Simulation of the Impacts of Urbanization on Winter Meteorological Fields over the Pearl River Delta Region

The influences of urbanization on weather in Guangdong Province, China, were studied using the Weather Research and Forecasting model from 31 December 2009 through 3 January 2010. Model outputs were compared with extensive monitoring of meteorological data to examine the simulation ability. Model results between tests (with and without land-use change) show that the urbanization had major effects on meteorological fields across nearly the entire Pearl River Delta region and particularly in urban areas. Studied fields (wind speed, temperature, precipitation, and sensible and latent heat fluxes) were affected by the urbanization of the PRD region. The major influences occurred in urban areas, where wind speeds decreased greatly, while the daytime surface upward sensible heat flux clearly increased. Unlike the sensible heat flux, the latent heat flux had a nonmonotonic increase or decrease. As a consequence of the two heat fluxes, 2-m temperature varied with location and time. Change of precipitation was complex. The main rain band became more concentrated, while precipitation decreased upwind of the urban area and increased downwind

The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating

The 5-HT7 receptor remains one of the less well characterized serotonin receptors. Although it has been demonstrated to be involved in the regulation of mood, sleep, and circadian rhythms, as well as relaxation of vascular smooth muscles in mammals, the precise mechanisms underlying these functions remain largely unknown. The fruit fly, Drosophila melanogaster, is an attractive model organism to study neuropharmacological, molecular, and behavioral processes that are largely conserved with mammals. Drosophila express a homolog of the mammalian 5-HT7 receptor, as well as homologs for the mammalian 5-HT1A, and 5-HT2, receptors. Each fly receptor couples to the same effector pathway as their mammalian counterpart and have been demonstrated to mediate similar behavioral responses. Here, we report on the expression and function of the 5-HT7Dro receptor in Drosophila. In the larval central nervous system, expression is detected postsynaptically in discreet cells and neuronal circuits. In the adult brain there is strong expression in all large-field R neurons that innervate the ellipsoid body, as well as in a small group of cells that cluster with the PDF-positive LNvs neurons that mediate circadian activity. Following both pharmacological and genetic approaches, we have found that 5-HT7Dro activity is essential for normal courtship and mating behaviors in the fly, where it appears to mediate levels of interest in both males and females. This is the first reported evidence of direct involvement of a particular serotonin receptor subtype in courtship and mating in the fly

Regulation of insulin signaling and its developmental and functional roles on peptidergic neurons in the Drosophila central nervous system

In Drosophila, eight insulin-like peptides (DILP1-8) are produced and secreted in different locations. They regulate many aspects of development and physiology, such as organism growth, metabolic homeostasis, reproduction, stress resistance and life span. DILP2, 3 and 5 are mainly produced by a cluster of median neurosecretory cells in the brain known as insulin producing cells (IPCs). Here we showed that IPCs are under tight regulation of two G-protein coupled receptors (GPCRs), serotonin receptor 5-HT1A and octopamine receptor OAMB. Genetic manipulations of these two receptors in IPCs affected transcription levels of DILPs, hence altered feeding, carbohydrate levels, and resistance to stress (Paper I and II). Moreover, we showed that the insulin receptor (dInR) is strongly expressed in leucokininergic neurons (LK neurons), and selectively regulates growth of around 300 neuropeptidergic neurons expressing the bHLH transcription factor DIMMED. Overexpression of dInR in DIMM-positive neurons led to substantial neuronal growth, including cell body size, golgi apparatus and nuclear size, while knockdown of dInR had the opposite effect (Paper III). Manipulations of components in the insulin signaling pathway in LK neurons resulted in the similar cell size phenotypes. Furthermore, dInR regulated size scaling of DIMM-postive neurons is nutrient-dependent and partially requires the presence of DIMM (Paper III). Finally, we investigated the roles of DILPs (2, 3, 5 and 7) and LK neurons in regulation of feeding and diuresis at the adult stage (Paper IV).  In summary, we have identified two more regulators for IPC activity and demonstrated developmental roles of  DILPs and dInR in regulating neuronal size. Moreover, DILPs regulate water homeostasis together with a diuretic hormone leucokinin and as a consequence affects feeding behavior.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: In press. Paper 4: Manuscript.</p

Transcriptional Reorganization of Drosophila Motor Neurons and Their Muscular Junctions toward a Neuroendocrine Phenotype by the bHLH Protein Dimmed

Neuroendocrine cells store and secrete bulk amounts of neuropeptides, and display morphological and molecular characteristics distinct from neurons signaling with classical neurotransmitters. In Drosophila the transcription factor Dimmed (Dimm), is a prime organizer of neuroendocrine capacity in a majority of the peptidergic neurons. These neurons display large cell bodies and extensive axon terminations that commonly do not form regular synapses. We ask which molecular compartments of a neuron are affected by Dimm to generate these morphological features. Thus, we ectopically expressed Dimm in glutamatergic, Dimm-negative, motor neurons and analyzed their characteristics in the central nervous system and the neuromuscular junction. Ectopic Dimm results in motor neurons with enlarged cell bodies, diminished dendrites, larger axon terminations and boutons, as well as reduced expression of synaptic proteins both pre and post-synaptically. Furthermore, the neurons display diminished vesicular glutamate transporter, and signaling components known to sustain interactions between the developing axon termination and muscle, such as wingless and frizzled are down regulated. Ectopic co-expression of Dimm and the insulin receptor augments most of the above effects on the motor neurons. In summary, ectopic Dimm expression alters the glutamatergic motor neuron phenotype toward a neuroendocrine one, both pre- and post-synaptically. Thus, Dimm is a key organizer of both secretory capacity and morphological features characteristic of neuroendocrine cells, and this transcription factor affects also post-synaptic proteins

Application of Bipolar Membrane Electrodialysis in Environmental Protection and Resource Recovery: A Review

Bipolar membrane electrodialysis (BMED) is a new membrane separation technology composed of electrodialysis (ED) through a bipolar membrane (BPM). Under the action of an electric field, H2O can be dissociated to H+ and OH&minus;, and the anions and cations in the solution can be recovered as acids and bases, respectively, without adding chemical reagents, which reduces the application cost and carbon footprint, and leads to simple operation and high efficiency. Its application is becoming more widespread and promising, and it has become a research hotspot. This review mainly introduces the application of BMED to recovering salts in the form of acids and bases, CO2 capture, ammonia nitrogen recovery, and ion removal and recovery from wastewater. Finally, BMED is summarized, and future prospects are discussed

Targeting human caseinolytic protease P (ClpP) as a novel therapeutic strategy in ovarian cancer

Abstract Ovarian cancer (OC) is currently one of the most life‐threatening types of gynecological malignancy with limited treatment options and poor clinical outcomes. Human caseinolytic protease P (HsClpP) is located in the mitochondria and plays an important role in several tumors. Moreover, HsClpP is overexpressed in OC and several other tumor cells. Thus, HsClpP modulation is regarded as a potential approach for OC treatment. In this study, we identified and validated a novel boron peptide Compound 43‐8F as a potent HsClpP inhibitor. Upon 43‐8F treatment, mitochondrial damage was observed to be closely correlated with upregulated intracellular reactive oxygen species production, decreasement of membrane potential, and ATP content suppression. Meanwhile, the expression level of SDHB and the ATF4 was increased after 43‐8F treatment, suggesting that 43‐8F treatment induces mitochondrial respiratory disorders and activates the integrated stress response pathway to inhibit tumor cell growth. Further, 43‐8F exhibited a good therapeutic and safety profile in OC xenograft model in nude mice. Together, these results suggest that 43‐8F exerts an anti‐ovarian cancer effect by inhibiting HsClpP pathway

Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor <i>Dimmed</i> in <i>Drosophila</i>

<div><p>Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS) in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the <i>Drosophila</i> CNS. By targeted genetic manipulations of insulin receptor (dInR) expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM). Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B), whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin) signaling components, such as Rheb (small GTPase), TOR and S6K (S6 kinase). After <i>Dimm</i>-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of <i>Dimm</i>. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.</p></div

Effects of diet on size of ABLK neurons.

<p>Larvae of different genotypes were reared on three different diets: 20% sucrose with either 0%, 5% or 20% protein (yeast) as detailed in the scheme in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004052#pgen.1004052.s015" target="_blank">Fig. S15A</a>. Late third instar larvae were labeled with anti-LK (magenta) and anti-5-HT (green). Statistics: *p<0.05, **p<0.01, ***p<0.001, n = 6–12 larvae for each genotype from 3 crosses; unpaired Student's T-test for comparison of genotypes; Two-way Anovas for comparisons of diet effects). <b>A</b> and <b>B</b> Manipulation of dInR expression in LK neurons affects the size of ABLK neurons in larvae fed protein-rich (20%; A) and protein-free (0%; B) and normal (5%; not shown) diet. Cell bodies of 5-HT immunolabeled neurons (arrows in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004052#pgen-1004052-g011" target="_blank">Fig. 11 A</a>) are used for reference. The size changes in CNS and different neurons are quantified in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004052#pgen-1004052-g011" target="_blank">Fig. 11 C–F</a> (cell bodies are shown in higher magnification in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004052#pgen.1004052.s015" target="_blank">Fig. S15</a> B). <b>C</b> The low protein (0%) diet significantly (p<0.001) affects the size of the entire CNS compared to “standard diet” (5%), whereas 20% protein does not increase the CNS (ns; p>0.05). Note that the CNS size is not affected by the dInR manipulations. <b>D</b> Quantification of ABLK cell body size in third instar larvae fed the three different diets, compared to those in first instar larvae (genotypes as in C). Under 0% protein conditions all genotypes display third instar ABLK cells with sizes corresponding to those in first instar larvae. These are significantly smaller than in flies fed 5% and 20% protein (p<0.001 for all genotypes compared for 0% and 5% protein; Two-way Anova). Larvae fed protein-rich food (20%) do not display increased ABLK cell bodies compared to those fed 5% protein. The significance values indicate differences to control flies (Lk>w1118) for each protein condition (*p<0.05, **p<0.01, ***p<0.001, ns, not significant, n = 6–10 larvae for each genotype from 3 crosses; unpaired Student's T-test) and comparisons between protein diets for dInR overexpression (Two-way Anova). <b>E</b> The ratio between the ABLK cell size and the size of 5-HT neuron cell bodies in corresponding abdominal neuromeres (same protein conditions and genotypes as in C). These were determined to establish whether the ABLK size is affected disproportionally by protein diet (the size of the 5-HT neuron cell bodies for the three protein diets are shown in <b>F</b>). It can be seen that with 5-HT cells as size reference the dInR overexpression only marginally (p<0.05; Two-way Anova) increased the ABLKs after dInR overexpression when comparing 0% and 5% (and 20%) protein. For each diet dInR over expression significantly increases the ratio between ABLK and 5-HT cell body sizes compared to control flies. Only small (but significant) effects can be seen after dInR-RNAi in 5% and 20% diets. <b>F</b> Size of cell bodies of 5-HT immunolabeled neurons in abdominal ganglia in larvae reared in the three different diets (genotypes as in C). Note that manipulations of the dInR in LK neurons do not affect the 5-HT neurons, but 0% protein diet results in significantly smaller cell bodies compared to 5% and 20% protein.</p