No abstract

Hypocalcemia is a metabolic disorder that affects dairy cows during the transition from pregnancy to lactation. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 days prepartum with either saline or 1.0 mg/kg bodyweight of the immediate precursor to serotonin synthesis, 5 hydroxy-l-tryptophan (5-HTP). On infusion days, blood was collected before, after, and at 2, 4, and 8 h postinfusion. Blood and urine were collected daily before the infusion period, for 14 days postpartum and on day 30 postpartum. Milk was collected daily during the postpartum period. Feed intake and milk yield were unaffected by 5-HTP infusion postpartum. Cows infused with 5-HTP had elevated circulating serotonin concentrations prepartum. Infusion with 5-HTP induced a transient hypocalcemia in Jersey cows prepartum, but not in any other treatment. Holstein cows infused with saline had the highest milk calcium on the day of and day after parturition. Postpartum, circulating total calcium tended to be elevated, and urine deoxypyridinoline (DPD) concentrations were elevated in Holstein cows infused with 5-HTP. Overall, Jerseys had higher urine DPD concentrations postpartum when compared with Holsteins. Taken together, these data warrant further investigation of the potential therapeutic benefit of 5-HTP administration prepartum for prevention of hypocalcemia. Further research should focus on delineation of mechanisms associated with 5-HTP infusion that control calcium homeostasis during the peripartum period in Holstein and Jersey cows. Serotonin improves calcium in peripartum periods r weaver and others

Executive SummaryAs the deployment of grid-connected solar photovoltaic (PV) systems has increased, so too has the desire to track the cost and price of these systems. This report helps to fill this need by summarizing trends in the installed price of grid-connected PV systems in the United States from 1998 through 2012, with preliminary data for 2013. The analysis is based on project-level data for more than 200,000 individual residential, commercial, and utility-scale PV systems, representing 72% of all grid-connected PV capacity installed in the United States through 2012.It is essential to note at the outset what the data presented within this report represent. First, the data are historical, focusing primarily on projects installed through the end of 2012, and therefore do not reflect the price of projects installed more recently (with the exception of the limited set of results presented for systems installed in the first half of 2013); nor are the data representative of prices currently being quoted for prospective projects to be installed at a later date. For this reason and others (see Text Box 1, within the main body), the results presented in this report may differ from current PV price benchmarks. Second, this report focuses on the installed price of PV -that is, the up-front price paid by the PV system owner, prior to receipt of incentives. As such, it does not capture trends associated with PV performance or other factors that would affect the levelized cost of electricity for PV, nor does it capture trends in the net cost to the owner after receipt of all incentives. Finally, the underlying data collected for this report include third party owned (TPO) projects where either the system is leased to the site-host or the generation output is sold to the site-host under a power purchase agreement. For a subset of TPO systems, the installed price data represents an appraised value rather than a transaction price, and those projects were removed from the data sample (see Section 2 and Appendix A for further details).The report presents one set of installed price trends for residential and commercial PV systems, and another set for utility-scale PV. In all cases, installed prices are identified in terms of real 2012 dollars per installed watt (DC-STC), prior to receipt of any direct financial incentives or tax credits.Key findings for residential and commercial PV 1 are as follows: Installed prices continued their precipitous decline in 2012, falling year-over-year by $0.9/W (14%) for systems ≤10 kW, $0.8/W (13%) for systems 10-100 kW, and $0.3/W (6%) for systems >100 kW. Among projects installed in 2012, median installed prices were $5.3/W for systems ≤10 kW, $4.9/W for systems 10-100 kW, and $4.6/W for systems >100 kW. Partial data for the first six months of 2013 indicate that installed prices have continued to fall, with the median installed price of projects funded through the California Solar Initiative declining by an additional $0.5/W to $0.8/W (10-15%) depending on system size, relative to sys...

A 4!4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-L-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre-and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre-and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (bHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism.

Executive SummaryAs the deployment of grid-connected solar photovoltaic (PV) systems has increased, so too has the desire to track the cost and price of these systems. This report helps to fill this need by summarizing trends in the installed price of grid-connected PV systems in the United States from 1998 through 2013, with partial data for the first half of 2014. The analysis is based on projectlevel data for more than 300,000 individual residential, commercial, and utility-scale PV systems installed across 33 states and representing 80% of all grid-connected PV capacity installed in the United States through 2013.It is essential to note at the outset what the data presented within this report represent. First, the data consist of prices paid to project developers or installers (prior to receipt of any incentives), and for a variety of reasons, those prices may differ from the underlying costs borne by project developers/installers. Second, the data are historical, focusing primarily on projects installed through the end of 2013, and therefore do not reflect the price of projects installed more recently (with the exception of the limited set of results presented for systems installed in the first half of 2014); nor are the data indicative of prices currently being quoted for prospective projects to be installed at a later date. For these reasons and others (see Text Box 1, within the main body), the results presented in this report may differ from current PV price or cost benchmarks. Third, by focusing on the up-front price paid by the PV system owner prior, the report does not capture trends associated with PV performance or other factors that impact the levelized cost of electricity for PV. Finally, the underlying data collected for this report include third party owned (TPO) projects where either the system is leased to the site-host or the generation output is sold to the site-host under a power purchase agreement. For a subset of TPO systems, the installed price data represent appraised values rather than transaction prices, and those projects were removed from the data sample in order to eliminate any associated bias (see Section 2 and Appendix A for further details).The report presents one set of installed price trends for residential and commercial PV systems, and another set for utility-scale PV. In all cases, installed prices are identified in terms of real 2013 dollars per installed watt (DC-STC), prior to receipt of any direct financial incentives or tax credits.Key findings for residential and commercial PV 1 are as follows:• Installed prices continued their precipitous decline in 2013, falling year-over-year by $0.7/W, or 12-15% depending on system size range. Among projects installed in 2013, median installed prices were $4.7/W for systems ≤10 kW, $4.3/W for systems 10-100 kW, and $3.9/W for systems >100 kW.• Data for the first six months of 2014 indicate that installed prices have continued to fall, with the median installed price of systems in a number of the larger state markets declining by ...

The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research.

Selective serotonin reuptake inhibitors (SSRIs) have been linked to osteopenia and fracture risk; however, their long-term impact on bone health is not well understood. SSRIs are widely prescribed to pregnant and breastfeeding women who might be at particular risk of bone pathology because lactation is associated with considerable maternal bone loss. We used microCT and molecular approaches to test whether the SSRI fluoxetine, administered to C57BL/6 mice from conception through the end of lactation, causes persistent maternal bone loss. We found that peripartum fluoxetine increases serum calcium and reduces circulating markers of bone formation during lactation but does not affect osteoclastic resorption. Peripartum fluoxetine exposure also enhances mammary gland endocrine function during lactation by increasing synthesis of serotonin and PTHrP, a hormone that liberates calcium for milk synthesis and reduces bone mineral volume. Peripartum fluoxetine exposure reduces the trabecular bone volume fraction at 3 months after weaning. These findings raise new questions about the long-term consequences of peripartum SSRI use on maternal health.

Calcium homeostasis during lactation is critical for maternal and neonatal health. We previously showed that nonneuronal/peripheral serotonin [5-hydroxytryptamine (5-HT)] causes the lactating mammary gland to synthesize and secrete PTHrP in an acute fashion. Here, using a mouse model, we found that genetic inactivation of tryptophan hydroxylase 1 (Tph1), which catalyzes the rate-limiting step in peripheral 5-HT synthesis, reduced circulating and mammary PTHrP expression, osteoclast activity, and maternal circulating calcium concentrations during the transition from pregnancy to lactation. Tph1 inactivation also reduced sonic hedgehog signaling in the mammary gland during lactation. Each of these deficiencies was rescued by daily injections of 5-hydroxy-L-tryptophan (an immediate precursor of 5-HT) to Tph1-deficient dams. We used immortalized mouse embryonic fibroblasts to demonstrate that 5-HT induces PTHrP through a sonic hedgehog-dependent signal transduction mechanism. We also found that 5-HT altered DNA methylation of the Shh gene locus, leading to transcriptional initiation at an alternate start site and formation of a variant transcript in mouse embryonic fibroblasts in vitro and in mammary tissue in vivo. These results support a new paradigm of 5-HT-mediated Shh regulation involving DNA methylation remodeling and promoter switching. In addition to having immediate implications for lactation biology, identification and characterization of a novel functional regulatory relationship between nonneuronal 5-HT, hedgehog signaling, and PTHrP offers new avenues for the study of these important factors in development and disease.