In vitro interaction network of a synthetic gut bacterial community

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM¹²) synthetic bacterial community, which is increasingly used as a model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments as well as in community batch culture. Metabolic network reconstruction in combination with metabolomics analysis of bacterial culture supernatants provided insights into the metabolic potential and activity of the individual community members. Thereby, we could show that the OMM¹² interaction network is shaped by both exploitative and interference competition in vitro in nutrient-rich culture media and demonstrate how community structure can be shifted by changing the nutritional environment. In particular, Enterococcus faecalis KB1 was identified as an important driver of community composition by affecting the abundance of several other consortium members in vitro. As a result, this study gives fundamental insight into key drivers and mechanistic basis of the OMM¹² interaction network in vitro, which serves as a knowledge base for future mechanistic in vivo studies.Subject terms: Microbiome, Microbial ecology     

Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer

Breast cancers can recur after removal of the primary tumor and treatment to eliminate remaining tumor cells. Recurrence may occur after long periods of time during which there are no clinical symptoms. Tumor cell dormancy may explain these prolonged periods of asymptomatic residual disease and treatment resistance. We generated a dormancy gene signature from published experimental models and applied it to both breast cancer cell line expression data as well as four published clinical studies of primary breast cancers. We found that estrogen receptor (ER) positive breast cell lines and primary tumors have significantly higher dormancy signature scores (P<0.0000001) than ER- cell lines and tumors. In addition, a stratified analysis combining all ER+ tumors in four studies indicated 2.1 times higher hazard of recurrence among patients whose tumors had low dormancy scores (LDS) compared to those whose tumors had high dormancy scores (HDS) (p<0.000005). The trend was shown in all four individual studies. Suppression of two dormancy genes, BHLHE41 and NR2F1, resulted in increased in vivo growth of ER positive MCF7 cells. The patient data analysis suggests that disseminated ER positive tumor cells carrying a dormancy signature are more likely to undergo prolonged dormancy before resuming metastatic growth. Furthermore, genes identified with this approach might provide insight into the mechanisms of dormancy onset and maintenance as well as dormancy models using human breast cancer cell lines.     

Track analysis and conservation priorities in the cloud forests of Hidalgo,Mexico

Abstract . A track analysis based on the distributional patterns of 967 species of vascular plant taxa (gymnosperms, angiosperms and pteridophytes) was performed to assess conservation priorities for cloud forests in the state of Hidalgo, Mexico, ranged in the municipalities of Chapulhuacán, Eloxochitlán, Molocotlán, Pisaflores, Tenango de Doria, Tlahuelompa and Tlanchinol, as well as five floristically equivalent areas in the states of Veracruz (Teocelo and Helechales), Tamaulipas (Gómez Farías), Morelos‐México (Ocuilan) and Oaxaca (Huautla de Jiménez). In order to detect generalized tracks we employed a new parsimony method, where clades (considered equivalent to generalized tracks) are defined forbidding homoplasy and acting like a compatibility algorithm. Several generalized tracks were found connecting these areas. Cloud forests of Chapulhuacán were connected according to three different generalized tracks and thus have a higher value, qualifying as a priority area for the conservation of cloud forests in the state of Hidalgo.     

Intracellular signaling mechanisms mediating catecholamine release upon activation of NPY Y1 receptors in mouse chromaffin cells

The adrenal chromaffin cells synthesize and release catecholamine (mostly epinephrine and norepinephrine) and different peptides, such as the neuropeptide Y (NPY). NPY stimulates catecholamine release through NPY Y1 receptor in mouse chromaffin cells. The aim of our study was to determine the intracellular signaling events coupled to NPY Y1 receptor activation that lead to stimulation of catecholamine release from mouse chromaffin cells. The stimulatory effect of NPY mediated by NPY Y1 receptor activation was lost in the absence of extracellular Ca2+. On the other hand, inhibition of nitric oxide synthase and guanylyl cyclase also decreased the stimulatory effect of NPY. Moreover, catecholamine release stimulated by NPY or by the nitric oxide donor (NOC-18) was inhibited by mitogen-activated protein kinase (MAPK) and protein kinase C inhibitors. In summary, in mouse chromaffin cells, NPY evokes catecholamine release by the activation the NPY Y1 receptor, in a Ca2+-dependent manner, by activating mitogen-activated protein kinase and promoting nitric oxide production, which in turn regulates protein kinase C and guanylyl cyclase activation.     

Value of cytology in papillary condylomatous lesions of the cervix

OBJECTIVE: To determine the value of cytology in detecting mature and immature papillary condylomas of the uterine cervix. STUDY DESIGN: We evaluated 240 cases of plane cervical intraepithelial neoplasia, grade 1 (CIN 1), and 23 papillary condylomas by Pap smear and biopsy and classified histologic sections according to maturity and keratinization. We reevaluated corresponding cytologic smears and identified criteria of low grade squamous lesion (LSIL) and human papillomavirus (HPV) infection. RESULTS: Thirteen (56.5%) papillary lesions were histologically classified as mature, 6 (26%) as immature and 4 (17.3%) as mixed. Fifteen lesions (65.2%) were nonkeratinized, 2 (8.6%) keratinized and 6 (26%) partially keratinized. Corresponding smears were cytologically diagnosed as LSIL (6, 26%), atypical squamous cells of undetermined significance (ASCUS) (7, 30.4%) and negative (10, 43.4%). Careful cytologic review diagnosed only two of the 13 mature lesions; few cytological criteria of LSIL and HPV infection were observed. Koilocytes were seen in just 1 case. Sample limiting factors occurred in 4 cases: 2 cytologically diagnosed as LSIL, 1 asASCUS and 1 as negative for lesion. CONCLUSION: Cytology was not effective in the detection of cervical condyloma acuminatum, independent of limitations in sample adequacy and of the degree of maturity or keratinization of the lesions.