bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strengthening strategic capacity for nutrition in four African countries (632.14)
Authors: Pelletier David , Gervais Suzanne , Hafeez‐ur‐Rehman Hajra , Natamba Barnabas , Sanou Dia , Tumwine Jackson 
Published: June 2021

Undernutrition has received significant attention at global and national levels in recent years, as evidenced by the Scaling Up Nutrition (SUN) movement with 43 participating countries and a G8 commitment of $4.2 billion to the Nutrition for Growth initiative, among others. The translation of this attention into effective action at the country level poses many challenges, as documented previously. Here we describe the results of an on‐going action research effort to address these challenges by strengthening strategic capacity in four Africa countries: Burkina Faso, Mali, Ethiopia and Uganda. All four of these countries have developed multisectoral national nutrition policies and/or plans of action, created coordinating committees and identified SUN focal points. Further multisectoral progress faces challenges seen elsewhere, such as the dominance of sectoral goals and incentives, uneven understanding of multisectoral roles, responsibilities and leadership; uneven participation and ownership; weak human and institutional capacities; lack of effective sub‐national multisectoral platforms; and the persistence of unaligned donor‐ and NGO‐driven approaches. Initial efforts to address these challenges by facilitating informal strategic and adaptive management approaches reveals second order constraints such as high turnover of key staff in and out of government, heavy workloads, rigidity and risk avoidance. Ongoing work focuses on formation of strategic alliances, leadership development, the strengthening of sub‐national experiences to inform the design of multisectoral strategies at the national level and strengthening linkages with global initiatives.Grant Funding Source: Supported by UNICEF
Prevalence of iron deficiency among Inuit preschool children attending childcare centres in Nunavik (632.8)
Authors: Turgeon O'Brien Huguette , Blanchet Rosanne , Gagné Doris , Lauziere Julie , Vézina Carole 
Published: June 2021

In infants and children, iron deficiency (ID) can have several adverse effects on health including lethargy, alterations of immune defense mechanisms and impaired growth and cognitive development. The purpose of this study was to determine the prevalence of ID in a group of preschool Inuit children attending childcare centres in Nunavik using conventional measurements of iron status and a relatively new parameter, soluble transferrin receptor (sTfR). sTfR is especially useful in the presence of inflammation or infection. Two hundred forty‐five Inuit children aged between 11 and 54 months (mean (SD) = 25.0 (9.6) months) were recruited between 2006 and 2010 in 10 of the 14 Nunavik communities. About half of the children were male and 52.3% (n=128) were less than 24 months old at the time of the study. Sixty‐five children were excluded because they lacked one or more of the parameters under analysis, leaving 180 subjects for the assessment of iron status. ID defined either as serum ferritin <15 mg/L, sTfR >1.55 or sTfR‐ferritin index (sTfR/log ferritin) >1.5 was found in 73.2% of subjects. Anemia (hemoglobin (Hb) <110 g/L (12‐35 months old) or <112 g/L (36‐59 months old)) was present in 15% of children, while 7.2% suffered from iron deficiency anemia (IDA) (ID and C‐reactive protein (CRP) <6 mg/L), and 5% from IDA and coexisting anemia of inflammation (ID and CRP 蠅6 mg/L). Iron deficiency constitutes a significant public health problem in these Canadian Aboriginal children. Measures to improve iron intake and bioavailability are required and consumption of traditional foods rich in iron must be encouraged.Grant Funding Source: Supported by Aboriginal Affairs and Northern Development Canada & Kativik Regional Government
Aldehyde dehydrogenase‐1a1 is an oncogene suppressor in B cell populations (639.5)
Authors: Yasmeen Rumana , Meyers Joseph , Alvarez Carlos , Benson Don , Boyaka Prosper , Ziouzenkova Ouliana 
Published: June 2021

Deregulated B cell differentiation contributes to autoimmune disorders, hematological cancers, and aging. Vitamin A metabolite retinoic acid regulates key immune responses. Here, we explore the role of the retinoic acid‐producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) in protection against B cell‐mediated oncogenesis. We showed that Aldh1a1 regulated oncogene suppressors during B cell differentiation sequentially through 1) retinoic acid receptor alpha (Rara) in IgG1+/CD19‐ and 2) zinc finger protein Zfp423 and peroxisome proliferator‐activated receptor gamma (Pparg) in IgG1+/CD19+ splenocytes. Aldh1a1‐deficient mice (Aldh1a1‐/‐ ), displaying pronounced expression of proto‐oncogenic genes c‐Fos, c‐Jun, and Hoxa10 in splenic IgG1+/CD19‐ and IgG1+/CD19+ B cells gave rise to splenomegaly. Human multiple myeloma (MM) B cells did not express Aldh1a1 (n=74 MM vs n=37 healthy patients). Moreover, ectopic Aldh1a1 expression in human MM B cell lines lacking Aldh1a1, rescued Rara and Znf423 expressions in these cells. Our data provide evidence that Aldh1a1 is an oncogene suppressor in specific splenic IgG1+/CD19‐ and IgG1+/CD19+ B cell populations and suggest a mechanism by which this enzyme can potentiate B cell resistance to oncogenesis.Grant Funding Source: Supported by National Center for Advancing Translational Sciences
Alternate day fasting is effective for weight loss and weight maintenance in obese adults (641.3)
Authors: Kroeger Cynthia , Trapanowski John , Klempel Monica , Bhutani Surabhi , Hoddy Kristin , Varady Krista 
Published: June 2021

Alternate day fasting (ADF; 75% restriction fast day alternated with ad libitum feed day) is effective for weight loss in obese individuals. Whether ADF can also be used for weight maintenance, is not yet known. Accordingly, we examined the effects of modified ADF versus a conventional weight maintenance approach on body weight, visceral fat, and markers of coronary heart disease (CHD) risk. Obese subjects (n = 32) were randomized into 1 of 3 groups: 1) ADF, 2) calorie restriction (CR; 25% restriction daily), or 3) control, for a 24‐­‐week weight loss period. After weight loss, subjects began a modified ADF program (50% restriction fast day alternated with ad libitum feed day) or CR‐­‐maintenance program (100% energy intake daily) for an additional 24 weeks. During the weight loss period, body weight and visceral fat decreased (P < 0.01) in the ADF (18 ± 4 kg; 0.5 ± 0.1 kg) and CR group (16 ± 3 kg; 0.3 ± 0.1 kg). Body weight and visceral fat mass remained stable during the weight maintenance period in both groups. Plasma lipids, glucose, insulin, CRP, and blood pressure did not change after 24‐­‐weeks of weight loss in the ADF and CR groups versus control. These CHD risk parameters remained unaltered during the maintenance period as well. These findings suggest that ADF may be just as effective as a conventional weight maintenance approach for maintaining weight loss and visceral fat loss, though the effects on CHD risk are not clear.Grant Funding Source: Supported by the National Institute of Health
Effects of pregnancy status, individual animal and age of pigs on plasma metabolome (643.4)
Authors: Moehn Soenke , Mandal Rupasri , Bjorndahl Trent , Yallou Faizath , Wishart David , Pencharz Paul , Ball Ronald , Plastow Graham 
Published: June 2021

The objective was to assess the metabolome of reproducing pigs. The effect of age and individual pigs was studied in non‐pregnant vs. pregnant pigs, and in early (EG) vs. late pregnancy (LG). The effect of stage of pregnancy was studied in adolescent (parity 2) vs. adult pigs (parity 4). The metabolome of 331 plasma samples from 19 sows was analyzed by nuclear magnetic resonance, gas chromatography‐mass spectroscopy (MS) and direct injection MS. Data were evaluated using partial least square‐discriminant analysis in www.metaboanalyst.ca. Parity affected (P=0.001) the metabolome in EG and LG but not at maintenance. There were no common features for EG and LG within parity, i.e. no metabolites changed with age of pig in both EG and LG. In EG, phospholipids were important features, in LG amino acids, urea and fatty acids. The metabolome differed among individual pigs in EG and LG (P<0.001) but not at maintenance. Aspartate was the only common feature in maintenance and at both stages of pregnancy, and was greater (P=0.039) in LG than EG. Among pigs, the majority of important features in EG were (glycero‐) phospholipids and fatty acids in LG. The stage of pregnancy affected the metabolome in parity 2 and 4 (P<0.01) with palmitic and linoleic acid and galactose common important features. The increase of palmitic and linoleic acid in LG may indicate lipid mobilization due to the energy deficit of pigs in LG. The greatest impact on the metabolome was the stage of pregnancy, individual animals and the maturity of pigs. These physical characteristics need consideration when assessing the metabolome of reproducing pigs.Grant Funding Source: Alberta Livestock and Meat Agency
Stichopus japonicus acid mucopolysaccharide inhibits growth of human liver cancer cells by modulating mitochondrial apoptosis pathway (644.15)
Authors: Song Yang , Chen Chen , Jin Yang 
Published: June 2021

Sea cucumber has traditionally been used as medicinal food for promoting health and warding off disease. Stichopus Japonicus Acid mucopolysaccharide (SJAMP) isolated from sea cucumbers have been shown to have anti‐tumor property. Several working mechanisms are proposed to explain SJAMP’s anti‐tumor effect. In this study we investigated whether SJAMP exerts its anti‐tumor effect via the mitochondrial apoptosis pathway in a cell‐based model. After incubating human liver cancer cell line Hep G2 cells with SJAMP at 0.25, 1, and 4 μg/mL for 24 h, we examined, using the indicated methods, cell morphology (transmission electron microscopy), mitochondrial membrane potential (flow cytometry), and expression of gene (real time RT‐PCR) and protein (immunohistochemistry) of apoptosis‐related molecules. Results showed that SJAMP treatment significantly reduced mitochondrial membrane potential, down‐regulated gene and protein expression of anti‐apoptotic Bcl‐2 and Survivin (P<0.05), and up‐regulated gene expression of pro‐apoptotic Bax, CytC, Caspase‐3, and Smac (P<0.05). These findings indicate that SJAMP may inhibit growth of Hep G2 cells by promoting mitochondria‐mediated apoptosis pathway.Grant Funding Source: Supported by National Natural Science Foundation
Connective tissue growth factor (CTGF/CCN2) expression in quiescent hepatic stellate cells is inhibited by a Twist‐1‐miR‐214 axis (649.7)
Authors: Chen Li , Charrier Alyssa , Brigstock David 
Published: June 2021

Connective tissue growth factor (CTGF/CCN2) drives hepatic fibrosis in vivo by stimulating fibrogenic pathways in hepatic stellate cells (HSC). Under normal conditions, CTGF/CCN2 expression is very low in quiescent HSC but CTGF/CCN2 expression is dramatically increased as HSC become activated during liver injury and adopt a fibrogenic phenotype. We have investigated the molecular basis for the suppressed CTGF/CCN2 levels in quiescent HSC. CTGF/CCN2 up‐regulation in fibrotic or steatotic livers, or in culture‐activated or ethanol‐treated primary mouse HSC was associated with a reciprocal down‐regulation of microRNA‐214 (miR‐214). By using protector or reporter assays to investigate the activity of the 3’‐untranslated region (UTR) of CTGF/CCN2 mRNA, induction of CTGF/CCN2 expression in HSC by fibrosis‐inducing stimuli was due to reduced expression of miR‐214 which otherwise inhibited CTGF/CCN2 expression by directly binding to the CTGF/CCN2 3’‐UTR. In primary mouse HSC, miR‐214 was co‐expressed with the transcription factor Twist‐1 which is a predicted target of an E box in the miR‐214 promoter. Expression of miR‐214 and Twist‐1 in HSC was dose‐dependently inhibited by ethanol or culture‐induced activation in a manner reciprocal to that of CTGF/CCN2. Transfection of primary D6 HSC (high endogenous Twist‐1 levels) with Twist‐1 siRNA reduced expression of miR‐214, but increased CTGF/CCN2 production. An opposite effect was shown by transfecting P6 HSC (low endogenous Twist‐1 levels) with Twist‐1 expression plasmids. Twist‐1 stimulated luciferase activity in HSC transfected with a wild‐type miR‐214 promoter but not with a mutant miR‐214 promoter lacking the E‐box site. We conclude that CTGF/CCN2 expression in HSC is dynamically regulated by an inhibitory Twist‐1‐miR214 axis. This regulatory mechanism may have utility for therapeutic intervention in pathways of CTGF/CCN2‐dependent fibrosis.Grant Funding Source: NIH 5 R01 AA021276
Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57BL/6 mouse heart (652.5)
Authors: El‐Kadi Ayman , Amara Issa , Elshenway Osama 
Published: June 2021

Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg2+‐mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp‐epoxygenases and Cyp‐ω‐hydroxylases; and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5 mg/kg of mercuric chloride (HgCl2). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg2+ significantly increased sEH protein expression and activity, in hearts of mercury‐treated mice, with a consequent decrease in 14,15‐, and 11,12‐epoxyeicosatrienoic acids (EETs) formation. Whereas the formation of 14,15‐, 11,12‐, 8,9‐dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg2+ toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg2+‐induced hypertrophy.Grant Funding Source: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN 250139
Discovery of combinational targets for Alzheimer’s disease based on traditional Chinese medicinal prescription (654.10)
Authors: Zhou Wen‐Xia , Cheng Xiao‐Rui , Zhang Yong‐Xiang 
Published: June 2021

The present one‐drug, one‐target paradigm for anti‐Alzheimer’s disease (AD) treatment appears to be clinically unsuccessful, the combinational targets which composed of several biomolecules based on bio‐network may be optimum for the discovery of anti‐AD drugs. This study aims to search the combinational targets for AD based on traditional Chinese medicine (TCM) using network pharmacology strategy. The nootropic effects of five TCM prescriptions, namely Liuwei‐Dihuang decoction (LW), Bawei‐Dihuang decoction (BW), Huanglian‐Jiedu decoction (HL), Danggui‐Shaoyao‐San (DSS) and Tiaoxin Recipe (TXF), were validated by cognitive behavior test in senescence accelerated mouse prone 8 (SAMP8), and the combinational therapeutic targets were investigated using cDNA microarray, RT‐PCR, bioinformatics and computational biology techniques. The results showed LW, BW, HL, DSS, and TXF significantly improve the cognitive behavior of SAMP8. There are 117 genes expression in hippocampus and 122 genes expression in cerebral cortex regulated by LW, BW, HL, DSS and TXF in SAMP8. These genes regulated by five prescriptions involve in the biomolecular network. The hub nodes included 9 molecules, that is STUB1, STRN4, RPS6KA1, ROCK1, MAP3K3, TICAM2, MAPT, UBE2D2 and PHB. Furthermore, RPS6KA1, SLC17A7 and FHIT are the common nodes effected by one of five prescriptions and may be potential therapeutic target candidates for AD.Grant Funding Source: the National Science and Technology Major Project (2012ZX09301003‐002‐001, 2013ZX09508104)
Patch clamp recordings of fast‐acting ion channels in rat dorsal root ganglion cells (654.3)
Authors: Svensson Dalén Jennie , Sinclair Jon , Karlsson Anna , Pihl Johan , Karila Paul 
Published: June 2021

Manual patch clamp recordings offer direct insight into ion channel properties through the characterization of ion channel activity. Due to the high quality data it is considered the gold standard for ion channel research. Still, the limited throughput means that maximizing data from each cell, especially sensitive primary cells, is important.We have developed a patch clamp‐based assay for characterization fast‐acting ion channels, in this case exemplified by P2X, in primary dorsal root ganglion (DRG) neurons. This assay is based on the use of primary DRG neurons in culture as a cell model for chronic pain. These neurons retain their sensory functionality and remain responsive to thermal, mechanical and functional stimuli, and when supplemented with nerve growth factor (NGF) they can be used to mimic peripheral sensitization. The assay utilizes a microfluidic perfusion system, Dynaflow Resolve, to facilitate a stable recording situation and fast and programmable solution exchange. At the start of the experiment, compounds and buffer are loaded in the 16 wells of the Dynaflow Resolve chip. Micro‐channels connect each well to a recording chamber where the cells are added. To be able to provide fast solution exchange the DRG neuron is lifted using the patch pipette and positioned in front of the micro‐channel outlets. Then, the cell is scanned through the discrete flow zones formed outside the channels.A comparison between conventional bath perfusion and the automated Dynaflow Resolve system showed that both systems have similar capacity when it comes to obtaining successful high resistance seals. However, for collecting full 5‐8 point dose‐responses from single cells, the success rate for the Dynaflow Resolve superseded the conventional system. This enables a dramatically increased productivity when performing more complex pharmacological characterizations.
Antibacterial activities of a novel silver(I) complex with furosemide (654.8)
Authors: Cóssia Silva Maria , Lazarini Silmara , De Carvalho Renata , Amaral André , Corbi Pedro , Lustri Wilton 
Published: June 2021

The use of metal complexes in medicine dates back to the 16th century. Nowadays one of the best examples of a metal‐based drug used in medicine is silver‐sulfadiazine (SSD). This compound is used topically as a cream in the treatment of burns and wounds preventing the appearance of skin bacterial infections. Due to the fact that several metal complexes are extensively applied in the treatment of various diseases the knowledge and understanding of their chemical and pharmacological properties are of high significance. The present research aims to establish conditions for the synthesis and evaluation of the antibacterial activities of a novel silver complex with furosemide (Ag‐fur). Elemental analysis of C, H and N showed a 1:1 metal/ligand composition for the complex, with the molecular formula AgC12H10ClN2O5S. Although insoluble in water, the Ag‐fur complex is soluble in dimethyl sulfoxide. The antibacterial activities of the complex were primarily evaluated by antibiogram assays using the disc diffusion method. The Ag‐fur complex has shown to possess significant antibacterial activity against Staphylococcus aureus (Gram‐positive), Escherichia coli and Pseudomonas aeruginosa (Gram negative) when compared to AgNO3 and to the standard antibiotic ceftriaxone.Grant Funding Source: Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico ‐ CNPq
Changes in extrasynaptic GABAA receptors in the periaqueductal gray with morphine tolerance (659.7)
Authors: Tonsfeldt Karen , Li Minghua , Suchland Katherine , Ingram Susan 
Published: June 2021

Mu‐opioid receptors (MOPrs) reduce GABA‐mediated inhibition of periaqueductal gray (PAG) output neurons to activate the descending pain modulatory system and induce antinociception. The role of extrasynaptic GABAA receptors and tonic inhibition of PAG neurons in antinociception has not been explored. Rats were treated twice a day with saline or morphine (5 mg/kg, sc.) for 3 days. Superfusion of the GABAA antagonist, bicuculline (10 µM), inhibited miniature inhibitory postsynaptic currents and blocked a resting current, indicating the presence of both synaptic and extrasynaptic GABAA‐mediated currents in the PAG. Bicuculline reduced the holding current in saline rats 18 ± 4 pA (n = 10), with less effect in morphine rats (2 ± 1 pA, n = 6, p < 0.05). The bicuculline currents reversed at the expected chloride potential in chloride (‐24 ± 3 mV) and gluconate (‐84 ± 2 mV) intracellular solutions, suggesting the current is mediated by GABAA receptors. Tonic currents are often mediated by extrasynaptic GABAA receptors containing the delta‐subunit. THIP (10 µM), a GABAA delta subunit receptor agonist, induced currents in naïve and morphine treated slices (84 ± 22 pA, n= 8; 77 ± 24 pA, n = 6). The THIP induced currents were reduced by prior administration of met‐enkephalin (10 µM) (30 ± 7 pA, n = 5) compared to control (74 ± 16 pA, n = 7 , p < 0.05). These results suggest GABAA delta receptors may be modulated by activation of MOPrs in the PAG.Grant Funding Source: DA027625
Expression dynamics of pro‐ and anti‐apoptotic proteins regulated by cAMP (663.19)
Authors: Wandrey Narine , Wilderman Andrea , Insel Paul 
Published: June 2021

The second messenger cyclic AMP (cAMP) promotes apoptosis in many cell types, including certain lymphoid cells, by poorly understood mechanisms. Murine S49 T‐lymphoma cells are a model system to study cAMP‐mediated apoptosis and have a distinct advantage for such studies: a clonal variant (kin‐) that lacks protein kinase A (PKA) activity and cAMP‐induced apoptosis, thereby facilitating analysis of PKA‐regulated apoptotic components. We have compared protein levels and subcellular localization of pro‐ and anti‐apoptotic Bcl family proteins in wild‐type (WT) and kin‐ S49 cells treated with the cell‐permeable analog CPT‐cAMP (CPT). We found that WT, but not kin‐, cells treated with CPT time‐dependently increase their level of the S, L and EL isoforms of the pro‐apoptotic protein Bim. We also examined PKA‐promoted phosphorylation of Bad, which is anti‐apoptotic when phosphorylated. We detected no phosphorylation of Bad at Ser155 (a PKA target site) in kin‐ cells during 72 hr treatment with CPT. Unexpectedly, WT cells showed strong Ser155 phosphorylation of Bad (and an increased ratio of p‐Ser155 Bad/total Bad) in response to 24‐72 h CPT treatment. Thus, cAMP acts via PKA to enhance both pro‐ and anti‐apoptotic proteins. We speculate that the late increase in pBAD in WT S49 cells may be an attempt by the cells to reverse their ultimate apoptotic response to cAMP/PKA activation.Grant Funding Source: Supported by: ASPET 2013 Summer Undergraduate Research Fellowship