Flourishing the Urban Environment: How Urban Gardens Affect Pollinators

The order of Hymenoptera is classified as bees, wasps, and ants and are widely recognized as pollinators. Some species of bees (family Apoidea) and hoverflies tend to focus on certain types of flowers and are attracted to patterns and colors. Native plants and crops that are specifically bee-friendly can encourage bees and other pollinators that are decreasing in biodiversity and population to come back. Urban gardens work to provide vegetables and organic produce to its communities and subsequently are also growing pollinator-friendly food. This study focuses on whether the biodiversity of Hymenoptera, hoverflies, and other significant pollinators are affected by these types of land use and resource availability. Urban gardens are an interesting way to gauge how human influence can possibly change how pollination occurs with either organic or artificial urging. The results of this thesis could lead to evolving the diversity of urban gardens, to include pollinator-friendly crops and plants, and promoting the implementation of urban gardens in cities in order to increase biodiversity of pollinators in those settings. This will lead to both healthier human and plant communities. Through examining three different communities of plants, visual surveys focused on Hymenoptera and Diptera observed differences in the species distribution

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms

SIRT1 in astrocytes regulates glucose metabolism and reproductive function

Sirtuin 1 (Sirt1) is an NAD-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, evidence suggests that SIRT1 in neurons plays a role in the central regulation of energy balance and reproduction, but no studies have addressed the contribution of astrocytes. We show here that overexpression of SIRT1 in astrocytes causes markedly increased food intake, body weight gain, and glucose intolerance, but expression of a deacetylase-deficient SIRT1 mutant decreases food intake and body weight and improves glucose tolerance, particularly in female mice. Paradoxically, the effect of these SIRT1 mutants on insulin tolerance was reversed, with overexpression showing greater insulin sensitivity. The mice overexpressing SIRT1 were more active, generated more heat, and had elevated oxygen consumption, possibly in compensation for the increased food intake. The female overexpressing mice were also more sensitive to diet-induced obesity. Reproductively, the mice expressing the deacetylase-deficient SIRT1 mutant had impaired estrous cycles, decreased LH surges, and fewer corpora lutea, indicating decreased ovulation. The GnRH neurons were responsive to kisspeptin stimulation, but hypothalamic expression of Kiss1 was reduced in the mutant mice. Our results showed that SIRT1 signaling in astrocytes can contribute to metabolic and reproductive regulation independent of SIRT1 effects in neurons.Fil: Choi, Irene. VA San Diego Healthcare System; Estados UnidosFil: Rickert, Emily. University of California at San Diego; Estados UnidosFil: Fernandez, Marina Olga. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Webster, Nicholas J.G.. VA San Diego Healthcare System; Estados Unidos. University of California at San Diego; Estados Unido

Neuronal SIRT1 regulates metabolic and reproductive function and the response to caloric restriction

Sirt1 is a NAD-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study we generated mice expressing an enzymatically inactive form (NMUT) or wild-type SIRT1 (N-OX) in mature neurons. Both N-OX male and female mice showed impaired glucose tolerance, and N-MUT female, but not male, mice showed improvedglucose tolerance compared to WT littermates. Furthermore, all mice showed improved glucose tolerance with caloric restriction (CR), but the N-OX mice showed the greatest change and now showed better glucose tolerance than their littermates. At the reproductive level, N-OX females showed impaired estrous cycles, with increased cycle length and more time in estrus. LH andprogesterone surges were absent on the evening of proestrus in the N-OX mice suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology with a reduced number of corpora lutea. Despite this defect, the mice were still fertile when mated to wild-type mice on the day of pro-estrus indicating that the mice can respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms.Fil: Rickert, Emily. University of California at San Diego; Estados Unidos. VA San Diego Healthcare System; Estados UnidosFil: Fernandez, Marina Olga. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of California at San Diego; Estados UnidosFil: Gorman, Michael. University of California at San Diego; Estados UnidosFil: Olefsky, Jerrold M.. University of California at San Diego; Estados UnidosFil: Webster, Nicholas J.G.. Va San Diego Healthcare System; Estados Unidos. University of California at San Diego; Estados Unido

RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals

DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre–B cell receptor (pre–BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre–BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre–B cells. Here, we show that RAG DSBs inhibit pre–BCR signals through the ATM- and NF-κB2–dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre–BCR signaling. This regulatory circuit prevents the pre–BCR from inducing additional Igl chain gene rearrangements and driving pre–B cells with RAG DSBs into cycle. We propose that pre–B cells toggle between pre–BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes

Synthesis and biological characterization of anti-estrogen conjugates

The overall function of estrogen receptor modulators and their role in the signaling of estrogen receptors through non-classical pathways is poorly understood. One possible method to answer to this question is to develop chemical tools to selectively target non-classical ER signaling pathways. The development of molecules that localize to specific subcellular areas offers a potential way to study non-classical ER signaling mechanisms. Conjugation of drugs to macromolecular scaffolds is a well-established strategy to modulate drug properties but stable conjugates have rarely been used to target steroid hormone receptors. Tamoxifen (TAM) is used extensively to treat breast cancer, but the signaling mechanisms associated with TAM are quite complex. In an effort to better understand tamoxifen action in cells and to explore the possibility of targeting nuclear receptors with conjugates, we have developed several polymer and fluorescent conjugates with unexpected cellular activities, and unique localization patterns

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms

Obese neuronal PPARγ KO mice are leptin sensitive but show impaired glucose tolerance and fertility

PPARγ is expressed in the hypothalamus in areas involved in energy homeostasis and glucose metabolism. In this study, we created a deletion of PPARγ (BKO) in mature neurons in female mice to investigate its involvement in metabolism and reproduction. We observed that there was no difference in age at puberty onset between female BKOs and littermate controls, but the BKOs gave smaller litters when mated and fewer oocytes when ovulated. The female BKO mice had regular cycles but showed an increase in the number of cycles with prolonged estrus. The mice also had increased LH levels during the LH surge and histological examination showed hemorrhagic corpora lutea. The mice were challenged with a 60% high fat diet. Metabolically the female BKO mice showed normal body weight, glucose and insulin tolerance, and leptin levels but were protected from obesity-induced leptin resistance. The neuronal knockout also prevented the reduction in estrous cycles due to the HFD. Examination of ovarian histology showed a decrease in the number of primary and secondary follicles in both genotypes due to the HFD, but the BKO ovaries showed an increase in the number of hemorrhagic follicles. In summary, our results show that neuronal PPARγ is required for optimal female fertility, but is also involved in the adverse effects of diet-induced obesity by creating leptin resistance potentially through induction of the repressor Socs3.Fil: Fernandez, Marina Olga. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of California at San Diego; Estados UnidosFil: Sharma, Shweta. University of California at San Diego; Estados UnidosFil: Kim, Sun. University of California at San Diego; Estados UnidosFil: Rickert, Emily. University of California at San Diego; Estados UnidosFil: Hsueh, Katherine. University of California at San Diego; Estados UnidosFil: Hwang, Vicky. University of California at San Diego; Estados UnidosFil: Olefsky, Jerrold M.. University of California at San Diego; Estados UnidosFil: Webster, Nicholas J.G.. University of California at San Diego; Estados Unidos. VA San Diego Healthcare System,; Estados Unido