bluuebunny/crossref_metadata_2025_split huggingface dataset:
An in silico model of Regulatory T cell function
Authors: Taylor Paul , von Herrath Matthias 
Published: June 2021

Regulatory T (Treg) cells participate in response to infection primarily involve chronic or persistent viral infections. The findings that Treg cells influence the functional immunity during viral infections however might indicate that in some cases, virus‐specific Treg cells not only influence immune pathology or prevent pathogen elimination but also can promote a generalized state of immuno‐suppression in vivo, such that the host is more susceptible to secondary infections with other pathogens or has reduced tumour resistance. The regulatory mechanism by which Tregs act has yet to be definitively characterized with opposing evidence suggesting either a cell‐to‐cell a cytokine mediated mechanism.We have developed a cellular model that is an in silico representation of the cells of the immune system. The model aims to faithfully reproduce these cells and their interactions with cognate rule sets derived from experimentation. This stochastic simulation of a Treg suppression assay which can be used to investigate the possible mechanisms behind their immuno‐suppressive effect. The model can rapidly simulate a large number of assays under a wide range of parameters and the detailed results allow for the analysis of the parameters at a detail level currently impossible in vitro. The insights obtained by using the automaton provide a powerful tool for directing in vitro research in to Treg function.
SHP‐1 plays a role in both conventional and CD4+CD25+Foxp3+ regulatory T cell function
Authors: Iype Tessy , Sankarshanan Mohan , Lorenz Ulrike 
Published: June 2021

While the importance of regulatory T (Treg) cells for immune tolerance has been increasingly appreciated, our mechanistic and molecular understanding of their function is still very limited. We have previously shown that mice lacking the SHP‐1, so‐called motheaten (me/me) mice, have increased numbers of Treg cells. SHP‐1 is a well‐recognized negative regulator of TCR‐mediated signaling. We therefore asked whether SHP‐1 also plays a role in Treg function. A comparison of the suppressive capabilities of wild type and me/me Treg cells demonstrated increased suppressive activity of me/me Treg cells in in vitro suppression assays. While this suppression is dependent on stimulation via the TCR, our data indicate that additional factors, which are critical for an effective Treg function, are regulated by SHP‐1. Interestingly when comparing wild type and me/me conventional T cells, we observed that SHP‐1 deficient CD4+CD25‐ T cells are more resistant to Treg‐mediated suppression than wild type T cells, indicating a role for SHP‐1 both in suppression as well as in resistance to suppression. We are currently addressing at the molecular level how SHP‐1 regulates these processes. We expect from these studies to not only better understand the regulatory role of SHP‐1 in conventional and Treg T cells but to also gain further insights into the mechanism of suppression by Treg cells.This work was supported by the NIH grant RO1 AI48672.
Epithelial‐Mesenchymal Interactions during Facial Development in Mice
Authors: Marcucio Ralph , Hu Diane 
Published: June 2021

Previously, we determined that when avian neural crest cells reach the Frontonasal Process (FNP) at Hamburger and Hamilton Stage 20 (HH), Sonic hedgehog (Shh) expression is induced in the stomodeal ectoderm and forms a boundary with a Fibroblast growth factor 8 (Fgf8) expression domain. The ectoderm flanking this boundary controls FNP growth and patterning, but the mechanisms used by this tissue to pattern the face are unknown. In this work, we examined the facial ectoderm of mice to determine whether a similar signaling center exists and how it functions. Fgf8 is expressed in the distal facial ectoderm at e9.5 and continues to be expressed at e10. At e10 Shh is expressed in both median nasal processes and forms a boundary with Fgf8 in each process. Next, we grafted the mouse ectoderm from e10 embryos onto the dorsal FNP of HH 25 chick embryos. Twenty‐four hours after transplantation the graft (n=4) maintained expression of Fgf8, Shh, Bmp‐2, Bmp‐4, and Bmp‐7, and in the neural crest mesenchyme we observed up‐regulation of Bmp‐4, Bmp‐7, and Msx‐1 and ‐2. By 13 days of development the chimeras exhibited a duplication of the upper beak that was comprised of correctly patterned bone and cartilage (n=4). We observed no hair follicles, but we did observe ectopic egg teeth. These results indicate that in mice a signaling center located in the ectoderm of each median nasal process regulates development of the middle and upper face by inducing signaling molecules that govern skeletogenesis within neural crest mesenchyme. The organization of this center is different from that in the chick where a single Shh domain spans the stomodeal ectoderm and forms a continuous boundary with Fgf8 in the FNP.NIH/NIDCR R01‐1DE018234 to R.M.
Compromised CD8 T cell recall responses in the aged mice
Authors: Decman Vilma , DiMenna Lauren J. , Ertl Hildegund C J , Wherry E. John 
Published: June 2021

Loss of effective immune responses with age has a fundamental impact on health and survival. As a consequence, the elderly are more susceptible to infections. To investigate the regulation of anti‐viral T cell responses during aging, we compared the generation and maintenance of effector and memory CD8 T cells in young versus aged mice during LCMV or influenza‐virus infection. By examining both systemic and local immune responses, we demonstrated that aged mice were able to mount primary anti‐viral CD8 and CD4 T cell responses. Aged mice, however, had higher morbidity and mortality compared to young mice and the generation of the effector CD8 T cell responses was delayed. Interestingly, many of antigen‐specific memory CD8 T cells in the aged mice were poorly functional. Nearly half of these antigen‐specific cells did not produce IFNγ and most did not make IL2 upon antigen stimulation. Most dramatically, virus‐specific memory CD8 T cells from aged mice had major defects in proliferative capacity in vivo upon rechallenge infection.Thus, many virus‐specific memory CD8 T cells in aged mice appear to have functional defects and poor proliferative potential of these memory CD8 T cells may underlie poor protective immunity in vivo.These studies were funded by grants from AHA, NIH (HHSN266200500030C) and the Ellison Medical Foundation.
The Cytokine and Chemokine Response to Influenza Virus Infection in Neonatal Mice
Authors: Lines Janet Louise , Hollifield Melissa , Cauley Linda , Garvy Beth A. 
Published: June 2021

Influenza virus is an important cause of mortality and morbidity in children. However, little data exists on the neonatal immune response to influenza virus. We studied intranasal influenza virus infection in adult and 2 day‐old mice, and found that the LD10 for pups is 10 fold lower than for adults. We also observed an interstitial distribution of T cells in the lungs of influenza virus infected pups. By 14 days post infection, the numbers of CD4 and CD8 T cells in the lung interstitia were comparable between pups and adults. However, in pups, T cells were absent from the airways. We therefore determined the mRNA levels of chemokines in lungs from infected pups and adults. Interestingly, in pups, CCL5 (RANTES) expression was elevated, while CXCL9 (MIG) expression was reduced by over 10 fold compared to adult mice. We previously found that TGFβ is constitutively expressed in neonatal lungs, so we examined TGFβ in the context of influenza virus infection. Total TGFβ levels dropped after infection in adults, but remained elevated in pup lungs throughout infection. This corresponded to reduced IFNγ. Consistent with this cytokine profile, a lower level of pup T cells expressed markers of activation. Together, these data suggest that the immune response to influenza infection in neonates is hindered by inappropriate expression of cytokines and chemokines.Supported by an AHA predoctoral fellowship.
Identification of a B cell epitope of enterohemorrhagic Escherichia coli O157:H7 EspA
Authors: Mao Xu‐Hu , Yu Shu , Gu Jiang , Wang Qingxu , Zou Quanï¼□ming 
Published: June 2021

BackgroundsEnterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food‐borne bacterial pathogen capable of posing serious challenge to the public health worldwide. EspA (E. coli secreted protein A) plays an important role in the attaching/effacing lesion. Determination of EspA epitopes will be facilitate to understanding of the multipler pathogenicity as well as the developing of vaccine anainst O157:H7.MethodsAnti‐EspA mAbs were produced by hybridoma technique. Epitope mapping was carried out by truncated EspA protein immuno‐blotting with mAb, and overlapping peptides were synthesized to identify the antigenicity and immuogenicity by competitive inhibition ELISA, dot‐blotting and mice immune. Immune‐fluorescence assay was performed to review the ability of antibody's blocking the actin polymerization and pedestal formation.ResultsThree mAbs against EspA, named 1H10,2A3 and 3E5 respectively, were obtained. The epitope recognized by 1H10 was located in 100–120aa, but 2A3 and 3E5 were detected to recognize conformational epitopes possibly. The conjugate of epitope‐BSA could produce high titer antibodies immunized with mice, the polyclonal sera aginst E100–120 and 1H10 could inhibitate the host cell actin rearrangement dramaticly.ConclusionsA novel B cell epitope in EspA, E100–120 was identified by the 1H10, and the epitopes recognized by 2A3 and 3E5 were possible conformationally.
Chimeric Solid Tissue Grafts Diminish Allospecific Immunity
Authors: Saban Daniel Raphael , Chauhan Sunil K , Dana Reza 
Published: June 2021

Purpose: All layers of a solid tissue graft do not contribute equally to rejection. In the cornea, corneal graft epithelium immunizes the host since it bears the crux of the antigenicity, while corneal graft endothelium is the critical target in rejection. We therefore hypothesized that chimeric corneal grafts, consisting of allodisparate epithelium (EPI) versus stroma/endothelium (S/E), can diminish allospecific immunity to graft S/E, and whether this can promote allograft survival.Methods: Donor corneal layers were separated for reassembly into chimeric allografts (C3H/He EPI + C57BL/6 S/E, or v.v.), and orthotopically placed onto BALB/c hosts. In vitro recall stimulation of host T cells with APC allomatched to graft S/E was used to measure allospecific immunity. Graft survival was also evaluated, via slit‐lamp biomicroscopy.Results: Relative to conventionally allografted hosts, T cells from chimeric engrafted hosts showed reduced levels of proliferation, IFN‐γ secretion, and CD4+ IFN‐γ+ frequencies to graft S/E. Also, an increase in graft survival of chimeric allografts (80%) over conventional allografts (30%) was observed.Conclusions: Chimeric allografts diminish allospecific immunity to graft S/E. This is important because graft endothelium is the critical target in corneal graft rejection, and thus diminishing alloimmunity to this tissue can apparently enhance survival substantially.
Logged on and plugged in: Diet assessment for a new generation
Authors: Sieber Jessica Lynne , Schoch Ashlee , Paulus Trena , Jahns Lisa 
Published: June 2021

Objective: This study compared traditional diet assessment techniques; food records and 24‐hour recalls (24 HR), with current technologies; e‐mail food records and instant messaging (IM) 24 HR. Today's freshmen grew up surrounded by technologies that enable instantaneous communications. Use of these technologies may provide similar or superior assessment and reduce respondent and researcher burden.Methods: Three days of dietary intake (2 weekdays, 1 weekend) were collected from freshman females (n=23) in 4 groups; 1) paper food record, 2) e‐mail food record, 3) phone 24 HR, 4) IM 24 HR. NDSR was used for analysis. Mean energy and macronutrient intake was compared across all groups and by traditional vs. new technologies. Time spent and overall retention rates were compared.Results: Mean energy intake was similar for all methods (2051 – 2129 kcal) except IM recalls (1696 kcal). IM recall subjects reported significantly lower % kcals from fat (p <0.01). All methods had full retention except for paper food records (n = 5). Mean IM 24 HR took longer than mean phone 24 HR (27 min vs. 15 min).Conclusion: Using new technologies may reduce reporting bias by providing an immediate, more comfortable environment. IM 24 HR were less efficacious than traditional methods, but potential for improvement exists. E‐mail food records were superior in clarity, time, and retention rates than paper records.
The effect of substrate supply in modulating plasma Glutathione (GSH) levels in HIV+ treated patients
Authors: Burini Roberto Carlos , Pereira Paulo Câmara Marques , Borges‐Santos Maria Dorotéia , Yu Yong‐Ming 
Published: June 2021

HIV+ patients usually present low levels of GSH and its precursors.PURPOSE: To investigate the responses of GSH and Sulfur amino acid (SAA)pathway to dietary supplements of N‐acetyl‐cysteine (NAC) and Gln.METHODS:12 HIV+ (25–36 yrs) patients (G2) under HAART and 20 (23–28 yrs) healthy controls (G1) were assessed at baseline for anthropometry and plasma biochemistry, and randomly assigned to two diets containing NAC (1g/d) or Gln (20g/d) supplementation. Blood samples were drawn before and by the end of the 7‐day diets to assay the plasma levels of SAA, GSH/GSSG, Ser, Gly, Glu and Gln. The effects of diets and HIV+ were analysed statistically (p=0.05).RESULTS: The measured BMI, albumin, vitamin B12, HDL‐cholesterol and Hcy were similar between G1 and G2. G2 showed higher values of glucose, triglycerides, and GSSG, but lower concentrations of uric acid, folic acid, and GSH. NAC diet significantly increased SAA and GSH in G2 but only Tau and GSH were comparable to G1. Gln supplementation also increased GSH comparable to G1, so did Gly.CONCLUSIONS: GSH deficiency in HIV+ patients can be replenished by dietary supplement of either NAC or Gln.Supported by FAPESP, CNPq.
Parenteral amino acid intakes in critically ill children
Authors: Sy Jama , Gordon William E , Verbruggen Sascha , Arrivillaga Ana , Lane Craig , Stein Fernando , Castillo Leticia 
Published: June 2021

Parenteral amino acid formulas used in parenteral nutrition have a variable composition. To determine the amino acid intake of parenterally fed, critically ill children, and compare it with recommended dietary allowances (RDA) established by the Institute of Medicine (IOM), we retrospectively reviewed parenteral methionine intakes of 47 critically ill children, age 1 to 3 y, weight 8.6+2.9kg, admitted to the PICU over a 6 month period, who received TPN at full maintenance needs at least for 3 days. Eleven children received Aminosyn and 36 received Trophamine. Results are shown in Table 1.Conclusions:Critically ill, parenterally fed children receive significantly higher (P<0.001) amounts of indispensable amino acids when compared to recommended enteral dietary intakes by the IOM, or to the estimated composition of amino acids incorporated into acute phase proteins. Indispensable amino acids are potentially toxic. Hence, specific functional and nutritional parenteral amino acid requirements in critically ill children need to be determined. NIH DK‐62363, T32 HD‐007445, Ajinomoto 3‐ARP; USDA/ARS 25337387, Sophia Foundation for Scientific Research
Animal source food (ASF) intake among women of reproductive age in rural Vietnam (VN)
Authors: Hall Andrew Greenleaf , Ngu Tu , Dirren Henri , King Janet 
Published: June 2021

Maternal anemia and low birth weight babies are common among rural VN women. Thus, we evaluated the ASF intake of non‐pregnant women of reproductive age with BMIs < 18.5. 218 women (18 to 30 yrs) from 21 communes participated in focus group sessions. 24‐hr dietary recalls were done in 24 women from different communes between harvests; 5 non‐consecutive repeats were done in 9 women (60 recalls total). Nutrient intakes were calculated using VN food composition tables. Mean (SD) energy intake was 1815 (501) kcal/d with14% from protein and 3.6% from ASF protein. Mean (SD) iron intake was 10.8 (3.9) mg/d, zinc 8.3 (2.7) mg/d, vitamin A 636 (757) μg RAE/d, and vitamin B12 3.2 (3.6) μg/d. 10% of iron, 13% of zinc, and 41% of vitamin A were from ASF. Nearly 100% had iron and zinc intakes below the VN RDA; about 50% had vitamin A and B12 intakes below the RDA. Eggs and fish were the primary sources of ASF. Women consumed more ASFs when pregnant if encouraged to do so by their husbands and mothers‐in‐law, when income was higher, during holidays, and between harvests when they could catch field crabs and fish. Often women abstained from eating ASFs to protect their image when ASFs were available for other family members. Thus, accessibility and cultural habits limit ASF intake by rural VN women putting them at risk for micronutrient deficiencies and poor pregnancy outcomes.Support: Jastro‐Shields UC Davis Graduate Student Scholarship
Dietary risk factors for dyslipidemia in urban Mexican children
Authors: Benitez Alejandra , Garcia Annarzhvaelig , Ramirez Helena , Valdes Roxana 
Published: June 2021

Background: There are not enough studies describing the risky food intake in different economic conditions that promote inadequate food intake practices. High total cholesterol (TC), triglycerides (TG) and LDL, and low HDL can already be found in children. These conditions promote cardiovascular disease in adult life. In order to evaluate food intake patterns in school‐age children we designed a cross‐sectional comparative study. Methods: Three‐hundred and thirty children from elementary school, 9 to 12 years old, 65.5% from high and 34.5% from low Socioeconomic Status (SES) were evaluated. Lipid profile was obtained from a capillary blood sample, dyslipidemias were considered when TC > 200mg/dl, TG > 125 mg/dl, LDL > 130 mg/dl and HDL < 35mg/dl. Food intake was evaluated by a validated Risk‐Foods Frequency Questionnaire (100 foods with 54 high risk and 46 without risk for dyslipidemia, Cronbach¡− s alpha = 0.86). Low risk diet was defined ¡Ý 10 points and high risk with ¡Ü 10. Association was calculated by Odds Ratio. Results:All subjects had an OR=0.94. High SES showed an OR=1.63, while Low SES had OR=0.49. Intake of simple sugar had and OR=0.94 for TG; saturated fatty acids were associated with LDL (OR=0.82), HDL (OR=0.72) and TC (OR=0.88)Conclusions: Risky dietary intake is higher in better soceioeconomic conditions. Acknowledgement: This project was financed by UAEMex
The effect of menarcheal age on anthropometric, limb length and bone measures in Hutterite and non‐Hutterite women
Authors: Grimsrud Courtney , Binkley Teresa , Specker Bonny 
Published: June 2021

The age women reach menarche may affect bone length and mass. Some studies show an earlier menarcheal age (MA) results in a shorter stature and increased body fat. We hypothesized that Hutterite women have a shorter height and limb length, but greater bone mass and areal bone mineral density (aBMD) than non‐Hutterites. Results are from a secondary analysis of 344 (198 Hutterite) healthy, pre‐menopausal women aged 20–40 years who participated in the South Dakota Rural Bone Health Study. Bone measures were obtained by DXA (spine, hip and total body) and pQCT (4 and 20% distal radius). MA correlated with current age (r=0.10, p=0.06) indicating a trend toward a younger MA for younger women. MA was inversely associated with current weight (r=−0.11, p<0.05), percent body fat (r=7minus;0.16, p<0.01), femoral neck BMC (r=−0.18, p=0.003), femoral neck aBMD (r=−0.21, p<0.001), hip aBMD (r=−0.22, p<0.001) and trabecular volumetric BMD (vBMD) (r=−0.14, p=0.03). Hutterite women had a younger MA than non‐Hutterite women (12.3±1.3 vs. 13.0±1.3 yr, p<0.001). In final regression models controlling for diet and activity patterns, Hutterite compared to non‐Hutterite women had shorter standing height (162±0.4 vs. 166±0.4 cm, p<0.001), forearm length (258±0.8 vs. 261±0.9 mm, p=0.04); and leg length (76±0.2 vs. 77±0.3 cm, p<0.01) as hypothesized, but MA did not predict these outcomes. In conclusion, younger MA in Hutterite women did not explain their shorter standing height and limb lengths, but total hip aBMD was inversely associated with MA and greater in Hutterite than non‐Hutterite women.Supported in part by NIH Grant AR47852
Effects of a Green Tea Intervention on Anthropometrics, Intake, and Glucose Levels in Breast Cancer Survivors
Authors: Sweet Cori Lyn , Apfel Jason S , Stendell‐Hollis Nicole R , Cussler Ellen C , Thomson Cynthia A 
Published: June 2021

Breast cancer recurrence is known to increase among overweight women. Green tea has been shown to modulate obesity and glucose levels in overweight subjects. Using a randomized, placebo‐controlled study design (N=39), we tested the hypothesis that overweight breast cancer survivors who consume 4 cups of green tea daily for 6 months would demonstrate a significant reduction in dietary intake, body weight, body fat, and serum glucose as compared to women consuming placebo tea. Outcome measures included weight, BMI, body fat, waist and hip circumference, dietary intake (Food Frequency Questionnaire) and serum glucose. Women randomized to green tea demonstrated a significant decrease in mean energy intake (−262±492 cal/d) which was related to a decrease in carbohydrate intake (−42.7 ± 87.8). A non‐significant mean decrease in body weight (−1.2±4.1kg), BMI (−0.5±1.5kg/m2), % body fat (−0.6±2.9), and waist to hip ratio was also shown in this group. No significant change in glucose levels was shown over time or in relation to tea assignment. These results suggest that daily intake of 4 cups green tea did not significantly change anthropometrics or glucose in overweight breast cancer survivors, although these markers did move in a favorable direction. Future studies should include higher EGCG exposure and a larger sample size of breast cancer survivors who demonstrate insulin resistance at the time of study entry.This research was funded by: The Susan Komen Foundation and USDA hatch 126660
Comparison of isoflavone yields and profiles from hairy root‐induced kudzu genotypes
Authors: Mun Jonathan , Reppert Nelson Adam , Lachcik Pamela , Grannan Michael , Yousef Gad , Rogers Randy , Janle Elsa , Weaver Connie , Lila Mary Ann 
Published: June 2021

Kudzu is a rich source of isoflavones, including puerarin which has positive effects on bone formation in vitro and in vivo, and may reduce bone loss associated with osteoporosis. Kudzu14C‐labeled isoflavones provide a means of studying their distribution and metabolic fate in vivo. In a recent pharmacokinetic trial, Sprague‐Dawley rats were gavaged using a crude extract containing P. lobata 14C‐isoflavones. Appreciable levels of radiolabel (0.42, 0.33, and 0.10% of the administered dose) were detected in femur, tibia, and vertebrae, respectively. In the current study, hairy roots of 4 kudzu selections, Pueraria montana var. lobata (USA), P. montana var. lobata (Japan), P. lobata (USA), and P. phaseoloides (Guatemala) were extracted with 80% methanol to determine isoflavone content. Extracts were evaluated by high‐performance liquid chromatography (HPLC) with puerarin, daidzin, daidzein, malonyl‐daidzin, genistin, genistein, and malonyl‐genistin standards. P. montana var. lobata (USA) contained the highest puerarin and total isoflavone content of the 4 selections, with concentrations of 53.4 and 112.4 mg/g dry extract respectively. This strain is under cultivation to enhance isoflavone yields and facilitate further radiolabel‐assisted pharmacokinetic studies.Supported by NIH, 2 P50 AT000477–06.