bluuebunny/crossref_metadata_2025_split huggingface dataset:
From the Bench to the Bedside, the Determination of the Etiology of Dry Eye Using Spectroscopy
Authors: Borchman Douglas 
Published: April 2020

PurposeMeibum lipids are believed to be important to tear film stability, but tear film lipid compositional, structural and functional relationships are not well established.MethodsNMR, Fourier transform infrared and Bruster angle spectroscopies were used to quantify meibum lipid composition, structure, and film lipid rheology, respectively.ResultsThe molar ratio of Cholesterylesters/Wax ester increased with age, in cohorts aged 1 to 19 years old, respectively. The same molar ratio decreased for cohorts aged 20 to 88 years old with and without meibomian gland dysfunction (MGD) that leads to dry eye, respectively. The molar ratio of =C‐CH2 /ester increased with age for cohorts aged 1 to 19 years old, respectively. The same molar ratio decreased for cohorts aged 20 to 88 years old, with and without MGD, respectively. Compared with meibum from donors without dry eye, meibum from donors with MGD contained less straight‐chains, more iso‐branched chains, and the same amount of anteisobranched hydrocarbon chains. Human meibum order increases with age between 0 and 25 years old, meibomian gland dysfunction and with donors who have had hematopoietic stem cell transplantation. Interestingly, tear film stability also increases in the same order. When symptoms of dry eye were ameliorated with treatment, lipid order was restored. Principal component analysis scores correlated with age and dry eye by 93 %.ConclusionsThe changes in meibum composition with age and MGD contribute to the increase in lipid order of the same samples from donors without compared with those with MGD. Higher lipid order is associated with a higher reciprocal compressibility modulus that results in a tear film lipid layer that is not as compressible and not as viscoelastic. Strong lipid‐lipid interactions could contribute to the aggregation of tear film lipids and contribute to a decrease in tear film spreading and dry eye.Support or Funding InformationMajor support was obtained from the National Institute of Health [grant number EYO RO126180] and an unrestricted grant from Research to Prevent Blindness Inc. New York, NY, USA [grant number GN151619B].Lipid order or stiffness correlates with tear film stability with age and dry eye symptoms.Figure 1
Renal Interstitial Injection of a‐Trinositol Increases Renal Interstitial Hydrostatic Pressure (RIHP) but Does Not Modify its Low Frequency Oscillatory Pattern
Authors: Rodríguez-Martínez Manuel , López-Rodriguez Juan Francisco , Flores-Sandoval Omar , Silva-Ramírez Ana Sonia , Guerrero-Ojeda Vianney 
Published: April 2020

RIHP increases after renal interstitial medullary injection (RIMI) of a 5μ bolus of saline solution (SS) + 2 μM α‐Trinositol (α –T, drug that increases collagen fiber network contraction, FASEB J 31:701.4: 2017). To assess whether this increase is induced by changes in the frequency and/or amplitude of oscillatory pattern of RIHP we evaluate in hydropenic rats the time course of RIHP before and after either an acute sham (CTR group, n = 9) or an acute (1s) real RIMI of a 5μ bolus of either vehicle (0.9% SS, SS group, n = 9) or SS + 2 μM α ‐ T (α – T group, n = 9). Left subcapsular RIHP (RIHP) was continuously measured (1 Hz) in anesthetized rats with right nephrectomy, acute left renal denervation, hormonal clamp and renal perfusion pressure control (100 mmHg), before (baseline phase = BL = 30 min) and 30 min after (experimental phase = EXP) sham or real RIMI of 5 μl bolus of either SS or SS + α‐T. The table
shows the 30 min average BL RIHP (1800 s, s = samples or seconds), ΔRIHP (EXP RIHP – BL RIHP) values (mean ± SEM) obtained 30 min after sham or real RIMI during 300 s. It also shows the RIHP frequency (F) of major oscillations (cycles/min = cpm) and the standard deviation (SD, an oscillatory amplitude index) of global RIHP oscillation before and 30 min after RIMI. Three were no differences among groups in BL RIHP, F or SD. For ΔRIHP data there were time * group interaction effect (P < 0.009); * P = 0.05, ** P < 0.001 vs. BL; • P < 0.04 vs. SS group, ¨P < 0.001 vs. CTR group. For SD data ° P <0.001 between phases.CONCLUSIONSThe results show that RIHP oscillates at an equally low frequency (≈ 0.03 Hz) before and after sham or real RIMI but with lower amplitude after sham or real RIMI in any of the groups. This suggests that α‐T increases RIHP but not through modify the frequency or amplitude of its low frequency oscillatory pattern.Support or Funding InformationOwn financial resources of Integrative Physiology Lab.

RIHP

RIHP

RIHP

(mmHg)

Frequency

SD

Delta

cpm

(mmHg)

BL

EXP‐BL

BL

EXP

BL

EXP

30 min

at min 30

last 5 min

at min 30

30 min

at min 30

Group

1800 s

300 s

300 s

300 s

1800 s

300 s

CTR

3.0 ± 0.10

−1.1 ± 0.16

2.2 ± 0.26**

2.1 ± 0.26

0.54 ± 0.07

0.20 ± 0.04°

SS

3.1 ± 0.03

−0.15 ± 0.36

2.1 ± 0.44

2.2 ± 0.46

0.50 ± 0.06

0.18 ± 0.03°

a‐T

3.1 ± 0.06

1.26 ± 0.51

2.2 ± 0.32*•♦

2.2 ± 0.25

0.35 ± 0.04

0.19 ± 0.04°
Ablation of RAGE Attenuated Cardiac Fibrosis by Inhibition of Autophagy medicated Endothelial‐to‐mesenchymal transition
Authors: ZHANG LU , HE JIAQI , LIANG BIRONG , XIAN SHAOXIANG , WANG LINGJUN 
Published: April 2020

Endothelial‐to‐mesenchymal transition (EndMT) has been found involved in the progression of heart failure (HF), which maybe one of the source of myofibroblasts. Emerging evidence support the notion that EndMT was regulated by autophagy. Our previous studies demonstrated deletion of receptor for advanced glycation end products (RAGE) inhibited autophagy and attenuated cardiac fibrosis in HF. Thus, here we investigated whether reduction of cardiac fibrosis by ablation of RAGE was through inhibition autophagy medicated EndMT. Using transverse aortic constriction (TAC) in mice as a model of pressure overload induced HF, we demonstrated that EndMT and autophagy were induced simultaneously at 8 weeks after TAC. Co‐localization of CD31 and α‐smooth muscle actin (α‐SMA) was observed in myocardium. Knockout of RAGE displayed reduced cardiac fibrosis and significantly improved cardiac function in TAC mice. Importantly, knockout of RAGE deceased the expression of autophagy related proteins (LC3BII/I and Beclin1), which was accompanied with the decrease of co‐expression of CD31 and α‐SMA in TAC mouse hearts. Moreover, 3‐methyladenine (3‐MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT and cardiac fibrosis in TAC mice. Taken together autophagy inducing EndMT may contribute to the development of cardiac fibrosis. Inhibition of this process by RAGE deletion lead to cardiac function improvement and reduction of cardiac fibrosis. Thus, we concluded that inhibition of the RAGE‐autophagy‐EndMT axis could be a novel strategy for treatment of heart failure.Support or Funding InformationThe National Natural Science Foundation of China (81373570, 81673920, 81473621, 81673796 and 81973776). The Natural Science Foundation of Guangdong Province(2016A030311030).Reduction of cardiac fibrosis especially cardiovascular fibrosis after TAC by inhibition of RAGE and autophagy (Scale bar= 1,000 μm. n = 4. Values are shown as means ± SEM, *P < 0.05 vs Sham group, #P < 0.05 vs TAC group.)Figure 1Deceased expression of autophagy and EndMT after TAC by inhibition of RAGE and autophagy. (n = 4. Values are shown as means ± SEM, *P < 0.05 vs Sham group, #P < 0.05 vs TAC group.)Figure 2
The Behavioral Effects of Omitting the α1T gene in Drosophila
Authors: Tran Kristen , Cheng Ryan , Luu Richard , Iniguez Jorge 
Published: April 2020

Voltage gated calcium channels regulate calcium influx and vesicular release of neurotransmitter at chemical synapses. In Drosophila, there are three genes, Dmca1D, 1A, and α1T encoding Cav1, Cav2 and Cav3‐type channels respectively. Studies have shown that the α1T channels are important in regulation of action potential firing in Drosophila at the neuromuscular junction and the central nervous system. The α1T has been shown to be expressed across the adult fly brain. These include sensory neuropils, motor‐associated neuropils, and neuropils associated with learning and memory. We explored the role the α1T gene in adult Drosophila plays in motor‐associated activity using a locomotor assay. Our data suggests that the α1T gene knockout results in a defect in regulating excitability in adult Drosophila that manifests in altered motor activity. Using a T‐maze assay, the Drosophila are exposed to two different odors separately: 3‐Octanol with no electric current, and 4‐Methylcyclohexanol (MCH) administered with electric currents. Exposure to MCH with electric currents will create a negative association towards MCH and condition the flies to favor 3‐Octanol. The flies without the α1T gene are expected to be greatly impacted in their capability to build a negative connotation towards MCH, when compared to flies with the α1T gene.Support or Funding InformationBuild PoderNational Institute of HealthPasadena City CollegeT‐MazeThis figure illustrates how the Drosophila will favor the 3‐Octanol odor over the 4‐Methylcyclohexanol (MCH) odor.Figure 1
The phases that separate RNA and transcription
Authors: Schwartz Jacob C. 
Published: April 2020

RNA‐binding proteins recruited to nascent transcripts have the ability to regulate transcription and to spontaneously assemble into granule bodies through a process referred to as phase separation. These proteins, such as FUS (Fused in sarcoma) and EWS (Ewing sarcoma related 1), are endowed with these two abilities through domains that have low‐complexity amino acid sequences and are intrinsically disordered. Despite recent progress dissecting the biophysical principles underlying protein phase separation, its contribution to RNA‐processing and transcription has remained obscure. We have found that these proteins do assemble into granules that are associated with RNA polymerase II in cells. The formation of these granules and their association with the polymerase is dependent on transcription activity itself. Surprisingly, when transcription and phase separation is recombined in vitro, we have uncovered that at least one such protein, FUS, not only affecting transcription through its direct interactions with the transcription machinery but also by sequestering RNA structures that can hinder progress of the polymerase. Taken together, the role these proteins play and their peculiar RNA‐binding and phase separating properties provide a sophisticated mechanism to concentrate transcription and RNA‐processing machinery at genes and possibly to coordinate crosstalk between transcription and the maintenance of chromosome integrity.Support or Funding InformationNational Institutes of Health (NIH), American Cancer Society (ACS)Figure 1
Functional antagonism between p53 and WWOX in vivo leads to protein aggregation in the brain
Authors: Chang Nan-Shan , Chou Pei-Yi , Lin Sing-Ru , Lee MIng-Hui , Schultz Lori , Sze Chun-I 
Published: April 2020

Tumor suppressor WW domain‐containing oxidoreductase WWOX is a newly defined risk factor for Alzheimer’s disease (AD) in 2019. We discovered WWOX in 2000 and have been working on how WWOX blocks AD progression since then. We reported that WWOX starts to downregulate in the brain cortex and hippocampus in the middle‐aged normal individuals. Consequently, a likely scenario of slow activation of a protein aggregation cascade occurs with age as shown in the normal and AD brains as follows: 1) TRAPPC6AΔ, TIAF1 and SH3GLB2 aggregation, 2) caspase activation and APP degradation, and 3) final aggregation of amyloid β and Tau. The protein aggregation event may last 20 to 30 years and even longer. Here, we identified a tumor suppressor WWOX/TIAF1/p53 triad, which is potent in cancer suppression by blocking cancer cell migration, anchorage‐independent growth and SMAD promoter activation, and causing apoptosis. Yet, when p53 functionally antagonizes with WWOX in the mouse brain, p53 blocks WWOX‐mediated inhibition of inflammatory immune response induced by cancer, and this leads to protein aggregation in the brain as seen in AD and other neurodegeneration. The aggregated proteins include APP, amyloid β, neurofibrillary tangles (or tangled tau), p‐ERK and α‐tubulin. Together, we have discovered for the first time that WWOX limitation of neurodegeneration is blocked by p53 under inflammatory conditions in vivo.Support or Funding InformationMinistry of Science and Technology, Taiwan, Department of Defense, USA, and National Health Research Institutes, Taiwan.Summary illustration. Three scenarios account for cancer growth or suppression: 1) loss of WWOX, p53 and TIAF1 increases cancer growth and metastasis; 2) stabilized p53/WWOX/TIAF1 triad suppresses cancer growth, inhibits metastasis, and induces apoptosis; 3) functional antagonism between p53 and WWOX allows cancer cell growth and yet induces inflammation for causing neural protein aggregation as seen in the Alzheimer’s disease.Figure 1
OvoceutinTM Attenuates Diarrhea Caused by Porcine Epidemic Diarrhea Virus in Piglets
Authors: Talukder Jamil , Srivastava Ajay , Rajamanickam Darwin , Lall Rajiv 
Published: April 2020

BackgroundPorcine epidemic diarrhea virus (PEDV), a coronavirus, infects the small intestinal epithelium of a pig. Older hogs mostly get sick and lose body weight after being infected, whereas newborn piglets usually die within five days of contracting the virus due to enteritis, severe diarrhea, and dehydration. PEDV is highly infectious, resulting in significant morbidity and mortality in piglets ‐ approaching 100% in suckling piglets, which leads to substantial economic burden on pig farms. Controlling enteritis, diarrhea, and dehydration in piglets remains a great challenge to reduce mortality. Lactoferrin and ovotransferrin are iron‐binding multifunctional glycoproteins belonging to the transferrin family, which not only prevent diarrhea but also function as antibacterial, anti‐inflammatory, anti‐viral, etc. In addition, ovotransferrin (OvoceutinTM) has been shown to bind with Marek’s disease virus to block binding with host cell in poultry. Thus, Ovoceutin may play important roles in enteritis and diarrhea in PEDV‐piglets.AimDetermine the effects of Ovoceutin on diarrhea caused by PEDV in piglets.MethodsPigs on a farm were diagnosed with PEDV in Wisconsin, USA. Newborn piglets showing severe diarrhea were divided into five groups with five piglets in each group. Ovoceutin was made at an in‐house facility of Vets Plus, Inc. The control group received only electrolytes in 50ml of lukewarm water (EW); treated groups received 1 or 2.5g of Ovoceutin and water, or along with EW, twice a day for five consecutive days. Consistency of feces was scored as watery to solid (1–5), and physical conditions were scored as laying down (1), no response to caretaker (2), or walking (3).ResultsThe control group (EW) showed poor survival rate (40%) while 2.5g of Ovoceutin‐water treated group had a higher survival rate (80%), better fecal score, and physical conditions. EW‐2.5g of Ovoceutin group showed the highest survival rate (100%), best fecal, and physical condition scores.ConclusionsWe conclude from these results that OvoceutinTM attenuates diarrhea in PEDV‐piglets and can be used to improve piglets’ digestive health.Support or Funding InformationResearch and Development Fund, Vets Plus, Inc.Effect of OvoceutinTM in diarrhea caused by Porcine Epidemic Virus Diarrhea in newborn piglets.Figure 1
3D pdb Structures as Native 3D Models into MS PowerPoint
Authors: Ouellet Jonathan 
Published: April 2020

An effective way to transmit knowledge is to share an image. In fields such as astronomy, engineering, morphology or biochemistry, the plain 2D paper format has limitations on the visualization of objects in 3D.Innovations such as 3D PDF from Adobe allowed publishers to integrate 3D objects into pdf while many researchers create 360‐degrees rotation movies of their molecule of interest. Still, the lack of easy insertion of 3D objects in common files makes the 3D visualization hard to share.In January 2018, Microsoft Office (MSO) introduced a new option within its Insert Menu by adding 3D Models. Stock 3D models can be added, rotated and animated. More importantly, multiple 3D file formats can be incorporated.This focus of this presentation is to demonstrate a “How to” guide to easily convert a pdb structure to a 3D format which is compatible with MSO. Such 3D model are lightweight, easy to create and very easy to share.Procedure to import pdb structures into MS PowerPointFigure 1
Maternal Exposure to Non‐nutritive Sweeteners Impacts Progeny’s Metabolism and Microbiome
Authors: Van Stichelen Stephanie Olivier , Rother Kristina I. , John Hanover A. 
Published: April 2020

Non‐nutritive sweeteners (NNS e.g. Splenda, Sweet’N’Low, Equal, Stevia, …) are highly prevalent in the diet of United States adults and children and are found in beverages, yogurt, cocoa powder, coffee sweeteners, medicine and kid electrolyte solution (Pedialyte). They are marketed as sugar alternatives providing sweet taste with few or no calories. First thought to be harmless, a growing number of research studies now questioning the safety of NNS consumption. In the past decades, NNS have been shown to alter gut hormonal secretion, glucose absorption, appetite, kidney function, insulin secretion, adipogenesis and gut microbiota. The wide range of action associated by NNS exposure is likely linked to their binding to the sweet taste receptor, found not only on the tongue but also in the intestines, lungs, bones, adipose tissue and testis.However, to date, the effects of NNS on early development are incompletely understood. In critical stage such as embryonic/ fetal development, small exposures can be serious as demonstrated for alcohol consumption or smoking. While there are many specific recommendations during pregnancy or lactation for various products, there are no guidelines for NNS consumption. Furthermore, it is interesting to know that only one of four parents are able to correctly identify NNS on food product suggesting that many are consuming NNS involuntarily Interestingly, at least 10 different studies demonstrated an association between increased BMI and NNS consumption suggesting a significant association in children. Furthermore, despite known transmission through amniotic fluid and breast milk, the impact of NNS on early metabolic development remains largely unknown.To answer this question, we exposed pregnant and lactating mice to NNS (sucralose, acesulfame‐K) at doses relevant for human consumption (Acceptable Daily Intake). While the pups’ exposure seemed minimal, metabolic changes were drastic, indicating extensive down‐regulation of hepatic detoxification mechanisms and changes in bacterial metabolites. Microbiome profiling confirmed a significant increase in firmicutes and a striking decrease of Akkermansia muciniphila. Similar microbiome alterations in humans have been linked to metabolic disease and obesity. Our finding corroborates the existing literature but required considerably shorter NNS exposure (only ~40 days). Therefore, we concluded that pregnancy is a vulnerable time for exposing offspring to NNS. While our findings need to be reproduced in humans, they suggest that NNS consumption during pregnancy and lactation have adverse effects on infant metabolism and potential predisposition to metabolic deregulation later in life.Summary figure of the effect of sucralose and acesulfame‐K consumption during pregnancy and lactation.Figure 1
Cardiac Autonomic Neuropathy and Hemodynamic Dysfunction as a Consequence of Mild Hypercaloric Intake: Modification by Phosphate Supplementation
Authors: Ajouz Ghina MohammadNabil , Dwaib Haneen Salem , Mougharbil Nahed , Mroueh Ali , Refaat Marwan , Obeid Omar , El-Yazbi Ahmed 
Published: April 2020

Cardiac autonomic neuropathy (CAN) has been linked to negative outcomes in diabetic patients, where it is associated with a high risk of cardiac arrhythmia and sudden death. Our previous research showed that prediabetic rats develop CAN in absence of overt signs of metabolic derangement or change in body weight. This was associated with vascular dysfunction and perivascular adipose tissue (PVAT) inflammation, which preceded inflammatory changes in other adipose pools, possibly linked to increased Uncoupling protein 1 (UCP1) and hypoxia‐inducible factor (HIF1‐a) expression. In parallel, phosphate supplementation is a simple intervention to improve body weight, energy metabolism, and glucose tolerance. Moreover, inorganic phosphate acts as a UCP1 inhibitor. Here, we examined the role of phosphate supplementation in ameliorating the early signs of cardiovascular dysfunction in metabolically challenged rats. Male SD rats (5–6 weeks) were randomly allocated into four groups fed either control diet (group 1) or high‐calorie (HC) diet for 12 weeks with three different levels of dietary phosphate; group 2: low phosphate (LP)‐ 0.37 mg/KCal, group 3: intermediate phosphate (IP)‐0.7 mg/KCal, group 4: high phosphate (HP)‐ 1.5 mg/KCal. Daily food intake, body weight, and body composition were recorded. Serum insulin was measured by ELISA. Invasive hemodynamic measurements were done and baroreceptor sensitivity (BRS) was assessed by the vasoactive method. After sacrifice, organs were collected for immunohistochemistry and western blotting. No changes in caloric intake, body weight, blood pressure, and blood glucose levels were observed. However, rats on HC diet showed an increase in serum insulin level and fat/lean ratio. Consistent with our previous work, HC‐feeding was associated with significant reduction in parasympathetic BRS in both the LP and IP groups. This was also accompanied by a reduced left ventricular systolic function. On the cellular level, Oil Red O stain showed a significant increase in the diameter of PVAT adipocytes in LP condition, together with increased expression of HIF‐1α, IL‐1β and UCP‐1. Of note, inflammatory changes observed in the PVAT were not detected in neither white nor brown adipose tissue. Furthermore, higher macrophage infiltration and total ROS score in the PVAT, heart mid‐section and brainstem were observed in LP when compared to control. Our present results highlight a role of phosphate supplementation in the amelioration of the HC induced parasympathetic dysfunction. This could be due to the reported ability of dietary phosphate to improve the assimilation of fat and reduce adipose tissue hypoxia possibly via UCP1 inhibition.Support or Funding InformationFunded by an AUB CRS grantIL1‐UCP1 for perivascular adipose tissue (PVAT), white adipose tissue (WAT), and brown adipose tissue (BAT)Figure 1