A single cell atlas of the mouse seminal vesicle.

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

Imaging-AMARETTO: An Imaging Genomics Software Tool to Interrogate Multiomics Networks for Relevance to Radiography and Histopathology Imaging Biomarkers of Clinical Outcomes.

PURPOSE: The availability of increasing volumes of multiomics, imaging, and clinical data in complex diseases such as cancer opens opportunities for the formulation and development of computational imaging genomics methods that can link multiomics, imaging, and clinical data. METHODS: Here, we present the Imaging-AMARETTO algorithms and software tools to systematically interrogate regulatory networks derived from multiomics data within and across related patient studies for their relevance to radiography and histopathology imaging features predicting clinical outcomes. RESULTS: To demonstrate its utility, we applied Imaging-AMARETTO to integrate three patient studies of brain tumors, specifically, multiomics with radiography imaging data from The Cancer Genome Atlas (TCGA) glioblastoma multiforme (GBM) and low-grade glioma (LGG) cohorts and transcriptomics with histopathology imaging data from the Ivy Glioblastoma Atlas Project (IvyGAP) GBM cohort. Our results show that Imaging-AMARETTO recapitulates known key drivers of tumor-associated microglia and macrophage mechanisms, mediated by STAT3, AHR, and CCR2, and neurodevelopmental and stemness mechanisms, mediated by OLIG2. Imaging-AMARETTO provides interpretation of their underlying molecular mechanisms in light of imaging biomarkers of clinical outcomes and uncovers novel master drivers, THBS1 and MAP2, that establish relationships across these distinct mechanisms. CONCLUSION: Our network-based imaging genomics tools serve as hypothesis generators that facilitate the interrogation of known and uncovering of novel hypotheses for follow-up with experimental validation studies. We anticipate that our Imaging-AMARETTO imaging genomics tools will be useful to the community of biomedical researchers for applications to similar studies of cancer and other complex diseases with available multiomics, imaging, and clinical data.

Caucasian endemic medicinal and nutraceutical plants: in-vitro antioxidant and cytotoxic activities and bioactive compounds.

OBJECTIVES: In order to assess traditional claims about the therapeutic potential of Caucasian endemic medicinal plants and to select plants for phytochemical research, nine plant species were selected and assessed for their in-vitro antioxidant and cytotoxic activities. The metabolite profiles of some priority plants were analysed. METHODS: Antioxidant effects were assessed using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) system, lipid peroxidation and Folin-Ciocalteu methods. Cytotoxic activities were examined against human liver cancer cells (HepG2) using the Alamar Blue assay. Terpenoids of selected species were analysed by GC and GC-MS. Polyphenols were separated by HPLC. KEY FINDINGS: Thymus transcaucasicus, Heracleum transcaucasicum, Ribes armenum, Crataegus armena showed most promising antioxidant activity in ABTS model system. Moreover, Rubus takhtadjanii, C. armena, T. transcaucasicus showed a high level of antioxidant activity by inhibiting lipid peroxidation. C. armena and T. transcaucasicus expressed high-to-moderate cytotoxicity against HepG2 cells. The main terpenoids and polyphenols of Centaurea hajastana, C. armena and T. transcaucasicus were quantified. CONCLUSIONS: This study provides in-vitro data relevant for assessing the use of Caucasian endemic medicinal plants, most importantly C. armena and T. transcaucasicus as traditional antioxidant supplements and potential anticancer remedies. Metabolite profiles of some lead plants showed the nature of bioactive compounds of medical interest.

The intermolecular dimer potential for guanine.

The ab initio intermolecular potential of guanine has been developed with the help of a combination of symmetry-adapted perturbation theory and density functional theory (DFT). The resulting potential has been globally optimized to locate the guanine cluster structures up to tetramers. It has been found that the new potential is able to reproduce the known guanine cluster structures, especially the guanine quartet stabilized by Hoogsteen hydrogen bonds, in addition to new low-energy conformers. The performance of the potential was also compared with the AMBER force field as well as DFT-D and MP2 levels of theory. The model potential is in agreement with the ab initio methods and it shows a better performance compared to AMBER. Therefore, it can be further exploited in molecular dynamics or global optimizations to determine the structure and energy of much larger guanine clusters.

First principles potential for the cytosine dimer.

We developed a new first principles potential for the cytosine dimer. The ab initio calculations were performed with a DFT-SAPT combination of the symmetry-adapted perturbation method and density functional theory, and fitted to a model site-site functional form. The model potential was used to predict cluster structures up to cytosine hexamers. The global cluster structure optimizations showed that the new potential is able to reproduce some of the 2D filament structures. Moreover many new non-planar cytosine cluster structures were also discovered. Interaction energies of these clusters were compared with B3LYP-D, MP2, SCS-MP2, SCS-MI-MP2 and AMBER. It has been shown that the model agrees well with all ab initio methods, especially for the cytosine hexamer. The model potential outperforms the AMBER force field and therefore it can be exploited to study more challenging larger systems.

Effects of PAR and UV-B radiation on herbal yield, bioactive compounds and their antioxidant capacity of some medicinal plants under controlled environmental conditions.

Photosynthetically active radiation (PAR) and Ultraviolet B (UV-B) radiation are among the main environmental factors acting on herbal yield and biosynthesis of bioactive compounds in medicinal plants. The objective of this study was to evaluate the influence of biologically effective UV-B light (280-315 nm) and PAR (400-700 nm) on herbal yield, content and composition, as well as antioxidant capacity of essential oils and polyphenols of lemon catmint (Nepeta cataria L. f. citriodora), lemon balm (Melissa officinalis L.) and sage (Salvia officinalis L.) under controlled greenhouse cultivation. Intensive UV-B radiation (2.5 kJ m(-2)  d(-1) ) influenced positively the herbal yield. The essential oil content and composition of studied herbs were mainly affected by PAR and UV-B radiation. In general, additional low-dose UV-B radiation (1 kJ m(-2) d(-1) ) was most effective for biosynthesis of polyphenols in herbs. Analysis of major polyphenolic compounds provided differences in sensitivity of main polyphenols to PAR and UV-B radiation. Essential oils and polyphenol-rich extracts of radiated herbs showed essential differences in antioxidant capacity by the ABTS system. Information from this study can be useful for herbal biomass and secondary metabolite production with superior quality under controlled environment conditions.