Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma

Trace amine-associated receptors (TAARs) interact with amine compounds called “trace amines” which are present in tissues at low concentrations. Recently, TAARs expression in neoplastic tumors was reported. In this study, TAARs expression was analyzed in public RNAseq datasets in nevi and melanoma samples and compared to the expression of dopamine receptors (DRDs) that are known to be involved in melanoma pathogenesis. It was found that all DRDs and TAARs are expressed in nevi at comparable levels. Differential expression analysis demonstrated the drastic decrease of TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8 expression in melanomas compared to benign nevi with only TAAR6, TAAR8, and TAAR9 remaining detectable in malignant tumors. No association of TAARs expression levels and melanoma clinicopathological characteristics was observed. TAARs co-expressed genes in melanoma and nevi were selected by correlation values for comparative pathway enrichment analysis between malignant and benign neoplasia. It was found that coexpression of TAARs with genes inquired in neurotransmitter signaling is lost in melanoma, and tumor-specific association of TAAR6 expression with the mTOR pathway and inflammatory signaling is observed. It is not excluded that TAARs may have certain functions in melanoma pathogenesis, the significance of which to tumor progression is yet to be understood.

Boar spermadhesin AWN: Novel insights in its binding behavior and localization on sperm

As a major spermadhesin first found in the seminal plasma of boars, AWN is described to fulfil a variety of reproduction related tasks. Although being the best investigated boar spermadhesin, information about its interaction with membranes is inconsistent. In this regard, previous reports locate AWN either inside or on the surface of sperm cells and at different regions, depending on the method and antibody used. Here, we localize native AWN in/on epididymal, ejaculated, capacitated and acrosome-reacted boar sperm using epifluorescence and electron microscopy, as well as an analysis of potential lipid binding partners of native and recombinant AWN. By applying a custom-made anti-AWN antibody, localization of AWN in the equatorial segment of ejaculated, capacitated and acrosome-reacted boar sperm was discovered. Electron microscopy showed that AWN is localized both on the sperm surface and on the cytoplasmic side of the plasma membrane, and in close vicinity to the nuclear and both acrosomal membranes of sperm. Analysis of epididymal sperm indicated migration of AWN from the retral postacrosomal part to the equatorial segment during the epididymal passage. In contrast to hypotheses claiming a specific association of AWN to phosphatidylethanolamine and in line with our previous study describing an interaction with phosphatidic acid, the current results show a rather electrostatically-driven binding mechanism of AWN to negative lipids. In conclusion, this work provides new insights into the arrangement of AWN in the equatorial segment that suggest a possible role in sperm-oocyte fusion.

Insomnia, Pre-Sleep Arousal, Psychosocial Factors and Changes in Sleep Pattern during the Second Wave Lockdown of the COVID-19 Pandemic in Georgia

Studies performed across the COVID-19 pandemic waves point to the persistent impact of the pandemic on sleep and mental health. We expand these data by examining insomnia, pre-sleep arousal, psychosocial factors, and retrospective changes in sleep pattern during the COVID-19 second wave lockdown period in Georgia. Data were collected through an online survey (n = 1117). The prevalence rate of probable insomnia disorder was 24.2%. Clinically relevant somatic and cognitive pre-sleep arousal was present in 49.8% and 58.0% of participants, and high levels of anxiety, depression and social isolation were found in 47.0%, 37.3%, 47.2% of respondents, respectively. We observed high prevalence rates of worse sleep quality, delayed bedtimes and risetimes, longer sleep latencies, higher awakenings and shorter sleep durations, relative to the pre-pandemic period. COVID-19-infected subjects showed more severe sleep and mental problems. Specific predictors differentially affected insomnia, somatic and cognitive pre-sleep arousal. Depression and COVID-19 infection emerged as vulnerability factors for pre-sleep arousal, which, in turn, wasassociated with a higher predisposition to insomnia disorder. We confirm the strong deteriorating impact of the COVID-19 pandemic on sleep and psychosocial well-being during the second wave lockdown period. The specific association between pre-sleep arousal, insomnia, and psychosocial factors is of clinical relevance for the prevention of severity and persistence of sleep and mental problems across the repeated lockdown/reopening waves. Modulation of pre-sleep arousal may prove beneficial to implement targeted interventions.

Association Between Occupational Sitting With High Sensitivity C-Reactive Protein: The Jackson Heart Study

Modifiable, behavioral risk factors like occupational sitting may contribute to inflammation, an important cardiovascular risk factor. This study evaluated the association of self-reported occupational sitting with changes in c-reactive protein (CRP) and the role of sex. We examined occupational sitting and baseline CRP levels for 2889 African American participants in the Jackson Heart Study. Four multivariable linear regression models were estimated to determine the association of occupational sitting and CRP. Analyses were conducted in 2020. The mean age was 50.8 years and 61% were female. Participants who reported occupational sitting as “often/always” had CRP levels of 4.9±6.8 mg/L, “sometimes” had levels of 4.8±8.1 mg/L, and “never/seldom” had levels of 4.3±6.8 mg/L. In the unadjusted model, “often/always” engaging in occupational sitting was significantly associated with higher levels of CRP when compared to “never/seldom” ( P < .05). This differed by sex with female participants who reported “often/always” occupational sitting had CRP levels of 6.0±7.6 mg/L compared to only 5.1±6.9 mg/L for “never/seldom.” Neither the overall association nor the female-specific association remained statistically significant in the adjusted models. We found an association between occupational sitting and inflammation, measured by CRP. This association varied by sex but did not remain significant after fully adjusting for covariates.

New Insights Into Cancer Chronotherapies

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances in the circadian rhythm and cancers are closely related. Circadian clock genes are differentially expressed in many tumors, and accelerate the development and progression of tumors. In addition, tumor tissues exert varying biological activities compared to normal tissues due to resetting of altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit the timing of circadian rhythms to achieve higher efficacy and mild toxicity. Due to interpatient differences in circadian functions, our findings advocate an individualized precision approach to chronotherapy. Herein, we review the specific association between circadian clocks and cancers. In addition, we focus on chronotherapies in cancers and personalized biomarkers for the development of precision chronotherapy. The understanding of circadian clocks in cancer will provide a rationale for more effective clinical treatment of tumors.

Filaggrin gene polymorphisms are associated with atopic dermatitis in women but not in men in the Caucasian population of Central Russia

Background and purpose This study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia. Methods The study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females. Results Significant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19–2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18–2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology. Conclusion Polymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia.

Review of the Existing Evidence for Sex-Specific Relationships between Prenatal Phthalate Exposure and Children’s Neurodevelopment

Phthalates are well-known, ubiquitous environmental contaminants influencing children’s health and their neurodevelopment. However, results of the previously conducted studies are not entirely conclusive. The aim of this review is to present the current state of knowledge with respect to the association between the prenatal phthalate exposure and sex-specific child neurodevelopmental outcomes. A systematic search of the literature was carried out to identify the studies that analyse the sex-specific association between prenatal exposure to phthalates and cognitive, psychomotor outcomes and behavioural and emotional problems. The search was conducted in May 2021, and it was limited to the papers published in English between January 2015 and April 2021. The following databases were used: PubMed, Scopus and Elsevier. The selection process was carried out by two independent authors according to the inclusion criteria. Of a total of 7542 records, 17 epidemiological studies met the inclusion criteria with regards to phthalate exposure and sex-specific differences in child neurobehavioural development. The review shows no clear pattern of association between maternal exposure to phthalates during pregnancy and offspring neurodevelopment. No clearly pronounced sex specific effects, except for BBzP exposure and decreased motor ablates among girls, have been indicated. Inconsistences in the results, as well as unsolved issues related to the interpretation of the results in the context of the exposure level, outcomes, confounders, and biological plausibility highlight the necessity for further research in the field.

Dissect Relationships Between Gene Co-expression and Functional Connectivity in Human Brain

Although recent evidence indicates an association between gene co-expression and functional connectivity in human brain, specific association patterns remain largely unknown. Here, using neuroimaging-based functional connectivity data of living brains and brain-wide gene expression data of postmortem brains, we performed comprehensive analyses to dissect relationships between gene co-expression and functional connectivity. We identified 125 connectivity-related genes (20 novel genes) enriched for dendrite extension, signaling pathway and schizophrenia, and 179 gene-related functional connections mainly connecting intra-network regions, especially homologous cortical regions. In addition, 51 genes were associated with connectivity in all brain functional networks and enriched for action potential and schizophrenia; in contrast, 51 genes showed network-specific modulatory effects and enriched for ion transportation. These results indicate that functional connectivity is unequally affected by gene expression, and connectivity-related genes with different biological functions are involved in connectivity modulation of different networks.