Miracle-dz/UniFAR-FTUs huggingface dataset:
The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin

Most soluble lysosomal proteins bind the mannose 6‐phosphate receptor (M6P‐R) to be sorted to the lysosomes. However, the lysosomes of I‐cell disease (ICD) patients, a condition resulting from a mutation in the phosphotransferase that adds mannose 6‐phosphate to hydrolases, have near normal levels of several lysosomal proteins, including the sphingolipid activator proteins (SAPs), GM2AP and prosaposin. We tested the hypothesis that SAPs are targeted to the lysosomal compartment via the sortilin receptor. To test this hypothesis, a dominant‐negative construct of sortilin and a sortilin small interfering RNA (siRNA) were introduced into COS‐7 cells. Our results showed that both the truncated sortilin and the sortilin siRNA block the traffic of GM2AP and prosaposin to the lysosomal compartment. This observation was confirmed by a co‐immunoprecipitation, which demonstrated that GM2AP and prosaposin are interactive partners of sortilin. Furthermore, a dominant‐negative mutant GGA prevented the trafficking of prosaposin and GM2AP to lysosomes. In conclusion, our results show that the trafficking of SAPs is dependent on sortilin, demonstrating a novel lysosomal trafficking.
Structure‐activity relationships of new agonists and antagonists of different metabotropic glutamate receptor subtypes

1 We investigated the agonist and antagonist activities of 22 new phenylglycine and phenylalanine derivatives for metabotropic glutamate receptors (mGluRs) by examining their effects on the signal transduction of mGluR1, mGluR2 and mGluR6 subtypes expressed in Chinese hamster ovary cells. This analysis revealed several structural characteristics that govern receptor subtype specificity of the agonist and antagonist activities of phenylglycine derivatives. 2 Hydroxyphenylglycine derivatives possessed either an agonist activity on mGluR1/mGluR6 or an antagonist activity on mGluR1. 3 Carboxyphenylglycine derivatives showed an agonist activity on mGluR2 but an antagonist activity on mGluR1. 4 α‐Methylation or α‐ethylation of the carboxyphenylglycine derivatives converts the agonist property for mGluR2 to an antagonist property, thus producing antagonists at both mGluR1 and mGluR2. 5 Structurally‐corresponding phenylalanine derivatives showed little or no agonist or antagonist activity on any subtypes of the receptors. 6 This investigation demonstrates that the nature and positions of side chains and ring substituents incorporated into the phenylglycine structure are critical in determining the agonist and antagonist activities of members of this group of compounds on different subtypes of the mGluR family. 7 We also tested two α‐methyl derivatives of mGluR agonists. (2S, 1′S, 2′S)‐2‐(2‐Carboxycyclopropyl)glycine (L‐CCG‐I) is a potent agonist for mGluR2 but α‐methylation of this compound changes its activity to that of an mGluR2‐selective antagonist. In contrast, α‐methylation of L‐2‐amino‐4‐phosphonobutyrate (L‐AP4) results in retention of an agonist activity on mGluR6. Thus, α‐methylation produces different effects, depending on the chemical structures of lead compounds and/or on the subtype of mGluR tested.
Tin whisker growth from Sn-Cu (0–5 wt%) surface finishes

The aim of this research is to examine the whisker growth behaviour of tin-copper alloy surface finishes in highly oxidizing environment. Samples from copper base substrates were plated with 10 μm thick tin-copper alloys between 0 and 5 wt% copper content (with 1% steps) by solder dipping technology. Two types of aging were being used to accelerate the whisker appearance; these were an elevated humidity and temperature condition (85°C/85%RH) and a Highly Accelerated Stress Test (HAST 105°C/100%RH) up to 2400 hours in order to keep the samples in highly corrosion environment. The whisker growth was observed by using Scanning Electron Microscopy (SEM) and was evaluated by the morphology of the whiskers, by the average and maximum whisker length and the average whisker density. Results indicate differences in whisker growth depending on the test circumstances and on the copper content. The series of tests has shown that the different test circumstances induce different whiskering mechanisms and the significance in whisker formation of humidity and melting temperature of the plating alloy were also proven.
Evidence-based clinical recommendations for the use of pit-and-fissure sealants: a report of the American Dental Association Council on Scientific Affairs.

BACKGROUND This article presents evidence-based clinical recommendations for use of pit-and-fissure sealants developed by an expert panel convened by the American Dental Association Council on Scientific Affairs. The panel addressed the following clinical questions: Under what circumstances should sealants be placed to prevent caries? Does placing sealants over early (noncavitated) lesions prevent progression of the lesion? Are there conditions that favor the placement of resin-based versus. glass ionomer cement sealants in terms of retention or caries prevention? Are there any techniques that could improve sealants' retention and effectiveness in caries prevention? TYPES OF STUDIES REVIEWED Staff of the ADA Division of Science conducted a MEDLINE search to identify systematic reviews and clinical studies published after the identified systematic reviews. At the panel's request, the ADA Division of Science staff conducted additional searches for clinical studies related to specific topics. The Centers for Disease Control and Prevention also provided unpublished systematic reviews that since have been accepted for publication. RESULTS The expert panel developed clinical recommendations for each clinical question. The panel concluded that sealants are effective in caries prevention and that sealants can prevent the progression of early noncavitated carious lesions. CLINICAL IMPLICATIONS These recommendations are presented as a resource to be considered in the clinical decision-making process. As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences. The evidence indicates that sealants can be used effectively to prevent the initiation and progression of dental caries.
Muse: a multimedia streaming enabled remote interactivity system for mobile devices

Recent years we have witnessed the rapid advent of mobile cloud computing, in which remote software is delivered as a service and accessed by mobile device users over the Internet. However, most existing remote display technologies for high motion application (e.g, movie) have defects in latency and bandwidth. In this paper, we designed an adaptive multimedia streaming enabled remote interactivity system, Muse, to utilize remote resources with reduced display update traffic and response latency. A window-aware updating mechanism is designed as an adaptation scheme, which allows users to focus on the current application in use and also enable them to switch between applications on the fly. Besides, a windowed display encoder using H.264 video codec is integrated into the remote frame buffer protocol to achieve high performance in compression to address the high latency limitation of mobile Internet. Experimental results show that the windowed display Muse mechanism can successfully reduce network traffic, loading time and response latency of remote display and interaction. Our system can achieve in average 22fps of 1024*768 desktop multimedia playbacks with good video quality under 1 Mbit/s of bandwidth limitation.
Partial conservation of the sn‐2 position of dietary triglycerides in fasting plasma lipids in humans

The authors investigated the effect of the position of fatty acids within dietary triglycerides on the composition of plasma lipids. Sixty volunteers consumed two diets of equal fatty acid compositions for 3 weeks each. In the palm oil diet 82% of palmitic acid was attached to the sn‐1 and sn‐3, and 18% to the sn‐2 position of glycerol. In the diet rich in a palm oil analogue, Betapol, these figures were 35% and 65% respectively. Oleic and linoleic acid in palm oil were mainly in the sn‐2 position, and in Betapol mainly in the sn‐1 and sn‐3 position. The proportion of palmitic acid in the 2 position of fasting plasma triglycerides was 10.2 g 100 g−1 on palm oil and 12.3 on Betapol; that of oleic acid was 46.9 vs. 43.6 (P < 0.0001). Overall oleic acid content of triglycerides was 1.4 g 100 g−1 lower on Betapol than on palm oil (P = 0.002). Betapol increased palmitic and palmitoleic acid in cholesteryl esters by 1 g 100 g−1 (P < 0.0001) at the expense of oleic and linoleic acid. The positional configuration of dietary fatty acids has small but consistent effects on lipid metabolism that persist beyond fat absorption and chylomicron clearance.
Equilibria Detection in Non-cooperative Game Theory . An Evolutionary Approach

The most important task in non-cooperative Game Theory is the equilibria detection. A computational method is presented in order to detect different types of equilibria. The method is based on generative relations. Generative relations are an algebraic tool for describing game equilibria. The generative relations of Nash, Aumann, Berge-Zhukovskii, Pareto and Lorenz equilibria are presented. The concept of meta-strategy is described that allows players to have different rationality types. The joint NashPareto and Nash Berge-Zhukovskii equilibrium is presented. Numerical experiments indicate the potential of the proposed method.
Chemotherapeutic efficacy of paclitaxel in combination with Withania somnifera on benzo(a)pyrene‐induced experimental lung cancer

Lung cancer is one of the leading causes of cancer death in the world and is notoriously difficult to treat effectively. In the present study, male Swiss albino mice were divided into five groups of six animals each: group I animals received corn oil orally and served as a control; group II cancer‐induced animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil, orally) twice weekly for four successive weeks; group III cancer‐bearing animals (after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight, i.p.) once weekly for 4 weeks; group IV cancer‐bearing animals were treated with paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once weekly for 4 weeks; and group V animals constituted the drug control treated with paclitaxel along with W. somnifera. The serum, lung and liver were investigated biochemically for aryl hydrocarbon hydroxylase, γ‐glutamyl transpeptidase, 5′‐nucleotidase, lactate dehydrogenase and protein‐bound carbohydrate components (hexose, hexosamine and sialic acid). These enzyme activities were increased significantly in cancer‐bearing animals compared with control animals. The elevation of these in cancer‐bearing animals was indicative of the persistent deteriorating effect of benzo(a)pyrene in cancer‐bearing animals. Our data suggest that paclitaxel, administered with W. somnifera, may extend its chemotherapeutic effect through modulating protein‐bound carbohydrate levels and marker enzymes, as they are indicators of cancer. The combination of paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene‐induced lung cancer in mice by offering protection from reactive oxygen species damage and also by suppressing cell proliferation. (Cancer Sci 2006; 97: 658–664)
Observer-Rated Alexithymia and its Relationship with the Five-Factor-Model of Personality

Studies examining the relationship between alexithymia and personality exclusively employed self-report measures of alexithymia. In the present study, we examined the relationship of both observer-rated and self-reported alexithymia with the Big Five personality dimensions. We administered the Toronto Structured Interview for Alexithymia (TSIA) as an interview-based measure of alexithymia and, in addition, two self-report questionnaires, the 20-item Toronto Alexithymia Scale (TAS-20) and the Bermond-Vorst Alexithymia Questionnaire (BVAQ). Fifty-one university students were interviewed and completed the alexithymia scales and the NEO Five-Factor Inventory. In contrast to TAS-20 and BVAQ, the Difficulty identifying feelings (DIF) scale of the TSIA was found to be unrelated to neuroticism, suggesting that the frequently reported association between DIF and neuroticism could be due to the use of self-report scales. In contrast, the affective dimension of alexithymia, measured by the BVAQ, was even negatively related with neuroticism. Thus, a paucity of fantasy and little emotional arousal goes together with increased emotional stability. Furthermore, we revealed negative correlations between interview-based alexithymia scores and openness to experience and agreeableness, which cross-validated the self-report findings. Finally, extraversion and conscientiousness each showed only one negative correlation, namely with subscales of the BVAQ. Taken together, our findings show that on the basis of interviews there is no evidence for a relation of DIF with neuroticism, while associations of alexithymia with low openness to experience and low agreeableness emerged irrespective of assessment approach. The relations of alexithymia with personality are discussed in the light of different measurement approaches.
[Measurement of tear evaporation from ocular surface].

A new method for measuring tear evaporation from the ocular surface is developed. The change of humidity in the closed chamber around the eye was recorded, with eyes open and eyes closed. Theoretical equations were used for data analysis, and the evaporation coefficient K, the tear evaporation volume at the environmental humidity of 40% were calculated. We examined 28 normal eyes and 58 eyes of dry eye patients. Evaporation coefficient K (x 10(-4)/sec) were 32.4 +/- 9.2 in normal and 16.5 +/- 11.3 in dry eyes (p less than 0.001). Tear evaporation volume at the environmental humidity of 40% (x 10(-7) g/sec.eye) were 16.2 +/- 4.7 in normal and 8.4 +/- 5.7 in dry eyes (p less than 0.001). This method is so simple and non-invasive that it could be used as a new examination for dry eye.
The Molecular Signature of Tissue Resident Memory CD8 T Cells Isolated from the Brain

Tissue resident memory (Trm) CD8 T cells represent a newly described memory T cell population. We have previously characterized a population of Trm cells that persists within the brain after acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm cells do not undergo recall expansion after dissociation from the tissue. Furthermore, these Trm cells do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells, we compared the gene expression profiles of Trm cells isolated from the brain with those of circulating memory T cells isolated from the spleen after an acute virus infection. Trm cells displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors, and overexpressed several inhibitory receptors. Cumulatively, these data indicate that Trm cells are a distinct memory T cell population disconnected from the circulating memory T cell pool and display a unique molecular signature that likely results in optimal survival and function within their local environment.
Phakic and Pseudophakic Eyes in Patients During Hyperbaric Oxygen Therapy

Purpose. To examine the optical components of phakic and pseudophakic eyes during hyperbaric oxygen (HBO) therapy, and to quantify their relative impact on ocular refractive changes. Methods. HBO therapy was given to 16 phakic and six pseudophakic patients for 90 min daily at a pressure of 240 kPa, 5 d a week for 20 days. An eye examination was performed on the first day of HBO therapy and repeated when the patients had completed 19 days of the treatment. Refractive error, best-corrected visual acuity, corneal power, radius, thickness and volume, anterior chamber depth, axial length, lens opacity, and intraocular pressure were measured in all patients. Serum glucose, glycosylated hemoglobin, serum electrolytes, and protein were measured in the phakic patients. Results. In the phakic group, a significant myopic shift (≥−0.50 D) occurred in 26 (81%) single eyes during the treatment. The median myopic shift was −0.63 D (min −0.25 D/max −1.88 D) in the OD, and −0.69 D (min −0.38 D/max −2.25 D) in the OS. No myopic shift appeared in the pseudophakic patients; the median refractive changes were +0.06 D (min −0.13 D/max +0.25 D) in the OD and +0.13 D (min 0.00 D/max +0.25 D) in the OS. Intraocular pressure, serum electrolytes, glucose, and glycosylated hemoglobin remained unchanged. Conclusions. Myopic shifts occurred in phakic but not in pseudophakic eyes during HBO therapy. The myopic shifts must be attributed to changes in the crystalline lens.
Oral Treatment of Chickens with Lactobacilli Influences Elicitation of Immune Responses

ABSTRACT Commensal microbes in the intestine are in constant interaction with host cells and play a role in shaping the immune system. Lactobacillus acidophilus, Lactobacillus reuteri, and Lactobacillus salivarius are members of the chicken intestinal microbiota and have been shown to induce different cytokine profiles in mononuclear cells in vitro. The objective of the present study was to examine the effects of these bacteria individually or in combination on the induction of antibody- and cell-mediated immune responses in vivo. The birds received lactobacilli weekly via oral gavage starting on day of hatch and subsequently, at 14 and 21 days, were immunized with sheep red blood cells (SRBC), keyhole limpet hemocyanin (KLH), Newcastle disease virus vaccine, and infectious bursal disease virus vaccine. Antibody responses in serum were measured weekly for 4 weeks beginning on the day of primary immunization. The cell-mediated immune response was evaluated at 21 days postimmunization by measurement of gamma interferon (IFN-γ) production in splenocytes stimulated with inactivated vaccine antigens. L. salivarius-treated birds had significantly more serum antibody to SRBC and KLH than birds that were not treated with probiotics. L. salivarius-treated birds also had decreased cell-mediated immune responses to recall antigen stimulation. L. reuteri treatment did not significantly affect the systemic immune response, while L. acidophilus treatment increased the antibody response to KLH. These results indicate that systemic antibody- and cell-mediated immune responses can be modulated by oral treatment with lactobacilli but that these bacteria may vary in their ability to modulate the immune response.
Syncytium-inhibiting and neutralizing activity in maternal sera fail to prevent vertical transmission of human immunodeficiency virus type 1.

OBJECTIVES To measure the prevalence and titers of syncytium-inhibiting (SI) and neutralizing (Nt) antibodies to HIV-1 in mothers' blood close to the time of delivery and to correlate such findings with the infection status of their offspring. METHODS We analyzed serum specimens from a convenience sample of 22 HIV-infected mothers. The HIV-1 infection status of their children was determined. Forty-five percent of the women transmitted and 55% did not transmit infection to their offspring. Cord blood samples from offspring of the mothers were also studied. We measured maternal SI antibody titers against cells infected with HIV-1/SB, a strain isolated from a transmitting mother in New Haven, as well as cells infected with the more prevalent MN strain of HIV-1. We compared SI antibody titers to the SB strain in 11 matched maternal and cord blood samples. Nt antibody titers to HIV-1/SB were also measured in 20 maternal sera. RESULTS Using the SB and MN strains of HIV-1, we found no difference in the prevalence or titer of SI antibody in the sera of transmitting and nontransmitting mothers. Only 35% of samples were concordant for presence or absence of SI antibody to the two strains. Furthermore the presence or absence of SI antibody in cord blood did not correlate with virus transmission. Both the frequency and titer of Nt antibody to HIV-1/SB were higher in the sera of mothers who transmitted infection when compared to those who did not. Only one-half of maternal blood samples were concordant for either the presence or absence of SI and Nt antibodies. CONCLUSIONS We could not demonstrate a correlation between the presence of two types of functional antibodies (i.e. SI and Nt) to HIV-1 in the sera of pregnant women and vertical transmission. Efforts to induce or to increase such antibodies in infected mothers by immunization with vaccines or hyperimmune globulins may not alter the risk of vertical transmission.
Posttranslational Influence of NADPH-Dependent Thioredoxin Reductase C on Enzymes in Tetrapyrrole Synthesis[W][OA]

A thioredoxin reductase influences chlorophyll biosynthesis by reducing target cysteines in its biosynthesis enzymes. The NADPH-dependent thioredoxin reductase C (NTRC) is involved in redox-related regulatory processes in chloroplasts and nonphotosynthetic active plastids. Together with 2-cysteine peroxiredoxin, it forms a two-component peroxide-detoxifying system that acts as a reductant under stress conditions. NTRC stimulates in vitro activity of magnesium protoporphyrin IX monomethylester (MgPMME) cyclase, most likely by scavenging peroxides. Reexamination of tetrapyrrole intermediate levels of the Arabidopsis (Arabidopsis thaliana) knockout ntrc reveals lower magnesium protoporphyrin IX (MgP) and MgPMME steady-state levels, the substrate and the product of MgP methyltransferase (CHLM) preceding MgPMME cyclase, while MgP strongly accumulates in mutant leaves after 5-aminolevulinic acid feeding. The ntrc mutant has a reduced capacity to synthesize 5-aminolevulinic acid and reduced CHLM activity compared with the wild type. Although transcript levels of genes involved in chlorophyll biosynthesis are not significantly altered in 2-week-old ntrc seedlings, the contents of glutamyl-transfer RNA reductase1 (GluTR1) and CHLM are reduced. Bimolecular fluorescence complementation assay confirms a physical interaction of NTRC with GluTR1 and CHLM. While ntrc contains partly oxidized CHLM, the wild type has only reduced CHLM. As NTRC also stimulates CHLM activity in vitro, it is proposed that NTRC has a regulatory impact on the redox status of conserved cysteine residues of CHLM. It is hypothesized that a deficiency of NTRC leads to a lower capacity to reduce cysteine residues of GluTR1 and CHLM, affecting the stability and, thereby, altering the activity in the entire tetrapyrrole synthesis pathway.