bluuebunny/crossref_metadata_2025 huggingface dataset:
Areas of endemism of small mammals are underprotected in the Atlantic Forest
Authors: Dalapicolla Jeronymo , Abreu Edson Fiedler , do Prado Joyce Rodrigues , de Almeida Chiquito Elisandra , de Oliveira Roth Paulo Ricardo , de Góes Brennand Pamella Gusmão , Pavan Ana Carolina D’Oliveira , Pereira Alex , Mendes Fabiana Rocha , del Valle Alvarez Martin Roberto , Rios Élson Oliveira , Cassano Camila Righetto , Miretzki Michel , Vélez Felipe , da Paixão Sevá Anaiá , Percequillo Alexandre Reis , Bovendorp Ricardo Siqueira
Published: June 2021

Atlantic Forest (AF) is amongst the most threatened forests in the world. To decide where conservation efforts should be focused to preserve species, assessment of ecological and biogeographic processes nowadays are crucial. Patterns of the distribution of organisms can provide an important source of information underlying the biogeographical history of a biota. Here, our main objective was to identify Areas of Endemism (AoE) for non-volant small mammals in the AF and to investigate if those AoE are covered by protected areas. We performed quantitative and qualitative approaches to delimit AoE and calculated the area overlaid by Conservation Units (CU) within each AoE. Our results supported the recognition of seven AoE for small mammals in the AF, which largely are congruent with previous studies undertaken on other organisms, thereby highlighting the importance of those regions as hotspots of endemism. Most of the AoE recovered in the present study have less than 12% of their territory covered by forest remnants, and less than 11% of their entire range is under legal protection. These findings bring to light an important discussion on how information pertaining to the representativeness of CU within regions of high endemicity could help to identify areas in need of urgent protection within a threatened biodiversity hotspot.
Re-evaluation of prophylactic cranial irradiation in limited-stage small cell lung cancer: a propensity score matched analysis
Authors: Inoue Yuko , Tsujino Kayoko , Sulaiman Nor Shazrina , Marudai Mitsuru , Kajihara Akifumi , Miyazaki Shuichiro , Sekii Shuhei , Uezono Haruka , Ota Yousuke , Soejima Toshinori
Published: June 2021

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups’ backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve.
Mirizzi syndrome type V complicated with both cholecystobiliary and cholecystocolic fistula: a case report
Authors: Rizzo Giacomo E M , Rizzo Giovanna , Di Carlo Giovanni , Corbo Giovanni , Ferro Giuseppina , Sciumè Carmelo
Published: June 2021

Mirizzi syndrome (MS) is a common bile duct (CBD) obstruction caused by extrinsic compression from an impacted stone in the cystic duct or infundibulum of the gallbladder. Patients affected by MS may present abdominal pain and jaundice. A 37-year-old male with neurologic residuals post-encephalitis arrived at the emergency department reporting abdominal pain, jaundice and fever. An ultrasound of the abdomen identified cholecystolithiasis with a dilated CBD. He did not undergo CT or MRI due to poor compliance and parents’ disagreement. Eventually, they accepted to perform endoscopic retrograde cholangiopancreatography, which diagnosed MS with both cholecystobiliary and cholecystocolonic fistula without gallstone ileum (type Va). Therefore, patient underwent cholecystectomy, wedge resection of the colon and choledochoplasty with ‘Kehr's T-tube’ insertion. A plastic biliary stent was successively placed and removed after 4 month. Ultimately, he did neither complain any other biliary symptoms nor alteration in laboratory tests after 4-years of follow-up.
Transcriptional, hormonal, and metabolic changes in susceptible grape berries under powdery mildew infection
Authors: Pimentel Diana , Amaro Rute , Erban Alexander , Mauri Nuria , Soares Flávio , Rego Cecília , Martínez-Zapater José M , Mithöfer Axel , Kopka Joachim , Fortes Ana Margarida
Published: June 2021

Grapevine (Vitis vinifera) berries are extremely sensitive to infection by the biotrophic pathogen Erysiphe necator, causing powdery mildew disease with deleterious effects on grape and wine quality. The combined analysis of the transcriptome and metabolome associated with this common fungal infection has not been previously carried out in any fruit. In order to identify the molecular, hormonal, and metabolic mechanisms associated with infection, healthy and naturally infected V. vinifera cv. Carignan berries were collected at two developmental stages: late green (EL33) and early véraison (EL35). RNA sequencing combined with GC–electron impact ionization time-of-flight MS, GC–electron impact ionization/quadrupole MS, and LC–tandem MS analyses revealed that powdery mildew-susceptible grape berries were able to activate defensive mechanisms with the involvement of salicylic acid and jasmonates and to accumulate defense-associated metabolites (e.g. phenylpropanoids, fatty acids). The defensive strategies also indicated organ-specific responses, namely the activation of fatty acid biosynthesis. However, defense responses were not enough to restrict fungal growth. The fungal metabolic program during infection involves secretion of effectors related to effector-triggered susceptibility, carbohydrate-active enzymes and activation of sugar, fatty acid, and nitrogen uptake, and could be under epigenetic regulation. This study also identified potential metabolic biomarkers such as gallic, eicosanoic, and docosanoic acids and resveratrol, which can be used to monitor early stages of infection.
At the root of quiescence: function and regulation of the quiescent center
Authors: Strotmann Vivien I , Stahl Yvonne
Published: June 2021

The quiescent center (QC) of roots consists of a rarely dividing pool of stem cells within the root apical meristem (RAM). The QC maintains the surrounding more frequently dividing initials, together constituting the stem cell niche of the RAM. The initials, after several rounds of division and differentiation, give rise to nearly all tissues necessary for root function. Hence, QC establishment, maintenance, and function are key for producing the whole plant root system and are therefore at the foundation of plant growth and productivity. Although the concept of the QC has been known since the 1950s, much of its molecular regulations and their intricate interconnections, especially in more complex root systems such as cereal RAMs, remain elusive. In Arabidopsis, molecular factors such as phytohormones, small signaling peptides and their receptors, and key transcription factors play important roles in a complex and intertwined regulatory network. In cereals, homologs of these factors are present; however, QC maintenance in the larger RAMs of cereals might also require more complex control of QC cell regulation by a combination of asymmetric and symmetric divisions. Here, we summarize current knowledge on QC maintenance in Arabidopsis and compare it with that of agriculturally relevant cereal crops.
Crater morphology of primordial black hole impacts
Authors: Yalinewich Almog , Caplan Matthew E
Published: June 2021

In this work, we propose a novel campaign for constraining relativistically compact massive compact halo object (MACHO) dark matter, such as primordial black holes (PBHs), using the Moon as a detector. PBHs of about 1019  to 1022 g may be sufficiently abundant to have collided with the Moon in the history of the Solar system. We show that the crater profiles of a PBH collision differ from traditional impactors and may be detectable in high-resolution lunar surface scans now available. Any candidates may serve as sites for in situ measurements to identify high-pressure phases of matter which may have formed near the PBH during the encounter. While we primarily consider PBH dark matter, the discussion generalizes to the entire family of MACHO candidates with relativistic compactness. Moreover, we focus on the Moon since it has been studied well, but the same principles can be applied to other rocky bodies in our Solar system without an atmosphere.
Electron temperature fluctuations in Seyfert galaxies
Authors: Riffel Rogemar A , Dors Oli L , Krabbe Angela C , Esteban César
Published: June 2021

We use Gemini GMOS-IFU observations of three luminous nearby Seyfert galaxies (Mrk 79, Mrk 348, and Mrk 607) to estimate the electron temperature (Te) fluctuations in the inner 0.4–1.1 kpc region of these galaxies. Based on Te determinations through the [O iii]λ5007/λ4363 emission line ratio of each spaxel, temperature variations are quantified by computing the integrated value of the temperature fluctuation parameter (t2) projected in the plane of the sky $t_{\rm A}^{\rm 2}$, for the first time in active galactic nuclei (AGNs). We find $t_{\rm A}^{\rm 2}$ values of 0.135, 0.039, and 0.015 for Mrk 79, Mrk 348, and Mrk 607, respectively, which are of the same order or larger than the maximum values reported in star-forming regions and planetary nebulae. Taking into account that $t_{\rm A}^{\rm 2}$ should be considered a lower limit of the total t2 in the nebular volume, the results suggest that the impact of such fluctuations on chemical abundance determinations can be important in some AGNs.
Application of Augmented Reality in Percutaneous Procedures—Rhizotomy of the Gasserian Ganglion
Authors: Rau Alexander , Roelz Roland , Urbach Horst , Coenen Volker Arnd , Demerath Theo , Reinacher Peter Christoph
Published: June 2021

BACKGROUND

Percutaneous rhizotomy of the Gasserian ganglion for trigeminal neuralgia is an effective therapeutic procedure. Yet, landmark-guided cannulation of the foramen ovale is manually challenging and difficult to learn.

OBJECTIVE

To overcome these limitations, we assessed the feasibility and accuracy of an augmented reality (AR)-guided puncture of the foramen ovale.

METHODS

A head phantom with soft tissue structures of the facial area was built. A three-dimensional (3D)-dataset of the phantom was generated using a stereotactic planning workstation. An optimal trajectory to the foramen ovale was created and then transferred to an AR headset. A total of 2 neurosurgeons and 2 neuroradiologists independently performed 8 AR-guided and 8 landmark-guided cannulations of the foramen ovale, respectively. For each AR-guided cannulation, the hologram was manually aligned with the phantom. Accuracy of the cannulation was evaluated using the Euclidean distance to the target point as well as the lateral deviation of the achieved trajectory from the planned trajectory at target point level.

RESULTS

With the help of AR guidance, a successful cannulation of the foramen ovale was achieved in 90.6% compared to the purely landmark-based method with 18.8%. Euclidean distance and lateral deviation were significantly lower with AR guidance than landmark guidance (P < .01).

CONCLUSION

AR greatly improved accuracy of simulated percutaneous rhizotomy of the Gasserian ganglion.
Microsurgical Clip Reconstruction of a Ruptured Internal Carotid Artery Terminus Blister Aneurysm Using a Reverse Picket Fence Technique
Authors: Glauser Gregory , Detchou Donald K E , Choudhri Omar A
Published: June 2021

BACKGROUND

Blister aneurysms are rare, technically challenging lesions that are typically ill defined and arise at nonbranch points of arteries.

OBJECTIVE

To describe the microsurgical treatment of a ruptured blister aneurysm at the internal carotid artery (ICA) terminus using the reverse picket fence clipping technique.

METHODS

The patient was a 60-yr-old male. He presented with a Hunt and Hess Grade 2, Fisher Grade 3 subarachnoid hemorrhage located in the bilateral sylvian fissures (right > left) and suprasellar cisterns. Computed tomography angiography demonstrated 2 aneurysms: a 2-mm right middle cerebral artery (MCA) aneurysm and a 2.5-mm right internal carotid artery (ICA) terminus blister aneurysm. Transradial cerebral angiography was undertaken which showed these similar sized aneurysms. Microsurgical treatment was chosen, and the patient underwent a right pterional craniotomy for clipping of his aneurysms. The patient consented to the procedure.

RESULTS

The combination of stacked fenestrated clips repaired the vessel, with intraoperative fluorescein and indocyanine green angiography demonstrated normal filling of the MCA and ICA circulation with no delay. Intraoperative angiography confirmed induced moderate stenosis of the ICA terminus at about 50%, which is essential to close the blister aneurysm site by utilizing a portion of the normal vessel wall.

CONCLUSION

Ruptured blister aneurysms at the ICA terminus can be safely repaired using the reverse picket fence technique for clipping.
Acartia arbruta (previously A. tonsa) in British Columbia: a bioindicator of climate-driven ecosystem variability in the northeast Pacific Ocean
Authors: Smith Julian A C , Galbraith Moira , Young Kelly , Perry R Ian , Sastri Akash , Nelson R John
Published: June 2021

Climate change is driving biogeographic shifts in marine zooplankton. In the northeast (NE) Pacific, the distribution of the estuarine copepod, Acartia tonsa ( Dana, 1849), is generally limited to California except during marine warming events where it is found as far north as British Columbia (BC). Documentation of such events relies on accurate species identification. Phylogenetic reconstruction of the genus Acartia using 768 mitochondrial cytochrome oxidase subunit I Deoxyribonucleic Acid (DNA) sequences collected worldwide demonstrates that NE Pacific A. tonsa is distinct from all conspecifics and congeners. Males of NE Pacific A. tonsa are larger with slight differences in the fifth pair of legs as compared to geographically isolated conspecifics. Accordingly, we propose NE Pacific A. tonsa be reclassified to Acartia arbruta. Analysis of mitochondrial 16S ribosomal RNA DNA sequences from 154 specimens of A. arbruta collected from California, Oregon and BC suggests that A. arbruta detected in BC is a mixture of southern populations. Southern populations are likely driven north during “warm” phases of the oceanographic processes indexed by the Pacific Decadal Oscillation, which is positively correlated with A. arbruta biomass anomalies on the continental shelf of Vancouver Island, BC. The presence of A. arbruta in BC waters is a useful bioindicator of marine warming events.
From hesitancy to confidence: Filipinos’ shifting attitude toward COVID-19 vaccination program
Authors: Macaraan Willard Enrique R
Published: June 2021

In earlier correspondence, the authors have explored the vaccine hesitancy among the Filipino public. But I argue that the current situation from the ground has already been seeing shifting attitude of many Filipinos toward the government’s vaccination program. There is a significant increase of confidence among the public in getting inoculated. This development is crucial in hastening the achievement of the so-called herd immunity.
Sustainable diet and cruciform ethics during COVID-19
Authors: Kahambing Jan Gresil S
Published: June 2021

Health inequalities in food challenge sustainable prospects during the pandemic. Basic sustainable diet practices may address this issue, but problems of nutrition arise due to unhealthy eating habits. An inductive approach through curbing one’s diet forms certain ethics, which takes into account one’s sacrifices for the collective. This article proposes that cruciform ethics can introduce a reimagination of sustainable diets during coronavirus disease 2019.
Living with COVID-19: mass gatherings and minimizing risk
Authors: Murakami M , Yasutaka T , Onishi M , Naito W , Shinohara N , Okuda T , Fujii K , Katayama K , Imoto S
Published: June 2021

During the COVID-19 pandemic, it has been important to both minimize the risk of infection and restore daily life. As a typical example, mass gathering events, such as sporting events, are gradually becoming more common, thanks to the measures taken to contain COVID-19. Some pilot studies have been launched at governments’ initiative to investigate the risk of infection without measures such as face masks and physical distancing at mass gathering events, but the ethics of these studies should be carefully considered. On the other hand, it is still beneficial to implement infection control measures at mass gathering events and, in parallel, to estimate the risk of infection with measures in place, especially under a lack of vaccination progress or the spread of mutant strains possibly resistant to vaccines. To help improve compliance with measures taken by spectators and organizers and to ensure their effectiveness, we have conducted quantitative evaluations of the implementation of such measures by monitoring CO2 concentrations, assessing the proportion of people wearing face masks and analysing human flow at the event. This approach allows us to share our observations with stakeholders and participants, enabling us to protect the culture of mass gathering events, minimize the risk of infection and restore a sense of well-being in daily life.
Oxidative stress-induced senescence mediates inflammatory and fibrotic phenotypes in fibroblasts from systemic sclerosis patients
Authors: Kizilay Mancini Ozge , Acevedo Mariana , Fazez Nesrine , Cuillerier Alexanne , Fernandez Ruiz Ana , Huynh David N , Burelle Yan , Ferbeyre Gerardo , Baron Murray , Servant Marc J
Published: June 2021

Objective

SSc is an autoimmune connective tissue disorder characterized by inflammation and fibrosis. Although constitutive activation of fibroblasts is proposed to be responsible for the fibrotic and inflammatory features of the disease, the underlying mechanism remains elusive, and effective therapeutic targets are still lacking. The aim of this study was to evaluate the role of oxidative stress-induced senescence and its contribution to the pro-fibrotic and pro-inflammatory phenotypes of fibroblasts from SSc patients.

Methods

Dermal fibroblasts were isolated from SSc (n = 13) and healthy (n = 10) donors. Fibroblasts’ intracellular and mitochondrial reactive oxygen species (ROS) were determined by flow cytometry. Mitochondrial function was measured by Seahorse XF24 analyser. Fibrotic and inflammatory gene expressions were assessed by qPCR and key pro-inflammatory components of the fibroblasts’ secretome (IL-6 and IL-8) were quantified by ELISA.

Results

Compared with healthy fibroblasts, SSc fibroblasts displayed higher levels of both intracellular and mitochondrial ROS. Oxidative stress in SSc fibroblasts induced the expression of fibrotic genes and activated the TGF-β-activated kinase 1 (TAK1)–IκB kinase β (IKKβ)–IFN regulatory factor 5 (IRF5) inflammatory signalling cascade. These cellular responses paralleled the presence of a DNA damage response, a senescence-associated secretory phenotype and a fibrotic response. Treatment of SSc fibroblasts with ROS scavengers reduced their pro-inflammatory secretome production and fibrotic gene expression.

Conclusions

Oxidative stress-induced cellular senescence in SSc fibroblasts underlies their pro-inflammatory and pro-fibrotic phenotypes. Targeting redox imbalance of SSc fibroblasts enhances their in vitro functions and could be of relevance for SSc therapy.
Characterization and Expression of Conserved Skeletal Proteins in Echinoderms
Authors: Flores Rachel Lauren , Livingston Brian Thomas
Published: June 2021

Specification of the cell fate of skeleton‐forming cells in developing sea urchin embryos has been well characterized and the skeletal proteome of both adult and larval skeleton has been determined. Little is known, however, of the mechanism and proteins involved in the mineralization process. A number of spicule matrix proteins have been identified in sea urchins and are present in the organic matrix during spicule formation. However, loss of function studies have indicated they may not be required for mineralization. We have taken a comparative, evolutionary approach to try and elucidate what proteins may be required for the process of mineralization. Here we report the characterization of the skeletal proteome of the sea star Patiria miniata. Our hypothesis is that there are proteins utilized in skeleton formation that are conserved between all echinoderm groups, and possibly among all deuterostomes. First we have isolated skeletal proteins from P. miniata, and then used LC/MS/MS to obtain peptide sequences of those proteins. Characterization of skeletal proteins was accomplished utilizing the NCBI non‐redundant protein database. By comparing the proteins present in all mineralized tissues of the sea urchin with those found in other echinoderm groups we have identified a set of conserved proteins containing similar functional domains. The skeletal proteome from the two echinoderms, P. miniata and Strongylocentrotus purpuratus, groups also shared novel proteins with similar functional domains. We have analyzed the sequences of the proteins we identified as potentially important to determine the evolutionary relationship and to identify the sequences most highly conserved. Additionally, some of these proteins are also found in vertebrate bone. We have also shown that some skeletal proteins prevalent in one group are not found in other echinoderms. This suggests independent co‐option of proteins utilized in mineralization in some groups. The conserved proteins were then analyzed for temporal expression at eight different stages of the developing embryo of S. purpuratus. Some of these stages, such as mesenchyme blastula, were predicted to show higher level of expression for some of the conserved skeletal proteins. Utilizing gel electrophoresis and quantitative polymerase chain reaction (qPCR), we analyzed the temporal expression of conserved skeletal proteins and the relative expression of those proteins during the eight stages of the developing embryo. We found that expression of the conserved skeletal proteins varied, but all were present when skeleton formation occurred in the embryo.

Support or Funding Information

NIH/NIGMS T34GM008074, NSF grant 09097979
Regulation of Notch signaling by O‐glucosylation: Notch‐modifying xylosyltransferase‐substrate complexes support an SNi‐like retaining mechanism
Authors: Haltiwanger Robert S , Yu Hongjun , Takeuchi Megumi , LeBarron Jamie , Kantharia Joshua , London Erwin , Bakker Hans , Li Huilin , Takeuchi Hideyuki
Published: June 2021

A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α‐1,3‐xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi‐like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor–like repeat acceptor substrate undergoes a large conformational change upon binding to the active site, providing a structural basis for substrate specificity. Importantly, XXYLT1 is amplified in a number of squamous cell carcinomas and may be a target for therapeutics. Our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.

Support or Funding Information

The work is supported by NIH grants GM061126 (to R.S.H) and AG029979 (to H.L.), SBU‐BNL Seed Grant (to R.S.H. and H.L.), DFG grant BA4091/5‐1 (to H.B.) and NSF grant DMR 1404985 (to E.L.).
The Roll of COMMD1 in Membrane Protein Trafficking
Authors: Stewart Davis , Short Kristopher , Buglo Elena , Burkhead Jason
Published: June 2021

Copper is essential for all life due to its role as a catalyst in redox reactions. However, it must be tightly regulated as excess copper can cause oxidative damage to the cell. One example of copper dyshomeostasis is the autosomal recessive condition is known as Wilson disease which can result in liver disease and neurological problems. To maintain copper homeostasis, cells rely on a system of chaperone proteins as well as three copper transporters; CRT1, ATP7A, and ATP7B. ATP7B is a large multidomain membrane‐spanning protein that exports copper from the cytosol and is highly expressed in liver, brain, and kidney cells. ATP7B has a dual role in maintaining copper homeostasis. In the liver, ATP7B functions in the trans‐Golgi network where it pumps copper into the lumen for biosynthesis of secreted cuproproteins. When cellular copper levels are elevated, ATP7B traffics in vesicles towards the apical membrane to move excess copper into bile for excretion from the body. This proves to be a complex decision for the cell as it must retain some ATP7B at the trans‐Golgi for continued biosynthesis of cuproproteins while simultaneously removing the excess. When copper levels are low, ATP7B returns to the Golgi, though it is likely that some is degraded. Although maintaining proper copper homeostasis is important, the mechanism that influences ATP7B distribution is poorly understood. Since being identified as mutated in Bedlington Terriers exhibiting canine copper toxicosis, the protein COMMD1 has been of particular interest as a regulator of cellular copper levels. COMMD1 exhibits both Phosphatidylinositol (PdtIns) effector and Ubiquitin ligase adaptor activity. COMMD1 interacts with a number of membrane proteins including ATP7B. Importantly, COMMD1 downregulation affects cellular copper levels. To investigate the relationship between COMMD1 and ATP7B we used quantitative immunofluorescence microscopy in HepG2 hepatoma cells to analyze the subcellular locations of ATP7B in response to misexpression of COMMD1. The overexpression of the COMMD1 T174M mutant, which was first identified in an atypical Wilson disease patient, significantly decreased the Golgi‐associated fraction of ATP7B and colocalization between ATP7B and lysosomes was also reduced during retrograde trafficking. The T174M mutation may affect PtdIns(4,5)P2 binding by COMMD1, thus we believe that PtdIns(4,5)P2 recruits and facilitates a functional interaction between COMMD1 and ATP7B.

Support or Funding Information

National Science Foundation (MCB‐1411890), NIH 8P20GM103395‐12 (JLB Sub‐Project)
Studies into the synthetic analogs of key intermediates, and ring precursors in the biosynthetic pathway of Coenzyme Q: Synthesis and metabolism
Authors: Nag Anish , He Cuiwen , Shepherd Jennifer N , Fernandez Lucia , Clarke Catherine F , Villalba Jose M
Published: June 2021

Coenzyme Q (ubiquinone or Q) is a redox active lipid molecule, with a fully substituted benzoquinone ring and a polyisoprenoid tail, containing up to ten isoprene units. Q is an essential component of the mitochondrial respiratory electron transport chain. The exact biosynthetic pathway has still not been completely characterized. In this study, farnesylated analogs of several Q intermediates have been been chemically synthesized. The synthesis of 2‐farnesyl‐1,4‐hydroquinone serves as an analog of 3‐hexaprenyl‐4‐hydroxyphenol, which accumulates in yeast coq6 and coq9 mutants that over‐express the Coq8 polypeptide. In addition farnesylated analogs of 5‐demethoxy‐Q3 (DMQ3), 2‐demethyl‐5‐demethoxy‐Q3 (DDMQ3), and 2‐demethyl‐5‐demethoxy‐4‐amino‐Q3 (IDDMQ3H2) were chemically synthesized. The farnesylated analogs are added to yeast cell cultures to determine whether they serve as precursors and/or intermediates in the biosynthesis of Q3. Also, other selected farnesylated substrates such as 3‐farnesyl‐4‐hydroxybenzoic acid, 3‐farnesyl‐4,5‐dihroxybenzoic acid and others are being synthesized for studying Q metabolism. These substrates can also serve as ligands in protein binding assays and as substrates with isolated enzymes. In addition, a number of different compounds are being tested in assays with mammalian cells, to analyze their roles as ring precursors for Q biosynthesis. Thereby we hope to understand and further characterize the biosynthetic and metabolic pathways responsible for Q biosynthesis and function in different living systems.

Support or Funding Information

This research was funded by NSF MCB‐1330803
In Silico Phage‐Hunting in Sinorhizobium Genomes: Incorporating Original Research in Undergraduate Molecular Biology and Microbiology Courses
Authors: Martinez‐Vaz Betsy , Jensen Autumn , Vang Mandy
Published: June 2021

The study of bacterial viruses (bacteriophages) is an excellent tool to teach basic principles of molecular biology and microbiology. The availability of numerous complete bacterial genome sequences in public databases provides a unique opportunity for in‐silico‐phage hunting. This approach consists of identifying and characterizing bacteriophages integrated in bacterial chromosomes using computational analyses. The objective of this project was to develop a set of investigative laboratory exercises to allow undergraduate students to participate in a study about the prevalence of bacteriophages in bacteria of the genus Sinorhizobium. These bacteria play a critical role in agriculture due their ability to form nitrogen‐fixing symbioses with alfalfa and related legumes. The role of bacteriophages in N2 fixation and on the physiology of rhizobia remains largely unexplored. The first part of the project consisted of searching Sinorhizobium genomes for the presence of bacteriophages using PHAST, a bioinformatics tool that identifies viral sequences integrated in bacterial chromosomes. Further bioinformatics analyzes were conducted to determine the numbers and types of proteins encoded by the viruses. The students then designed several procedures to activate and excise the predicted bacteriophages out of the Sinorhizobium genomes. Exposure to UV light and Mitomycin treatments led to the successful isolation and molecular characterization of three novel bacteriophages. This set of laboratory exercises was field tested in two undergraduate molecular biology and microbiology courses. The learning objectives of the project were assessed by comparing the scores of pre and post‐tests and by evaluating the bacteriophage characterization protocols designed by the students. Post‐tests were higher than pre‐test scores at or below p=0.005. Normalized learning gains showed improvement in the student's of bioinformatics analyzes skills, basic virology concepts and the structure and function of proteins encoded by bacteriophage genomes.

Support or Funding Information

This project was supported by a grant of the National Science Foundation.
Metabolic Changes Underlying Interactions Between Obesity and Non‐Alcoholic Fatty Liver Disease in South Asian Adults
Authors: Albracht‐Schulte Kembra , Kalupahana Nishan , Ramalingam Latha , Rosairo Shanthini , Wijetunge Sulochana , Kotakadeniya H.M.S.R.B. , Ratnayake R.M.C.J. , Moustaid‐Moussa Naima
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD) is often referred to as the hepatic manifestation of the metabolic syndrome, which is characterized by at least three of the following: hypertension, hyperglycemia, abdominal obesity, elevated plasma triglycerides and reduced plasma high‐density lipoproteins. While hepatic steatosis has been well studied in animal models, the relationship between body weight, hepatic steatosis and insulin resistance is not well characterized in humans. Moreover, not all human subjects with obesity develop metabolic complications. In addition, it is unclear why South Asian adults develop insulin resistance and diabetes even at lower levels of adiposity and body mass index compared to their Western counterparts. To address this question, we used a convenient sample of Sri Lankan adult females (n = 30) who underwent routine abdominal surgery at the Teaching Hospital of Peradeniya. Anthropometric data, adipose tissue specimens and fasted serum samples were collected for analyses of glucose, lipid and inflammatory markers. Histological sections of adipose tissue were obtained from omental fat (OF) and anterior abdominal wall fat (AF), and adipocyte cross‐sectional area was measured using the ImageJ software. Further, the presence of hepatic steatosis was assessed using ultrasound scanning by a radiologist. Participants with higher grade of fatty liver had a significantly higher body mass index (BMI), fasting blood glucose and aspartate aminotransferase levels. Additionally, participants with higher grade of fatty liver also had significantly higher serum levels of non‐HDL cholesterol and the pro‐inflammatory adipokine, resistin. Interestingly, there were no significant differences in serum adiponectin levels between the groups. Individuals with fatty liver also had a higher mean adipocyte area in both OF and AF, indicating a higher degree of adipocyte hypertrophy associated with fatty liver. Currently, the measurements of additional biomarkers of inflammation and insulin resistance are underway. These findings indicate distinct metabolic differences between South Asian adults with varying degrees of fatty liver, and may help in establishing effective treatment strategies for obesity‐associated NAFLD.

Support or Funding Information

Funded by an International Research/Development Seed grant from the Office of International Affairs and the Office of the Vice President for Research at Texas Tech university (TTU), and an International Research Seed Grant from The College of Human Sciences at TTU, and by the International Research Center, University of Peradeniya.
HomeStyles: Tracking Participant Progress in a Randomized Control Trial
Authors: Delaney Colleen , Martin‐Biggers Jennifer T , Koenings Mallory , Byrd‐Bredbenner Carol
Published: June 2021

Tracking participant progress in large Randomized Control Trials (RCT) is essential to success, yet tracking procedures are seldom discussed in the research literature. This abstract describes the procedures used during recruitment and retention to track participants in the 18‐month HomeStyles RCT. Microsoft Excel was used to create recruitment‐tracking and retention‐tracking spreadsheets that organized participants by group (experimental, control), geographic location (NJ, AZ), delivery mode (online, home visitation), and language (English, Spanish). Recruitment‐spreadsheet data were used to plot recruited participants by group x location x mode x language to enable researchers to assess and target recruitment resources (e.g., staff time, recruitment flyer printing and distribution, recruitment activities) and project when recruitment goals would be reached. The retention‐tracking spreadsheet included participant stage of RCT participation (Survey 1, Instructional Guide [IG]1, IG2, IG3, IG4, Survey 2, IG5, IG6, IG7, IG8, Survey 3, IG9, Survey 4, IG10, Survey 5), and days elapsed since last communication with RCT team or website. Charting retention‐tracking spreadsheet data permitted researchers to visualize participant progress throughout the time course of the RCT; monitor the rate at which participants completed the RCT; and rapidly intervene when participants appeared to be experiencing barriers that may cause them to become inactive and drop out. The retention‐tracking spreadsheet was annotated to indicate when and how inactive participants were contacted. Staff training and twice weekly generation of recruitment and retention data summaries were essential to making timely, informed research management decisions. Recruitment and retention tracking procedures and algorithms from this RCT have the potential to improve RCT monitoring and management practices in a wide array of health promotion and nutrition communication research studies.

Support or Funding Information

USDA NIFA #2011‐68001‐30170
Relationship Between Breast Feeding and Eating Patterns in a Rural, Mexican‐origin Population during a Nutrition Intervention
Authors: Cabrera Roxana , Aguilera Alberto Leopoldo , de la Torre Adela , Kaiser Lucia Lynn
Published: June 2021

Breastfeeding has demonstrated a promising effect on health outcomes later in life. European cohort studies have found a positive relationship between exclusive breastfeeding and increased fruit and vegetable (F/V) intake in children. The purpose of this study was to observe the relationship between retrospectively parent‐reported breastfeeding practices and eating patterns in young Mexican‐origin children. The Niños Sanos, Familia Sana (Healthy Children, Healthy Family) study is a multi‐year intervention aimed at reducing obesity and increasing F/V consumption among Mexican‐origin children. Participants included 172 mother and child dyads (ages 3–8 years) from a rural community in California. Spanish‐speaking interviewers asked mothers to recall breastfeeding practices during the first year of life. Breastfeeding practices were defined as: “Not breastfed” if child never breastfed and/or formula fed only; “Combined feeding” if formula fed and breastfed < 6 months; and “Exclusively breastfed” if breastfed for ≥ 6 months and child not formula fed until after age of 6 months or older. Eating patterns were assessed using a 26‐item food frequency questionnaire. An analysis of variance examined changes in vegetable intake over a 2‐year period by intervention group and breastfeeding practices. Preliminary results show a significant positive independent effect of exclusive breastfeeding on more frequent vegetable intake (F= 3.64, p=0.014). These results need to be confirmed by biomarkers or other measures of vegetable intake.

Support or Funding Information

Funded by USDA‐NIFA Fund number: 82705
Improvement in Long‐term Household Food Security among Indiana Households with Children did not Differ between Rural and Urban Counties after a Supplemental Nutrition Assistance Program‐Education Intervention
Authors: Rivera Rebecca L , Maulding Melissa K , Abbott Angela R , Wang Qi , Eicher‐Miller Heather A
Published: June 2021

Objective

To determine the relationship of rural and urban county household status to long‐term food security among households with children in Indiana after a Supplemental Nutrition Assistance Program‐Education (SNAP‐Ed) intervention.

Methods

A randomized, controlled parallel nutrition education intervention study using SNAP‐Ed as the intervention was implemented across 38 Indiana counties from August 2013 to March 2015. Study participants (n=575) were low‐income SNAP‐Ed eligible adults ≥ 18 years with ≥ 1 child living in the household. SNAP‐Ed paraprofessionals recruited and randomized participants to either the control or intervention treatment group. Intervention group participants received at least the first 4 SNAP‐Ed lessons over an intervention period of 4–10 weeks. All participants completed a baseline, post‐intervention, and 1 year follow‐up assessment. Food security score was assigned using the 18‐item United States Household Food Security Survey Module. Urban or rural county status was assigned using the classifications provided by the United States Office of Management and Budget. A linear mixed regression model adjusted for household characteristics and urban or rural county status was included as an independent variable to compare study treatment group and urban or rural county status effects over time on food security.

Results

Rural or urban county status was not significantly associated with improvement in household food security score from baseline to 1 year follow‐up assessment (p=0.6).

Conclusion

SNAP‐Ed was consistently effective at improving long‐term food security between rural and urban county Indiana households with children.

Support or Funding Information

Funding: This project was supported with a grant from the University of Kentucky Center for Poverty Research through funding by the U.S. Department of Agriculture, Food and Nutrition Service, contract number AG‐3198‐S‐12‐0044.
Obesogenic diets enriched in oleic acid vs saturated fatty acids differentially modify polyunsaturated fatty acid composition in liver and visceral adipose
Authors: Picklo Matthew , Murphy Eric
Published: June 2021

Emerging evidence indicates that the fatty acid composition of obesogenic diets impacts physiologic outcomes. Much attention is focused on the biologic effects of consuming monounsaturated fatty acids (MUFA) vs saturated fatty acids (SFA). We investigated the extent to which an obesogenic diet high in MUFA vs SFA modified lipid composition in liver and visceral adipose tissue with a focus upon polyunsaturated fatty acids (PUFA).

Adult male mice were fed (8 wks) (1) a control 16% fat energy (en) diet with 6% en MUFA as oleic acid (18:1n‐9) and 4 % en SFA, (2) a 50% fat en high MUFA diet with 33% en MUFA and 10% en SFA, or (3) 50% a high SFA diet with 9% en MUFA and 33% en SFA. Intake of linoleic acid (LA; 18:2n‐6) and alpha‐linolenic acid (ALA;18:3n‐3) were kept constant at 3% en and 2% en, respectively. By the end of the study, mice on the high MUFA diet were heavier with a higher total fat content and liver mass than the control mice.

Total hepatic fatty acid content was elevated (78%) in the high MUFA group only, mostly as a result of oleic acid (18:1n‐9) in the neutral lipid fraction. ALA content was lower (30%) in the high MUFA group than the low fat and high‐SFA‐fed mice. However, both high fat diets elevated hepatic content of arachidonic acid (ARA; 20:4n‐6) by 10% and docosahexaenoic acid (DHA; 22:6n‐3) by 48% (MUFA group) and 22% (SFA group).

Epididymal adipose tissue mass was 45% higher in both high fat groups than the control group. When evaluated as amount/gram tissue, the content of LA, ALA, ARA, and DHA was reduced by both high fat diets. However, the high MUFA diet caused a greater reduction in ALA and LA than the SFA diet. Normalizing PUFA content to the entire adipose depot mass removed the reductions in ARA and DHA in both groups. While normalization yielded similar levels of ALA and LA in the SFA group compared to the controls, ALA and LA contents were still lower in the entire epididymal adipose pool in the MUFA group.

These data indicate that dietary MUFA and SFA in high‐fat diets impact hepatic and adipose PUFA metabolism. These data indicate that these obesogenic diets, at least in the short term, increase long chain PUFA content in liver. Moreover, these data show that MUFA has selective effects upon PUFA distribution in adipose tissue.

Support or Funding Information

USDA/ARS funding
Javamide‐I found in coffee is a potent p38 MAP kinase inhibitor suppressing MCP‐1 expression significantly in LPS‐stimulated monocytic THP‐1 cells
Authors: Park Jae , Wang Thomas
Published: June 2021

Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory cytokine, profoundly implicated in pathogeneses of several chronic diseases such as rheumatoid arthritis, atherosclerosis, CVD and CKD. Coffee is one of most consumed drinks worldwide with potential health effects. Javamide‐I (N‐coumaroyltryptophan) is a phenolic amides found in coffee, which is believed to contain some important biological activities including anti‐inflammatory activity. However, its anti‐inflammatory actions have not been fully investigated related to MCP‐1. Interestingly, p38 MAP kinase plays a crucial role in regulating the production of several pro‐inflammatory cytokines including MCP‐1. Therefore, blocking p38 kinase may offer an effective therapy for treating many inflammatory diseases. Therefore, in this study, potential effects of javamide‐I on p38 MAP kinase and the production of MCP‐1expression were investigated in LPS‐stimulated monocytic THP‐1 cells. Javamide‐I was able to inhibit p38 MAP kinase, and also showed noncompetitive inhibition of p38 MAP kinase against ATP. In supporting the inhibition, a docking simulation showed stronger binding pose of javamide‐I to p38 MAP kinase than SB‐203580. Additionally, javamide‐I decreased ATF‐2 phosphorylation in LPS‐stimulated monocytic THP cells. Consequently, the treatment of javamide‐I (1–20 μM) showed significant decrease not only in the expression of MCP‐1 mRNA but also the production of MCP‐1 protein in the stimulated cells (P < 0.05). In addition, in this study, potential effects of javamide‐I on NF‐kB and other MAP kinases will be also discussed related to MCP‐1 expression.

Support or Funding Information

USDA
The Role of NADPH Oxidase Isoform 1 (NOX1) in L‐NAME‐Induced Leukocyte‐Endothelial Interactions in Rat Mesenteric Postcapillary Venules
Authors: Zabrecky Alita , Pham Hung , Koon Amber , Rueter Brian , Barsotti Robert , Young Lindon , Chen Qian
Published: June 2021

Vascular endothelial dysfunction and subsequent inflammation underlie many pathological diseases such as cardiovascular disease, diabetes, and hypertension. Both events are principally initiated by reduced endothelial‐derived nitric oxide (NO) bioavailability and/or activation of vascular/leukocyte NADPH oxidase. NADPH oxidase has 7 isoforms (NOX1‐5 and Duox1‐2). We currently have limited knowledge regarding the roles of individual NOX isoforms in diseases, particularly NOX1, which is a major NADPH oxidase isoform in the vasculature but not in leukocytes. In this study, we evaluated the roles of NOX1 in vascular endothelial dysfunction‐induced inflammation by recording leukocyte rolling, adherence, and transmigration in a postcapillary venule of rat mesenteric tissue in real time via intravital microscopy. We superfused the mesenteric tissue with Krebs’ buffer, and Krebs’ buffer with a non‐selective NO synthase inhibitor, NG‐nitro‐L‐arginine‐methyl‐ester (L‐NAME, 50 μM) with/without a selective NOX1 inhibitor, ML171. We found that at 2 hrs of superfusion, leukocyte rolling (21±8 cells/min), adherence (3±2 cells/100 μm), and transmigration (2±1 cells/200 μm2) was minimal in Krebs’ control (n=8). By contrast, L‐NAME (n=6) significantly increased leukocyte rolling (74±12), adhesion (19±6), and transmigration (18±4) (all P<0.05 compared to Krebs’ control). Whereas, ML171 (1 μM, n=7) prevented the L‐NAME‐induced effect on leukocyte rolling (25±5), adhesion (5±2), and transmigration (5±1). These findings suggest that NOX‐1 activation participates in L‐NAME induced inflammatory responses; whereas inhibition of NOX1 can mitigate inflammation following vascular endothelial dysfunction.

Support or Funding Information

This study was supported by Division of Research, the Center for Chronic Disorders of Aging, and Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.