bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Eph Receptors and their Ligands in Palate
Authors: Serrano Maria J , Miguel Symone San , Sachar Ashneet , Svoboda Kathy , Benson M Douglas 
Published: June 2021

Cleft palate is one of the most common birth defects. Understanding of the molecular events in palate development is a prerequisite to more effective treatment of this condition. The hard palate of humans and mice forms from shelves of mesenchyme covered with a layer of epithelial cells. These shelves adhere at the midline to form the midline epithelial seam (MES). It has been well understood that epithelial to mesenchymal transition (EMT) and apoptosis in the MES require Transforming Growth Factor β3 (TGFβ3). Eph receptor tyrosine kinases and their ephrin ligands are responsible for many contact‐mediated developmental processes. Binding of ephrins causes receptor activation in Eph‐bearing cells (forward signaling), and intracellular signaling inside ephrin‐bearing cells (reverse signaling). We discovered that ephrin‐B reverse signaling is required for palate fusion and is sufficient to do so in the absence of TGFβ3 in chicken palates. This leads us to propose that ephrin reverse signaling directs palatal EMT and fusion. To find out, we dissected palatal shelves from chicken and mice at different embryonic stages of fusion. We isolated RNA from these tissues and performed reverse transcription‐PCR for a panel of Ephs and ephrins. We found that all but a few of those genes were present in both chicken and mouse palatal tissues. Our future work will spatially locate the mRNA to specific cell layers.Grant Funding Source : March of Dimes 6‐FY06‐321
Analysis of Junctions in RNA with Coaxial Stacked Helices
Authors: Fuhr Katherine Niccole , Laing Christian , Kim Namhee , Schlick Tamar 
Published: June 2021

The structure of RNA is hierarchical and complex. The secondary and tertiary structure is related to the function of RNA. In order to help predict the structure of RNA, analysis of motifs (commonly occurring interactions and sequences) must be done. In coaxial stacked helices of 3–10 way junctions, we measured the length (number of nucleotides) of the single strand, Ji/(i+1), which connects the two helices, and predicted that as the length of the single strand increases, that the distance between the midpoints of the terminal base pairs of the helices will also increase.Using the C1’ atom of each terminal base pair, we measure the respective midpoints and calculate the overall Euclidean distance. Use of Protein Data Bank data allowed us to gather the Cartesian coordinates of the atoms for use in our calculations. We analyzed junctions with degrees 3–10.We found that 3 and 4‐way junctions are highly correlated to the length of the single strand. We also found that frequency of coaxial stacks in junctions do not signify that there will be high correlation in a linear relationship. Outliers in the data often were involved in other interactions, such as RNA‐RNA complexes, RNA‐ligand complexes, and other factors such as unusual conformations.Further analysis of 3 and 4‐way junctions according to their respective family type gave us the normal distributions of lengths and how they correspond to the previously set parameters of the family. The distributions can act as a guide in synthesis for creating certain motifs in RNA. These results can be used in prediction software of RNA and can be further investigated as more RNA is discovered.
Mechanism of processive and cap‐stimulated mRNA poly(A) tail degradation
Authors: Virtanen Anders , Henriksson Niklas , Nilsson Per , Lindell Magnus 
Published: June 2021

Poly(A)‐specific ribonuclease (PARN) is an oligomeric, processive and cap‐interacting exoribonuclease that efficiently degrades mRNA poly(A) tails. PARN is a key regulator of AU‐rich element (ARE) containing mRNAs encoding proto‐oncogenes and cytokines. Here, we propose a mechanistic framework for PARN action. The model has been experimentally tested and is supported by structural evidence. In the model the RNA recognition motif (RRM) of PARN pushes the poly(A) tail into the active site, which simultaneously pulls the substrate into the hydrolytic site where the movement of a catalytically essential histidine residue is coordinated with the pushing of the RRM. The model provides a mechanistic explanation for how the cap‐structure of the mRNA can stimulate poly(A) tail hydrolysis. We have also investigated the functional significance of divalent metal ions in the active site and revealed that divalent metal ions are required for both hydrolysis and substrate translocation in the active site. Our data imply that three divalent metal ions are required for proper action. Two ions participate in hydrolysis while the third plays a key role during translocation. The generality of this proposal in relationship to other processive enzymes participating in cleavage or formation of phosphodiester bonds will be discussed.Supported by the Swedish Research Council and VR Linnaeus Support.
Investigation of 2‐Fold Disorder of Inhibitors and Relative Potency by Crystallizations of HIV‐1 Protease in Ritonavir and Saquinavir Mixtures
Authors: Olajuyigbe Folasade M. , Demitri Nicola , Geremia Silvano 
Published: June 2021

HIV‐1 protease (PR) was cocrystallized in competitive mixtures of saquinavir (SQV) and ritonavir (RTV) in an attempt to compare the relative potencies of inhibitors using a crystallographic approach. The mixture ratio of RTV/SQV was in the range of 1:1 to 50:1. The crystal form obtained with 1:1 and 5:1 ratios of RTV/SQV was monoclinic, while ratios 15:1 and 50:1 gave orthorhombic crystal form. The four crystal structures of PR/RTV/SQV were solved at 1.03, 1.12, 1.25, and 1.72 Å resolutions. The X‐ray crystal structures reveal that the crystal forms are dependent on the occupancy of either SQV or RTV in the active site of PR. At low RTV/SQV concentrations, PR/SQV complex is dominant, and at higher ratios, PR/RTV is found. The absence of a crystal structure having both inhibitors statistically disordered in the catalytic site of PR suggests that the two protein complexes are sufficiently different in properties to be discriminated in crystal growth process. The X‐ray structures of the dimeric enzyme with C2 pseudosymmetry show a 2‐fold‐disorder phenomenon for the SQV, while the RTV inhibitor is detected in a single orientation. The dominancy of PR/SQV crystal form at an equimolar mixture of inhibitor and the presence/absence of the 2‐fold disorder of inhibitors have given new insight into the relative potency of these drugs and both suggest a higher potency of SQV with respect to RTV.Research supported by Schlumberger FFTF.
Inhibition of cell growth by an elevated turnover number of melibiose/Na+ symport catalyzed by melibiose permease of Salmonella typhimurium
Authors: Jakkula S. Vivek , Hodkoff Alexey A. , Guan Lan 
Published: June 2021

Melibiose permease of Salmonella typhimurium (MelBSt) catalyzes melibiose/cation (H+, Na+ or Li+) symport. The transport mechanism is still poorly understood. Threading model indicates that a conserved Gly117 (helix IV) is part of the Na+‐binding site. Recently, mutation analyses suggested that Gly117 plays an important role in cation binding and translocation in MelBSt. In this study, we observed that Gly117→Cys MelBSt mutant drastically inhibited cell growth in the presence of melibiose in a concentration‐dependent fashion. The mutant G117C increased Vmax value for melibiose transport by >3 fold with little changes in Km and protein expression. A spontaneous mutation Pro148→Leu was isolated from mutant G117C. Strikingly, the double mutant G117C/P148L grew at a similar rate in the absence or presence of melibiose and also largely decreased the Vmax value, with 2‐fold lower than obtained from WT. A good correlation between the Vmax values and the cell‐growth rates in the presence of melibiose indicates that the Na+/melibiose symport dissipates cell membrane potential. With a largely elevated turnover number of melibiose transport, it is likely that the cotransported Na+ may collapse the membrane potential and inhibit cell growth.This work was supported by Texas Norman Hackerman Advanced Research Program 010674‐0034‐2009 to LG.
Receptor for Advanced Glycation End Products Functions as a Receptor for Glycosaminoglycans in Lung Metastasis
Authors: Sugahara Kazuyuki , Takahashi Jun , Mizumoto Shuji 
Published: June 2021

Glycosaminoglycans (GAGs) at cell surfaces of cancer cells play roles in malignant transformation and metastasis. Highly metastatic Lewis lung carcinoma cells showed a strong expression of the chondroitin sulfate E (CS‐E) epitope consisting of the E‐disaccharide unit GlcUA‐GalNAc(4, 6‐O‐disulfate). The metastasis was efficiently inhibited in a mouse system by enzymatic removal of CS from the tumor cell surface or by pre‐injection of CS‐E in a dose‐dependent manner (Li et al., J. Biol. Chem. 2008). These findings prompted us to investigate the roleof the CS and/or GAG structure of the tumor cells in the experimental lung metastasis.In this study to characterize CS‐E‐binding proteins in a mouse lung, an extract of a mouse lung homogenate was analyzed by affinity chromatography using a CS‐E‐immobilized column. A CS‐E‐binding putative receptor was identified as Receptor for Advanced Glycation End products (RAGE) by SDS‐PAGE followed by MALDI‐TOF‐MS of the trypsin digest of a protein band, suggesting that the E‐unit‐containing epitopes of CS chains as well as heparan sulfate chains at the tumor cell surfaces are recognized by RAGE in the lung, and are promising targets for diagnosis and therapy of malignant tumors (S. Mizumoto, J. Takahashi, and K. Sugahara, submitted).This work was supported by a Grant‐in‐aid for Scientific Research (B) and Future Drug Discovery and Medical Care Innovation Program from MEXT (to KS).
How to Structure Small Groups for Better Performance in Medical Biochemistry
Authors: Sadik Amina , Bondarenko Vladimir , Fulop Csaba 
Published: June 2021

Kolb's learning styles inventory was chosen to determine the best team settings for better small group performance in the Medical Biochemistry course.Students were randomly grouped in the first half of the course, and then regrouped based on their learning style in the second half.The majority of students belonged to the converging learning style followed by the assimilating style. The accommodating and diverging styles were rare.We compared grade changes in collaborative work; concept maps (CM) and group quizzes, as well as assignments not related to collaborative work; individual quizzes (IQ). Approximately, 41% of the students had better grades in all grade categories. Although similar number of students achieved better grades in CM and IQ, only 54% of the total number of students showed improvement in both, indicating no strong correlation between the two grades. In fact, most students (79%) improved their grades of the IQ.In teams formed by students of similar learning styles, the collaborative CM scores increased considerably; whereas their IQ scores did not seem to be affected significantly. The IQ scores of students belonging to diverse groups seemed to increase in the second part of the course. This finding might be due to the increased effort and/or familiarity with the assessment methods.
Anatomy taught integration of multiple image mediums, dissection and pathology reports with donor‐cadaver‐patients
Authors: Niemeyer Matt , Delamarter Taylor , Benninger Brion 
Published: June 2021

INTRODUCTIONIntegrating multiple imaging modalities from a donated‐cadaver‐patient (DCP) with graded dissection and pathology recognition provides realistic clinical anatomy experience. Imaging allows students to view dissected areas and discover pathologies. Student pathology reports reinforce anatomy and radiology learning. The objective of this study was to integrate DCP imaging, dissection and pathology to provide a realistic clinical anatomy experience.METHODSLiterature search was conducted regarding common multiple imaging modalities on DCPs during an anatomy course. Dissection and a pathology report were required.RESULTSLiterature search revealed no studies integrating multiple image mediums on DCPs during an anatomy course. Students analyzed DCP imaging, dissected and confirmed pathology.DISCUSSIONA vertical curriculum requires educators to integrate basic and clinical sciencesin order to develop critical thinking skills. Clinical anatomy could include radiology, surgical techniques and pathology. DCP was imaged using multiple common modalities, quality of dissection was assessed and pathology was confirmed. A DCP from this pilot study revealed bilateral popliteal aneurysms and Baker's cysts on imaging and during dissection.CONCLUSIONThis pilot study integrated radiology, dissection and pathology from DCP's to provide a realistic clinical anatomy experience.
The relationship between dietary intake and allergic disease in Korean adolescents: The Fourth Korea National Health and Nutrition Examination Survey (2007–2009)
Authors: Kim Hyesook , Kim Ki-Nam , Hur Jinhee , Kim Soyeon , Kim Yuri , Oh Se-Young , Kang Myung-Hee , Chang Namsoo 
Published: June 2021

We investigated the relationship between dietary factors and allergic disease (AD) in Korean adolescents, aged 12–18 years, using the data of the Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007–2009). From a total of 2,485 subjects, 112 had asthma, 269 atopy, and 354 either asthma or atopy. Adolescents with AD were found to consume more total energy. After adjusting for potential confounders, adolescents with AD were found to consume more energy from carbohydrates than those without. Among micronutrients iron intake was higher in subjects with AD than those without. When we further examined gender difference in the relationship between nutrient intake and AD, boys with AD consumed more energy from carbohydrates, and iron. Girls on the other hand, the relationship between nutrient intake and AD was not observed except for total energy intake. Further studies are needed to identify specific dietary patterns that are associated with AD in South Korean adolescents.This work was supported by the research grant (#911047‐1) from the projects for the ‘Globalization of Korean Foods’ and the Brain Korea 21 project.
Prevalence of multimorbidity among U.S. adults: data from the National Health and Nutrition Examination Survey
Authors: Staimez Lisa Rachel , Wei Melissa Y , Ramakrishnan Usha , Narayan K.M. Venkat , Saydah Sharon 
Published: June 2021

BackgroundChronic diseases have common modifiable risk factors, among them poor nutrition. Multimorbidity, the presence of two or more chronic diseases in an individual, and its associated risk factors have not been well characterized.MethodsWe analyzed data from non‐pregnant adults = 20 years in the National Health and Nutrition Examination Survey, 2003–2008. Cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD) and diabetes were based on self‐report. Chronic kidney disease (CKD) was computed using clinical parameters. Results were age‐standardized to the 2000 US census population.ResultsOf 13446 individuals with data on CVD, COPD, CKD and diabetes, 8.8% (standard error (SE), 0.3) had multimorbidity. Specifically, 6.6% (SE 0.2) had two diseases, 2.0% (SE 0.2) had three diseases, and 0.4% (SE 0.1) had four diseases, while 19.4% (SE 0.4) had one disease. CKD was most prevalent (15.5%, SE 0.4), then CVD (8.8%, SE 0.4), diabetes (7.8%, SE 0.4) and COPD (7.6%, SE 0.4). Multimorbidity was highest among adults >60 years (25.7%, SE 1.0), then 40–59 years (6.5%, SE 0.5) and 20–39 years (1.2%, SE 0.2). Multimorbidity was similar across sex.ConclusionsOne‐third of U.S. adults have at least one chronic disease, and about nine percent have two or more chronic diseases. Targeting common risk factors such as nutrition may have high impact on the prevention of multimorbidity.
Universal Adapter for Telecytopathology
Authors: Markovic Olivera , Markovic Nenad 
Published: June 2021

We present a prototype of a Universal Adapter to connect “any” microscope with “any” cellphone camera. It is intended to be used as an accessory medical device for wireless and digital telecytopathology – mass cervical cancer screening in particular.For the first time, at EB 2004, we presented our proprietary, biomarker‐based MarkPap® platform technology for detection of abnormal cells on cervical specimens. At the subsequent meetings we followed with further developments, from simple manual MarkPap® Test through semi‐automated processing, self‐home specimen's collection, to digital and mobile telecytopathology. The universal adapter has two platforms, one for the microscope and the other for cellphone cameras and has a capability for 4D movements to achieve the best optical conditions for image capturing.In case of mass cervical cancer screening, the health care providers (even low trained technicians) at the point of care processes the specimen with the customer‐friendly MarkPap® Kit, searches for biomarker‐highlighted abnormal cells, captures those images with cellphone camera using the adapter and forwards only those images for distant diagnosis. The result can be returned while women are still on the premises.This work is a part of our current project for development of simple, low‐cost medical devices for low‐resource areas worldwide.This work was supported by BioSciCon, Inc., Rockville, Maryland.
Biological characterization of THRX‐956485, a peripherally‐selective serotonin transport reuptake inhibitor
Authors: McConn Donavon , Tsuruda Pamela , McNamara Alexander , Hegde Sharath , Stangeland Eric 
Published: June 2021

Peripheral serotonin has been implicated in many therapeutic indications including thrombosis, pulmonary hypertension and osteoporosis. A peripheral selective serotonin reuptake inhibitor (SSRI) without CNS activity could provide a therapeutic index exceeding standard SSRIs. We describe a novel compound that selectively inhibits peripheral serotonin reuptake.THRX‐956485 is a potent (hSERT uptake IC50/binding Ki = 2.5nM/1.0nM) and selective SERT inhibitor in vitro and is >2500‐ fold selective over other reuptake transporters and serotonin receptors. In rat PK studies (single 5 mg/kg PO), or 14‐day osmotic mini‐pump infusions (0.3, 0.7 and 1.6 mg/kg/day), THRX‐956485 showed pronounced peripheral selectivity compared to a CNS‐penetrant SSRI, fluoxetine. Based on unbound CNS vs. plasma exposures and measured SERT occupancy ex vivo, THRX‐ 956485 was >20‐fold peripherally selective (CSF:unbound plasma concentration ratios varied from 1–5%). Additionally, THRX‐956485 demonstrated a dose‐dependent reduction in blood serotonin concentrations in rats. Following 14‐day infusions, blood serotonin concentrations decreased from 94 ng/mL (vehicle) to 43, 25, and 11 ng/mL at 0.3, 0.7 and 1.6 mg/kg/day, respectively. These findings are consistent with inhibition of platelet serotonin uptake, and suggest that THRX‐956485 is a peripherally selective SSRI.
Comparative Ultrasound: novel finger probe versus classic probe
Authors: Corbett Rebecca , Delamarter Taylor , Benninger Brion 
Published: June 2021

INTRODUCTIONUltrasonography (USS) is the stethoscope of the future. USS probes have evolved to improve structural identification. This study investigated a novel shaped probe used by first‐year medical students (FMS) conducting a clinical procedure.METHODSLiterature search was conducted on texts, specialty journals and websites regarding the use USS finger probe by FMS performing invasive techniques. FMS performed timed USS‐guided cannulation to the internal jugular (IJV) and subclavian (SCV) veins on a blue phantom torso, and identified them on a volunteer using a novel USS finger and a classic probe. A questionnaire asked about probe preference.RESULTSLiterature search revealed no studies comparing finger and classic probes, nor USS‐guided central line techniques being conducted by FMS. FMS identified and cannulated the IJV and SCV using both probes within 6 minutes with statistical significance. Questionnaire revealed FMS preferred the finger probe.DISCUSSIONUSS is a safe, non‐invasive imaging medium proven successful for invasive procedures. This study demonstrated FMS could interpret USS while conducting a common procedure. Finger probe proved successful in structure identification and was preferred to the classic probe due to its combined tactile presence.CONCLUSIONThis pilot study of a novel finger USS probe was successful identifying structures by FMS, suggesting future studies.
Formyl peptide receptor ligands exert differential effects on corticosterone secretion from the hypothalamo‐pituitary‐adrenal (HPA) axis
Authors: Naughton Vance Alexander , John Christopher David , Buckingham Julia Clare 
Published: June 2021

The stress response results in increased secretion of cortisol in man and corticosterone (CORT) in rodents. Our previous studies have identified roles for annexin A1 (ANXA1) and its receptor, a member of the formyl peptide receptor (FPR) family (possibly Fpr2) within the hypothalamus and pituitary gland in regulating CORT secretion. The FPRs are expressed in abundance in the adrenal gland but their role has not been determined. We hypothesised that FPRs contribute to the local mechanisms regulating CORT release. Adrenal glands from male Wistar rats (n = 6, 220 – 250 g) were dispersed in Earle's balanced salt solution (EBSS) and collagenase (95% O2, 5% CO2, 37 °C, 2 h) then stimulated (4 h) with a submaximal concentration of ACTH1–24 [Tetracosactide, 10−7 mol.L−1] in the presence and absence of various FPR ligands. ACTH stimulation resulted in a 60% increase in CORT release (P < 0.001). Versus basal release, fMLF (Fpr1), Ac2–26 (Fpr2/3), and 15‐epi‐LXA4 (Fpr3) were inhibitory, whereas F2L (Fpr2) was stimulatory (P < 0.001). Versus ACTH alone, ACTH‐stimulated CORT release was reduced in cells treated with fMLF [10−7], peptide Ac2–26 [10−7], and 15‐epi‐LXA4 [10−9] by 80%, but was increased in the presence F2L [10−10] by 50% (P < 0.001). Our work showed certain Fpr1/Fpr3 agonists inhibit adrenal CORT release whereas Fpr2 appears to be stimulatory.This was funded by the BBSRC.
Exercise‐induced increase in plasma volume and albumin content is enhanced by protein and CHO intake just after exercise
Authors: Okazaki Kazunobu , Takeda Ryosuke , Suzuki Akina , Naghavi Nooshin , Imai Daiki , Miyagawa Toshiaki 
Published: June 2021

Plasma volume (PV) expands with plasma albumin content (Albcont) after a bout of exercise, which is known to be enhanced by post‐exercise protein and CHO intake. It is unknown which is a key condition to enhance PV and Albcont expansion; the timing of protein and CHO intake after exercise or the total amount of daily protein and energy intake.METHODSSeven young men (~23 yrs) completed two trials those of which differ in the timing of intake (immediately after exercise, 0H; and 2.5 hours later, 2.5H) of a mixture of protein and CHO (3.2 kcal and 0.18 g protein/kg). Subjects performed a bout of 72‐min intense and intermittent exercise (8 sets of 4 min at 80% VO2max intermittent by 5 min at 20% VO2max) by using an upright cycling ergometer. PV and Albcont (PV x [plasma albumin concentration]) were determined before exercise, at the end of exercise, every hour from the 1st to the 5th hour and at the 23rd hour after exercise during.RESULTSIn 2.5H, Albcont and PV increased from before exercise by 0.5% and −3.5% at the 5th hour and by 1.6% and 1.8% at the 23rd hour, respectively. In 0H, on the other hand, Albcont and PV increased by 3.1% and −0.6% at the 5th hour and by 2.1% and 3.5% at the 23rd hour, respectively. The increase in Albcont and PV at the 5th and 23rd hour was significantly higher in 0H than in 2.5H.CONCLUSIONSProtein and CHO intake just after exercise is a key condition to enhance the increase in Albcont and PV.