Enantio- and Diastereoselective 1,2-Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-Diborylalkanes

The catalytic enantioselective synthesis of boronate-substituted tertiary alcohols through additions of diborylmethane and substituted 1,1-diborylalkanes to α-ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine/copper(I) complexes and produce β-hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 e.r. and greater than 20:1 d.r. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates the reactions occur via an enantioenriched α-boryl-copper-alkyl intermediate

Growing Collaborative Outreach Efforts to Support the Well-Being of Communities

Libraries of all types provide outreach efforts for their patrons to reduce stress and promote well-being. Public, school, and academic libraries often partner with external entities to provide yoga, therapy dogs, and other creative activities for their patrons. Although collaboration is expected in public, school, and academic libraries, how to collaborate and/or grow collaborative efforts is lacking in the library literature. A former public library employee and a former school librarian came together to pilot a de-stressing program for students at their academic library and each semester have continued to grow their collaborative efforts with partners on and off-campus. Strategies for how to create partnerships and expand collaborative efforts are discussed within the framework of providing programs and activities to support the well-being of library visitors. Additional planning materials, such as a list of resources, budgets, and marketing ideas are provided.Ope

The energy based devices for vaginal "rejuvenation," urinary incontinence, vaginal cosmetic procedures, and other vulvo-vaginal disorders: An international multidisciplinary expert panel opinion

Aims: Energy-based devices using radiofrequency and laser technologies have gained popularity as therapies for vaginal atrophy, urinary incontinence, and vaginal prolapse. They have been promoted by cosmetic and aesthetic industries for vaginal "laxity" and vaginal "rejuvenation," both of which are undefined conditions and terms. This article aims to review the current available literature and its quality on this emerging technology. Methods: An international panel of gynaecologists, urogynaecologists, and urologists undertook a review of the available published literature, identifying articles, guidance, and society statements on the use vaginal energy-based devices. Results: There is currently no formal guidance for the use of vaginal energy based therapies. No randomized controlled trials have been published. No comparative studies to existing treatment has been carried out. Studies suggest that vaginal laser can be used in the treatment of vaginal prolapse or "vaginal laxity" and stress urinary incontinence with no quality evidence supporting the use of the therapy for vaginal atrophy or lichen sclerosis. Conclusions: This international group propose that whilst there remains a paucity of good quality data describing the safety, benefits, and appropriate use of vaginal radiofrequency or laser treatments in gynaecology and urogynaecology, a consensus best practice document by an established scientific community needs to be developed.info:eu-repo/semantics/publishedVersio

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche.

A major challenge in stem cell differentiation is the availability of bioassays to prove cell types generated in vitro are equivalent to cells in vivo. In the mouse, differentiation of primordial germ cell-like cells (PGCLCs) from pluripotent cells was validated by transplantation, leading to the generation of spermatogenesis and to the birth of offspring. Here we report the use of xenotransplantation (monkey to mouse) and homologous transplantation (monkey to monkey) to validate our in vitro protocol for differentiating male rhesus (r) macaque PGCLCs (rPGCLCs) from induced pluripotent stem cells (riPSCs). Specifically, transplantation of aggregates containing rPGCLCs into mouse and nonhuman primate testicles overcomes a major bottleneck in rPGCLC differentiation. These findings suggest that immature rPGCLCs once transplanted into an adult gonadal niche commit to differentiate towards late rPGCs that initiate epigenetic reprogramming but do not complete the conversion into ENO2-positive spermatogonia

TLR2 and TLR4 as Potential Biomarkers of Environmental Particulate Matter Exposed Human Myeloid Dendritic Cells

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution

Report of AAPM Therapy Physics Committee Task Group 74: Inâ air output ratio, Sc, for megavoltage photon beams

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134830/1/mp7367.pd

Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2

Background & Aims Progastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R) - partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R. Methods We performed microarray analysis to compare changes in gene expression in the colonic mucosa of mice that express a human progastrin transgene, gastrin knockout mice, and C57BL/6 mice (controls); the effects of progastrin were also determined on in vitro colonic crypt cultures from cholecystokinin 2 receptor knockout and wild-type mice. Human colorectal and gastric cancer cells that expressed CCK2R were incubated with progastrin or Bmp2; levels of β-arrestin 1 and 2 were knocked down using small interfering RNAs. Cells were analyzed for progastrin binding, proliferation, changes in gene expression, and symmetric cell division. Results The BMP pathway was down-regulated in the colons of human progastrin mice compared with controls. Progastrin suppressed transcription of Bmp2 through a pathway that required CCK2R and was mediated by β-arrestin 1 and 2. In mouse colonic epithelial cells, down-regulation of Bmp2 led to decreased phosphorylation of Smads1/5/8 and suppression of inhibitor of DNA binding 4. In human gastric and colorectal cancer cell lines, CCK2R was necessary and sufficient for progastrin binding and induction of proliferation; these effects were blocked when cells were incubated with recombinant Bmp2. Incubation with progastrin increased the number of CD44+, bromodeoxyuridine+, and NUMB+ cells, indicating an increase in symmetric divisions of putative cancer stem cells. Conclusions Progastrin stimulates proliferation in colons of mice and cultured human cells via CCK2R- and β-arrestin 1 and 2-dependent suppression of Bmp2 signaling. This process promotes symmetric cell division. © 2013 by the AGA Institute

Obesity accelerates Helicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response

Objective: To investigate the role of obesity-associated inflammation and immune modulation in gastric carcinogenesis during Helicobacter-induced chronic gastric inflammation. Design: C57BL/6 male mice were infected with H felis and placed on a high-fat diet (45% calories from fat). Study animals were analysed for gastric and adipose pathology, inflammatory markers in serum, stomach and adipose tissue, and immune responses in blood, spleen, stomach and adipose tissue. Results: H felis-induced gastric carcinogenesis was accelerated in diet-induced obese mice compared with lean controls. Obesity increased bone marrow-derived immature myeloid cells in blood and gastric tissue of H felis-infected mice. Obesity also led to elevations in CD4 T cells, IL-17A, granulocyte macrophage colony-stimulating factor, phosphorylated STAT3 and prosurvival gene expression in gastric tissue of H felis-infected mice. Conversely, in adipose tissue of obese mice, H felis infection increased macrophage accumulation and expression of IL-6, C-C motif ligand 7 (CCL7) and leptin. Finally, the combination of obesity and gastric inflammation synergistically increased serum proinflammatory cytokines, including IL-6. Conclusions: Here, we have established a model to study the molecular mechanism by which obesity predisposes individuals to gastric cancer. In H felis-infected mice, obesity increased proinflammatory immune responses and accelerated gastric carcinogenesis. Interestingly, gastric inflammation augmented obesity-induced adipose inflammation and production of adipose-derived factors in obese, but not lean, mice. Our findings suggest that obesity accelerates Helicobacter-associated gastric cancer through cytokine-mediated cross-talk between inflamed gastric and adipose tissues, augmenting immune responses at both tissue sites, and thereby contributing to a protumorigenic gastric microenvironment.National Institutes of Health (U.S.) (grant 5R01CA093405-11)Columbia University Medical Center (Naomi Berrie Diabetes Center, grant P30DK063608