bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of TCTP Over‐expression in Bacteria
Authors: Parmar Nitika 
Published: November 2023

TCTP (Tumor protein, translationally‐controlled 1) has been implicated in many cellular functions that are related to growth. TCTP has been shown to interact with the G‐protein Rheb, a key player of the PI3 Kinase/mTOR signal transduction pathway and thought to function as its GEF (Guanine Nucleotide Exchange Factor). This study was designed to understand the effects and role of TCTP in prokaryotic physiology. Although no homologs of TCTP have been found in prokaryotes, the expression of wild type and a mutant version of mammalian TCTP on bacterial metabolism under stress conditions was investigated. Wild type mammalian TCTP coding sequence was cloned in a bacterial expression vector and expressed in E. coli under an inducible promoter. Recombinant protein expression was confirmed via polyacrylamide gel electrophoresis and immunoblotting. The impact of TCTP on bacterial growth characteristics in rich and synthetic media was studied under a variety of stress conditions including heat stress, with temperatures ranging from 37–55°C; oxidative stress using hydrogen peroxide; osmotic stress using NaCl; nutrient stress using nutrient depleted medium and pH stress. A mutant version of the protein was made using random mutagenesis and studied as well. Expression of TCTP rendered the cells more sensitive to temperature, pH and oxidative stress. Significant differences were observed with regard to the growth profiles and sensitivity to these stresses when TCTP expression was induced. While the wild type version rendered the cells sensitive at 37°C, 45°C and 50°C, the mutant version rescued this phenotype. H2O2 exposure led to sensitivity by both versions. At alkaline pH (10, 11), cell death was observed in cells expressing TCTP but not in controls. These results indicate that TCTP may play an important role in bacterial growth under stress conditions and although this protein is a mammalian protein, this study provides evidence that it is influencing the metabolic profile of bacteria. TCTP over‐expression in bacteria causes significant changes in physiological responses and may provide useful insights into its role in mammalian physiology.Support or Funding InformationThis work was supported by a CSUCI Faculty Development Minigrant and a UNIV498 award to Nitika Parmar.
Phosphodiesterase 3B (PDE3B) Regulates NLRP3 Inflammasome and Metabolic Cross Talk in Adipose Tissue
Authors: Khan Faiyaz Ahmad , Chung Youn Wook , Tang Yan , Hockman Steven C , Liu Steve , Khan Yusuf , Huo Kevin , Amar Marcelo J , Remaley Alan T , Manganiello Vincent C 
Published: November 2023

Activation of inflammation in white adipose tissue (WAT) which includes infiltration/expansion of WAT macrophages contributes to pathogenesis of obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. The inflammasome protein complex comprises an intracellular sensor (typically a Nod‐like receptor, NLR), caspase‐1 (a cysteine protease) and the adaptor ASC (apoptosis‐associated speck‐like protein). Inflammasome activation leads to the maturation of caspase‐1 and processing of IL1β contributing to many metabolic disorders and directing adipocytes to a more insulin‐resistant phenotype. Ablation of PDE3B in SVJ129 mice epididymal white adipose tissue (EWAT) prevents inflammasome activation by reducing the expressions of NLRP3, caspase‐1, ASC, interferon‐inducible protein AIM2, TNFα, IL1β and proinflammatory genes (i.e, cyclooxygenase2). Following IP (intraperitoneal) injection of lipopolysaccharide (LPS), serum levels of IL1β and TNFα were reduced in PDE3B−/− mice compared to WT. Moreover, chemokine (C‐C motif) ligand 2 (CCL2)/monocyte chemotactic protein‐1 (MCP‐1) and its receptor CCR2, which play an important role in the macrophage chemotaxis, were less highly expressed in EWAT of PDE3B−/− mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE−/−/PDE3B−/− and LDL‐R−/−/PDE3B−/− mice compared to apoE−/− and LDL‐R−/− mice, respectively. Collectively, these data establish a role for PDE3B in modulating the inflammatory response which may contribute to the decreased inflammatory state and reduced aortic plaque formation in PDE3B−/− mice.Support or Funding InformationSupported by the NHLBI Intramural Research Program
Investigation of a Mitochondrial Twin Arginine Transport Pathway in Arabidopsis thaliana
Authors: Weerakoon Tasmeen Shiny , Ma Qianqian , Dabney‐Smith Carole 
Published: November 2023

Most proteins are synthesized at a location different to their site of function. For example, most of the proteins found in cell organelles such as mitochondria or chloroplasts are encoded by nuclear genes, which are transcribed in the nucleus and translated in the cytoplasm. Cells therefore, must have efficient protein transport processes to allow proteins to cross membranes such as those bounding cell organelles like mitochondria or chloroplasts. Proteins destined for organelles are synthesized as larger molecular weight precursors, containing targeting sequences, which direct the precursor to the appropriate transport apparatus at the membrane.One such vital protein transport pathway is the Tat (Twin Arginine Translocation) pathway. The Tat pathway has been found in a wide variety of organisms including bacteria, archaea and eukaryotic organelles such as the chloroplast. The chloroplast Tat pathway (or analogous Tat pathways in bacteria) is capable of transporting fully folded proteins across membranes using only a proton motive force instead of ATP for energy. It is composed of three protein components, namely cpTatC (TatC), Tha4 (TatA) and Hcf106 (TatB) that work together to allow the transport of precursor proteins containing an obligate twin arginine motif in the targeting sequence.However, recent experiments using Nicotiana tabacum cells showed an up‐regulation of a mitochondrial gene coding for a mtTatC protein when the cells was subjected to salicylic acid treatment, which mimics a defense response in the plant to attack by pests. However, single nuclear genes encode both of the other Tat components. Analogous transport pathways in certain Gram (+) bacteria demonstrate that a minimal functional Tat pathway is composed of TatC and TatA (Tha4 homologue). We have confirmed a similar upregulation under stress of salicylic acid of the putative mitochondrial tatC gene in Arabidopsis thaliana. The presence and upregulation under stress of the mttatC gene suggests the possible presence of a mitochondrial Tat pathway, which would require the dual localization of a TatA homology, such as Tha4.To test the possible dual localization of Tha4 to mitochondrial, we have transformed Arabidopsis thaliana with Tha4‐GFP constructs and looked for its localization in the presence or absence of various biotic or abiotic stresses. In addition, we will look at changes in gene expression using RT‐PCR technique to look for Tha4 upregulation in the presence or absence of the stress.Evaluating the presence of a mitochondrial Tat pathway will shed light on a unique protein sorting and transport mechanism in plant mitochondria, a facility previously thought to be lost during the mitochondrial evolutionary process. Therefore investigating this protein sorting pathway in mitochondria may further our understanding of acquired innate immunity within flowering plant species.
Evaluating Programmatic Effectiveness and Implementation: An Assessment of Factors Affecting Change in the Practice of Exclusive Breastfeeding in Ethiopia and Mali
Authors: Baxter Jo‐Anna B , Barac Raluca , Davidson Marnie , Salim Laila , Zlotkin Stanley , Barwick Melanie 
Published: November 2023

Exclusive breastfeeding (EBF) to six months of age is one of the most effective interventions to ensure the survival of newborns and children, yet programmatic activities implemented to increase EBF rates are only variably successful. With funding from the Canadian government's Muskoka Initiative Partnership Program, two NGOs (CARE and Save the Children) implemented programs in Ethiopia and Mali to improve maternal, newborn, and child health outcomes, including EBF. Programmatic activities were diverse, including the development of educational material, community‐based counselling, radio messaging, and mother‐to‐mother support groups. This study aimed to quantitatively assess the observed change in EBF coverage from cross‐sectional survey data, and qualitatively determine contextual factors that influenced the implementation of EBF programmes from focus group discussions (n=15; included mothers and community leaders) and key informant interviews (n=17; included government officials and NGO personnel). Baseline and endline data showed a net increase in the EBF rate in both countries (Mali: 27.3% [95% CI: 19.2 to 35.3] to 66.3% [95% CI: 57.0 to 75.7], P<0.05; Ethiopia: 69.4% [95% CI: 62.4 to 76.3] to 75.1% [95% CI: 69.9 to 80.3], not significant). When analyzed inductively (themes identified from the qualitative data) and deductively (categories assigned to the qualitative data from an existing framework), some of the most influential factors that emerged for EBF adoption were engaging influential community members as ‘champions’ for change; repeated exposure to information about EBF practice and benefits; exposure to community members’ EBF testimonials; and community recognition of a strong need for change to improve infant health outcomes. Traditional beliefs, knowledge, and practices regarding infant feeding and gender role‐related expectations were also found to be important factors for EBF behavioural change. Ultimately, the identified factors for successful implementation and uptake of EBF activities will help to guide and refine existing implementation frameworks, as well as programmatic approaches to increase the number of mothers who practice EBF.Support or Funding InformationFinancial support was provided by the Government of Canada through Foreign Affairs, Trade, and Development Canada (DFATD).
Body Image Perceptions and Breastfeeding Practices among HIV‐Positive Malawian Women with Young Children
Authors: Croffut Samantha , Hamela Gloria , Mofolo Innocent , Hosseinipour Mina , Hoffman Irving , Maman Suzanne , Bentley Margaret , Flax Valerie 
Published: November 2023

Before the prevention of mother‐to‐child transmission (PMTCT) program was widely implemented in Malawi, HIV‐positive women were concerned that exclusive breastfeeding could accelerate disease progression and felt that an HIV‐positive woman could more successfully breastfeed if she had a larger body size. Body image perceptions and their relationship to breastfeeding practices have not been explored in the context of the current Option B+ PMTCT program, which offers lifelong antiretroviral therapy and recommends exclusive breastfeeding for 6 months and continued breastfeeding for 24 months. To fill this gap, we conducted in‐depth interviews with 32 HIV‐positive women enrolled in PMTCT and 32 HIV‐positive women who had dropped out of the PMTCT program in Lilongwe District, Malawi. Interview guides included questions about current, preferred, and healthy body size perceptions using nine body‐image silhouettes, ranging from very thin to obese. We also used narrative scenarios to elicit discussion of the breastfeeding practices of two fictitious HIV‐positive women with different body sizes. More than 80% of participants preferred an overweight (67%), obese (11%), or morbidly obese (3%) figure, and about half of participants selected a morbidly obese figure as healthy. Participants described their preference for overweight figures as having “good health status” and obese figures as “looking good.” No significant differences were found between PMTCT and defaulter participant perceptions of body size. While about half of participants thought that an HIV‐positive woman who was underweight would be able to breastfeed, nearly all participants believed that an HIV‐positive woman who was overweight would be able to breastfeed. One participant described an underweight woman's inability to exclusively breastfeed, “She will grow thin, worse than she looks now.” Another participant stated that an overweight woman will be able to exclusively breastfeed because “she has a strong, fresh body.” In conclusion, among HIV‐positive women, the preference for overweight and obese body figures may be related to fears that underweight women are unable to breastfeed. The consistency of our findings with those from the pre‐PMTCT era indicate a strong cultural preference for large female body size, perhaps because of the perception that it facilitates breastfeeding. In light of evidence from the Demographic and Health Survey of the increasing prevalence of overweight and obesity among Malawian women, including those who are HIV‐positive, we recommend that counseling and health education for Malawian women focus on messaging around a healthy weight range and its relationship with breastfeeding practices.Support or Funding InformationNIH BIRCWH K12 program, UNC CFAR developmental award
Effect of Vitamin D3 Supplementation on Telomerase Activity in Hispanics with Type 2 Diabetes
Authors: Zarini Gustavo G. , McLean Michael , Vaccaro Joan , Exebio Joel , Ajabshir Sahar , Huffman Fatma G. 
Published: November 2023

SignificanceLow levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle, cell senescence and apoptosis. Low telomerase activity and short telomere length are linked to type 2 diabetes and mortality. Hispanics are shown to have shorter telomere lengths as compared to Whites. Hispanics are also at high risk for type 2 diabetes and vitamin D deficiency.ObjectiveThis study investigated whether daily vitamin D3 supplementation at 4000 IU can increase telomerase activity over time in Hispanics with type 2 diabetes and hypovitaminosis D (25‐hydroxy vitamin D < 30 ng/mL).MethodsParticipants (n=34) were recruited from two clinics in Miami‐Dade County, FL, US (Borinquen Health Care Center and Clinical Care Medical Center). Twenty milliliters of venous blood (at least 8 hours fasting) was collected from each participant by a certified phlebotomist using standard laboratory methods. Serum 25‐hydroxy vitamin D levels were determined using a commercial ELISA kit from Immunodiagnostic Systems Limited (Scottsdale, AZ, USA). Telomerase activity was assayed by the TeloTAGGG Telomerase PCR ELISA kit (Roche Applied Science, Indianapolis, IN, USA). Final quantified telomerase activity levels were expressed as Relative Telomerase Activities (RTA). Participants were given 4000 IU/day of vitamin D3 supplementation for 6 months. All data analyses were conducted on an “intent to treat” basis. Statistical analysis included descriptive statistics and one‐way repeated‐measures ANOVA.ResultsMean levels for telomerase activity differed statistically significantly between time points (F(2,66) = 78.57), p < 0.001). Post hoc test using Bonferroni correction indicated that telomerase activity levels increased from baseline to 6 months (49.3 ± 6.8 vs. 63.1 ± 7.2 RTA, respectively) which was statistically significant (p < 0.001). However, baseline to 3 months telomerase activity levels (49.3 ± 6.8 vs. 45.9 ± 3.9 RTA, respectively) were not statistically significant (p = 0.068).ConclusionVitamin D3 supplementation at 4000 IU/day significantly increased telomerase activity in Hispanics with type 2 diabetes. Vitamin D3 supplementation may prevent/delay disease progression in type 2 diabetes through telomerase re‐activation and maintenance of DNA. Larger randomized controlled trials are needed to confirm these results in this and other racial/ethnic groups.
Milk Proteins and Amino Acids Modulate Inflammatory Gene Expression in Vascular Endothelial Cells
Authors: Da Silva Marine S , Bigo Cyril , Barbier Olivier , Rudkowska Iwona 
Published: November 2023

The digestion of milk proteins releases bioactive peptides and amino acids which may be beneficial for cardiovascular protection. However, mechanisms underlying the lowering effect of milk proteins on systemic inflammation, a cardiovascular disease (CVD) risk factor, remain to be elucidated.ObjectiveTo investigate the effect of milk proteins and their major amino acid components on inflammatory gene expression in vitro.MethodsHuman umbilical vein endothelial cells (HUVEC), stimulated or not with TNFα to trigger inflammation, were incubated for 24h with 1‐ milk proteins: whey protein (0.5 or 5 mg/ml); isolate (WPI) or hydrolysate ((WPH) a mixture of bioactive peptides and amino acids); caseins (CN, 1 mg/ml); a mixture of WPI and CN (WPCN, 1:4 w/w); or 2‐ amino acids (0.2–20 mM): branched‐chain amino acids ((BCAA) including leucine, isoleucine and valine), glutamine or proline. Expression of pro‐inflammatory genes TNF and VCAM‐1 was measured by RT‐PCR.ResultsWPI caused a down‐regulation of the two pro‐inflammatory genes, whereas WPH and its major BCAA, leucine and isoleucine, had no effect in unstimulated cells. Furthermore in these cells, both CN and WPCN decreased VCAM‐1 expression; however, TNF expression was increased by the mixture WPCN. Glutamine‐ the major amino acid of CN, and valine‐ a BCAA found in both milk proteins, up‐regulated the pro‐inflammatory genes in unstimulated cells. Stimulation of HUVEC with TNFα caused increased expression of TNF and VCAM‐1. This effect was partially inhibited by WPH and the three BCAA; whereas WPI had no effect in stimulated cells. In addition, CN and WPCN lowered VCAM‐1 together with an increased TNF gene expression in stimulated cells. Glutamine increased VCAM‐1 expression in stimulated cells. Proline had no effects.ConclusionWhey proteins (WPI and WPH) and BCAA exerted anti‐inflammatory effects; whereas CN, the mixture WPCN and glutamine showed pro‐inflammatory properties according to the inflammatory state of endothelial cells. These results support the potential of whey proteins for CVD prevention.
The Effects of Folate Deficiency and Arsenic Exposure on Thymidylate Synthesis in Serine Hydroxymethyltransferase 1‐Deficient Mouse Embryonic Fibroblasts
Authors: DiRisio Aislyn , Kamynina Elena , Field Martha S. , Stover Patrick J. 
Published: November 2023

Low maternal folate is associated with the failure of the neural tube to close during development, leading to a class of developmental anomalies referred to as Neural Tube Defects (NTDs). NTDs are observed in mouse embryos with impaired de novo thymidylate (dTMP) biosynthesis resulting from decreased SHMT1 expression when the mother is fed a folate‐deficient diet. 5,10‐methylenetetrahydrofolate is a cofactor for thymidylate synthase (TYMS) in the conversion of deoxyuridylate (dUMP) to dTMP via one‐carbon metabolism. De novo thymidylate synthesis is critical to prevent uracil misincoporation, which can lead to double strand breaks (DSBs). Tetrahydrofolate (THF) is converted into 5,10‐methyleneTHF by serine hydroxymethyltransferase 1 and 2 (SHMT1, SHMT2) and the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) at the replication fork. Arsenic is also shown to induce NTDs in animal models. Reduced SHMT1, SHMT2, and MTHFD1 expression, either alone or in combination, lead to a greater extent of γH2AX phosphorylation in HeLa cells, indicating that these proteins contribute to genomic stability. Additionally, we observed that As2O3 exposure increased genome instability and changed the distribution of cells across the cell cycle in HeLa cells. Here, we present the extent of DNA DSBs, apoptosis, and p53 expression in mouse embryonic fibroblasts in response to arsenic exposure and folate deficiency. Shmt1 −/− MEFs were isolated from embryos derived from dams fed either a folate‐deficient or control diet and cultured in folate‐replete or folate‐depleted media with or without 5μM As2O3. Folate deficiency and As2O3 exposure result in the formation of DNA DSBs, with the greatest effect seen with folate deficiency and As2O3 exposure in combination. These data indicate that folate deficiency and As2O3 exposure affect genome stability in SHMT1‐deficient MEFs.Support or Funding InformationPublic Health Services grant HD059120
The Impact of Lipid‐Based Nutrient Supplements on Maternal Depression at 6 mo Postpartum in Ghana: A Randomized‐Controlled Trial
Authors: Okronipa Harriet Eyram T. , Adu‐Afarwuah Seth , Lartey Anna , Ashorn Per , Vosti Steva A. , Young Rebecca Tree , Dewey Kathryn G. 
Published: November 2023

BackgroundMaternal postpartum depression (PPD) has been reported to affect 13% of women globally and has been linked to poor child health. Poor maternal nutrition, including low dietary intake of essential fatty acids, may be a risk factor for PPD.ObjectiveWe examined the impact on depression at 6 months postpartum of maternal supplementation with lipid‐based nutrient supplement (LNS) compared to supplementation with iron and folic acid (IFA) or multiple micronutrients (MMN).MethodIn this partially double‐blinded randomized controlled trial, pregnant women ≤20 wk gestation (n=1320) were randomly assigned to receive either 1) LNS during pregnancy and for 6 months postpartum, or 2) IFA during pregnancy only, or 3) MMN during pregnancy and for 6 months postpartum. Maternal depressive symptoms were measured at 6 mo postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Women who scored 12 or more on the EPDS were considered to show symptoms of depression.Results1151 women were included in this analysis (LNS=382, IFA=387 and MMN=382). Characteristics of the three groups were similar at baseline and there were no significant differences between women who were included in the analysis (n=1151) and those who were not (n=169). At 6 months postpartum, 13% of women overall showed symptoms of depression, and this did not differ by group (LNS=13.3%, IFA = 10.6% and MMN = 14.4%. P=0.36). The median (25, 75 percentile) EPDS scores did not differ by group (LNS 4.0 (1.0, 8.0), IFA 4.0 (1.0, 8.0), MMN 5.0 (2.0, 9.0), Ptransformed =0.13). Season of depression data collection was a significant effect modifier for depression scores (P=0.02): in women assessed during the dry (post‐harvest) season, the LNS group compared to the MMN group had lower EPDS scores (P=0.015).ConclusionMaternal supplementation with LNS compared to MMN or IFA did not affect postnatal depressive symptoms in this sample of Ghanaian women. However the lower depression scores in the LNS group among those evaluated during the dry season warrants further investigation.Support or Funding InformationThis study was funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Davis, USA
Effects of Chromium Supplements on Wound Healing
Authors: White Pandora E. , Chen Tsung‐Sheng , Chen Yi‐Ting , Liu Chia‐Hsin , Sun Chi‐Ching , Vincent John B. , Mao Frank Chiahung , Lee Wei‐Ming 
Published: November 2023

Glucocorticoids, such as dexamethasone, are anti‐inflammatory drugs that are used to treat inflammatory conditions such as arthritis. However, over time the constant use of anti‐inflammatory drugs impairs wound healing. Insulin like growth factor (IGF‐1) plays a role in promoting wound healing. Cr(III) has been proposed to enhance levels of IGF‐1 and increase wound healing. CrCl3 has previously been shown to improve wound healing in animals receiving dexamethasone. The specific objective of this study was to test the ability of various Cr(III) compounds to enhance wound healing in C57BL6/JNarl mice. Wounds were inflicted on mice and then Cr(III) compounds were administered to see if wound healing was accelerated in mice receiving dexamethasone. The results indicate that the Cr(III) compounds did not significantly enhance wound healing.Support or Funding InformationFunding was provided by the Ministry of Science of Taiwan, the National Science Foundation East Asia and Pacific Summer Institute, and Maxluck Biotechnology Corporation.