bluuebunny/crossref_metadata_2025_split huggingface dataset:
an3-Mediated Compensation Is Dependent on a Cell-Autonomous Mechanism in Leaf Epidermal Tissue
Authors: Nozaki Mamoru , Kawade Kensuke , Horiguchi Gorou , Tsukaya Hirokazu 
Published: April 2020

AbstractLeaves are formed by coordinated growth of tissue layers driven by cell proliferation and expansion. Compensation, in which a defect in cell proliferation induces compensated cell enlargement (CCE), plays an important role in cell-size determination during leaf development. We previously reported that CCE triggered by the an3 mutation is observed in epidermal and subepidermal layers in Arabidopsis thaliana (Arabidopsis) leaves. Interestingly, CCE is induced in a non-cell autonomous manner between subepidermal cells. However, whether CCE in the subepidermis affects cell size in the adjacent epidermis is still unclear. We induced layer-specific expression of AN3 in an3 leaves and found that CCE in the subepidermis had little impact on cell-size determination in the epidermis, and vice versa, suggesting that CCE is induced in a tissue-autonomous manner. Examination of the epidermis in an3 leaves having AN3-positive and -negative sectors generated by Cre/loxP revealed that, in contrast to the subepidermis, CCE occurred exclusively in AN3-negative epidermal cells, indicating a cell autonomous action of an3-mediated compensation in the epidermis. These results clarified that the epidermal and subepidermal tissue layers have different cell autonomies in CCE. In addition, quantification of cell-expansion kinetics in epidermal and subepidermal tissues of the an3 showed that the tissues exhibited a similar temporal profile to reach a peak cell-expansion rate as compared to wild type. This might be one feature representing that the two tissue layers retain their growth coordination even in the presence of CCE.
Physical Function in the Hospital Is Associated With Patient-Centered Outcomes in an Inpatient Rehabilitation Facility
Authors: Johnson Joshua K , Fritz Julie M , Brooke Benjamin S , LaStayo Paul C , Thackeray Anne , Stoddard Gregory , Marcus Robin L 
Published: April 2020

Abstract

Objective
Poor knowledge of the relationships between physical function (PF) in the hospital and patient outcomes in an inpatient rehabilitation facility (IRF) limits the identification of patients most appropriate for discharge to an IRF. This study aimed to test for independent associations between PF measured via the AM-PAC “6-clicks” basic mobility short form in the hospital and outcomes in an IRF.

Methods
This was a retrospective cohort study. Primary data were collected from an acute hospital and IRF at 1 academic medical center. Associations were tested between PF at hospital admission or discharge and PF improvement in the IRF, discharge from the IRF to the community, and 30-day hospital events by estimating adjusted relative risk (aRR) using modified Poisson regression and the relative difference in IRF length of stay (LOS) using Gamma regression.

Results
A total of 1323 patients were included. Patients with moderately low, (aRR = 1.50; 95% CI = 1.15–1.93), moderately high (aRR = 1.52; 95% CI = 1.16–2.01), or high (aRR = 1.37; 95% CI = 1.02–1.85) PF at hospital discharge were more likely than those with very low PF to improve their PF while in the IRF. These same patients were more likely to discharge from IRF to the community and had significantly shorter IRF LOS. Hospital-measured PF did not differentiate risk for 30-day hospital events.

Conclusion
Patients with moderate—but not very low or very high—PF measured near the time of acute hospital discharge were likely to achieve meaningful PF improvement in an IRF. They also had a shorter IRF LOS so may be ideal candidates for discharge to IRF. Prospective studies with larger samples are necessary to test this assertion.

Impact
Providers in the hospital should identify patients with moderate PF near the time of hospital discharge as those who may benefit most from post-acute rehabilitation in an IRF.
An e-mental health intervention to support burdened people in times of the COVID-19 pandemic: CoPE It
Authors: Bäuerle Alexander , Graf Johanna , Jansen Christoph , Dörrie Nora , Junne Florian , Teufel Martin , Skoda Eva-Maria 
Published: April 2020

Abstract
The outbreak of the novel SARS CoV-2-virus (COVID-19) is pushing national and international healthcare systems to their limits. The aspect of mental health issues, which has been neglected (so far) in times of social isolation and governmental restrictions, now demands innovative and situation-based approaches to support psychological burdened people. The developed e-mental health intervention ‘CoPE It’ offers manualized, evidence-based psychotherapeutic/psychological support to overcome psychological distress in times of COVID-19. E-mental health approaches offer great possibilities to support burdened people during the SARS-CoV-2 pandemic effectively.
Changing (?) Gender Roles Within Conservative Communities: An Analysis of Group Interview Narratives of Bedouin Women
Authors: Harel-Shalev Ayelet , Kook Rebecca , Elkrenawe Feniar 
Published: April 2020

AbstractThis article focuses on the creative and innovative modes of negotiation that women in severely patriarchal societies often exhibit in their attempts to actively pursue their own goals in the face of risk. Based on group interviews with Bedouin women in southern Israel about their everyday lives, the research explores both the risks and the ways in which the women deal with them. The research expands on discussions about the nature of women’s agency in the context of the power relations prevalent in specific communities, paying attention to the multiple modes of subordination experienced by the women of such communities.
Participant food and activity costs in a translational Diabetes Prevention Program
Authors: Schafer Gerald L , Songer Thomas J , Arena Vincent C , Kramer M Kaye , Miller Rachel G , Kriska Andrea M 
Published: April 2020

Abstract
The Diabetes Prevention Program (DPP) and its translational adaptations have been shown to be effective. However, individual-level economic impacts, such as the out-of-pocket costs borne by participants due to involvement in these programs have not been consistently and thoroughly evaluated. As cost is an important consideration that will impact the willingness of individuals to participate in such programs, this study examined direct monetary costs to participants in the Group Lifestyle Balance (GLB) DPP. Older adults (n = 134, mean age 62.8 years) with body mass index (BMI) ≥24 kg/m2 and prediabetes and/or metabolic syndrome participated in this GLB intervention, with two-thirds randomized to begin the intervention immediately and one-third functioning as a control for 6 months before receiving the entire intervention. Food and activity time and costs borne by participants were measured by self-report at baseline and after 6 months. Significant improvements in clinical metabolic measures, weight, and physical activity levels were achieved after 6 months in the intervention group compared both with baseline and the controls. Food costs did not increase among intervention participants. Costs related to physical activity did not change consistently over the course of the intervention. This DPP–GLB lifestyle intervention was effective in reducing risk factors for Type 2 diabetes mellitus among a diverse group of older participants without significantly increasing their out-of-pocket costs for food or physical activity over the course of the intervention. These results should help reduce concerns of individuals who are hesitant to participate in similar programs due to costs. The clinical trial registration number of this study is NCT01050205.
Eliciting Cell Death Using Recombinant IgA Fc‐Folate Antibody Mimetics
Authors: Turnbull Alissa , Tepe Gokturk , Mohammed Saimaa , Peraino Nicholas , Speyer Cecilia 
Published: April 2020

High grade serous ovarian carcinoma (HGSC) is a very deadly and aggressive subtype of ovarian cancer that lacks common receptors frequently targeted by cancer therapeutic agents. Its high mortality rate is due in part to the lack of an effective targeted therapy. Many types of cancer cells have been shown to overexpress folate receptor alpha (FRA), a protein that binds folic acid and mediates the delivery of folate into the cell. FRA has been shown to be highly expressed in HGSC and therefore it has been hypothesized that FRA can be utilized as a cellular target for redirecting neutrophils (PMNs) against this type of aggressive cancer cell. To test this, three IgA1 Fc fragment variants were synthesized utilizing the baculovirus insect cell system and purified by IgA affinity chromatography. After characterization by MALDI‐TOF, folate was attached to the Fc fragments by coupling it to lysine amine groups. Excess activated folate was removed using 7kD Zeba desalting spin columns and the Fc‐folates were concentrated using Pierce’s PES protein concentrators (10kD MWCO). Once synthesized, binding of Fc‐folates to FRA on a variety of HGSC cells was confirmed by running 3H‐folate binding assays and observing their ability to elicit neutrophil activity. Neutrophils were activated through the Fc‐folates binding to the IgA Fc receptors (CD89) resulting in killing of the cancer cells through a process known as antibody‐dependent cellular cytotoxicity (ADCC), which was determined by measuring lysis of cancer cells loaded with green tracker dye. All three Fc‐folate antibody mimetics bound FRA and induced potent ADCC against HGSC cells, suggesting a possible competent targeted treatment for this aggressive subtype of cancer.Support or Funding InformationNIH STTR Grant #R41CA213548
Glucose Metabolism on Gastrulation: Interference Causes Morphological and Gene Expression Defects in Embryoid Bodies
Authors: Li Aileen Sok Wan , Marikawa Yusuke 
Published: April 2020

Tight blood glucose control is important during pregnancy for the conceptus. Studies have found high incidences of severe drops in blood glucose level (hypoglycemia) in pregnant women during the first trimester, the most crucial period to embryo development and when the conceptus is most vulnerable to maternal environment. Here, we utilized aggregated P19C5 mouse embryonal carcinoma stem cells or embryoid bodies (EBs) to investigate changes during gastrulation when glucose metabolism is altered. We used morphometrics and real‐time quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and detected differential shape and gene expression in EBs which glucose metabolism pathways were targeted. We found evidence that glucose metabolism is essential for posterior elongation of the axis. Our results implicate glucose metabolism in germ layer formation by acting on Wnt and Nodal signaling. In the future, we want to elucidate the mechanism glucose metabolism mediates gastrulation and to establish whether our conclusions of the model system are similar to that of other mammalian species.Support or Funding InformationNational Institutes of Health
Glucose Regulated Protein (GRP78) as a Biomarker of Response to Bortezomib‐based Regimen in Multiple Myeloma
Authors: Gupta Pooja , Ramachandran Suganthi S. , Gupta Ritu , Kumar Lalit 
Published: April 2020

IntroductionGRP78 overexpression has been associated with bortezomib resistance in multiple myeloma (MM) cells. However, serum GRP78 as a maker of bortezomib based treatment response remains unexplored. The objective of the study was to evaluate serum GRP78 levels in MM patients who underwent bortezomib based induction regimen.MethodsAfter ethical approval, this cross‐sectional study was done in adult MM patients who had completed at least 4 cycles of bortezomib based induction therapy. They were classified into responders (complete response (CR), very good partial response (VGPR), partial response (PR)) and non‐responders (stable disease (SD) and progressive disease (PD)). Thirty healthy volunteers and twenty newly diagnosed multiple myeloma patients were also recruited to identify the disease associated change in GRP78 levels. Serum GRP78 was estimated by ELISA. Surface and intracellular expression of GRP78 in bone marrow plasma cells was evaluated in a subset of MM patients by flowcytometry.ResultsThirty MM patients who completed at least 4 cycles of bortezomib based induction therapy [median(range): 52 (38–68) years; Male:20] were enrolled. Out of 30 patients, 20 were responders and 10 were non‐responders. They were comparable at baseline in all clinical and laboratory parameters except serum M protein which was significantly higher in non‐responders (p=0.04). Serum GRP78 levels were not significantly different between responders [median (IQR): 5.2 (3.1,8.0) μg/ml] and non‐responders [median (IQR): 4.3 (0.1,7.1) μg/ml] (p=0.356). Although non‐significant (p=0.342), median serum GRP78 was higher in newly diagnosed patients when compared to healthy volunteers. Bone marrow plasma cell percentage ranged between 0.2 to 57.8% in the analyzed samples. Intracellular GRP78 expression was found to be higher (1.6 to 5 times) when compared to surface expression in plasma cells as well as in malignant subset of plasma cells.ConclusionSerum GRP78 did not differ between responders from non‐responders in MM patients who underwent bortezomib based induction regimen.Support or Funding InformationIntramural Research Grant
Assessment of Ion Affinity for the Lipid Bilayer Interface
Authors: Hills Ronald D. , White Jessica L. , Chalmers Kathryn A. , Lotana Humphrey L. 
Published: April 2020

Calcium ions play a key role in cell signaling processes, yet the molecular nature of their interaction with heterogenous membranes is difficult to study with traditional techniques. Parameters were developed for sodium, calcium and chloride ions for use with the CgProt force field for molecular dynamics simulations of membrane‐protein systems. Similar to atomistic simulations, highly attractive behavior was observed for calcium with zwitterionic POPC/POPE membrane interfaces. Both sodium and calcium preferentially bound to the phosphate region of anionic POPG bilayers. The addition of CaCl2 to implicit solvent simulations had the effect of stabilizing the lipid bilayer. Sub‐molar concentrations of calcium adsorb onto POPE and POPG membranes and enable low or zero tension simulations. Close agreement in the area per lipid was obtained compared to results from atomistic simulations, indicating the utility of the model for large scale membrane simulations.Support or Funding InformationNational Science Foundation, grant MCB 1516826
Cell Unclumping Assay in Drug Discovery: Sodium Sulfate
Authors: Zem Greg , Crocker Kristel , Deleon Jonie , Telliyan Lucy , Aprelian Kevin , Rosenberg Aryeh , Pouri Nikole , Beltran Gerard , Ramirez Vivian , Kaufman David , Petrosyan Arpineh , Nazarian Deanna , Magistrado Monikajane , Matinian Suren , Hanna Daniel , Eskandari Sera , Atanante Faisal , Nerses Adees , Oppenheimer Steven B. 
Published: April 2020

Clumped cells are generally more dangerous than single cells in cancer spread, thrombocytosis and biofilm infectivity. Here a simple 3 component direct kinetic assay is used to examine 2 reagents for anti‐clumping activity using a Prefer (Anatech Ltd., Battle Creek, MI) fixed yeast (Saccharomyces cerevisiae) model that has been recently described by us in detail using other reagents (Amer J Applied Scientific Research 5:28–34 March 2019). In 1212 trials by 17 investigators sodium sulfate and sodium bicarbonate (1–3 mg per ml deionized water) were examined by measuring percentage single cells, number of clumps and number of cells per clump over a 60 min time course, with standard deviations and t‐tests to determine any significant differences between controls and experimentals. Both reagents showed sometimes inconsistent unclumping activity especially in magnitude of effects. When percentage of single cells increased, clump number and/or number of cells per clump generally decreased, helping to validate the assay. An example of these findings in 60 trials at 60 min with 1–3 mg sodium sulfate per ml deionized water: 1 mg 15% increased singles (p<0.01), 29% decreased clumps (p<0.01), 11% decreased cells per clump (p>0.05); 2 mg 12% increased singles (p<0.01), 20% decreased clumps (p<0.01), 30% decreased cells per clump (p<0.01); 3 mg 27% increased singles (p<0.01), 36% decreased clumps (p<0.01), 28 % decreased cells per clump (p<0.02).Here sodium sulfate showed promise as an anti‐cell‐clumping reagent together with sodium citrate reported previously (Amer J Applied Scientific Research 5: 28–34 March 2019). Sodium citrate is a known human anticoagulant (Platelets 29 (2018) 21–26) independently identified with this assay, helping to validate the assay for drug discovery applications.Support or Funding InformationSupported by California State University, Northridge, Department of Biology and Center for Cancer and Developmental Biology
Effect of Hypoxia on RAGE Signaling in Pancreatic Cancer
Authors: Taneja Sakshi , Vetter Stefan , Leclerc Estelle 
Published: April 2020

Pancreatic cancer (PC) is one of the deadliest cancers owing to its late diagnostic and poor response to chemotherapeutic agents. PC tumors are characterized by large hypoxic regions that contribute to tumor growth, formation of metastasis and resistance to chemotherapeutic agents. Studies have shown that the Receptor for Advanced Glycation End products (RAGE) is upregulated in hypoxic conditions. The goal of this study was to determine the effect of hypoxia on RAGE signaling in two pancreatic cancer cell lines (Panc‐1 and CFPAC). In particular we investigated if hypoxia dependent RAGE upregulation could aftect RAGE signaling and lead to NF‐κB activation. To interrogate RAGE signaling, we first investigated the effect of hypoxia on KRAS upregulation, as well as on ERK and NF‐KB activity levels by Western blot analysis. We use cobalt chloride to create hypoxic‐like conditions by stabilizing HIF‐1α in cells. We confirmed up‐regulation of HIF‐1α and RAGE in cells incubated with cobalt chloride. We also observed increased expression levels of KRAS in hypoxic‐like conditions. Additionally, higher levels of NF‐κB (p65) and of phosphorylated ERK were observed in cells treated with cobalt chloride as compared to untreated cells. In many cell types, RAGE signaling leads to NF‐κB activation resulting in further RAGE upregulation through a feedforward mechanism. Based on these observations, we hypothesize that in hypoxic conditions, stabilization of HIF‐1α leads to RAGE upregulation and signaling, resulting in NF‐κB activation through the activation of KRAS and ERK. We will use a small molecule RAGE inhibitor (FPS‐ZM1) to interrogate the role of RAGE in the proposed KRAS/ERK/NF‐κB pathway.Support or Funding InformationDepartment of Pharmaceutical Sciences, College of Health Professions, NDSU, NIH‐COBRE: P20GM109024
Effects of Gold Nanoparticles on Capillary Tube Formation with Special Reference to the Alteration of Pericyte Morphology and Function
Authors: Looprasertkul Sasikarn , Sereemaspun Amornpun , Jindatip Depicha 
Published: April 2020

Pericytes are perivascular cells that wrap around endothelial cells to form wall of capillaries and post‐capillary venules. These cells are primary importance in physiological and pathological processes, especially, involved in angiogenesis. At present, gold nanoparticles (AuNPs) were used for anti‐angiogenesis by inhibiting the activity of endothelial cell proliferation, migration, and tube formation. However, the effects of gold nanoparticles on the alteration of pericyte morphology and theirs function were not reported. Therefore, in this study, 20 nm‐AuNPs were applied to human placenta pericyte monoculture with concentration of 30 ppm. Morphology of pericytes was observed by transmission electron microscopy and cell migration was evaluated by transwell migration assay. Real‐time qRT‐PCR was used to determine Ki‐67, as a proliferation marker, and PDGFR‐β mRNA expression. Moreover, these AuNPs 30 ppm‐treated pericytes were co‐cultured with human umbilical cord endothelial cells on Matrigel® to investigate the 3D tube formation. The results revealed that AuNPs significantly suppressed migration, proliferation, and PDGFR‐β mRNA expression of pericytes. The ultrastructure of pericytes showed AuNPs in several organelles, i.e., swollen or damaged mitochondria, engulfed late endosomes and lysosomes. Moreover, the number of capillary tube formations was essentially reduced and we found that a number of pericytes on these capillary tubes were round shape and did not extend the processes along the tube, which in turn increased incomplete tube formation compared with the control. In conclusion, AuNPs could effect on pericyte biology including proliferation, migration, morphology, and tube formation property. Moreover, the results highlighted the potential application of AuNPs in anti‐angiogenesis by pericyte‐targeted therapy.Support or Funding InformationThe Ratchadaphiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number RA61/100 and Overseas Academic Presentation Scholarship for Graduate Students from the Graduate School, Chulalongkorn University
Developmental Changes in Total Cardiac mRNA: RNA Complicates Interpretation of Reference Genes
Authors: Jonker Sonnet S , Espinoza Herbert M 
Published: April 2020

Finding genes that do not vary with age for use as reference or “housekeeping” can be difficult, as can understanding what experimental gene normalization means in a developmental context. We analyzed expression levels of several potential reference genes in the developing sheep heart, as well as global myocardial mRNA levels compared to total nucleic acid levels. Total nucleic acid, total RNA, messenger RNA (mRNA), and individual gene levels were determined by spectroscopy, dot blot, and PCR. Results were analyzed by ANOVA followed by Tukey’s test, and results reported at P<0.05. Potential reference genes hyaluronidase 2, beta‐2‐microglobulin and ribosomal protein L37a were all found to vary by developmental age. The ribosomal RNA 18s did not vary with age. While total RNA relative to total nucleic acid was constant across development, mRNA was a greater fraction of total RNA in the late‐term fetal heart. These results demonstrate of the difficulty of interpreting normalization of myocardial mRNA expression levels across development.Support or Funding InformationR01HL142483