bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the TRIB1 tribbles homolog 1 gene rs17321515 A>G polymorphism and serum lipid levels in the Mulao and Han populations
Authors: Aung Lynn Htet Htet , Yin Rui-Xing , Wu Dong-Feng , Li Qing , Yan Ting-Ting , Wang Yi-Ming , Li Hui , Wei Dai-Xun , Shi Yuan-Lu , Yang De-Zhai
Published: December 2011

Background

The association of rs17321515 single nucleotide polymorphism (SNP) near TRIB1 gene and serum lipid profiles has never been studied in the Chinese population. Therefore, the present study was undertaken to detect the association of rs17321515 SNP and several environmental factors on serum lipid levels in the Mulao and Han populations.

Methods

A total of 639 unrelated subjects of Mulao nationality and 644 participants of Han nationality were randomly selected from our previous stratified randomized cluster samples. Genotypes of the TRIB1 rs17321515 A>G SNP were determined via polymerase chain reaction and restriction fragment length polymorphism, and then confirmed by direct sequencing.

Results

Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.05). There were no differences in the genotypic and allelic frequencies between the two ethnic groups (P > 0.05). High- and low-density lipoprotein cholesterol (HDL-C and LDL-C) levels in Han were different among the genotypes (P < 0.05 for each), the subjects with AG/GG genotypes had higher HDL-C and LDL-C levels than the subjects with AA genotype. Total cholesterol (TC), HDL-C, LDL-C, ApoA1 and ApoB levels in Han males were different among the genotypes (P < 0.05-0.001), the G carriers had higher TC, HDL-C, LDL-C, ApoA1 and ApoB levels than the G noncarriers. HDL-C levels in Mulao males were different among the genotypes (P < 0.05), the G carriers had lower HDL-C levels than the G noncarriers. Serum HDL-C and LDL-C levels in both ethnic groups and TG levels in Han were correlated with the genotypes or alleles (P < 0.05-0.01). TG and HDL-C levels in Mulao males and TG, HDL-C, LDL-C and ApoA1 levels in Han males were correlated with genotypes or alleles (P < 0.05-0.001). TG and ApoA1 levels in Han females were associated with genotypes (P < 0.05 for each). Serum lipid parameters were also associated with several environmental factors in both ethnic groups.

Conclusions

The associations of TRIB1 rs17321515 SNP and serum lipid levels are different between the Mulao and Han populations. These discrepancies might partly result from different TRIB1 gene-environmental interactions in both ethnic groups.
Complete and safe resection of challenging retroperitoneal tumors: anticipation of multi-organ and major vascular resection and use of adjunct procedures
Authors: Tseng William W , Wang Sam C , Eichler Charles M , Warren Robert S , Nakakura Eric K
Published: December 2011

Background

Retroperitoneal tumors are often massive and can involve adjacent organs and/or vital structures, making them difficult to resect. Completeness of resection is within the surgeon's control and critical for long-term survival, particularly for malignant disease. Few studies directly address strategies for complete and safe resection of challenging retroperitoneal tumors.

Methods

Fifty-six patients representing 63 cases of primary or recurrent retroperitoneal tumor resection between 2004-2009 were identified and a retrospective chart review was performed. Rates of complete resection, use of adjunct procedures, and perioperative complications were recorded.

Results

In 95% of cases, complete resection was achieved. Fifty-eight percent of these cases required en bloc multi-organ resection, and 8% required major vascular resection. Complete resection rates were higher for primary versus recurrent disease. Adjunct procedures (ureteral stents, femoral nerve monitoring, posterior laminotomy, etc.) were used in 54% of cases. Major postoperative complications occurred in 16% of cases, and one patient died (2% mortality).

Conclusions

Complete resection of challenging retroperitoneal tumors is feasible and can be done safely with important pre- and intraoperative considerations in mind.
Single-incision laparoscopic colectomy without using special articulating instruments: an initial experience
Authors: Trakarnsanga Atthaphorn , Akaraviputh Thawatchai , Wathanaoran Pakpong , Phalanusitthepha Chainarong , Methasate Asada , Chinswangwattanakul Vitoon
Published: December 2011

Background

Single-incision laparoscopic colectomy (SILC) was introduced as a novel minimally invasive technique. The benefits of this technique include reducing number of the incision and cosmetic improvement. Unlike the conventional laparoscopic colectomy, majority of previously reported SILC need to be performed using special curved or articulated instruments. The purpose of this study is to demonstrate our initial experience of SILC, which could be performed using the standard laparoscopic instruments.

Material and methods

Retrospective review of 14 patients who underwent SILC at Siriraj Hospital from May to December 2010, patient's demographic data, perioperative outcomes, early postoperative complications and pathological data were collected and analyzed.

Results

The mean age of all patients was 60 years. The most common operation with SILC was sigmoidectomy (n = 9), followed by right hemicolectomy (n = 2), left hemicolectomy (n = 1), anterior resection (n = 1), and total colectomy (n = 1). The trocar insertion techniques were multi-fascial incision using regular port (n = 11) and GelPOINT®(n = 3). The mean operative time was 155 minutes (range 90-280) and the mean estimate blood loss was 32.1 mL (range 10-100). All patients were successfully operated without conversion. The mean length of hospital stay was 9 days (range 5-20). There was no mortality. The pathological results revealed colorectal cancer (n = 12), neoplastic polyp (n = 1) and Familial adenomatous polyposis (FAP) (n = 1). The mean number of lymph nodes retrieval was 16.6 (range 3-34).

Conclusion

SILC can successfully and safely be performed with standard laparoscopic instruments. This technique might be an alternative procedure to conventional laparoscopic colectomy with better cosmetic result.
Homoepitaxial regrowth habits of ZnO nanowire arrays
Authors: Liu Jian , Xie Shufan , Chen Yanglong , Wang Xianying , Cheng Hongbin , Liu Fang , Yang Junhe
Published: December 2011

Synthetic regrowth of ZnO nanowires [NWs] under a similar chemical vapor transport and condensation [CVTC] process can produce abundant ZnO nanostructures which are not possible by a single CVTC step. In this work, we report three different regrowth modes of ZnO NWs: axial growth, radial growth, and both directions. The different growth modes seem to be determined by the properties of initial ZnO NW templates. By varying the growth parameters in the first-step CVTC process, ZnO nanostructures (e.g., nanoantenna) with drastically different morphologies can be obtained with distinct photoluminescence properties. The results have implications in guiding the rational synthesis of various ZnO NW heterostructures.
Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors
Authors: Urbán Patricia , Estelrich Joan , Adeva Alberto , Cortés Alfred , Fernàndez-Busquets Xavier
Published: December 2011

Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusively to the selected targets. In a previous work, we engineered an immunoliposomal nanovector for the targeted delivery of its contents exclusively to Plasmodium falciparum-infected red blood cells [pRBCs]. In preliminary assays, the antimalarial drug chloroquine showed improved efficacy when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal antibody BM1234. Because difficulties in determining the exact concentration of the drug due to its low amounts prevented an accurate estimation of the nanovector performance, here, we have developed an HPLC-based method for the precise determination of the concentrations in the liposomal preparations of chloroquine and of a second antimalarial drug, fosmidomycin. The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs. The targeting antibody used binds preferentially to pRBCs containing late maturation stages of the parasite. In accordance with this observation, the best performing immunoliposomes are those added to Plasmodium cultures having a larger number of late form-containing pRBCs. An average of five antibody molecules per liposome significantly improves in cell cultures the performance of immunoliposomes over non-functionalized liposomes as drug delivery vessels. Increasing the number of antibodies on the liposome surface correspondingly increases performance, with a reduction of 50% parasitemia achieved with immunoliposomes encapsulating 4 nM chloroquine and bearing an estimated 250 BM1234 units. The nanovector prototype described here can be a valuable platform amenable to modification and improvement with the objective of designing a nanostructure adequate to enter the preclinical pipeline as a new antimalarial therapy.
A new time-hopping/direct-sequence biorthogonal PPM UWB communication system
Authors: Shen Ye-Shun , Ueng Fang-Biau , Jeng Li-Der
Published: December 2011

In order to increase the capacity and diminish the multiple access interference (MAI) of an ultra-wideband (UWB) system, we propose a new time-hopping/direct-sequence (TH/DS) scheme using N-ary biorthogonal pulse position modulation (BPPM). In contrast with the conventional TH/DS systems employing fixed partition of the TH slots (Shen and Ueng, Proceedings of the IEEE VTC-Spring, 2010), the proposed TH/DS system can put the start location of the TH slot in any one of Q available pulse positions within the frame. In the proposed TH/DS system, the modulation level of BPPM can be increased and the multiple access capability can be improved without degrading the system performance. Compared with the existing TH-UWB system that employs the whole frame to carry out TH process (Shen et al. IEEE Trans. Veh. Technol. 59(2), 742-753, 2010), the proposed system has the merits of smooth power spectral density and low receiver complexity. In this article, we also derive the probability distribution of MAI for each correlator's output of the proposed TH/DS system based on the analytic characteristic function technique. In order to verify the correctness of the performance analyses and to demonstrate the effectiveness of the proposed TH/DS system, some simulation results are given in both the additive white Gaussian noise channel and the realistic UWB fading channels. From the simulation results, we find that the proposed TH/DS system outperforms the conventional TH/DS scheme.
Applications of some basic theorems in the KKM theory
Authors: Park Sehie
Published: December 2011

In this review, we introduce a new KKM-type theorem for intersectionally closed-valued KKM map on abstract convex spaces and its direct consequences such as a Fan-Browder-type fixed point theorem and maximal element theorems. For these basic theorems of the KKM theory, we review previously obtained particular consequences of them mainly due to the author and their recent applications obtained by other authors. Therefore, those applications might be improved by following our new results.

2010 Mathematics Subject Classification: 47H04; 47H10; 52A99; 54H25; 55M20; 58E35; 90D13.
An improved method for color image editing
Authors: Dizdaroğlu Bekir , İkibaş Cevat
Published: December 2011

In this article, an improved approach for editing color images has been presented. In this approach, using the Poisson equation, a guided vector field is created by employing source and target images within a selected region at the first step. Next, the guided vector is used in generating the result image. Most of the existing techniques in the literature perform image editing without taking color information into account. However, without utilizing color information, image geometry cannot be created properly in some cases which may result in unsatisfactory results. Unlike the existing methods, the proposed study utilizes all the information contained in each of the color channels in computing gradient norm and performing inpainting process. The test results show that the suggested technique generates satisfactory results in editing color images.
A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours
Authors: Liu Cong , Krishnan J , Xu Xiao Yun
Published: December 2011

Background

Elucidating the effects of drugs on solid tumours is a highly challenging multi-level problem, since this involves many complexities associated with transport and cellular response, which in turn is characterized by highly non-linear chemical signal transduction. Appropriate systems frameworks are needed to seriously address the sources of these complexities, especially from the cellular side.

Results

We develop a skeletal modelling framework incorporating interstitial drug transport, intracellular signal processing and cell population descriptions. The descriptions aim to appropriately capture the nature of information flow. The model is deliberately formulated to start with simple intracellular descriptions so that additional features can be incorporated in a modular fashion. Two kinds of intracellular signalling modules which describe the drug effect were considered, one a monostable switch and the other a bistable switch. Analysis of our model revealed how different drug stimuli can lead to cell killing in the tumour. Interestingly both modules considered exhibited similar trends. The effects of important parameters were also studied.

Conclusions

We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical) stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli.
Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers
Authors: Takamori Ayako , Hasegawa Atsuhiko , Utsunomiya Atae , Maeda Yasuhiro , Yamano Yoshihisa , Masuda Masato , Shimizu Yukiko , Tamai Yotaro , Sasada Amane , Zeng Na , Choi Ilseung , Uike Naokuni , Okamura Jun , Watanabe Toshiki , Masuda Takao , Kannagi Mari
Published: December 2011

Background

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+T-cells in various clinical status of HTLV-1 infection.

Results

By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8+T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8+T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8+T-cells.

Conclusions

These findings indicated that Tax-specific CD8+T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8+T-cells in early stages.
Histological damage and inflammatory response elicited by Monobothrium wageneri (Cestoda) in the intestine of Tinca tinca (Cyprinidae)
Authors: Sayyaf Dezfuli Bahram , Giari Luisa , Squerzanti Samantha , Lui Alice , Lorenzoni Massimo , Sakalli Sidika , Shinn Andrew P
Published: December 2011

Background

Among the European cyprinids, tench, Tinca tinca (L.), and the pathological effects their cestodes may effect, have received very little or no attention. Most literature relating to Monobothrium wageneri Nybelin, 1922, a common intestinal cestode of tench, for example, has focused on aspects of its morphology rather than on aspects of the host-parasite interaction.

Results

Immunopathological and ultrastructural studies were conducted on the intestines of 28 tench, collected from Lake Piediluco, of which 16 specimens harboured tight clusters of numerous M. wageneri attached to the intestinal wall. The infection was associated with the degeneration of the mucosal layer and the formation of raised inflammatory swelling surrounding the worms. At the site of infection, the number of granulocytes in the intestine of T. tinca was significantly higher than the number determined 1 cm away from the site of infection or the number found in uninfected fish. Using transmission electron microscopy, mast cells and neutrophils were frequently observed in close proximity to, and inside, the intestinal capillaries; often these cells were in contact with the cestode tegument. At the host-parasite interface, no secretion from the parasite's tegument was observed. Intense degranulation of the mast cells was seen within the submucosa and lamina muscularis, most noticeably at sites close to the tegument of the scolex. In some instances, rodlet cells were encountered in the submucosa. In histological sections, hyperplasia of the mucous cells, notably those giving an alcian blue positive reaction, were evident in the intestinal tissues close to the swelling surrounding the worms. Enhanced mucus secretion was recorded in the intestines of infected tench.

Conclusions

The pathological changes and the inflammatory cellular response induced by the caryophyllidean monozoic tapeworm M. wageneri within the intestinal tract of an Italian population of wild tench is reported for the first time.
Malacological survey and geographical distribution of vector snails for schistosomiasis within informal settlements of Kisumu City, western Kenya
Authors: Opisa Selpha , Odiere Maurice R , Jura Walter GZO , Karanja Diana MS , Mwinzi Pauline NM
Published: December 2011

Background

Although schistosomiasis is generally considered a rural phenomenon, infections have been reported within urban settings. Based on observations of high prevalence of Schistosoma mansoni infection in schools within the informal settlements of Kisumu City, a follow-up malacological survey incorporating 81 sites within 6 informal settlements of the City was conducted to determine the presence of intermediate host snails and ascertain whether active transmission was occurring within these areas.

Methods

Surveyed sites were mapped using a geographical information system. Cercaria shedding was determined from snails and species of snails identified based on shell morphology. Vegetation cover and presence of algal mass at the sites was recorded, and the physico-chemical characteristics of the water including pH and temperature were determined using a pH meter with a glass electrode and a temperature probe.

Results

Out of 1,059 snails collected, 407 (38.4%) were putatively identified as Biomphalaria sudanica, 425 (40.1%) as Biomphalaria pfeifferi and 227 (21.5%) as Bulinus globosus. The spatial distribution of snails was clustered, with few sites accounting for most of the snails. The highest snail abundance was recorded in Nyamasaria (543 snails) followed by Nyalenda B (313 snails). As expected, the mean snail abundance was higher along the lakeshore (18 ± 12 snails) compared to inland sites (dams, rivers and springs) (11 ± 32 snails) (F1, 79 = 38.8, P < 0.0001). Overall, 19 (1.8%) of the snails collected shed schistosome cercariae. Interestingly, the proportion of infected Biomphalaria snails was higher in the inland (2.7%) compared to the lakeshore sites (0.3%) (P = 0.0109). B. sudanica was more abundant in sites along the lakeshore whereas B. pfeifferi and B. globosus were more abundant in the inland sites. Biomphalaria and Bulinus snails were found at 16 and 11 out of the 56 inland sites, respectively.

Conclusions

The high abundance of Biomphalaria and Bulinus spp. as well as observation of field-caught snails shedding cercariae confirmed that besides Lake Victoria, the local risk for schistosomiasis transmission exists within the informal settlements of Kisumu City. Prospective control interventions in these areas need to incorporate focal snail control to complement chemotherapy in reducing transmission.
Parasites of vectors - Ixodiphagus hookeri and its Wolbachia symbionts in ticks in the Netherlands
Authors: Tijsse-Klasen Ellen , Braks Marieta , Scholte Ernst-Jan , Sprong Hein
Published: December 2011

Background

Ixodiphagus hookeri is a parasitic wasp of ixodid ticks around the world. It has been studied as a potential bio-control agent for several tick species. We suspected that the presence of Wolbachia infected I. hookeri eggs in ticks is responsible for incidental detection of Wolbachia DNA in tick samples.

Methods

The 28S rRNA and 16S rRNA genes of a specimen of I. hookeri was amplified and sequenced. PCR on part of the 28S rRNA gene was used to detect parasitic wasp DNA in 349 questing Ixodes ricinus ticks from various sampling sites. Furthermore, the wsp gene of Wolbachia was sequenced from the I. hookeri specimen and a subset of ticks was tested using this marker.

Results

Several sequences from tick specimens were identical to the Wolbachia sequence of the I. hookeri specimen. Ixodiphagus hookeri was detected in 9.5% of all tested ticks, varying between 4% and 26% depending on geographic location. Ten out of eleven sampling sites throughout the Netherlands were positive for I. hookeri. Eighty-seven percent of I. hookeri- positive but only 1.6% of I. hookeri-negative ticks were Wolbachia positive. Detection of I. hookeri DNA was strongly associated with the detection of Wolbachia in ticks.

Conclusion

This is the first reported case of I. hookeri in the Netherlands. Furthermore I. hookeri harbours Wolbachia species and is broadly distributed in the Netherlands. While detection of Wolbachia DNA in ticks might often be due to parasitism with this wasp, other sources of Wolbachia DNA in ticks might exist as well.
Opposing roles of CXCR4 and CXCR7 in breast cancer metastasis
Authors: Hernandez Lorena , Magalhaes Marco AO , Coniglio Salvatore J , Condeelis John S , Segall Jeffrey E
Published: December 2011

Introduction

CXCL12-CXCR4 signaling has been shown to play a role in breast cancer progression by enhancing tumor growth, angiogenesis, triggering cancer cell invasion in vitro, and guiding cancer cells to their sites of metastasis. However, CXCR7 also binds to CXCL12 and has been recently found to enhance lung and breast primary tumor growth, as well as metastasis formation. Our goal was to dissect the contributions of CXCR4 and CXCR7 to the different steps of metastasis - in vivo invasion, intravasation and metastasis formation.

Methods

We overexpressed CXCR4, CXCR7 or both in the rat mammary adenocarcinoma cell line MTLn3. Stable expressors were used to form tumors in severe combined immunodeficiency (SCID) mice, and in vivo invasiveness, intravital motility, intravasation, and metastasis were measured.

Results

We found that CXCR4 overexpression increased the chemotactic and invasive behavior of MTLn3 cells to CXCL12, both in vitro and in vivo, as well as in vivo motility and intravasation. CXCR7 overexpression enhanced primary tumor growth and angiogenesis (as indicated by microvessel density and VEGFA expression), but decreased in vivo invasion, intravasation, and metastasis formation. In vitro, expression of CXCR7 alone had no effect in chemotaxis or invasion to CXCL12. However, in the context of increased CXCR4 expression, CXCR7 enhanced chemotaxis to CXCL12 but decreased invasion in response to CXCL12 in vitro and in vivo and impaired CXCL12 stimulated matrix degradation. The changes in matrix degradation correlated with expression of matrix metalloproteinase 12 (MMP12).

Conclusions

We find that CXCR4 and CXCR7 play different roles in metastasis, with CXCR4 mediating breast cancer invasion and CXCR7 impairing invasion but enhancing primary tumor growth through angiogenesis.
Impact of Ovarian Sex Steroids on Ovulation and Ovulatory Gene Induction in Aromatase-Null Mice
Authors: Toda Katsumi , Hayashi Yoshihiro , Ono Masafumi , Saibara Toshiji
Published: December 2011

Female mice deficient in the aromatase gene [aromatase knockout (ArKO)] fail to ovulate owing to an inability to produce estrogens. Here, we demonstrated that sequential administration of adequate amounts of 17β-estradiol (E2), pregnant mare serum gonadotropin, and human chorionic gonadotropin could induce ovulation in immature ArKO mice; nevertheless, significantly fewer oocytes were released into the oviducts in ArKO mice than in wild-type mice. Analysis of ovarian steroids by liquid chromatography coupled with electrospray ionization-tandem mass spectrometry identified a trace amount of E2 in the untreated immature ArKO ovary. The analysis further detected significant increases and decreases in progesterone and testosterone contents, respectively, in addition to an increase of E2 in the ovulation-induced ArKO ovaries compared with the levels in untreated ArKO ovaries. Gene expression analysis demonstrated marked elevation in the mRNA levels of members of the epidermal growth factor family and extracellular matrix-related proteins at 4 h after human chorionic gonadotropin injection in the ovaries of ArKO mice treated for ovulation, as observed in the ovulation-induced wild-type ovaries. Collectively, these findings suggest the vital contribution of the intraovarian milieu of sex steroids to ovulatory regulation in vivo.
Hypothalamic JNK1 and IKKβ Activation and Impaired Early Postnatal Glucose Metabolism after Maternal Perinatal High-Fat Feeding
Authors: Rother Eva , Kuschewski Ruth , Alcazar Miguel Angel Alejandre , Oberthuer André , Bae-Gartz Inga , Vohlen Christina , Roth Bernhard , Dötsch Jörg
Published: December 2011

Hypothalamic inflammation has been demonstrated to be an important mechanism in the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant and lactating rodents a diet rich in saturated fatty acids has consistently been shown to predispose the offspring for the development of obesity and impaired glucose metabolism. However, hypothalamic inflammation in the offspring has not been addressed as a potential underlying mechanism. In this study, virgin female C57BL/6 mice received high-fat feeding starting at conception until weaning of the offspring at postnatal d 21. The offspring developed increased body weight, body fat content, and serum leptin concentrations during the nursing period. Analysis of hypothalamic tissue of the offspring at postnatal d 21 showed up-regulation of several members of the toll-like receptor 4 signaling cascade and subsequent activation of c-Jun N-terminal kinase 1 and IκB kinase-β inflammatory pathways. Interestingly, glucose tolerance testing in the offspring revealed signs of impaired glucose tolerance along with increased hepatic expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. In addition, significantly increased hepatic and pancreatic PGC1α expression suggests a role for sympathetic innervation in mediating the effects of hypothalamic inflammation to the periphery. Taken together, our data indicate an important role for hypothalamic inflammation in the early pathogenesis of glucose intolerance after maternal perinatal high-fat feeding.
Differential Responses of Progesterone Receptor Membrane Component-1 (Pgrmc1) and the Classical Progesterone Receptor (Pgr) to 17β-Estradiol and Progesterone in Hippocampal Subregions that Support Synaptic Remodeling and Neurogenesis
Authors: Bali Namrata , Arimoto Jason M. , Iwata Nahoko , Lin Sharon W. , Zhao Liqin , Brinton Roberta D. , Morgan Todd E. , Finch Caleb E.
Published: December 2011

Progesterone (P4) and estradiol (E2) modulate neurogenesis and synaptic remodeling in the hippocampus during the rat estrous cycle and in response to deafferenting lesions, but little is known about the steroidal regulation of hippocampal progesterone receptors associated with these processes. We examined the neuronal expression of progesterone receptor membrane component-1 (Pgrmc1) and the classical progesterone receptor (Pgr), by in situ hybridization and immunohistochemistry. Pgr, a transcription factor, has been associated with synaptic remodeling and other major actions of P4, whereas Pgrmc1 is implicated in P4-dependent proliferation of adult neuroprogenitor cells and with rapid P4 effects on membranes. Ovariectomized adult rats were given E2, P4, or E2+P4 on two schedules: a 4-d model of the rodent estrous cycle and a 30-d model of postmenopausal hormone therapy. Pgr was hormonally responsive only in CA1 pyramidal neurons, and the induction of Pgr by E2 was partly antagonized by P4 only on the 30-d schedule. In CA3 pyramidal and dentate gyrus (DG) neurons, Pgr was largely unresponsive to all hormone treatments. In contrast to Pgr, Pgrmc1 was generally induced by E2 and/or P4 throughout the hippocampus in CA1, CA3, and DG neurons. In neuroprogenitor cells of the DG (immunopositive for bromodeoxyuridine and doublecortin), both Pgrmc1 and Pgr were detected. The differential regulation of hippocampal Pgrmc1 and Pgr by E2 and P4 may guide drug development in hormonal therapy for support of neurogenesis and synaptic regeneration.
Liganded Thyroid Hormone Receptor Induces Nucleosome Removal and Histone Modifications to Activate Transcription during Larval Intestinal Cell Death and Adult Stem Cell Development
Authors: Matsuura Kazuo , Fujimoto Kenta , Fu Liezhen , Shi Yun-Bo
Published: December 2011

Thyroid hormone (T3) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T3 signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T3-dependent Xenopus metamorphosis as a model to study how T3 regulates transcription during vertebrate development. T3 exerts its metamorphic effects through T3 receptors (TR). TR recruits, in a T3-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T3 target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.
Selected regulation of gastrointestinal acid–base secretion and tissue metabolism for the diamondback water snake and Burmese python
Authors: Secor Stephen M. , Taylor Josi R. , Grosell Martin
Published: December 2011

Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI) performance with feeding and fasting; frequently feeding species modestly regulate intestinal function whereas infrequently feeding species rapidly upregulate and downregulate intestinal function with the start and completion of each meal, respectively. The downregulatory response with fasting for infrequently feeding snakes is hypothesized to be a selective attribute that reduces energy expenditure between meals. To ascertain the links between feeding habit, whole-animal metabolism, and GI function and metabolism, we measured preprandial and postprandial metabolic rates and gastric and intestinal acid–base secretion, epithelial conductance and oxygen consumption for the frequently feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding Burmese python (Python molurus). Independent of body mass, Burmese pythons possess a significantly lower standard metabolic rate and respond to feeding with a much larger metabolic response compared with water snakes. While fasting, pythons cease gastric acid and intestinal base secretion, both of which are stimulated with feeding. In contrast, fasted water snakes secreted gastric acid and intestinal base at rates similar to those of digesting snakes. We observed no difference between fasted and fed individuals for either species in gastric or intestinal transepithelial potential and conductance, with the exception of a significantly greater gastric transepithelial potential for fed pythons at the start of titration. Water snakes experienced no significant change in gastric or intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near-doubling of gastric metabolism and a tripling of intestinal metabolic rate. For fasted individuals, the metabolic rate of the stomach and small intestine was significantly lower for pythons than for water snakes. The fasting downregulation of digestive function for pythons is manifested in a depressed gastric and intestinal metabolism, which selectively serves to reduce basal metabolism and hence promote survival between infrequent meals. By maintaining elevated GI performance between meals, fasted water snakes incur the additional cost of tissue activity, which is expressed in a higher standard metabolic rate.
Interactive effects of salinity and elevated CO2 levels on juvenile eastern oysters,Crassostrea virginica
Authors: Dickinson Gary H. , Ivanina Anna V. , Matoo Omera B. , Pörtner Hans O. , Lannig Gisela , Bock Christian , Beniash Elia , Sokolova Inna M.
Published: December 2011

Rising levels of atmospheric CO2 lead to acidification of the ocean and alter seawater carbonate chemistry, which can negatively impact calcifying organisms, including mollusks. In estuaries, exposure to elevated CO2 levels often co-occurs with other stressors, such as reduced salinity, which enhances the acidification trend, affects ion and acid–base regulation of estuarine calcifiers and modifies their response to ocean acidification. We studied the interactive effects of salinity and partial pressure of CO2 (PCO2) on biomineralization and energy homeostasis in juveniles of the eastern oyster, Crassostrea virginica, a common estuarine bivalve. Juveniles were exposed for 11 weeks to one of two environmentally relevant salinities (30 or 15 PSU) either at current atmospheric PCO2 (∼400 μatm, normocapnia) or PCO2 projected by moderate IPCC scenarios for the year 2100 (∼700–800 μatm, hypercapnia). Exposure of the juvenile oysters to elevated PCO2 and/or low salinity led to a significant increase in mortality, reduction of tissue energy stores (glycogen and lipid) and negative soft tissue growth, indicating energy deficiency. Interestingly, tissue ATP levels were not affected by exposure to changing salinity and PCO2, suggesting that juvenile oysters maintain their cellular energy status at the expense of lipid and glycogen stores. At the same time, no compensatory upregulation of carbonic anhydrase activity was found under the conditions of low salinity and high PCO2. Metabolic profiling using magnetic resonance spectroscopy revealed altered metabolite status following low salinity exposure; specifically, acetate levels were lower in hypercapnic than in normocapnic individuals at low salinity. Combined exposure to hypercapnia and low salinity negatively affected mechanical properties of shells of the juveniles, resulting in reduced hardness and fracture resistance. Thus, our data suggest that the combined effects of elevated PCO2 and fluctuating salinity may jeopardize the survival of eastern oysters because of weakening of their shells and increased energy consumption.
Electromyography of wrist and finger flexor muscles in olive baboons (Papio anubis)
Authors: Patel Biren A. , Larson Susan G. , Stern Jack T.
Published: December 2011

Some non-human primates use digitigrade hand postures when walking slowly on the ground. As a component of an extended limb, a digitigrade posture can help minimize wrist joint moments thereby requiring little force production directly from wrist flexors (and/or from the assistance of finger flexors) to maintain limb posture. As a consequence, less active muscle volume would be required from these anti-gravity muscles and overall metabolic costs associated with locomotion could be reduced. To investigate whether the use of digitigrade hand postures during walking in primates entails minimal use of anti-gravity muscles, this study examined electromyography (EMG) patterns in both the wrist and finger flexor muscles in facultatively digitigrade olive baboons (Papio anubis) across a range of speeds. The results demonstrate that baboons can adopt a digitigrade hand posture when standing and moving at slow speeds without requiring substantial EMG activity from distal anti-gravity muscles. Higher speed locomotion, however, entails increasing EMG activity and is accompanied by a dynamic shift to a more palmigrade-like limb posture. Thus, the ability to adopt a digitigrade hand posture by monkeys is an adaptation for ground living, but it was never co-opted for fast locomotion. Rather, digitigrady in primates appears to be related to energetic efficiency for walking long distances.
Vocal tract articulation revisited: the case of the monk parakeet
Authors: Ohms Verena R. , Beckers Gabriël J. L. , ten Cate Carel , Suthers Roderick A.
Published: December 2011

Birdsong and human speech share many features with respect to vocal learning and development. However, the vocal production mechanisms have long been considered to be distinct. The vocal organ of songbirds is more complex than the human larynx, leading to the hypothesis that vocal variation in birdsong originates mainly at the sound source, while in humans it is primarily due to vocal tract filtering. However, several recent studies have indicated the importance of vocal tract articulators such as the beak and oropharyngeal–esophageal cavity. In contrast to most other bird groups, parrots have a prominent tongue, raising the possibility that tongue movements may also be of significant importance in vocal production in parrots, but evidence is rare and observations often anecdotal. In the current study we used X-ray cinematographic imaging of naturally vocalizing monk parakeets (Myiopsitta monachus) to assess which articulators are possibly involved in vocal tract filtering in this species. We observed prominent tongue height changes, beak opening movements and tracheal length changes, which suggests that all of these components play an important role in modulating vocal tract resonance. Moreover, the observation of tracheal shortening as a vocal articulator in live birds has to our knowledge not been described before. We also found strong positive correlations between beak opening and amplitude as well as changes in tongue height and amplitude in several types of vocalization. Our results suggest considerable differences between parrot and songbird vocal production while at the same time the parrot's vocal articulation might more closely resemble human speech production in the sense that both make extensive use of the tongue as a vocal articulator.
Belief in a Just World: Consumer Intentions and Behaviors toward Ethical Products
Authors: White Katherine , MacDonnell Rhiannon , Ellard John H.
Published: December 2011

Although consumers report positive attitudes toward ethical goods, their intentions and behaviors often do not follow suit. Just-world theory highlights the conditions under which consumers are most likely to prefer fair-trade products. This theory proposes that people are motivated to construe the world as a just place where people get what they deserve. In the current research, when people are confronted with high levels of injustice (communicated need is high) and avenues for justice restoration seem uncertain or unavailable, assisting others by supporting fair trade decreases. However, highlighting how injustice can be redressed through purchases enhances fair-trade support under conditions of high need. The effects are moderated by justice sensitivity factors, such as just-world beliefs and whether the product type (indulgence vs. necessity) makes the injustice of consumer privilege salient. The results suggest that communicating high need when requesting consumer prosocial actions can sometimes backfire. Marketers employing high need appeals should heighten perceptions of justice restoration potential and activate fairness-related thoughts through product positioning to encourage fair-trade purchases.
Satiating Effects of Cocaine Are Controlled by Dopamine Actions in the Nucleus Accumbens Core
Authors: Suto Nobuyoshi , Wise Roy A.
Published: December 2011

Intravenous cocaine intake in laboratory animals is characterized by periods of apparent drug satiety between regularly spaced earned injections. The reinforcing properties of cocaine are linked primarily to dopaminergic neurotransmission in the shell and not the core of nucleus accumbens. To determine whether the satiating effects of cocaine are similarly mediated, we perfused dopamine receptor agonists into the core or the shell during intravenous cocaine self-administrations by rats. Neither D1-type (SKF38393) nor D2-type (quinpirole) agonist was effective when given alone. However, a combination of the two agonists perfused into the core but not the shell significantly increased the time between cocaine self-injections, decreasing the amount of earned intake. Together with previous findings, the current data suggest that the satiating and reinforcing effects of cocaine are mediated by different ventral striatal output neurons.
Regulation of Hypothalamic Signaling by Tuberoinfundibular Peptide of 39 Residues Is Critical for the Response to Cold: A Novel Peptidergic Mechanism of Thermoregulation
Authors: Dimitrov Eugene L. , Kim Yoon Yi , Usdin Ted B.
Published: December 2011

Euthermia is critical for mammalian homeostasis. Circuits within the preoptic hypothalamus regulate temperature, with fine control exerted via descending GABAergic inhibition of presympathetic motor neurons that control brown adipose tissue (BAT) thermogenesis and cutaneous vascular tone. The thermoregulatory role of hypothalamic excitatory neurons is less clear. Here we report peptidergic regulation of preoptic glutamatergic neurons that contributes to temperature regulation. Tuberoinfundibular peptide of 39 residues (TIP39) is a ligand for the parathyroid hormone 2 receptor (PTH2R). Both peptide and receptor are abundant in the preoptic hypothalamus. Based on PTH2R and vesicular glutamate transporter 2 (VGlut2) immunolabeling in animals with retrograde tracer injection, PTH2R-containing glutamatergic fibers are presynaptic to neurons projecting from the median preoptic nucleus (MnPO) to the dorsomedial hypothalamus. Transneuronal retrograde pathway tracing with pseudorabies virus revealed connectivity between MnPO VGlut2 and PTH2R neurons and BAT. MnPO injection of TIP39 increased body temperature by 2°C for several hours. Mice lacking TIP39 signaling, either because of PTH2R-null mutation or brain delivery of a PTH2R antagonist had impaired heat production upon cold exposure, but no change in basal temperature and no impairment in response to a hot environment. Thus, TIP39 appears to act on PTH2Rs present on MnPO glutamatergic terminals to regulate their activation of projection neurons and subsequent sympathetic BAT activation. This excitatory mechanism of heat production appears to be activated on demand, during cold exposure, and parallels the tonic inhibitory GABAergic control of body temperature.
Felt and Seen Pain Evoke the Same Local Patterns of Cortical Activity in Insular and Cingulate Cortex
Authors: Corradi-Dell'Acqua Corrado , Hofstetter Christoph , Vuilleumier Patrik
Published: December 2011

The discovery of regions in the human brain (e.g., insula and cingulate cortex) that activate both under direct exposure to pain and when perceiving pain in others has been interpreted as a neural signature of empathy. However, this overlap raises the question of whether it may reflect a unique distributed population of bimodal neurons or, alternatively, the activity of intermingled but independent populations. We used fMRI on 28 female volunteers and used multivariate pattern analysis techniques to probe for more fine-grain spatial representations of seen and felt pain. Using a whole-brain approach, we found that only in the anterior insula (bilaterally) the distribution of cortical activity evoked by seeing another person's hand in pain was spatially similar to that of pain felt on one's own hand. Subsequent region of interest analyses also implicated the middle insula (right hemisphere) and the middle cingulate cortex. Furthermore, for the anterior insula, the spatial distribution of activity associated with one's pain also replicates that of the perception of negative but painless stimuli. Our data show how the neural representations of aversive events affecting oneself are also recruited when the same events affect others, and provide the stronger evidence thus far of a unique distributed cortical ensemble coding for aversive events regardless of the subject who is affected.