bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vectorial status and insecticide resistance of Anopheles funestus from a sugar estate in southern Mozambique
Authors: Kloke R Graham , Nhamahanga Eduardo , Hunt Richard H , Coetzee Maureen 
Published: February 2011

Abstract

Background
The dual problems of rising insecticide resistance in the malaria vectors and increasing human malaria cases since 2001 in southern Mozambique are cause for serious concern. The selection of insecticides for use in indoor residual spraying (IRS) programmes is highly dependent on the extent to which local mosquitoes are susceptible to the approved classes of insecticides. The insecticide resistance status and role in malaria transmission of Anopheles funestus was evaluated at the Maragra Sugar Estate in southern Mozambique where an IRS vector control programme has been in operation for seven years using the carbamate insecticide bendiocarb.

Results
No Anopheles species were captured inside the sugar estate control area. Anopheles funestus group captured outside of the estate represented 90% (n = 475) of the total collections. Of the specimens identified to species by PCR (n = 167), 95% were An. funestus s.s. One An. rivulorum was identified and seven specimens did not amplify. The Anopheles gambiae complex was less abundant (n = 53) and of those identified (n = 33) 76% were An. arabiensis and 24% An. merus. Insecticide susceptibility tests showed that wild-caught and F-1 family An. funestus were resistant to deltamethrin (32.5% mortality) and lambda-cyhalothrin (14.6% mortality), less so to bendiocarb (71.5% mortality) and fully susceptible to both malathion and DDT (100%). Bendiocarb and pyrethroid resistance was nullified using 4% piperonyl butoxide (Pbo), strongly suggesting that both are mediated by P450 monooxygenase detoxification. ELISA tests of An. funestus for Plasmodium falciparum, gave a sporozoite rate of 6.02% (n = 166). One unidentified member of the An. gambiae complex tested positive for P. falciparum sporozoites.

Conclusion

Anopheles funestus was found to be the most abundant and principle vector of malaria in this area, with members of the An. gambiae complex being secondary vectors. Despite the continual use of bendiocarb within the estate for seven years and the level of An. funestus resistance to this insecticide, the IVC programme is still effective against this and other Anopheles in that no vectors were found inside the control area. However, the Mozambique National Malaria Control Programme ceased the use of DDT and bendiocarb in this area of its operations in 2009, and replaced these insecticides with a pyrethroid which will increase insecticide resistance selection pressure and impact on control programmes such as the Maragra IVC.
Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause
Authors: Lefèvre Pavine L. C. , Palin Marie-France , Chen Gary , Turecki Gustavo , Murphy Bruce D. 
Published: February 2011

AbstractEmbryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation and growth, it was hypothesized that they trigger embryo reactivation. To test this, mated mink females were treated with α-difluoromethylornithine, an inhibitor of ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, or saline as a control during the first 5 d of reactivation. This treatment induced polyamine deprivation with the consequence of rearrest in embryo cell proliferation. A mink trophoblast cell line in vitro subjected to α-difluoromethylornithine treatment likewise displayed an arrest in cell proliferation, morphological changes, and intracellular translocation of ornithine decarboxylase 1 protein. The arrest in embryo development deferred implantation for a period consistent with the length of treatment. Successful implantation and parturition ensued. We conclude that polyamine deprivation brought about a reversible rearrest of embryo development, which returned the mink embryo to diapause and induced a second delay in embryo implantation. The results are the first demonstration of a factor essential to reactivation of embryos in obligate diapause.
Hyperphagia and Central Mechanisms for Leptin Resistance during Pregnancy
Authors: Trujillo M. L , Spuch C. , Carro E. , Señarís R. 
Published: February 2011

Abstract
The purpose of this work was to study the central mechanisms involved in food intake regulation and leptin resistance during gestation in the rat. Sprague Dawley rats of 7, 13, and 18 d of pregnancy [days of gestation (G) 7, G13, and G18] were used and compared with nonpregnant animals in diestrus-1. Food intake was already increased in G7, before hyperleptinemia and central leptin resistance was established in midpregnancy. Leptin resistance was due to a reduction in leptin transport through the blood-brain barrier (BBB) and to alterations in leptin signaling within the hypothalamus based on an increase in suppressor of cytokine signaling 3 levels and a blockade of signal transducer and activator of transcription-3 phosphorylation (G13), followed by a decrease in LepRb and of Akt phosphorylation (G18). In early gestation (G7), no change in hypothalamic neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) expression was shown. Nevertheless, an increase in NPY and AgRP and a decrease in POMC mRNA were observed in G13 and G18 rats, probably reflecting the leptin resistance. To investigate the effect of maternal vs. placental hormones on these mechanisms, we used a model of pseudogestation. Rats of 9 d of pseudogestation were hyperphagic, showing an increase in body and adipose tissue weight, normoleptinemia, and normal responses to iv/intracerebroventricular leptin on hypothalamic leptin signaling, food intake, and body weight. Leptin transport through the BBB, and hypothalamic NPY, AgRP and POMC expression were unchanged. Finally, the transport of leptin through the BBB was assessed using a double-chamber culture system of choroid plexus epithelial cells or brain microvascular endothelial cells. We found that sustained high levels of prolactin significantly reduced leptin translocation through the barrier, whereas progesterone and β-estradiol did not show any effect. Our data demonstrate a dual mechanism of leptin resistance during mid/late-pregnancy, which is not due to maternal hormones and which allows the maintenance of hyperphagia in the presence of hyperleptinemia driven by an increase in NPY and AgRP and a decrease in POMC mRNA. By contrast, in early pregnancy maternal hormones induce hyperphagia without the regulation of hypothalamic NPY, AgRP, or POMC and in the absence of leptin resistance.
Lack of Action of Exogenously Administered T3 on the Fetal Rat Brain Despite Expression of the Monocarboxylate Transporter 8
Authors: Grijota-Martínez Carmen , Díez Diego , Morreale de Escobar Gabriella , Bernal Juan , Morte Beatriz 
Published: February 2011

Abstract
Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized pregnant dams treated with methyl-mercapto-imidazol to produce maternal and fetal hypothyroidism. Gene expression was then measured in the fetal cerebral cortex. T4 increased Camk4, Sema3c, and Slc7a3 expression, but T3 was without effect. To investigate the cause for the lack of T3 action we analyzed the expression of organic anion transport polypeptide (Oatp14, Slco1c1), a T4 transporter, and Mct8 (Slc16a2), a T4 and T3 transporter, by confocal microscopy. Both proteins were present in the brain capillaries forming the blood-brain barrier and in the epithelial cells of the choroid plexus forming the blood-cerebrospinal fluid barrier. It is concluded that T4 from the maternal compartment influences gene expression in the fetal cerebral cortex, possibly after transport via organic anion transporter polypeptide and/or Mct8, and conversion to T3 in the astrocytes. On the other hand, T3 does not reach the target neurons despite the presence of Mct8. The data indicate that T4, through local deiodination, provides most T3 in the fetal rat brain. The role of Mct8 as a T3 transporter in the fetal rat brain is therefore uncertain.
Transgenic Overexpression of the Extra-Large Gsα Variant XLαs Enhances Gsα-Mediated Responses in the Mouse Renal Proximal Tubule in Vivo
Authors: Liu Zun , Segawa Hiroko , Aydin Cumhur , Reyes Monica , Erben Reinhold G. , Weinstein Lee S. , Chen Min , Marshansky Vladimir , Fröhlich Leopold F. , Bastepe Murat 
Published: February 2011

AbstractXLαs, a variant of the stimulatory G protein α-subunit (Gsα), can mediate receptor-activated cAMP generation and, thus, mimic the actions of Gsα in transfected cells. However, it remains unknown whether XLαs can act in a similar manner in vivo. We have now generated mice with ectopic transgenic expression of rat XLαs in the renal proximal tubule (rptXLαs mice), where Gsα mediates most actions of PTH. Western blots and quantitative RT-PCR showed that, while Gsα and type-1 PTH receptor levels were unaltered, protein kinase A activity and 25-hydroxyvitamin D 1-α-hydroxylase (Cyp27b1) mRNA levels were significantly higher in renal proximal tubules of rptXLαs mice than wild-type littermates. Immunohistochemical analysis of kidney sections showed that the sodium-phosphate cotransporter type 2a was modestly reduced in brush border membranes of male rptXLαs mice compared to gender-matched controls. Serum calcium, phosphorus, and 1,25 dihydroxyvitamin D were within the normal range, but serum PTH was ∼30% lower in rptXLαs mice than in controls (152 ± 16 vs. 222 ± 41 pg/ml; P &lt; 0.05). After crossing the rptXLαs mice to mice with ablation of maternal Gnas exon 1 (E1m−/+), male offspring carrying both the XLαs transgene and maternal Gnas exon 1 ablation (rptXLαs/E1m−/+) were significantly less hypocalcemic than gender-matched E1m−/+ littermates. Both E1m−/+ and rptXLαs/E1m−/+ offspring had higher serum PTH than wild-type littermates, but the degree of secondary hyperparathyroidism tended to be lower in rptXLαs/E1m−/+ mice. Hence, transgenic XLαs expression in the proximal tubule enhanced Gsα-mediated responses, indicating that XLαs can mimic Gsα in vivo.
Angiotensin III Stimulates Aldosterone Secretion from Adrenal Gland Partially via Angiotensin II Type 2 Receptor But Not Angiotensin II Type 1 Receptor
Authors: Yatabe Junichi , Yoneda Minoru , Yatabe Midori S. , Watanabe Tsuyoshi , Felder Robin A. , Jose Pedro A. , Sanada Hironobu 
Published: February 2011

AbstractAngiotensin II (Ang II) and Ang III stimulate aldosterone secretion by adrenal glomerulosa, but the angiotensin receptor subtypes involved and the effects of Ang IV and Ang (1–7) are not clear. In vitro, different angiotensins were added to rat adrenal glomerulosa, and aldosterone concentration in the medium was measured. Ang II-induced aldosterone release was blocked (30.3 ± 7.1%) by an Ang II type 2 receptor (AT2R) antagonist, PD123319. Candesartan, an Ang II type 1 receptor (AT1R) antagonist, also blocked Ang II-induced aldosterone release (42.9 ± 4.8%). Coadministration of candesartan and PD123319 almost abolished the Ang II-induced aldosterone release. A selective AT2R agonist, CGP42112, was used to confirm the effects of AT2R. CGP42112 increased aldosterone secretion, which was almost completely inhibited by PD123319. In addition to Ang II, Ang III also induced aldosterone release, which was not blocked by candesartan. However, PD123319 blocked 22.4 ± 10.5% of the Ang III-induced aldosterone secretion. Ang IV and Ang (1–7) did not induce adrenal aldosterone secretion. In vivo, both Ang II and Ang III infusion increased plasma aldosterone concentration, but only Ang II elevated blood pressure. Ang IV and Ang (1–7) infusion did not affect blood pressure or aldosterone concentration. In conclusion, this report showed for the first time that AT2R partially mediates Ang III-induced aldosterone release, but not AT1R. Also, over 60% of Ang III-induced aldosterone release may be independent of both AT1R and AT2R. Ang III and AT2R signaling may have a role in the pathophysiology of aldosterone breakthrough.
Maternal Fructose Intake during Pregnancy and Lactation Alters Placental Growth and Leads to Sex-Specific Changes in Fetal and Neonatal Endocrine Function
Authors: Vickers M. H. , Clayton Z. E. , Yap C. , Sloboda D. M. 
Published: February 2011

AbstractThe effects of maternal fructose intake on offspring health remain largely unknown, despite the marked increase in consumption of sweetened beverages that has paralleled the obesity epidemic. The present study investigated the impact of maternal fructose intake on placental, fetal, and neonatal development. Female Wistar rats were time-mated and allocated to receive either water [control (CONT)] or fructose solution designed to provide 20% of caloric intake from fructose (FR). FR was administered from d 1 of pregnancy until postnatal day (P) 10. All dams had ad libitum access to standard laboratory chow and water. Dams and offspring were killed at embryonic day (E) 21 and P10. FR dams demonstrated increased total caloric intake and maternal hyperinsulinemia at E21 as well as increased maternal plasma fructose levels at E21 and P10. FR intake did not alter maternal blood glucose, β-hydroxybutyrate (BHB), or electrolyte levels at either time point. Fetal weights at E21 were unchanged, although placental weights were reduced in FR female but not FR male fetuses. Plasma leptin, fructose, and blood glucose levels were increased and BHB levels decreased in FR female but not male fetuses. Plasma insulin levels were not different between CONT and FR groups. Male and female FR neonates had higher plasma fructose levels and were hypoinsulinemic but euglycemic at P10 compared with CONT. Blood BHB levels were increased in FR male neonates but not females at P10. P10 plasma leptin levels were not different between groups. Stomach content leptin levels were increased in all FR offspring at P10, but no differences in stomach content insulin or fructose levels were observed. This study reports for the first time that maternal FR intake resulted in sex-specific changes in offspring development, whereby females appear more vulnerable to metabolic compromise during neonatal life. Independent follow-up studies are essential to investigate the long-term consequences of maternal FR consumption on offspring health.
Overexpression of Pregnancy-Associated Plasma Protein-A in Ovarian Cancer Cells Promotes Tumor Growth in Vivo
Authors: Boldt Henning B. , Conover Cheryl A. 
Published: February 2011

Abstract
Pregnancy-associated plasma protein-A (PAPP-A) is an important regulatory component of the IGF system. Through proteolysis of inhibitory IGF binding proteins (IGFBPs), PAPP-A acts as a positive modulator of local IGF signaling in a variety of biological systems. A role of IGF in the progression of several common forms of human cancer is now emerging, and therapeutic intervention of IGF receptor signaling is currently being explored. However, little is known about the activities of other components of the IGF system in relation to cancer. We hypothesized that PAPP-A acts to enhance tumor growth in vivo. To test this hypothesis, we overexpressed wild-type PAPP-A or a mutant PAPP-A with markedly reduced IGFBP protease activity in SKOV3 cells, a human ovarian carcinoma cell line with low tumorigenic potential. In vitro, SKOV3 clones with elevated PAPP-A expression (PAPP-A-1, PAPP-A-28) showed accelerated anchorage-independent growth in soft agar assays compared to clones overexpressing mutant PAPP-A (E483Q-1, E483Q-5) and vector controls. PAPP-A-28, with the highest PAPP-A expression and IGFBP proteolytic activity, also had markedly increased cell invasion through Matrigel. In vivo, we found significantly accelerated tumor growth rates of PAPP-A-overexpressing SKOV3 clones compared with mutant PAPP-A and controls. Investigation of angiogenesis indicated that overexpression of PAPP-A favored development of mature tumor vasculature and that tumor precursors of PAPP-A-28 in particular had a significantly higher degree of vascularization months before obvious tumor development. In conclusion, our data show that PAPP-A proteolytic activity enhances the tumorigenic potential of ovarian cancer cells and establish a novel tumor growth-promoting role of PAPP-A.
A Promising Culture Model for Analyzing the Interaction between Adipose Tissue and Cardiomyocytes
Authors: Anan Mayumi , Uchihashi Kazuyoshi , Aoki Shigehisa , Matsunobu Aki , Ootani Akifumi , Node Koichi , Toda Shuji 
Published: February 2011

Abstract
The heart has epicardial adipose tissue that produces adipokines and mesenchymal stem cells. Systemic adipose tissue is involved in the pathophysiology of obesity-related heart diseases. However, the method for analyzing the direct interaction between adipose tissue and cardiomyocytes has not been established. Here we show the novel model, using collagen gel coculture of adipose tissue fragments (ATFs) and HL-1 cardiomyocytes, and electron microscopy, immunohistochemistry, real-time RT-PCR, and ELISA. HL-1 cells formed a stratified layer on ATF-nonembedded gel, whereas they formed almost a monolayer on ATF-embedded gel. ATFs promoted the apoptosis, lipid accumulation, and fatty acid transport protein (FATP) expression of FATP4 and CD36 in HL-1 cells, whereas ATFs inhibited the growth and mRNA expression of myosin, troponin T, and atrial natriuretic peptide. Treatment of leptin (100 ng/ml) and adiponectin (10 μg/ml) neither replicated nor abolished the ATF-induced morphology of HL-1 cells, whereas that of FATP4 and CD36 antibodies (25 μg/ml) never abolished it. HL-1 cells prohibited the development of CD44+/CD105+ mesenchymal stem cell-like cells and lipid-laden preadipocytes from ATFs. HL-1 cells increased the production of adiponectin in ATFs, whereas they decreased that of leptin. The data indicate that our model actively creates adipose tissue-HL-1 cardiomyocyte interaction, suggesting first that ATFs may be related to the lipotoxiciy of HL-1 cells via unknown factors plus FATP4 and CD36 and second that HL-1 cells may help to retain the static state of ATFs, affecting adipokine secretion. Our model will serve to study adipose tissue-cardiomyocyte interaction and mechanisms of obesity-related lipotoxicity and heart diseases.
Genetic Identification of GnRH Receptor Neurons: A New Model for Studying Neural Circuits Underlying Reproductive Physiology in the Mouse Brain
Authors: Wen Shuping , Götze Iris N. , Mai Oliver , Schauer Christian , Leinders-Zufall Trese , Boehm Ulrich 
Published: February 2011

Abstract
GnRH signaling regulates reproductive physiology in vertebrates via the hypothalamic-pituitary-gonadal axis. In addition, GnRH signaling has been postulated to act on the brain. However, elucidating its functional role in the central nervous system has been hampered because of the difficulty in identifying direct GnRH signaling targets in live brain tissue. Here we used a binary genetic strategy to visualize GnRH receptor (GnRHR) neurons in the mouse brain and started to characterize these cells. First, we expressed different fluorescent proteins in GnRHR neurons and mapped their precise distribution throughout the brain. Remarkably, neuronal GnRHR expression was only initiated after postnatal day 16, suggesting peri- and postpubertal functions of GnRH signaling in this organ. GnRHR neurons were found in different brain areas. Many GnRHR neurons were identified in areas influencing sexual behaviors. Furthermore, GnRHR neurons were detected in brain areas that process olfactory and pheromonal cues, revealing one efferent pathway by which the neuroendocrine hypothalamus may influence the sensitivity towards chemosensory cues. Using confocal Ca2+ imaging in brain slices, we show that GnRHR neurons respond reproducibly to extracellular application of GnRH or its analog [D-TRP6]-LH-RH, indicating that these neurons express functional GnRHR. Interestingly, the duration and shape of the Ca2+ responses were similar within and different between brain areas, suggesting that GnRH signaling may differentially influence brain functions to affect reproductive success. Our new mouse model sets the stage to analyze the next level of GnRH signaling in reproductive physiology and behavior.
Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy
Authors: Machuca-Tzili Laura E. , Buxton Sarah , Thorpe Aaran , Timson Cathy M. , Wigmore Peter , Luther Pradeep K. , Brook J. David 
Published: February 2011

SUMMARYMyotonic dystrophy (DM; also known as dystrophia myotonica) is an autosomal dominant disorder that affects the heart, eyes, brain and endocrine system, but the predominant symptoms are neuromuscular, with progressive muscle weakness and wasting. DM presents in two forms, DM1 and DM2, both of which are caused by nucleotide repeat expansions: CTG in the DMPK gene for DM1 and CCTG in ZNF9 (CNBP) for DM2. Previous studies have shown that the mutant mRNAs containing the transcribed CUG or CCUG repeats are retained within the nuclei of cells from individuals with DM, where they bind and sequester the muscleblind-like proteins MBNL1, MBNL2 and MBNL3. It has been proposed that the sequestration of these proteins plays a key role in determining the classic features of DM. However, the functions of each of the three MBNL genes are not completely understood. We have generated a zebrafish knockdown model in which we demonstrate that a lack of mbnl2 function causes morphological abnormalities at the eye, heart, brain and muscle levels, supporting an essential role for mbnl2 during embryonic development. Major features of DM are replicated in our model, including muscle defects and splicing abnormalities. We found that the absence of mbnl2 causes disruption to the organization of myofibrils in skeletal and heart muscle of zebrafish embryos, and a reduction in the amount of both slow and fast muscle fibres. Notably, our findings included altered splicing patterns of two transcripts whose expression is also altered in DM patients: clcn1 and tnnt2. The studies described herein provide broader insight into the functions of MBNL2. They also lend support to the hypothesis that the sequestration of this protein is an important determinant in DM pathophysiology, and imply a direct role of MBNL2 in splicing regulation of specific transcripts, which, when altered, contributes to the DM phenotype.