAM (immunotyrosine activation motifs)-like motifs. These structural features suggest that the IRTA receptors may play a role in regulating activation of normal B cells and possibly in the development of neoplasia.
Hypoactive sexual desire disorder in postmenopausal women: US results from the Women's International Study of Health and Sexuality (WISHeS) (2006)

HSDD is prevalent among women at all reproductive stages, with younger surgically postmenopausal women at greater risk, and is associated with a less active sex life and decreased sexual and relationship satisfaction.
Wavelet-based lossless compression of coronary angiographic images (1999)

The final diagnosis in coronary angiography has to be performed on a large set of original images. Therefore, lossless compression schemes play a key role in medical database management and telediagnosis applications. This paper proposes a wavelet-based compression scheme that is able to operate in the lossless mode. The quantization module implements a new way of coding of the wavelet coefficients that is more effective than the classical zerotree coding. The experimental results obtained on a set of 20 angiograms show that the algorithm outperforms the embedded zerotree coder, combined with the integer wavelet transform, by 0.38 bpp, the set partitioning coder by 0.21 bpp, and the lossless JPEG coder by 0.71 bpp. The scheme is a good candidate for radiological applications such as teleradiology and picture archiving and communications systems (PACS's).
The chromatoid body of male germ cells: Similarity with processing bodies and presence of Dicer and microRNA pathway components (2006)

The chromatoid body is a perinuclear, cytoplasmic cloud-like structure in male germ cells whose function has remained elusive. Here we show that the chromatoid body is related to the RNA-processing body of somatic cells. Dicer and components of microRNP complexes (including Ago proteins and microRNAs) are highly concentrated in chromatoid bodies. Furthermore, we show that Dicer interacts with a germ cell-specific chromatoid body component, the RNA helicase MVH (mouse VASA homolog). Thus, chromatoid bodies seem to operate as intracellular nerve centers of the microRNA pathway. Our findings underscore the importance of posttranscriptional gene regulation and of the microRNA pathway in the control of postmeiotic male germ cell differentiation.
Analysis of endogenous glutathione‐adducts and their metabolites (2009)

The ability to conduct validated analyses of glutathione (GSH)-adducts and their metabolites is critically important in order to establish whether they play a role in cellular biochemical or pathophysiological processes. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides the highest bioanalytical specificity possible for such analyses. Quantitative studies normally require the high sensitivity that can be obtained by the use of multiple reaction monitoring (MRM)/MS rather than the much less sensitive but more specific full scanning methodology. The method employs a parent ion corresponding to the intact molecule together with a prominent product ion that obtained by collision induced dissociation. Using SID LC-MRM/MS, analytes must have the same relative LC retention time to the heavy isotope internal standard established during the validation procedure, the correct parent ion and the correct product ion. This level of specificity cannot be attained with any other bioanalytical technique employed for biomarker analysis. This review will describe the application of SID LC-MR/MS methodology for the analysis of GSH-adducts and their metabolites. It will also discuss potential future directions for the use of this methodology for rigorous determination of their utility as disease and exposure biomarkers.
Diversity among clinical isolates of Histoplasma capsulatum detected by polymerase chain reaction with arbitrary primers (1992)

Clinical isolates of the fungal respiratory and systemic pathogen Histoplasma capsulatum have been placed in several different classes by using genomic restriction fragment length polymorphisms (RFLPs), but in general have not been distinguished further. We report here that a polymerase chain reaction (PCR)-based DNA fingerprinting method that has been termed arbitrary primer or random amplified polymorphic DNA (RAPD) PCR can distinguish among isolates in a single RFLP class. In this method, arbitrarily chosen oligonucleotides are used to prime DNA synthesis from genomic sites that they fortuitously match, or almost match, to generate strain-specific arrays of DNA fragments. Each of 29 isolates of RFLP class 2, the group endemic in the American Midwest, was distinguished by using just three arbitrary primers. In contrast, laboratory-derived S and E colony morphology variants of two strains were not distinguished from their R parents by using 18 such primers. Thus, the clinical isolates of H. capsulatum are quite diverse, but their genomes remain stable during laboratory culture. These outcomes suggest new possibilities for epidemiological analysis and studies of fungal populations in infected hosts.
Evaluation of Immunoassay Methods for the Screening of Cocaine Metabolites in Urine (1991)

Immunoassay kits for urine cocaine (and metabolite) screening, obtained from two commercial sources, were examined for correlation of their results, expressed in terms of equivalent benzoylecgonine concentration, with the gas chromatography/mass spectrometry (GC/MS) concentration of benzoylecgonine. The correlation coefficients obtained, based on 62 (out of a total sample population of 3295) highly relevant samples, were 0.467 and 0.766 for Abuscreen (ARIA) and TDx (TDX), respectively. The preliminary screen cutoff values, which correspond to 150 ng/mL benzoylecgonine (as determined by GC/MS), were calculated based on the resulting regression equations and found to be 380 and 190 ng/mL for ARIA and TDX, respectively. With these cutoff values, ARIA generates 5 false negatives and 16 unconfirmed presumptive positives, while TDX results in 3 false negatives and 6 unconfirmed presumptive positives.