julilili42/papers huggingface dataset:
Faculty Opinions recommendation of Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice.
2007-08-16

In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, express the opsin-like protein melanopsin, and project to brain nuclei involved in non-image-forming visual functions such as pupillary light reflex and circadian photoentrainment. We report that in mice with the melanopsin gene ablated, RGCs retrograde-labeled from the suprachiasmatic nuclei were no longer intrinsically photosensitive, although their number, morphology, and projections were unchanged. These animals showed a pupillary light reflex indistinguishable from that of the wild type at low irradiances, but at high irradiances the reflex was incomplete, a pattern that suggests that the melanopsin-associated system and the classical rod/cone system are complementary in function. PMID: 12522249 Funding information This work was supported by: NEI NIH HHS, United States Grant ID: R37 EY006837-15 NEI NIH HHS, United States Grant ID: R01 EY006837-16A1 NEI NIH HHS, United States Grant ID: R37 EY006837-14 NEI NIH HHS, United States Grant ID: R37 EY006837-13 NEI NIH HHS, United States Grant ID: R37 EY006837 NEI NIH HHS, United States Grant ID: R01 EY014596-01 NEI NIH HHS, United States Grant ID: R37 EY006837-15S1 NEI NIH HHS, United States Grant ID: R01 EY014596 NEI NIH HHS, United States Grant ID: R01 EY006837 More Less keyboard_arrow_down
Faculty Opinions recommendation of Origin of the relative afferent pupillary defect in optic tract lesions.
2007-08-16

OBJECTIVE: To determine the percent decussation of pupil input fibers in humans and to explain the size and range of the log unit relative afferent pupillary defect (RAPD) in patients with optic tract lesions.DESIGN: Experimental study.PARTICIPANTS AND CONTROLS: Five patients with a unilateral optic tract lesion.METHODS: The pupil response from light stimulation of the nasal hemifield, temporal hemifield, and full field of each eye of 5 patients with a unilateral optic tract lesion was recorded using computerized binocular infrared pupillography. Six stimulus light intensities, separated by 0.5-log unit steps, were used; 12 stimulus repetitions were given for each stimulus condition.MAIN OUTCOME MEASURES: For each stimulus condition, the pupil response of each eye was characterized by plotting the mean pupil contraction amplitude as a function of stimulus light intensity. The percentage of decussating afferent pupillomotor input fibers was calculated from the ratio of the maximal pupil contractions elicited from each eye. The RAPD was determined pupillographically from full-field stimulation to each eye.RESULTS: In all patients, the pupil response from the functioning temporal hemifield ipsilateral to the tract lesion was greater than that from the functioning contralateral nasal hemifield. This temporal-nasal asymmetry increased with increasing stimulus intensity and was similar in hemifield and full-field stimuli, eventually saturating at maximal light intensity. The log unit RAPD did not correlate with the estimated percentage of decussating pupil fibers, which ranged from 54% to 67%.CONCLUSIONS: In patients with a unilateral optic tract lesion, the pupillary responses from full-field stimulation to each eye are the same as comparing the functioning temporal field with the functioning nasal field. The percentage of decussating fibers is reflected in the ratio of the maximal pupil contraction amplitudes resulting from stimulus input between the two eyes. The RAPD that occurs in this setting reflects the difference in light sensitivity between the intact temporal and nasal hemifields. Its magnitude does not correlate with the difference in the number of crossed and uncrossed axons, but its sidedness contralateral to the side of the optic tract lesion is consistent with the greater percentage of decussating pupillomotor input. PMID: 16877073
Crb1 is a determinant of retinal apical Müller glia cell features
2007-08-17

Abstract Mutations in the human Crumbs homologue‐1 ( CRB1 ) gene cause retinal blinding diseases, such as Leber congenital amaurosis and retinitis pigmentosa. In the previous studies we have shown that Crb1 resides in retinal Müller glia cells and that loss of Crb1 results in retinal degeneration (particularly in the inferior temporal quadrant of the mouse eye). Degeneration is increased by exposure to white light. Here, we studied the role of light and aging to gain a better understanding of the factors involved in the progress of retinal disease. Our data reveal that light is neither sufficient nor required to induce retinal disorganization and degeneration in young Crb1 −/− mutant mice, suggesting that it rather modulates the retinal phenotype. Gene expression profiling showed that expression of five genes is altered in light‐exposed Crb1 −/− mutant retinas. Three of the five genes are involved in chromosome stabilization (Pituitary tumor transforming gene 1 or Pttg1 , Establishment of cohesion 1 homolog 1 or Esco1 , and a gene similar to histone H2B ). In aged retinas, degeneration of photoreceptors, inner retinal neurons, and retinal pigment epithelium was practically limited to the inferior temporal quadrant. Loss of Crb1 in Müller glia cells resulted in an irregular number and size of their apical villi. We propose that Crb1 is required to regulate number and size of these Müller glia cell villi. The subsequent loss of retinal integrity resulted in neovascularization, in which blood vessels of the choroid protruded into the neural retina. © 2007 Wiley‐Liss, Inc.
Small but powerful: the oribatid miteArchegozetes longisetosusAoki (Acari, Oribatida) produces disproportionately high forces
2007-08-17

SUMMARY We investigated the holding and pulling forces generated by claws of the microarthropod Archegozetes longisetosus (Chelicerata, Acari,Oribatida) on three substrates with different roughness(Ra=0.05 μm, 1 μm, 30 μm). Holding forces were measured perpendicular to the substrate using a strain gage force transducer;pulling forces were measured parallel to the substrate using an analytical scale. We found a significant positive correlation of surface roughness and the forces generated. Mites produced holding forces on horizontal rough surfaces (Ra=30 μm) of up to 1180 times their weight;on vertical rough surfaces (Ra=30 μm) they can pull with 530 times their weight, effectively involving only two pairs of legs. The relative forces are five times higher than theoretically expected for organisms of this size (&amp;lt;1 mm, 100 μg) and higher than any relative forces reported for insect claws. Muscles involved in claw action produced stresses up to 1170 kN m–2, a value that is only excelled by decapod crustacean claw closer muscles. Ours is the first study of performance by chelicerate apoteles and claws and also the first to measure forces generated by any microarthropod.
Demonstration of autoantibodies to recombinant human sulphite oxidase in patients with chronic liver disorders and analysis of their clinical relevance
2007-08-17

Summary It has been shown previously that sera from patients with cholestatic liver diseases react with sulphite oxidase (SO) prepared from chicken liver. In order to analyse this reactivity and the clinical relevance of anti-SO antibodies in more detail, we produced human recombinant SO. Human recombinant SO (60 kDa) was expressed in Escherichia coli and applied to enzyme-linked immunosorbent assay and Western blot. Sera from patients with autoimmune liver disorders [primary biliary cirrhosis (PBC) n = 96; autoimmune hepatitis (AIH) n = 77; primary sclerosing cholangitis (PSC) n = 39], and from patients with other hepatic (n = 154) and non-hepatic chronic inflammatory disorders (n = 113) were investigated. Highest incidence and activities of IgG-anti-SO antibodies were observed in PSC patients. Nine of 16 untreated (56%) and four of 23 PSC patients treated with ursodeoxycholic acid (UDCA) (17%) were positive. Antibody activity decreased significantly during UDCA treatment. Five per cent of PBC and 9% of AIH patients, but also 15% of patients with alcoholic liver disease, were IgG anti-SO-positive. In patients with viral hepatitis and non-hepatic disorders they could be hardly detected. Anti-SO antibodies are further anti-mitochondrial antibodies in chronic liver diseases. They occur predominantly in PSC, and UDCA treatment seams to decrease antibody activity. Whether these antibodies are primary or secondary phenomena and whether they are related to the aetiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.
Colored Simultaneous Geometric Embeddings
2007-08-17

We introduce the concept of concept simultaneous geometric embeddings as a generalization of simultaneous graph embeddings with and without mapping. We show that there exists a universal pointset of size n for paths colored with two or three colors. We use these results to show that colored simultaneous geometric embeddings exist for: (1) a 2-colored tree together with any number of 2-colored paths and (2) a 2-colored outerplanar graph together with any number of 2-colored paths. We also show that there does not exist a universal pointset of size n for paths colored with five colors. We finally show that the following simultaneous embeddings are not possible: (1) three 6-colored cycles, (2) four 6-colored paths, and (3) three 9-colored paths. © Springer-Verlag Berlin Heidelberg 2007.
Mutations of theCEP290gene encoding a centrosomal protein cause Meckel-Gruber syndrome
2007-08-18

Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the list of ciliary disorders (ciliopathies). By positional cloning in a distantly related multiplex family, we mapped a novel locus for MKS to a 3-Mb interval on 12q21. Sequencing of the CEP290 gene located in the minimal critical region showed a homozygous 1-bp deletion supposed to lead to loss of function of the encoded centrosomal protein CEP290/nephrocystin-6. CEP290 is thought to be involved in chromosome segregation and localizes to cilia, centrosomes, and the nucleus. Subsequent analysis of another consanguineous multiplex family revealed homozygous haplotypes and the same frameshift mutation. Our findings add to the increasing body of evidence that ciliopathies can cause a broad spectrum of disease phenotypes, and pleiotropic effects of CEP290 mutations range from single organ involvement with isolated Leber congenital amaurosis to Joubert syndrome and lethal early embryonic multisystemic malformations in Meckel-Gruber syndrome. We compiled clinical and genetic data of all patients with CEP290 mutations described so far. No clear-cut genotype-phenotype correlations were apparent as almost all mutations are nonsense, frameshift, or splice-site changes and scattered throughout the gene irrespective of the patients' phenotypes. Conclusively, other factors than the type and location of CEP290 mutations may underlie phenotypic variability.
The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5‐lipoxygenase products
2007-08-20

Background and purpose: Licofelone is a dual inhibitor of the cyclooxygenase and 5‐lipoxygenase (5‐LO) pathway, and has been developed for the treatment of inflammatory diseases. Here, we investigated the molecular mechanisms underlying the inhibition by licofelone of the formation of 5‐LO products. Experimental approach: The efficacy of licofelone to inhibit the formation of 5‐LO products was analysed in human isolated polymorphonuclear leukocytes (PMNL) or transfected HeLa cells, as well as in cell‐free assays using respective cell homogenates or purified recombinant 5‐LO. Moreover, the effects of licofelone on the subcellular redistribution of 5‐LO were studied. Key results: Licofelone potently blocked synthesis of 5‐LO products in Ca 2+ ‐ionophore‐activated PMNL (IC 50 =1.7 μ M) but was a weak inhibitor of 5‐LO activity in cell‐free assays (IC 50 ≫10 μ M ). The structures of licofelone and MK‐886, an inhibitor of the 5‐LO‐activating protein (FLAP), were superimposable. The potencies of both licofelone and MK‐886 in ionophore‐activated PMNL were impaired upon increasing the concentration of arachidonic acid, or under conditions where 5‐LO product formation was evoked by genotoxic, oxidative or hyperosmotic stress. Furthermore, licofelone prevented nuclear redistribution of 5‐LO in ionophore‐activated PMNL, as had been observed for FLAP inhibitors. Finally, licofelone as well as MK‐886 caused only moderate inhibition of the synthesis of 5‐LO products in HeLa cells, unless FLAP was co‐transfected. Conclusions and implications: Our data suggest that the potent inhibition of the biosynthesis of 5‐LO products by licofelone requires an intact cellular environment and appears to be due to interference with FLAP. British Journal of Pharmacology (2007) 152 , 471–480; doi: 10.1038/sj.bjp.0707416 ; published online 20 August 2007
Mutant and Misfolded Human Growth Hormone is Rapidly Degraded Through the Proteasomal Degradation Pathway in a Cellular Model for Isolated Growth Hormone Deficiency Type II
2007-08-20

Autosomal dominant isolated growth hormone deficiency type II (IGHD II) is mainly caused by splice site mutations of the GH‐1 gene, leading to deletion of amino acids 32–71 of the human growth hormone (hGH). The severe hGH deficit in IGHD II suggests a dominant negative effect of the partially deleted del(32–71)‐hGH on the production, storage or secretion of normal wild‐type (wt)‐hGH in somatotrophic cells of the pituitary. To shed more light on the cellular and molecular basis of IGHD II, we established and analysed diverse clones of the rat somatotrophic cell line GH 4 C 1 stably expressing either wt‐hGH, del(32–71)‐hGH, or both proteins concomitantly. The cellular morphology of all transfected GH 4 C 1 cell clones showed moderate differences to untransfected GH 4 C 1 cells. On the molecular level, both cDNA‐constructs induced transcription but, under normal culture conditions, only wt‐hGH protein was found to be synthesised and secreted in readily detectable amounts. By contrast, only after inhibition of proteasomes did high amounts of del(32–71)‐hGH show up. The solubility of del(32–71)‐hGH in nondenaturing buffer was poor compared to wt‐hGH, hinting at molecular aggregation, and several epitopes recognised by monoclonal hGH antibodies were not present on del(32–71)‐hGH, confirming the assumption that del(32–71)‐hGH must be severely misfolded. Expression of both proteins in Escherichia coli mirrored the findings from the GH 4 C 1 cell clones in terms of solubility and immunological reactivity. The results of the present study indicate that, in IGHD II, somatotrophs continuously have to remove misfolded del(32–71)‐hGH via the proteasomal degradation pathway, suggesting a mechanism that may result in chronic cellular stress.
Light-driven liquid-crystalline nonlinear oscillator under optical periodic forcing
2007-08-20

An all-optically driven strategy to govern a liquid-crystalline collective molecular nonlinear oscillator is discussed. It does not require external feedback of any kind while the oscillator and a time-dependent perturbation both are sustained by incident light. Various dynamical regimes such as frequency-locked, quasiperiodic, forced, and chaotic are observed, in agreement with a theoretical approach developed in the limit of the plane-wave approximation.
Increasing the Efficiency of Paraffin Tissue Microarrays by Packing the Paraffin Tissue Core Biopsies in a Honeycomb Pattern
2007-08-21

Paraffin tissue microarrays (PTMAs) are blocks of paraffin holding up to 1000 paraffin tissue core biopsies (PTCBs) for high throughput molecular analysis. The number of PTCBs in a PTMA depends on the surface area of the PTMA, the diameter of and the distance between the PTCBs and on their arrangement inside the assembled PTMA. The PTCBs are usually arranged in a rectangular x-y pattern of rows and columns. This design facilitates the construction of a PTMA because the operator simply turns the wheels of an x-y-table for a set, unchanging distance. The evaluation of the stained sections is also relatively easy. However, this rectangular arrangement means wasted space in the PTMA. To reclaim this space, the PTCBs could be arranged in a honeycomblike pattern. For every 8 rows in the conventional rectangular arrangement, 1 additional row of PTCBs can be packed. However, the researcher has to become accustomed to this uncommon arrangement when filling and evaluating the PTMA. Automatic slide readers and specially designed computer programs for the digital evaluation of the PTMAs can be helpful. In summary, the arrangement of PTCBs in a honeycomblike pattern increases the density and number of specimens stored in a PTMA, thereby enhancing its efficiency.
Accumbal dopamine D2 receptors are important for sensorimotor gating in C3H mice
2007-08-21

One operational measure of sensorimotor gating that is deficient in many psychiatric disorders is prepulse inhibition (PPI) of the startle response. To investigate the role of dopamine D1 and D2 receptors within the nucleus accumbens (NAC) in sensorimotor gating in mice, we infused dopamine D1 and D2 receptor agonists (dihydrexidine and quinpirole respectively) directly into the NAC and measured the effects on PPI and on prepulse facilitation. Quinpirole infusions increased PPI and attenuated prepulse facilitation, whereas dihydrexidine had no effects. These results stand in contrast to data after systemic injections in mice and rats and intra-accumbal infusions in rats, suggesting that the role of dopamine D2 receptors within the NAC in mice differs from their role in rats.
Comparison of Pure-Tone Audiometry Analysis in Sudden Hearing Loss Studies
2007-08-23

The lack of an acceptable agreement between most measurement methods assessed in this report prevents a meaningful comparison of published clinical studies on ISSHL. For comparison of efficacy between different treatments in ISSHL and for the planning of controlled clinical trials, it is necessary to agree on standardized outcome measures, including the frequencies averaged and the criteria of success.
The Classical Fields
2007-08-23

The classical fields are the real, rational, complex and p-adic numbers. Each of these fields comprises several intimately interwoven algebraical and topological structures. This comprehensive volume analyzes the interaction and interdependencies of these different aspects. The real and rational numbers are examined additionally with respect to their orderings, and these fields are compared to their non-standard counterparts. Typical substructures and quotients, relevant automorphism groups and many counterexamples are described. Also discussed are completion procedures of chains and of ordered and topological groups, with applications to classical fields. The p-adic numbers are placed in the context of general topological fields: absolute values, valuations and the corresponding topologies are studied, and the classification of all locally compact fields and skew fields is presented. Exercises are provided with hints and solutions at the end of the book. An appendix reviews ordinals and cardinals, duality theory of locally compact Abelian groups and various constructions of fields.
Completion
2007-08-23

In Chapter 1, the basic properties of the real numbers were taken for granted. In Chapter 3, devoted to the rational numbers, we sometimes used the fact that they are embedded in the real numbers. In the present chapter, we shall discuss standard procedures which allow us to construct the domain of real numbers from the domain of rational numbers by so-called completion. (A non-standard procedure was already presented in Section 23.)
Real numbers
2007-08-23

This chapter is devoted to various aspects of the structure of R, the field of real numbers. Since we do not intend to give a detailed account of a construction of the real numbers from the very beginning, we need to clarify the basis of our subsequent arguments. What we shall assume about the real numbers is that they form an ordered field whose ordering is complete, in the sense that every non-empty bounded set of real numbers has a least upper bound. All these notions will be explained in due course, but presumably they are familiar to most readers. It is well known and will be proved in Section 11 that the properties just mentioned characterize the field of real numbers.
The p-adic numbers
2007-08-23

The idea of p-adic numbers is due to Hensel, who was inspired by local power series expansions of meromorphic functions (see Warner 1989 p. 469f, Ebbinghaus et al. 1991 Chapter 6 and Ullrich 1998). We treat the p-adic numbers as relatives of the real numbers. In fact, completion of the rational field Q with respect to an absolute value leads either to the reals R or to a field Qp of p-adic numbers, where p is a prime number (see 44.9, 44.10, 51.4, 55.4), and these fields are locally compact. We consider the additive and the multiplicative group of Qp in Sections 52 and 53, and we study squares and quadratic forms over Qp in Section 54. It turns out (see 53.2) that the additive and the multiplicative group of Qp are locally isomorphic, in the sense that some open (and compact) subgroup of Q×p is isomorphic to an open subgroup of Q+p; this is similar to the situation for R.
Rational numbers
2007-08-23

This chapter treats the different kinds of structures on the field Q of rational numbers (algebra, order and topology) and various combinations of them in the same way as it was done in Chapter 1 for the field R of real numbers.