Assessment of gene-covariate interactions by incorporating covariates into association mapping

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies

Incorporation of covariates in simultaneous localization of two linked loci using affected relative pairs

<p>Abstract</p> <p>Background</p> <p>Many dichotomous traits for complex diseases are often involved more than one locus and/or associated with quantitative biomarkers or environmental factors. Incorporating these quantitative variables into linkage analysis as well as localizing two linked disease loci simultaneously could therefore improve the efficiency in mapping genes. We extended the robust multipoint Identity-by-Descent (IBD) approach with incorporation of covariates developed previously to simultaneously estimate two linked loci using different types of affected relative pairs (ARPs).</p> <p>Results</p> <p>We showed that the efficiency was enhanced by incorporating a quantitative covariate parametrically or non-parametrically while localizing two disease loci using ARPs. In addition to its help in identifying factors associated with the disease and in improving the efficiency in estimating disease loci, this extension also allows investigators to account for heterogeneity in risk-ratios for different ARPs. Data released from the collaborative study on the genetics of alcoholism (COGA) for Genetic Analysis Workshop 14 (GAW 14) were used to illustrate the application of this extended method.</p> <p>Conclusions</p> <p>The simulation studies and example illustrated that the efficiency in estimating disease loci was demonstratively enhanced by incorporating a quantitative covariate and by using all relative pairs while mapping two linked loci simultaneously.</p

Embryo Development and Behavior in Sea Urchin (Tripneustes gratilla) Under Different Light Emitting Diodes Condition

This study aims to evaluate the effect of light-emitting diodes (LEDs) of different wavelengths on the embryonic development, covering behavior, righting behavior, and phototaxis of collector urchins (Tripneustes gratilla). The collector urchins were divided into three groups according to the type of LED illumination they received: full-spectrum (400–750 nm wavelength), red light (630 nm), or blue light (450 nm). The results of the embryonic development experiment indicated that the blue LED group had the highest proportion of embryos reaching the prism stage at the 24th hour and the highest proportion of embryos entering the 4-arm pluteus stage, but it also had the highest death rate at the 48th hour. The full-spectrum and red LED groups exhibited similar speeds of embryonic development. In the experiment on covering behavior performed on adult urchins, our findings indicated that the blue LED group gripped the most acrylic sheets for cover, exhibiting the most covering behavior, followed by the full-spectrum group and then the red LED group. Moreover, behavior varied with coloration, as collector urchins with a lower level of melanin exhibited more covering behavior than those with a higher melanin level. In addition, the righting behavior experiments demonstrated that the blue LED group spent the longest time righting themselves. It is possible that the relatively strong stimulation from the blue LED illumination led to a higher level of stress in the collector urchins and hence slowed their righting. The phototaxis experiment revealed the most significant negative phototactic response in collector urchins when they were under the blue LED light, followed by the full-spectrum light; the red LED light did not induce any positive or negative phototactic response in the collector urchins. This experimental result verified collector urchins’ high sensitivity to and dislike of the blue LED light. The study results confirmed that the blue LED light environment accelerated the embryonic development of collector urchins; however, the relatively strong stimulation from that light also caused them to engage in covering behavior or move away from the light. These results indicate that short-wavelength irradiation significantly affects the embryonic development and behavior pattern of this species

Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB × NZW) F1 mice

AbstractBackgroundFew studies have evaluated the effects and precise molecular mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of MMF in a UVB-induced NZB × NZW (NZBW) F1 CLE mouse model.MethodsContinuous MMF treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB induction (Day 0; 20 weeks old), as the pathologic features of CLE are present after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were examined by comparing histopathological changes, lupus band test (deposition of immune complexes at the dermal–epidermal junction) and colocalization of autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations of local matrix metalloprotease activities.ResultsMMF improved survival in the NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and interleukin 6 levels were significantly reduced after MMF treatment. The dermal lymphocytic infiltration, deposition of immune complexes at the dermal–epidermal junction, colocalized autoantibodies with Dsg3, and epidermal matrix metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice.ConclusionThe results confirmed that MMF could substantially attenuate skin damage due to CLE in the NZBW F1 mouse model

Extracts of Artocarpus communis

Artocarpus communis is an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts of A. communis have been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well as α-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract of A. communis (ACM) and various organic partition fractions of A. communis on melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics

Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug ratio (P &amp;lt; 0.001). Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects.Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically.Keywords: repeated focused ultrasound, interleukin-4 receptor, blood-brain barrier, brain tumor, target drug deliver

Committed Private Information Retrieval

A private information retrieval (PIR) scheme allows a client to retrieve a data item $x_i$ among $n$ items $x_1,x_2,\ldots,x_n$ from $k$ servers, without revealing what $i$ is even when $t < k$ servers collude and try to learn $i$. Such a PIR scheme is said to be $t$-private. A PIR scheme is $v$-verifiable if the client can verify the correctness of the retrieved $x_i$ even when $v \leq k$ servers collude and try to fool the client by sending manipulated data. Most of the previous works in the literature on PIR assumed that $v < k$, leaving the case of all-colluding servers open. We propose a generic construction that combines a linear map commitment (LMC) and an arbitrary linear PIR scheme to produce a $k$-verifiable PIR scheme, termed a committed PIR scheme. Such a scheme guarantees that even in the worst scenario, when all servers are under the control of an attacker, although the privacy is unavoidably lost, the client won't be fooled into accepting an incorrect $x_i$. We demonstrate the practicality of our proposal by implementing the committed PIR schemes based on the Lai-Malavolta LMC and three well-known PIR schemes using the GMP library and blst, the current fastest C library for elliptic curve pairings.Comment: Accepted at ESORICS 202