A weighted q-gram method for glycan structure classification

<p>Abstract</p> <p>Background</p> <p>Glycobiology pertains to the study of carbohydrate sugar chains, or glycans, in a particular cell or organism. Many computational approaches have been proposed for analyzing these complex glycan structures, which are chains of monosaccharides. The monosaccharides are linked to one another by glycosidic bonds, which can take on a variety of comformations, thus forming branches and resulting in complex tree structures. The <it>q</it>-gram method is one of these recent methods used to understand glycan function based on the classification of their tree structures. This <it>q</it>-gram method assumes that for a certain <it>q</it>, different <it>q</it>-grams share no similarity among themselves. That is, that if two structures have completely different components, then they are completely different. However, from a biological standpoint, this is not the case. In this paper, we propose a weighted <it>q</it>-gram method to measure the similarity among glycans by incorporating the similarity of the geometric structures, monosaccharides and glycosidic bonds among <it>q</it>-grams. In contrast to the traditional <it>q</it>-gram method, our weighted <it>q</it>-gram method admits similarity among <it>q</it>-grams for a certain <it>q</it>. Thus our new kernels for glycan structure were developed and then applied in SVMs to classify glycans.</p> <p>Results</p> <p>Two glycan datasets were used to compare the weighted <it>q</it>-gram method and the original <it>q</it>-gram method. The results show that the incorporation of <it>q</it>-gram similarity improves the classification performance for all of the important glycan classes tested.</p> <p>Conclusion</p> <p>The results in this paper indicate that similarity among <it>q</it>-grams obtained from geometric structure, monosaccharides and glycosidic linkage contributes to the glycan function classification. This is a big step towards the understanding of glycan function based on their complex structures.</p

Ultraviolet Action Spectrum and Effect of EPC-K1 on Ultraviolet Radiation-induced Injury in Cultured Normal Human Epidermal Keratinocytes

This study was aimed to determine the ultraviolet (UV: 235-310nm) action spectrum for killing normal human epidermal keratinocytes (NHEK) and to investigate the preventive effect of EPC-K1, a phosphate diester of vitamin C and vitamin E on UV radiation-induced NHEK injury. NHEK were cultured in EpiLife medium supplemented with Human Keratinocyte Growth Supplement Kit. NHEK viability was determined by crystal violet (CV) staining 48 h after the UV irradiation. The mRNA expressions of the C/EBP homologous protein (Chop) transcription factor and endoplasmic reticulum-resident molecular chaperone, Bip, were determined by RT-PCR analyses. UV was especially effective in killing NHEK when applied in the wavelength region of 250-280nm. The minimum exposure dose required to kill 50% of cells (LD50) was 1.64mJ/cm2 at 269nm. At 235 and 310nm, the LD50 for NHEK was 6.62 and 293mJ/cm2, respectively. Irradiation of 660-mJ/cm2 at 310nm significantly decreased the cell viability to 30% of control (without irradiation). The addition of 0.1mM EPC-K1 after irradiation returned the cell viability to 118%. Six hours after the 660-mJ/cm2 irradiation at 310nm, Chop and Bip mRNA levels in NHEK were increased to 487% and 283%, respectively, and were not significantly affected by EPC-K1. Chop and Bip are responsive to ER stress. These results suggested that EPC-K1 exerts a protective effect against UV-induced NHEK injury, and further studies should investigate the molecular mechanism underlying this effect

Impaired CD4⁺ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination

高齢者のT細胞応答は立ち上がりが遅く収束は早い --新型コロナワクチン接種機会を活用した免疫応答の個人差・年齢差の解明--. 京都大学プレスリリース. 2023-01-13.T-Cell Responses in the Elderly Rise Slowly and Contract Quickly --Learning About Individual and Age Differences in Immune Response From COVID-19 Vaccinations--. 京都大学プレスリリース. 2023-01-13.Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4⁺ T cells including CXCR3⁺ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8⁺ T cell responses. Thus, an inefficient CD4⁺ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4⁺ T cell response following the first dose is key to improving vaccine efficacy in older adults

生後早期の心理的ストレスが雌雄ラットの性成熟、性行動に与える影響

Purpose: We studied the influence of psychological stress during the early neonatal period on sexual maturation and sexual behavior in rats. Methods: Neonatal male and female rats were divided into control (C) and maternal separation (MS) groups (n = 20‐24 per group). The pups in the MS groups were placed in isolation cages for 240 minutes/d from postnatal days 2‐11. Vaginal opening (VO) in females and preputial separation (PS) in males (indicators of sexual maturation) were monitored, as was the estrous cycle in females. Thereafter, sexual behavior was monitored twice at 13 and 15 weeks of age. Results: As for sexual maturation, the onset of PS occurred significantly earlier in the MS group than in the C group, whereas the onset of VO did not differ between the groups. The length of the estrous cycle did not differ between the groups. The frequencies of sexual behaviors did not differ between the groups in either sex. Conclusions: In conclusion, early‐life psychological stress induced by MS advanced sexual maturation in male rats, whereas it did not affect sexual maturation in female rats. On the other hand, early‐life psychological stress might not affect sexual behavior in adulthood in either sex

The Effects of Maxillomandibular Advancement and Genioglossus Advancement on Sleep Quality

Maxillomandibular advancement (MMA) using a standardized surgical procedure consisting of a LeFort I osteotomy and bilateral sagittal split ramus osteotomy and genioglossus advancement (GA) using a genioplasty improve airway volume, oxygen desaturation, and the AHI in patients with OSA. However, there are few reports on changes in sleep quality following MMA and GA. We assessed the effects of MMA and GA on sleep quality by comparing oxygen desaturation, AHI, and sleep architecture before and after surgery. Methods: Eight patients underwent polysomnography (PSG) and CT scan before and after surgery. Conclusions: Our study finds that %TST and %REM were both increased, while %S1 and NA both decreased. Based on these results, it appears that both the quality and quantity of sleep were improved. MMA and GA improve sleep respiratory disturbance and can also improve sleep quality

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes

Background: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. Purpose: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. Methods: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). Results: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. Conclusions: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research

Biotin levels in blood and follicular fluid

It has been shown that biotin, a water-soluble vitamin (B7), plays roles in reproductive functions, such as oocyte maturation and embryo development, in experimental animals. On the other hand, little is known about the clinical effects of biotin on human reproduction. In this study, serum and follicular fluid biotin levels were measured in patients who underwent in vitro fertilization / intracytoplasmic sperm injection (IVF / ICSI), and their associations with reproductive outcomes were evaluated. As a result, biotin was detected in follicular fluid, as well as serum, and the biotin levels of follicular fluid were found to be positively correlated with those of serum. The biotin levels of serum were higher than those of follicular fluid, suggesting that biotin may be taken up into the follicular fluid from the blood. Although serum and follicular fluid biotin levels tended to be higher in pregnant patients than in non-pregnant patients, these data did not show the significant statistical difference. These findings indicate that biotin does not contribute to the maintenance of oocyte quality, and hence, it does not increase fertilization and pregnancy rates

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84

食事性肥満から肝炎発症に関わる制御因子の同定 --中鎖脂肪酸油による予防・GPR84標的NASH治療薬の可能性--. 京都大学プレスリリース. 2023-01-18.Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH

Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis

Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses

Clozapine is the first atypical antipsychotic, and improves positive and negative symptoms of many patients with schizophrenia resistant to treatment with other antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but is more often associated with seizures. A large number of studies have been conducted to elucidate pharmacological profiles of clozapine and its major active metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number of electrophysiological studies examining their effects on synaptic transmission. In this study, we examined effects of clozapine and NDMC on synaptic transmission by measuring inhibitory and excitatory postsynaptic currents in rat cultured hippocampal neurons. We found that clozapine and NDMC have qualitatively similar actions. They depressed the inhibitory transmission at 1-30 μM, and the excitatory transmission at 30 μM, the former being much more sensitive. The depression of IPSCs by 30 μM of these drugs was associated with an increase in the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs, but less sensitive than IPSCs. The AMPA-induced currents were slightly potentiated by these drugs at 30 μM. At 30 μM, clozapine and NDMC slightly suppressed Ca2+ and Na+ channels. These results strongly suggest that clozapine and NMDC depress the inhibitory synaptic transmission mainly by antagonizing postsynaptic GABAA receptors, but at higher concentrations additionally by acting on presynaptic site, possibly in part through inhibition of presynaptic Ca2+ and Na+ channels. Preferential depression of inhibitory synaptic transmission by clozapine and NDMC might contribute to therapeutic actions and/or side-effects of clozapine. © 2011 Elsevier B.V. All rights reserved