Miracle-dz/UniFAR-FTUs huggingface dataset:
Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770) is a rare hereditary cause of presenile dementia with autosomal recessive inheritance. Its unique feature is the cystic bone lesions that accompany the dementia. About 160 cases have been reported to date, mostly in Finland and Japan. The etiology and pathogenesis of PLOSL are unknown. We recently assigned the locus for PLOSL in the Finnish population to chromosome 19q13.1 (P. Pekkarinen et al., 1998, Am. J. Hum. Genet. 62, 362-272). In the present study, we restrict the critical region for PLOSL to 153 kb by linkage-disequilibrium mapping. First, three new microsatellite markers were revealed in the PLOSL critical region. These and three other markers spanning the critical region were analyzed in Finnish PLOSL families. Strong linkage disequilibrium (multipoint P value < 10(-47)) was detected between the markers and PLOSL, and for two markers, D19S1176 and D19S610, all the PLOSL chromosomes shared identical 171- and 218-bp alleles, respectively. Haplotype analysis revealed five different haplotypes in the Finnish PLOSL chromosomes. But all of them shared the region between markers D19S1175 and D19S608 that could be traced to one ancestor haplotype by single recombination events, thus defining the critical region as 153 kb. Multipoint association analysis also assigned the most likely location of the PLOSL locus within this interval to the immediate vicinity of marker D19S610. A promising positional candidate for PLOSL, an amyloid precursor-like protein, was studied by sequencing, but no mutations were detected. These results lay the basis for the cloning of this novel dementia gene and for diagnostics in the Finnish population using haplotype analysis.
FISHing for chick genes: Triple‐label whole‐mount fluorescence in situ hybridization detects simultaneous and overlapping gene expression in avian embryos

Multi‐color whole‐mount in situ hybridization is a powerful technique for comparing the spatial expression patterns of two or more genes in developing embryos. We have developed an amplified triple‐label whole‐mount fluorescence in situ hybridization (FISH) protocol that permits detection of three different mRNAs in a single embryo. Our protocol uses simultaneous in situ hybridization to haptenylated riboprobes, followed by sequential antibody detection using anti‐hapten antibodies conjugated to horseradish peroxidase, and the tyramide signal amplification (TSA) fluorescence detection system. Conventional fluorescence microscopy identifies areas of overlapping gene expression at the tissue level, whereas confocal fluorescence microscopy permits single‐cell resolution and differentiates specialized cell types within a given tissue. This protocol will provide researchers engaged in the use of FISH with a solid starting point for adapting their own in situ hybridization protocols, either alone or in combination with immunohistochemistry or green fluorescence protein colocalization. Developmental Dynamics 229:651–657, 2004. © 2004 Wiley‐Liss, Inc.
The Influence of Learning Style and Cognitive Ability on Recall of Names and Faces in an Older Population

Abstract The present study examined whether, for older adults, a verbal or imagery cognitive style is associated with recall of names and faces learned in an experimental condition. Cognitive abilities that are represented in current models of face recognition and name recall were also examined. Those abilities included picture naming, verbal fluency (i.e., naming items within a given category), vocabulary comprehension, visual memory, and the learning of unassociated word pairs. Fifty older adults attempted to learn first and last names of 20 student actors and actresses pictured on videotapes (40 names total). On average, participants learned the most first names, followed by last names, and the fewest full names. The greater the number of responses on a questionnaire associated with an imagery cognitive style, the more the names of faces were correctly identified by participants. There was no significant relationship between a verbal cognitive style and the number of names and faces recalled. As for cognitive abilities, all of the abilities measured—with the exception of vocabulary comprehension—were significantly associated with the number of names and faces learned. A regression analysis indicated that the best predictor of successful name-face learning was the participants' ability to learn and recall 5 unrelated word pairs. When that cognitive measure was deleted from the regression analysis, delayed visual memory and verbal fluency were the next best predictors of the older adults' ability to learn names and faces.
Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers

Background Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific's Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. Methods 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Results Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. Conclusions While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers.
Alcohol consumption and academic performance in a population of Spanish high school students.

OBJECTIVE The present study was designed to identify patterns of alcohol consumption among Spanish high school students and describe the relationship between alcohol intake and school performance. METHOD The sample population consisted of students, aged 14 to 19 years, who were attending high school during the academic year 1994-95 in the city of Granada in southern Spain. We studied 1,602 (861 female) students (alpha error - 0.05, sampling error = 5%), using a self-administered questionnaire that contained items about individual and family demographics, quantity and frequency of alcohol consumption, and school performance. Total alcohol consumption was recorded as grams (g) of alcohol per week and per day for three categories of alcoholic drinks: wine, beer and distilled spirits. RESULTS The percentage of nondrinkers was 21.05% for male adolescents and 28.56% for female adolescents. The mean amount of alcohol consumed per week was larger in male than in female students (F= 18.36, l/l,594 df, p < .001) and distilled spirits accounted for the largest proportion of alcohol consumed. No significant differences in drinking patterns were found between students at public and private schools. The risk of academic failure increased considerably when more than 150 g of alcohol were consumed per week (OR: 2.91; 95% CI: 1.94-4.43). CONCLUSIONS Although we cannot draw any conclusions about the causes of the association between academic failure and teenage drinking, our results do show that the risk of failing increases together with alcohol intake. However, it should be noted that academic achievement is also influenced by many factors other than alcohol consumption.
Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va

Targeting of glutamate receptors (GluRs) to synapses involves rapid movement of intracellular receptors. This occurs in forms of synaptic upregulation of receptors, such as long‐term potentiation. Thus, many GluRs are retained in a cytoplasmic pool in dendrites, and are transported to synapses for upregulation, presumably via motor proteins such as myosins travelling along cytoskeletal elements that extend up into the spine. In this ultrastructural immunogold study of the cerebellar cortex, we compared synapses between normal rats/mice and dilute lethal mutant mice. These mutant mice lack myosin Va, which has been implicated in protein trafficking at synapses. The postsynaptic spine in the cerebellum lacks the inositol trisphosphate receptor (IP3R) ‐laden reticular tubules that are found in normal mice and rats (Takagishi et al., Neurosci. Lett., 1996, 215, 169). Thus, we tested the hypothesis that myosin Va is necessary for transport of GluRs and associated proteins to spine synapses. We found that these spines retain a normal distribution of (i) GluRs (delta 1/2, GluR2/3 and mGluR1α), (ii) at least one associated MAGUK (membrane‐associated guanylate kinase) protein, (iii) Homer (which interacts with mGluR1α and IP3Rs), (iv) the actin cytoskeleton, (v) the reticulum‐associated protein BiP, and (vi) the motor‐associated protein, dynein light chain. Thus, while myosin Va may maintain the IP3R‐laden reticulum in the spine for proper calcium regulation, other mechanisms must be involved in the delivery of GluRs and associated proteins to synapses. Other possible mechanisms include diffusion along the extrasynaptic membrane and delivery via other motors running along the spine's actin cytoskeleton.
SCFFbx2‐E3‐ligase‐mediated degradation of BACE1 attenuates Alzheimer’s disease amyloidosis and improves synaptic function

BACE1 (β‐secretase) plays a central role in the β‐amyloidogenesis of Alzheimer’s disease (AD). The ubiquitin–proteasome system, a major intracellular protein quality control system, has been implicated recently in BACE1 metabolism. We report that the SCFFbx2‐E3 ligase is involved in the binding and ubiquitination of BACE1 via its Trp 280 residue of F‐box‐associated domain. Physiologically, we found that Fbx2 was expressed in various intracellular organelles in brain neurons and that BACE1 is colocalized with Fbx2 and the amyloid precursor protein (APP), mainly at the early endosome and endoplasmic reticulum. The former are believed to be the major intracellular compartments where the APP is cleaved by BACE1 and β‐amyloid is produced. Importantly, we found that overexpression of Fbx2 in the primary cortical and hippocampal neurons derived from Tg2576 transgenic mice significantly promoted BACE1 degradation and reduced β‐amyloid production. In the search for specific endogenous modulators of Fbx2 expression, we found that PPARγ coactivator‐1α (PGC‐1α) was capable of promoting the degradation of BACE1 through a mechanism involving Fbx2 gene expression. Interestingly, we found that the expression of both Fbx2 and PGC‐1α was significantly decreased in the brains of aging Tg2576 mice. Our in vivo studies using a mouse model of AD revealed that exogenous adenoviral Fbx2 expression in the brain significantly decreased BACE1 protein levels and activity, coincidentally reducing β‐amyloid levels and rescuing synaptic deficits. Our study is the first to suggest that promoting Fbx2 in the brain may represent a novel strategy for the treatment of AD.
Celiac disease serology in dermatitis herpetiformis. Which is the best option for detecting gluten sensitivity?

BACKGROUND Dermatitis herpetiformis (DH), a well-established gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. OBJECTIVE Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. METHODS We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n = 6) to total villous atrophy (TVA) (n = 6) through partial villous atrophy (PVA) (n = 6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derived peptides (a-GDP). RESULTS Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identifed by a single assay detecting both isotypes of a-GDR CONCLUSION: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CD having mild enteropathy.
Toward three-dimensional quantum state-resolved collision dynamics at the gas-liquid interface: theoretical investigation of incident angle.

Quantum state-resolved energy transfer dynamics at the gas-liquid interface are explored through a comparison of classical molecular dynamics (MD) simulations and previously reported experimental studies (Perkins, B. G.; et al. J. Phys. Chem. A 2008, 112, 9234). Theoretically, large scale MD trajectory calculations have been performed for collisions of CO(2) with a model fluorinated self-assembled monolayer surface (F-SAMs), based on an explicit atom-atom interaction potential obtained from earlier theoretical studies (Martinez-Nunez, E.; et al. J. Phys. Chem. C 2007, 111, 354). Initial conditions for the simulations match those in the experimental studies where high-energy jet-cooled CO(2) molecules (E(inc) = 10.6(8) kcal/mol, approximately 10 cm(-1)) are scattered from a 300 K perfluorinated liquid surface (PFPE) from a range of incident angles (theta(inc) = 0-60 degrees ). Nascent CO(2) rotational distributions prove to be remarkably well characterized by a simple two-temperature trapping-desorption (TD) and impulsive scattering (IS) model with nearly quantitative agreement between experimental and theoretical column integrated densities. Furthermore, three-dimensional (3D) quantum state resolved flux maps for glancing incident angles (theta(inc) approximately 60 degrees ) reveal broad, lobular distributions peaking strongly in the forward subspecular direction as cos(n)(theta(scat) - theta') with n approximately 5.6(1.2) and theta' approximately 49(2) degrees .
The rise and fall of the European Defence Community: Anglo-American relations and the crisis of European defence, 1950-55

Dedication Acknowledgements Introduction: Agonizing Reappraisals PART I: THE CRISIS LOOMS Britain, the United States and the Rearming of Germany: October 1950 to May 1952 Anglo-American Relations and the EDC: May 1952 to December 1953 PART II: THE CRISIS BREAKS A Parting of the Ways: The Bermuda Conference and Paris NATO Council, December 1953 French Ratification of the EDC: Competing Anglo-American Approaches, January to July 1954 The Death of the EDC: July to August 1954 PART III: THE CRISIS RESOLVED Selling the Solution: British Crisis Management: August to September 1954 Anglo-American Divorce and Reconciliation: September 1954 Phoenix from the Ashes: The Birth of the Western European Union, October 1954 to May 1955 PART IV: CONCLUSION Agonizing Reappraisals: Anglo-American Relations and the Crisis of European Defence Bibliography Index
Acquisition of Retinoic Acid Signaling Pathway and Innovation of the Chordate Body Plan

Abstract Retinoic acid (RA) regulates many of the chordate-specific and vertebrate-specific characters. These include the anteroposterior pattern of the dorsally located central nervous system, pharynx with gill slits, neural crest cells, limb morphogenesis and anteroposteriorly organized vertebrae. The necessity of endogenous RA and the RA receptor (RAR) has been demonstrated by mutant analyses, vitamin Adeficient animals and various other methods. Since RAR has been identified only in chordates, the acquisition of the RAR-mediated RA signaling pathway is thought to be an important event for the innovation of the chordate body plan. RA-synthesizing aldehyde dehydrogenases and RA-degrading enzymes also seem to be chordate-specific. The expression pattern of these genes in ascidian embryos is similar to that in vertebrate embryos. These results suggest that the RA signaling cascade, with various regulators and modifiers, had been already well established in the common chordate ancestor. RA also regulates morphogenesis during the asexual reproduction of ascidians, suggesting that RA may also have played a part in producing diversity within the chordate groups.
Biodiversity of Volatile Organic Compounds from Five French Ferns

Five French ferns belonging to different families were investigated for volatile organic compounds (VOC) by GC-MS using organic solvent extraction. Fifty-five VOC biosynthesized from the shikimic, lipidic and terpenic pathways including monoterpenes, sesquiterpenes and carotenoid-type compounds were identified. The main volatile compound of Adiantum Capillus-Veneris L. (Pteridaceae) was (E)-2-decenal with a plastic or “stink bug” odor. The volatile profiles of Athyrium filix-femina (L.) Roth (Woodsiaceae) and Blechnum spicant (L.) Roth (Blechnaceae) showed similarities, with small amounts of isoprenoids and the same main volatile compounds, i.e., 2-phenylethanal (odor of lilac and hyacinth) and 1-octen-3-ol (mushroom-like odor). The main volatile compound of Dryopteris filix-mas (L.) Schott (Dryopteridaceae) was (E)-nerolidol with a woody or fresh bark note. Polyketides, as acylfilicinic acids, were mainly identified in this fern. Oreopteris limbosperma (Bellardi ex. All.) J. Holub (Thelypteridaceae), well-known for its lemon smell, contained the highest biodiversity of VOC. Eighty percent of the volatiles was issued from the terpenic pathway. The main volatiles were (E)-nerolidol, α-terpineol, β-caryophyllene and other minor monoterpenes (for example, linalool, pinenes, limonene, and γ-terpinen-7-al). It was also the fern with the highest number of carotenoid-type derivatives, which were identified in large amounts. Our results were of great interest underlying new industrial valorisation for ferns based on their broad spectrum of volatiles.
Combination of Engineered Schwann Cell Grafts to Secrete Neurotrophin and Chondroitinase Promotes Axonal Regeneration and Locomotion after Spinal Cord Injury

Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. SCs introduced into lesions support axon regeneration, but because these axons do not exit the transplant, additional approaches with SCs are needed. Here, we transplanted SCs genetically modified to secrete a bifunctional neurotrophin (D15A) and chondroitinase ABC (ChABC) into a subacute contusion injury in rats. We examined the effects of these modifications on graft volume, SC number, degradation of chondroitin sulfate proteoglycans (CSPGs), astrogliosis, SC myelination of axons, propriospinal and supraspinal axon numbers, locomotor outcome (BBB scoring, CatWalk gait analysis), and mechanical and thermal sensitivity on the hind paws. D15A secreted from transplanted SCs increased graft volume and SC number and myelinated axon number. SCs secreting ChABC significantly decreased CSPGs, led to some egress of SCs from the graft, and increased propriospinal and 5-HT-positive axons in the graft. SCs secreting both D15A and ChABC yielded the best responses: (1) the largest number of SC myelinated axons, (2) more propriospinal axons in the graft and host tissue around and caudal to it, (3) more corticospinal axons closer to the graft and around and caudal to it, (4) more brainstem neurons projecting caudal to the transplant, (5) increased 5-HT-positive axons in the graft and caudal to it, (6) significant improvement in aspects of locomotion, and (7) improvement in mechanical and thermal allodynia. This is the first evidence that the combination of SC transplants engineered to secrete neurotrophin and chondroitinase further improves axonal regeneration and locomotor and sensory function.
Ultra-fast on-chip load-current adaptive linear regulator for switch mode power supply load transient enhancement

A fully on-chip linear regulator is presented in this paper to enhance the load transient response in a switch mode power supply (SMPS). Different from the conventional linear regulator, it employs a push-pull output structure, allowing both step-up and step-down transient current compensation. A multi-level self-biased controller is designed to adaptively compensate the instantaneous current difference between the SMPS and the load, achieving ultra-fast and smooth load transient response. An IC prototype is designed and fabricated with a standard 0. 35μm digital CMOS process. 40.3ns load transient response time is achieved for a 100-mA load step change. In addition, it is also capable of dynamic voltage scaling (DVS), with a measured tracking speed of about 1 V/μs.
Precision Interferometric Measurements of Mirror Birefringence in High-Finesse Optical Resonators.

High-finesse optical resonators found in ultrasensitive laser spectrometers utilize supermirrors ideally consisting of isotropic high-reflectivity coatings. Strictly speaking, however, the optical coatings are often non-uniformly stressed during the deposition process and therefore do possess some small amount of birefringence. When physically mounted the cavity mirrors can be additionally stressed in such a way that large optical birefringence is induced. Here we report a direct measurement of optical birefringence in a two-mirror Fabry-Pérot cavity with R = 99.99 % by observing TEM00 mode beating during cavity decays. Experiments were performed at a wavelength of 4.53 μm, with precision limited by both quantum and technical noise sources. We report a splitting of δν = 618(1) Hz, significantly less than the intrinsic cavity linewidth of δcav ≈ 3 kHz. With a cavity free spectral range of 96.9 MHz, the equivalent fractional change in mirror refractive index due to birefringence is therefore Δn/n = 6.38(1) × 10-6.