bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pivotal role of p53 in doxorubicin‐induced acute versus chronic cardiotoxicity
Authors: Zhu Wuqiang , Reuter Sean , Wagner Gregory R , Payne Ronald M , Field Loren J 
Published: June 2021

We examined the role of p53 in doxorubicin (DOX)‐induced acute and chronic cardiotoxicities with a clinically relevant juvenile mouse model. Two week old MHC‐CB7 mice (which express dominant‐interfering p53 in cardiomyocytes, CMs) and their non‐transgenic (NON‐TXG) littermates were given weekly DOX injections for 5 weeks (25 mg/kg total dose). Animals were studied 1 week (acute stage) or 13 weeks (late stage) after last DOX injection. Cardiac function was measured with echocardiography. CM apoptosis was quantified using immunohistology. During acute stage, cardiac function was preserved (Fractional Shortening, FS, 58±2.0% vs. 45±1.3%, p<0.01) and CM apoptosis was reduced (0.003±0.002/mm2 vs. 0.011±0.002/mm2, p<0.01) in CB7 mice vs. NON‐TXG mice. During late stage, cardiac function in CB7 mice markedly deteriorated, reaching values similar to those in NON‐TXG mice (FS=52±2.5% vs. 50±2.0%, p>;0.05). CM apoptosis was elevated in CB7 mice as compared to NON‐TXG mice (0.076±0.007 mm2 vs. 0.042±0.008 mm2, p<0.01). In conclusion, although inhibition of p53 activity protects against DOX‐induced CM apoptosis and preserves cardiac function during acute stage, it exacerbates CM apoptosis and cardiac dysfunction during late stage. We are determining the correlation between mitochondrial DNA damage during acute stage and CM apoptosis during late stage.Grant Funding Source: NIH, American Cancer Society
Reciprocal interactions between mitral valvular endothelial and interstitial cells regulate endothelial‐to‐mesenchymal transformation and myofibroblast activation
Authors: Shapero Kayle , Bischoff Joyce , Mayer John 
Published: June 2021

Mitral valve pathologies are characterized by thickening of the valve leaflets, activated myofibroblasts, and excessive matrix remodeling. The mechanisms leading to these alterations are not well‐understood due to a lack of understanding of valve endothelial cells (VEC) and valve interstitial cells (VIC), and how the two cells interact to maintain valve structure and function.HypothesisWe propose that VEC‐VIC interactions are required for normal growth, integrity and function of valves.ResultsWe characterized mitral VEC and VIC populations isolated from ovine mitral valves. We modeled VEC‐VIC interactions in vitro using indirect co‐culture in Transwells. In these assays, VICs suppressed TGFβ‐mediated endothelial‐to‐mesenchymal transformation (EndMT) in the VECs. Conversely, co‐culture of VECs and VICs suppressed the activated myofibroblast phenotype in VICs.ConclusionsThese results suggest that interactions between VEC and VIC are important for 1) suppressing EndMT in VECs and 2) suppressing the activated VIC phenotype. Healthy adult mitral valves exhibit little to no EndMT or activated VICs, two cellular processes implicated in valve disease. We speculate that disturbance of reciprocal interactions between VEC and VICs in vivo may contribute to pathologies characteristic of cardiac valves.Supported by internal funding and the Leducq Foundation Mitral Valve Network Grant.
The effect of electrical stimulation and testosterone on the expression of regeneration‐associated genes
Authors: Meadows Rena Marie , McMillan Kathryn P. , Batka Richard J. , Brown Todd J. , Jones Kathryn J. 
Published: June 2021

Despite robust regenerative potential following peripheral nerve injury, suboptimal outcomes often result in clinical situations. Our laboratory has recently shown that electrical stimulation (ES) and testosterone propionate (TP) can target two different phases of the regeneration process: delay time before sprout formation and regeneration rate, respectively. Furthermore, our laboratory has recently published that the combinatorial treatment of ES and TP significantly increased the expression of several regeneration‐associated genes (RAGs) compared to untreated animals after facial nerve crush injury. Since lower limb nerve injuries following trauma comprise a significant portion of peripheral nerve injuries, we investigated whether the combinatorial treatment of ES and TP improves axonal regeneration after injury to the sciatic nerve. We examined whether the expression profile of RAGs seen after facial nerve crush injury also occurred after sciatic nerve crush injury. To test this, rats received a crush injury to the sciatic nerve. Following injury, animals received either no treatment or treatment with ES and/or TP. After treatment, animals were euthanized at 6 hrs and 1, 2, 7, and 21 days post‐crush. Differences in mRNA expression of RAGs between the different treatment groups was determined by qPCR.Grant Funding Source: Indiana University Collaborative Research Grant
Interconverting conformations of slipped‐DNA junctions formed by trinucleotide repeats affect repair outcome
Authors: Slean Meghan , Reddy Kaalak , Wu Bin , Edamura Kerrie Nichol , Kekis Mariana , Nelissen Frank , Aspers Ruud , Tessari Marco , Schärer Orlando , Wijmenga Sybren , Pearson Christopher 
Published: June 2021

Slipped‐strand DNAs, formed by out‐of‐register mispairing of repeat units on complementary strands, are transient intermediates in repeat length mutations causing at least 30 neurodegenerative diseases. Expansions of (CTG)•(CAG) repeated DNAs are the mutagenic cause of 14 neurological diseases, likely arising through the formation and processing of slipped‐strand DNAs. The three‐way slipped‐DNA junction, at which the excess repeats slip‐out from the duplex, is a poorly understood feature common to these mutagenic intermediates. Here, we reveal that slipped‐junctions can assume a surprising number of interconverting conformations where the strand opposite the slip‐out is either fully base‐paired, or has one‐ or two‐unpaired nucleotides. These unpaired nucleotides can also arise opposite either of the non‐slipped junction arms. Junction conformation can alter correct nick‐directed repair levels. Junctions that have the potential to contain unpaired nucleotides are repaired with a significantly higher efficiency than constrained fully‐paired junctions. Surprisingly, certain junction conformations are aberrantly repaired to expansion mutations: mis‐direction of repair to the non‐nicked strand opposite the slip‐out leads to integration of the excess slipped‐out repeats rather than their excision. Thus, slipped‐junction structure can determine whether repair attempts lead to correction or expansion mutations.Funding: Canadian Institutes of Health Research (CIHR MOP97896) (C.E.P.); National Institutes of Health (GM080454) (O.S.); the Chemistry section of the Dutch Science Organization (S.S.W.)
Study on the anti‐atherosclerotic mechanisms of immune tolerance induced by heat shock protein 60
Authors: Hao Chunyan , Duan Hubin , Li Shuzhen , Wang Suping , Xiao Chuanshi , Liu Xuejun , Xi Ling , Wang Fengzhi 
Published: June 2021

Backgroud and purposeTo study the anti‐atherosclerotic mechanisms of immune tolerance induced by Heat shock protein 60 (HSP60)Methods40 male SD rats were randomly divided into healthy control group, atherosclerosis group (AS group), H1 group (oral HSP60 before modeling AS) and H2 group (oral HSP60 after modeling AS). The content of CD36, SR‐A, NF‐κB, HSP60 and regulatory T cells (Treg) in the aorta, lymph nodes and peripheral blood were detection by immunohistochemistry, flow cytometry, Western blot, PCR and ELISA. The intimal and vessel diameter ratios were calculated by the image analysis system.ResultsThe levels of Treg cells in blood and lymphoid tissue increased. The pathological lesions of H1 group lighter than that of H2 group. The gene and protein expression of HSP60, SR‐A, CD36, NF‐κB in aorta of AS group were higher than that in the control group.The level of expression in the H1 group was lower than that in the H2 group. (P <0.05).ConclusionThe immune tolerance induced by oral HSP60 could inhibit the arteries immune and inflammatory response, reduce the intimal injury and HSP60 antigen exposure and the degree of autoimmune response. Thereby it could also inhibit smooth muscle hyperplasia and maintain the stability of the fibrous plaques. Moreover, the earlier the oral HSP60, the better anti‐atherosclerosis effect.
Membrane‐protein structure determination by solid‐state NMR spectroscopy of microcrystals: The autotransport domain of Yersinia YadA
Authors: Linke Dirk , Shahid Shakeel , Habeck Michael , Bardiaux Benjamin , van Rossum Barth 
Published: June 2021

Membrane proteins are largely underrepresented among available atomic‐resolution structures. The use of detergents in protein purification procedures hinders the formation of well‐ordered crystals for X‐ray crystallography and leads to slower molecular tumbling, impeding the application of solution‐state NMR. Solid‐state magic‐angle spinning NMR spectroscopy is an emerging method for membrane‐protein structural biology that can overcome these technical problems. Here we present the solid‐state NMR structure of the transmembrane domain of the Yersinia enterocolitica adhesin A (YadA). The sample was derived from crystallization trials that yielded only poorly diffracting microcrystals.We solved the structure using a single, uniformly 13C‐ and 15N‐labeled sample. In addition, solid‐state NMR allowed us to acquire information on the flexibility and mobility of parts of the structure, which, in combination with evolutionary conservation information, presents new insights into the autotransport mechanism of YadA.Funding: This work was supported by contract research ‘Forschungsprogramm Methoden für die Lebenswissenschaften’ of the Baden‐Württemberg Stiftung
Structural basis of urea permeation through HpUreI, the urea channel of the human pathogen Helicobacter pylori
Authors: Strugatsky David , McNulty Reginald , Munson Keith , Sachs George , Luecke Hartmut 
Published: June 2021

The proton‐gated urea channel, HpUreI of the human pathogen, Helicobacter pylori, plays an essential role in gastric acid survival. We used both crystal structure analysis of HpUreI in its open form and site‐directed mutagenesis to investigate the structural basis of urea passage through the channel. The crystal structure of the HpUreI revealed that the channel is hour‐glass shaped with a wide entry and exit with two constriction sites in the middle of the channel comprised of aliphatic and aromatic side chains highly conserved in all members of the UreI/AmiS superfamily. We mutated conserved residues lining the constriction sites and measured uptake of [14C]‐urea and [14C]‐thiourea, mediated by the mutants expressed in Xenopus oocytes. Mutation of residues L6, F84 and W149 in the periplasmic constriction site severely impaired the urea transport rate, while mutation of residues L13, Y88 and W153 in cytoplasmic constriction site altered both rate and substrate selectivity. Moreover, mutation of other channel conserved residues, L83, T87, W146, L152, affected both transport rate and substrate selectivity of the channel. Therefore, a complex network of residues defines the urea pathway.Supported by NIH grants: R01AI78000, P30CA062203, R01DK53462, R01DK58333 and NCI institutional training grant 5 T32 CA9054–34.
Interleukin‐4 stimulates collagen production through activation of cardiac fibroblasts via interleukin‐4 receptor α
Authors: Peng Hongmei , Carretero Oscar , Yang Xiao‐Ping , Peterson Edward , Rhaleb Nour‐Eddine 
Published: June 2021

Elevated interleukin‐4 (IL‐4) levels have been implicated in cardiac fibrosis and dysfunction in heart failure, hypertension, and aging in both experimental animal models and patients. We sought to determine the pharmacological effects of IL‐4 on cardiac fibroblasts (CFs) in vitro and hypothesized that IL‐4 stimulates collagen production through activation of signal transducer and activator of transcription 6 (STAT6) via IL‐4 receptor α (IL‐4Rα). Using primary rat CFs, we found that 1) IL‐4Rα was constitutively expressed by Western blot and immunocytochemical staining, 2) IL‐4 induced phosphorylation of STAT6 (Fig. 1), 3) IL‐4 at 0.6 to 50 ng/mL concentration‐dependently increased collagen production assessed by hydroxyproline assay (Fig. 2), and 4) IL‐4 concentration‐dependently induced cell proliferation. This study implicates that IL‐4 is a potent cytokine that stimulates collagen production, and could represent a therapeutic target for cardiac fibrosis and dysfunction.Supported by Henry Ford Hospital Institutional Fund A10163 to N.‐E. Rhaleb.
A 2DE‐Tandem MS Simulation with a Structural Interface
Authors: Sekera Emily Rose , Sawyer Aidan , Craig Paul A. 
Published: June 2021

2DE‐Tandem MS is a computer program designed for use in the biochemistry, proteomics, or bioinformatics classroom. The program currently contains two simulations ‐ 2D Electrophoresis and Tandem Mass Spectrometry. These integrated simulations are designed to teach the concept of proteome analysis of simple organisms. 2DE‐Tandem MS can be used as a freestanding simulation or in conjunction with a wet lab, to introduce proteomics in the undergraduate classroom, and is freely available at https://sourceforge.net/projects/jbf/. 2DE‐Tandem MS functions in Mac OSX, Windows, and Linux, ensuring that every student sees a consistent and informative GUI no matter the computer platform they choose. Peptide sequences from the Mass Spectrometer can now be displayed in a familiar structural format through the popular freeware program, Marvin Sketch (http://www.chemaxon.com/products/marvin/marvinsketch/).Planned future applications include Ion Exchange and Reversed Phase Chromatography.
The Spontaneous Plants’ Recipes Project for enhancing Mediterranean Diet profile change: A sustainable strategy for obesity prevention in childhood, and for contributing to biodiversity maintenance. An intervention of the Italian Food and Nutrition Public Provincial Service
Authors: Trovato Guglielmo M. , Alonzo Elena , Cacciola Salvatore , Cannizzaro Virginia , La Carrubba Rosanna , Pisana Patrizia , Purrello Agata , Raiti Maria Enza , Fardella Maristella 
Published: June 2021

Since 2009 the SIAN is monitoring BMI and dietary habits of 5.220 children, (48.6% males) aged 3–14 years, providing a multi‐sectoral community‐oriented intervention. It was articulated with a core focus on Mediterranean Diet, a proxy of healthy nutrition recommendation. Traditional food and cookery recipes were collected and processed by children. Different types of cultivated and spontaneous plants are still a niche component of Mediterranean dietary profile and wild beet, chard (beta vulgaris), borage, chicory, fennel, cabbages and cardoons are still used in Mediterranean cookery: addressing children to recognizing, collecting, cooking and eating spontaneous plants is a strategic tool supported by the collaboration of teachers, relatives (grandmothers), parents and volunteers. Preliminary results. Initial prevalence of Obesity was 27.6%. At the second year of intervention, a significant drop to 21.27% was already reported with a concurrent increase of Mediterranean Diet Adherence. No such effect was observed by the current educational programs provided nationwide (Italy prevalence: 34.0%). Within the Spontaneous Plants’ Recipes Project at the third year of intervention there is a satisfactory adherence.ConclusionThis exercise allows a closer approach to natural environment, traditional food, green plants, fresh and cooked, and to a more active daily life, moving children in the countryside.
Stunting at birth: An under‐recognized phenomenon with implications for maternal health and nutrition
Authors: Chomat Anne Marie , Vossenaar Marieke , Ruíz Elena Maria Diaz , Wren Hilary , Koski Kristine G , Scott Marilyn E , Solomons Noel W 
Published: June 2021

BackgroundMeasurements of length at birth or in the neonatal period are challenging to obtain and often discounted for lack of standardization and validity. Classical “under‐five” stunting rates derive from surveys on children from 6 to 59 mo of age.ObjectiveTo assess length‐for‐age (LAZ) within the first 1.5 mo of life among infants from urban (U) and rural (R) sites in the Quetzaltenango Province in the Western Highlands of Guatemala.MethodsSupine length was measured to the nearest 0.5 cm by standardized anthropometrics on a SECA 210 infantometer. 104 infants (39% F) were enrolled in 8 rural Mam‐speaking R villages at 2–46 d of life. 106 infants (50% F) were recruited at an urban U health clinic at 4–33 d of life. Stunting was defined as ≤2 SD of LAZ in relation to the 2006 WHO growth standards.ResultsIn R sites, 100% were indigenous (Mam); in the U site, 27% were of indigenous ascent and 73% non‐indigenous. The median R LAZ was −1.55 and prevalence of stunting was 36.5%; the respective U values were −1.41, and 25.5%. The Pearson correlation coefficient of LAZ vs maternal stature for combined U+R was r=0.202 (n=210, p=0.02).ConclusionAs linear growth failure in this setting begins in utero, its prevention cannot begin at birth, but must be linked to maternal care strategies during gestation, or even before. Funded by the Nestle Foundation, McGill University, and Graduate Women in Science
Prevalence of malnutrition in infants, young children, and school‐age children in Milot Region, Haiti
Authors: Rollet Michelle , Siew Elaine , Previl Harold , Etienne Nadia , Forrester Janet 
Published: June 2021

This cross‐sectional study, conducted May–July 2012, measured underweight, stunting, and acute malnutrition in the Milot region of Haiti. Type and severity of malnutrition were determined using z‐score calculations and WHO international growth standards. Children 0–15 years were recruited, with caregiver consent, through random door‐to‐door field visits in four communities. Anthropometric measurements were taken for all surveyed children, and caregivers were asked questions about the child's health history.A total of 358 children were measured and surveyed. Among infants and young children, 55% were underweight, 50% were stunted, and 45% were acutely malnourished. Among school‐age children, 50% were underweight, 44% were stunted, and 42% were too thin for their age and height. Two‐thirds (69%) of all children age 0–15 years were affected by at least one type of malnutrition of differing severity (mild, moderate, severe). For children under age 5, 42% of mothers ended exclusive breastfeeding before the recommended 6 months.This study provides local data that can serve as evidence for informing interventions in the Milot region and nationwide. Reducing high levels of malnutrition requires a multi‐pronged, integrated approach combining effective community outreach and monitoring, inpatient and outpatient nutrition therapy, and partnerships with regional, nutrition‐related organizations.Grant Funding Source: None
Potential impact of the national food fortification program on adequacy of vitamin A intake among women in Cameroon: simulations using nationally‐representative 24‐hour recall data
Authors: Engle‐Stone Reina , Nankap Martin , Ndjebayi Alex O , Brown Kenneth H 
Published: June 2021

The WHO recommends assessing food and nutrient intakes to design food fortification programs, but national‐level dietary data are seldom available in low‐income countries. Prior to initiation of food fortification in Cameroon, we measured intake of vitamin A (VA) and fortifiable foods (oil and sugar) and simulated the effects of fortification with different foods and VA levels on VA intake and dietary inadequacy. 24h recalls were conducted among 912 women (with duplicates in a subset) in a nationally‐representative, cluster survey. Usual intake distributions were estimated by the NCI method. Nationally, the median (25th, 75th percentile) VA intake was 431 (279, 650) μg RAE/d, and 60% of women had usual intakes < 500 μg RAE/d, although the results differed by region (South, 28%; North, 100%; Cities, 52%). 54% of women consumed refined oil, 54% consumed sugar, 73% consumed either and 35% consumed both in the previous 24h. The current fortification level (12 mg VA per kg oil) would decrease the prevalence of inadequate intakes to 36% nationally (South, 19%; North, 64%; Cities, 16%) without affecting the prevalence of intakes >; 3000 μg RAE/d (< 0.5%). Increasing the VA in oil or fortifying a second food (sugar) would further decrease the proportion of women with VA intake < 500 μg RAE/d. Food fortification should substantially improve dietary VA adequacy without increasing the risk of excess intake among women in Cameroon.Grant Funding Source: Michael and Susan Dell Foundation; Sight & Life
Antenatal care quality and its effect on nutrition interventions
Authors: Phillips Erica Lyn , Pelletier David , Stoltzfus Rebecca , Michaud Lesly , Gracia Lionel 
Published: June 2021

Essential nutrition interventions for pregnant women such as iron‐folic acid and calcium supplementation are most frequently delivered through clinic‐based antenatal care (ANC). However, ANC is frequently of poor quality, reducing the impact of these interventions and women's uptake of these services. In order to evaluate ANC quality and describe recipient and provider perspectives of ANC quality, we performed a mixed‐methods study composed of direct observations of ANC consultations (n=999), an exit survey with ANC recipients (n=582) and qualitative interviews with ANC providers (n=20) in central Haiti.Observation results revealed that few providers deliver ANC in accordance with national or WHO guidelines. When asked to identify components of high‐quality care, ANC providers cited physical measurements, such as blood pressure and uterine height, necessary equipment and nutrition supplements. Few providers identified non‐tangible components such as counseling, education or communication as elements of high‐quality ANC. Consequently, a low proportion of women could state why they received the services they did or were informed of their own lab results. These findings show that ANC providers tend to give less emphasis to information, education and communication, which is likely to limit the effectiveness of nutritional interventions of ANC.
Effect of timed and targeted counseling (ttC) by peer mothers in changing infant and young child feeding practices among mothers of children 0 to 18 months in four districts in Southern Ethiopia
Authors: Beyero Mesfin , Reider Kathryn , Mekonnen Yared 
Published: June 2021

ObjectiveTo evaluate changes in infant and young child feeding (IYCF) practices resulting from peer mother's visits delivering age‐appropriate messages on breast feeding and complementary feeding to mothers of children 0 to 18 months after two years of project implementation.MethodsThe evaluation used a quasi‐experimental study design in four implementation and four control districts. The sample size included 1600 children with 800 mothers interviewed from each of the intervention and control districts i.e. 400 for 0 to 5.9 months and 400 for 6 to 23.9 months group.ResultsInitiation of breast feeding within one hour of birth increased from 65.5% to 75.2% (p<0.05); colostrum feeding increased from 71.2% to 83.0% (p<0.0001); exclusive breast feeding increased from 57.9% to 82.8% (p<0.05) in the intervention areas after adjusting for women's education, age, religion, number of children ever born, and economic status. Minimum dietary diversity increased from 7.2% to 10.0% (p<0.0001); minimum acceptable diet increased from 5.0% to 7.5% (p<0.0001); and stunting has decreased from 32.3% to 29.0%.ConclusionAge – appropriate counseling coupled with demonstration on complementary food preparation is an effective way of improving IYCF practices in rural Ethiopia. Dietary diversity remains a challenge and the changes are gradual.Source of research support:FHI360 through the Alive & Thrive Project.