Computing linkage disequilibrium aware genome embeddings using autoencoders.

MOTIVATION: The completion of the genome has paved the way for genome-wide association studies (GWAS), which explained certain proportions of heritability. GWAS are not optimally suited to detect non-linear effects in disease risk, possibly hidden in non-additive interactions (epistasis). Alternative methods for epistasis detection using e.g. deep neural networks (DNNs) are currently under active development. However, DNNs are constrained by finite computational resources, which can be rapidly depleted due to increasing complexity with the sheer size of the genome. Besides, the curse of dimensionality complicates the task of capturing meaningful genetic patterns for DNNs; therefore necessitates dimensionality reduction. RESULTS: We propose a method to compress single nucleotide polymorphism (SNP) data, while leveraging the linkage disequilibrium (LD) structure and preserving potential epistasis. This method involves clustering correlated SNPs into haplotype blocks and training per-block autoencoders to learn a compressed representation of the block's genetic content. We provide an adjustable autoencoder design to accommodate diverse blocks and bypass extensive hyperparameter tuning. We applied this method to genotyping data from Project MinE, and achieved 99% average test reconstruction accuracy-i.e. minimal information loss-while compressing the input to nearly 10% of the original size. We demonstrate that haplotype-block based autoencoders outperform linear Principal Component Analysis (PCA) by approximately 3% chromosome-wide accuracy of reconstructed variants. To the extent of our knowledge, our approach is the first to simultaneously leverage haplotype structure and DNNs for dimensionality reduction of genetic data. AVAILABILITY AND IMPLEMENTATION: Data are available for academic use through Project MinE at https://www.projectmine.com/research/data-sharing/, contingent upon terms and requirements specified by the source studies. Code is available at https://github.com/gizem-tas/haploblock-autoencoders. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Acetyl-L-carnitine attenuates chronic ethanol-induced oxidative stress, ER stress and apoptosis in rat gastric tissue.

Consuming alcohol affects almost all organs. Acetaldehyde, formed as the main product as a result of alcohol metabolism, causes the production of free superoxide radicals when oxidized, and accordingly oxidative and apoptotic processes are triggered. There are studies showing that carnitine has effects on oxidative and apoptotic processes that occur in various conditions. However, the mechanisms showing the effects of L-carnitine on these effects of alcohol have not been fully elucidated. In our study, the effects of acetyl-L-carnitine administration on the molecular mechanisms of oxidative stress, endoplasmic reticulum stress, and apoptotic parameters in gastric tissue of rats chronically exposed to alcohol were investigated. Hematoxylin-eosin staining was used for histopathological studies. Endoplasmic reticulum stress markers were detected with immunohistochemical staining and western blotting. Apoptotic index was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Total oxidant and antioxidant status were examined by ELISA. Our results showed that chronic alcohol administration caused a significant increase in TOS levels, an indicator of oxidative stress, the levels of ER-stress-associated proteins XBP1, GRP78, and CHOP, and % apoptotic index values in rat gastric tissues. Additionally, it was determined that acetyl-L-carnitine administration caused an improvement in those values. Based on our data, we can conclude that acetyl-L-carnitine has a tissue protective effect by scavenging free oxygen radicals and reducing ER stress-related proteins XBP1, GRP78, and CHOP and apoptosis in chronic ethanol-administered rats, and that this natural antioxidant may be beneficial in the treatment of oxidative stress-induced diseases.

A comprehensive investigation of human endogenous retroviral syncytin proteins and their receptors in men with normozoospermia and impaired semen quality.

PURPOSE: The study aims to investigate first the presence of Syncytin 2 and its receptor, MFSD2, in human sperm, and second whether the expressions of Syncytin 1, Syncytin 2, and their receptors, SLC1A5 and MFSD2, differ between normozoospermic, asthenozoospermic, oligozoospermic, and oligoasthenozoospermic human sperm samples. METHODS: The localization patterns and expression levels of syncytins and their receptors were evaluated in normozoospermic (concentration = 88.9 ± 5.5 × 106, motility = 79.2 ± 3.15%, n = 30), asthenozoospermic (concentration = 51.7 ± 7.18 × 106, motility = 24.0 ± 3.12%, n = 15), mild oligozoospermic (concentration = 13.5 ± 2.17 × 106, motility = 72.1 ± 6.5%, n = 15), moderate oligozoospermic (concentration = 8.4 ± 3.21 × 106, motility = 65.1 ± 8.9%, n = 15), severe oligozoospermic (concentration = 2.1 ± 1.01 × 106, motility = 67.5 ± 3.2%, n = 15), and oligoasthenozoospermic (concentration = 5.5 ± 3.21 × 106, motility = 18.5 ± 1.2%, n = 15) samples by immunofluorescence staining and western blot. RESULTS: Syncytins and their receptors visualized by immunofluorescence showed similar staining patterns with slight staining of the tail in all spermatozoa regardless of normozoospermia, asthenozoospermia, oligozoospermia, or oligoasthenozoospermia. The localization patterns were categorized as equatorial segment, midpiece region, acrosome, and post-acrosomal areas. The combined staining patterns were also detected as acrosomal cap plus post acrosomal region, the midpiece plus equatorial segment, and midpiece plus acrosomal region. However, some sperm cells were categorized as non-stained. Both syncytin proteins were most intensely localized in the midpiece region, while their receptors were predominantly present in the midpiece plus acrosomal region. Conspicuously, syncytins and their receptors showed decreased expression in asthenozospermic, oligozoospermic, and oligoasthenozoospermic samples compared to normozoospermic samples. CONCLUSION: The expression patterns of HERV-derived syncytins and their receptors were identical regardless of the spermatozoa in men with normozoospermia versus impaired semen quality. Further, asthenozoospermia, oligozoospermia, and oligoasthenozoospermia as male fertility issues are associated with decreased expression of both syncytins and their receptors.

Acute and Chronic Exposure to 900 MHz Radio Frequency Radiation Activates p38/JNK-mediated MAPK Pathway in Rat Testis.

The use of electronic devices such as mobile phones has had a long stretch of rapid growth all over the world. Therefore, exposure to radio frequency radiation (RFR) has increased enormously. Here, we aimed to assess the balance between cell death and proliferation and also investigate the involvement of the JNK/p38 MAPK signaling pathway in the testis of rats exposed to 900 MHz RFR in acute and chronic periods (2 h/day, 5 days/week) for 1 or 10 weeks, respectively. The expression of proliferating cell nuclear antigen (PCNA), Bcl-xL, cleaved caspase-3, phosphorylated-JNK (p-JNK), and phosphorylated-p38 (p-p38) was analyzed in line with histopathology and TUNEL analysis in rat testis. There were no histopathological differences between sham and RFR groups in the acute and chronic groups. PCNA expression was not altered between groups in both periods. However, alterations for cleaved caspase-3 and Bcl-xL were observed depending on the exposure period. TUNEL analysis showed a significant increase in the RFR group in the acute period, whereas no difference in the chronic groups for the apoptotic index was reported. In addition, both p-p38 and p-JNK protein expressions increased significantly in RFR groups in both periods. Our study indicated that 900 MHz RFR might result in alterations during acute period exposure for several parameters, but this can be ameliorated in the chronic period in rat testis. Here, we also report the involvement of the p38/JNK-mediated MAPK pathway after exposure to 900 MHz RFR. Hence, this information might shed light in future studies toward detailed molecular mechanisms in male reproduction and infertility.

Effect of calcium hydroxide mixed with lidocaine hydrochloride on postoperative pain in teeth with irreversible pulpitis and symptomatic apical periodontitis: a preliminary randomized controlled prospective clinical trial.

OBJECTIVES: To investigate the effect of calcium hydroxide mixed with lidocaine HCl on postoperative spontaneous pain. MATERIALS AND METHODS: Sixty patients having irreversible pulpitis and symptomatic apical periodontitis with a preoperative spontaneous pain and percussion pain which was more than 50 on a visual analogue scale (100 mm VAS) were included in this study. After the preparation of the root canals, the patients were randomly distributed into two groups according to the calcium hydroxide vehicle, control group (mixed with saline) and calcium hydroxide mixed with lidocaine HCl (n = 30). Postoperative spontaneous pain scores were recorded by a VAS every day for a week. Data were analysed using one-way analysis of variance, chi-squared test and Mann-Whitney U tests (p = 0.05). RESULTS: The calcium hydroxide mixed with lidocaine HCl group resulted in significantly less pain compared with the calcium hydroxide mixed with saline group during days 1 to 4 (p < 0.05). There were no significant differences between the groups in terms of postoperative percussion pain levels (p > 0.05). CONCLUSION: Within the limitations of this study, it can be concluded that the calcium hydroxide mixed with lidocaine HCl can be beneficial in reducing postoperative pain in teeth with irreversible pulpitis and symptomatic apical periodontitis. CLINICAL RELEVANCE: The calcium hydroxide mixed with lidocaine HCl can be beneficial in reducing postoperative pain in teeth with irreversible pulpitis and symptomatic apical periodontitis. CLINICAL REGISTRATION NUMBER: TCTR20181121003.

Effects of continuous irrigation at room temperature or +4ºC on the cyclic fatigue resistance of K3XF instruments.

Background. The present study aimed to evaluate the impact of continuous irrigation with saline solution at room temperature or +4°C on the cyclic fatigue resistance of K3XF files. Methods. Forty-eight new K3XF files (#30, .04 taper) were randomly assigned to three groups: control group (no irrigation), continuous irrigation with saline solution at room temperature, and continuous irrigation with saline solution at +4°C. The instruments were tested in an artificial, stainless steel root canal with a double curvature at body temperature (37±1°C). Time to fracture was converted to the number of cycles to fracture (NCF). The lengths of the fractured fragments were recorded. Kruskal-Wallis H test and one-way ANOVA were used to analyze data. Results. K3XF files' cyclic fatigue resistance was significantly higher in the continuous irrigation groups than in the control group. Continuous irrigation with saline solution at +4°C resulted in higher cyclic fatigue resistance than continuous irrigation with saline solution at room temperature. There were no significant differences between the groups in terms of the fractured fragments' length. Conclusion. Within this study's limitations, continuous irrigation with saline solution increased the NCF of NiTi instruments; decreasing the saline solution's temperature increased this effect.

Duration of ultrasonic activation causing secondary fractures during the removal of the separated instruments with different tapers.

OBJECTIVES: The aim of the present study was to determine the effect of taper (.08, .06, and .04) of separated K3XF instruments on duration taken for the secondary fracture formation during ultrasonic activation. MATERIALS AND METHODS: Ten 25/.08 K3XF (SybronEndo, Orange, CA, USA), ten 25/.06 K3XF, and ten 25/.04 K3XF instruments were used for the study. The apical 5 mm of the instruments was cut to simulate the fragments in root canals. Fragments of the instruments were sandwiched between two straight dentin blocks. An ultrasonic tip was used to cause a secondary fracture of the fragment. The time needed for the secondary fracture was recorded for each instrument. The data were statistically analyzed using the Kruskal-Wallis H test (alpha = 0.05). RESULTS: Secondary fractures occurred in all instruments. In the .08 taper group, secondary fractures took longer than in the case of the .06 and the .04 taper groups (P < 0.05). There were no significant differences between the .06 and the .04 taper groups in terms of the time required for the occurrence of a secondary fracture (P > 0.05). CONCLUSIONS: In the .08 taper group, secondary fracture took longer time than in the case of the .06 and the .04 taper groups due to its larger cross-sectional area involved. CLINICAL RELEVANCE: Typically, when removing separated instruments, a much lower power setting is chosen. The purpose of this in vitro study was to determine which tapered files were more resilient to secondary fracture, thus allowing a higher power setting to be chosen. Thus, the results of the present study cannot be used in clinical practice. If the clinician knows the taper of the broken file, the clinician should be very careful with regard to secondary fractures when using ultrasonics to remove the separated smaller tapered instruments.