Exposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity. Our objective was to determine individual variation in expression of estrogen receptor (ER) and estrogen-induced responses in the normal human breast. Human breast tissue from female donors undergoing reduction mammoplasty surgery were collected for microarray analysis of ER expression. To examine estrogen-induced responses, breast tissue from 23 female donors were cultured ex- vivo in basal or 10 nM 17β-estradiol (E2) media for 4 days. Expression of ER genes (ESR1 and ESR2) increased significantly with age. E2 induced consistent increases in global gene transcription, but expression of target genes AREG, PGR, and TGFβ2 increased significantly only in explants from nulliparous women. E2-treatment did not induce consistent changes in proliferation or radiation induced apoptosis. Responses to estrogen are highly variable among women and not associated with levels of ER expression, suggesting differences in intracellular signaling among individuals. The differences in sensitivity to E2-stimulated responses may contribute to variation in risk of breast cancer.Diffusion MRI (dMRI) is commonly used to map large axonal pathways in the white matter.  https://www.selleckchem.com/Bcl-2.html  Recent technical advances have also enabled dMRI to resolve the small and complex axonal and dendritic projections in the gray matter. This study investigated whether high-resolution dMRI can resolve the hippocampal neuronal projections and detect abnormal connections due to neurological injury. We performed 3D high spatial and angular resolution dMRI of the mouse brains of the offspring survivors from a model of intrauterine (UI) inflammation, who had known functional deficiency in the hippocampus. We used a novel hippocampal connection mapping method to quantify the intra- and inter-hippocampal projections among 34 automatically segmented hippocampal sub-regions. The results demonstrated wide-spread intra-hippocampal projections, but rather specific intra-hippocampal projections that primarily connected through the CA3 region. Compared with the control group (n = 9), UI-injured mice (n = 11) exhibited significantly reduced inter-hippocampal projection strength (p  less then  0.01), which correlated well with the neurobehavioral assessments (R2 = 0.47). Furthermore, using a whole-brain fixel-based analysis, we identified reduced fiber-density in the CA3 and the ventral hippocampal commissure of the UI-injured mice, which may explain the reduced inter-hippocampal projections. Histological findings also indicated reduced commissural fibers due to the UI-injury. Our study suggested that the dMRI-based connectivity mapping technique can potentially characterize abnormal hippocampal projections in neurological disorders.Siglecs are a family of transmembrane receptor-like glycan-recognition proteins expressed primarily on leukocytes. Majority of Siglecs have an intracellular sequence motif called immunoreceptor tyrosine-based inhibitory motif (ITIM) and associate with Src homology region 2 domain-containing tyrosine phosphatase-1 (SHP-1), and negatively regulate tyrosine phosphorylation-mediated intracellular signaling events. On the other hand, some Siglecs have a positively charged amino acid residue in the transmembrane domain and associate with DNAX activation protein of 12 kDa (DAP12), which in turn recruits spleen tyrosine kinase (Syk). These DAP12-associated Siglecs play diverse functions. For example, Siglec-15 is conserved throughout vertebrate evolution and plays a role in bone homeostasis by regulating osteoclast development and function. Human Siglec-14 and -16 have inhibitory counterparts (Siglec-5 and -11, respectively), which show extremely high sequence similarity with them at the extracellular domain but interact with SHP-1. The DAP12-associated Siglec in such "paired receptor" configuration counteracts the pathogens that exploit the inhibitory counterpart. Polymorphisms (mutations) that render DAP12-associated inactive Siglecs are found in humans, and some of these appear to be associated with sensitivity or resistance of human hosts to bacterially induced conditions. Studies of mouse Siglec-H have revealed complex and intriguing functions it plays in regulating adaptive immunity. Many questions remain unanswered, and further molecular and genetic studies of DAP12-associated Siglecs will yield valuable insights with translational relevance.Siglecs are sialic acid (Sia) recognizing immunoglobulin-like receptors expressed on the surface of all the major leukocyte lineages in mammals. Siglecs recognize ubiquitous Sia epitopes on various glycoconjugates in the cell glycocalyx and transduce signals to regulate immunological and inflammatory activities of these cells. The subset known as CD33-related Siglecs is principally inhibitory receptors that suppress leukocyte activation, and recent research has shown that a number of bacterial pathogens use Sia mimicry to engage these Siglecs as an immune evasion strategy. Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. Siglecs are positioned in crosstalk with other host innate immune sensing pathways to modulate the immune response to infection in complex ways. This chapter summarizes the current understanding of Siglecs at the host-pathogen interface, a field of study expanding in breadth and medical importance, and which provides potential targets for immune-based anti-infective strategies.Galectins are a family of ß-galactoside-binding lectins characterized by a unique sequence motif in the carbohydrate recognition domain, and evolutionary and structural conservation from fungi to invertebrates and vertebrates, including mammals. Their biological roles, initially understood as limited to recognition of endogenous ("self") carbohydrate ligands in embryogenesis and early development, dramatically expanded in later years by the discovery of their roles in tissue repair, cancer, adipogenesis, and regulation of immune homeostasis. In recent years, however, evidence has also accumulated to support the notion that galectins can bind ("non-self") glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity. Thus, this evidence has established a new paradigm by which galectins can function not only as pattern recognition receptors but also as effector factors, by binding to the microbial surface and inhibiting adhesion and/or entry into the host cell, directly killing the potential pathogen by disrupting its surface structures, or by promoting phagocytosis, encapsulation, autophagy, and pathogen clearance from circulation.