bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short term effect of tetrahydrocurcumin on adipose angiogenesis in very high-fat diet-induced obesity mouse model
Authors: Yoysungnoen Bhornprom , Srisawat Umarat , Piyabhan Pritsana , Sookprasert Nattapon , Duansak Naphatsanan , Mathuradavong Nakorn , Poomipark Natwadee , Munkong Narongsuk , Changtam Chatchawan 
Published: May 2023

AbstractTetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally)(VHFD+THC group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), VEGF, MMP-2 and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, VEGF, MMP-2 and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of VEGF, MMP-2 and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of VEGF, MMP-2 and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.Author summaryConceptualization, B.Y, U.S., P.P., N.D., N.S. and N.M3.; methodology, B.Y., U.S., P.P., N.D., N.S., N.M3., and C.C; validation, B.Y., U.S., P.P., N.D., N.S., N.M1., and N.M3.; formal analysis, B.Y., U.S, N.S., N.M1., N.P., and N.M3; investigation, B.Y., U.S, N.S., N.M1., N.P., and N.M3.; resources, B.Y. and C.C.; data curation, B.Y. and N.M1.; writing—original draft preparation, BY; writing—review and editing, B.Y; visualization, B.Y., U.S., P.P., and N.D.; supervision, B.Y.; project administration, B.Y., U.S., P.P., N.S., and N.P.; funding acquisition, B.Y., U.S., P.P., N.S., and N.P.
Lipidomic Profiling Unveils Sex Differences in Diabetes Risk: Implications for Precision Medicine
Authors: Pina Ana F. , Meneses Maria João , Carli Fabrizia , Patrício Bárbara , Ribeiro Rogério T. , Patarrão Rita S. , Gardete-Correia Luís , Duarte Rui , Boavida José M. , Raposo João F. , Gastaldelli Amalia , Macedo Maria Paula 
Published: May 2023

AbstractType 2 diabetes (T2D) is a multifactorial condition whose greatest impact comes from its complications. Not only impaired glucose homeostasis, but also lipid alterations have a relevant role, with insulin derived mechanisms behind this milieu, i.e., glycemia and lipidemia. Thus, we hypothesized that a) distinct glucose and lipid profiles and b) sex differences, particularly in lipids patterns, may be used to identify subjects at higher risk to develop T2D.The PREVADIAB2 study evaluated metabolic alterations after 5 years in subjects without T2D when participating to PREVADIAB1. Herein, 953 subjects from the PREVADIAB2 cohort were stratified using a hierarchical clustering algorithm, informed by HOMA-IR, IGI,fISR andfIC. The resulting clusters were profiled and the lipidome of a subset (n=488) was assessed by LC/MS-QTOF.We identified four clusters, named according to their main metabolic features: Liver Sensitive (LS); Pancreas Glucose Sensitive (PGS); Insulin Deficient (ID); and Insulin Resistant (IR). These cluster metabolic patterns were similar between sexes. However, men and women had distinct parameters cut-offs and lipidomic profiles. Overall, women presented higher long chain ceramides. Nonetheless, men had higher ceramide to sphingomyelin ratio and higher lysophosphatidylcholine to phosphatidylcholine ratio. For both genders, the LS cluster had the most advantageous lipid profile, whereas the other clusters presented lipid specificities towards dysmetabolism. This work shows that clustering individuals by distinct insulin-related metabolic features and sex identifies different phenotypes with distinct lipidome profile, thus demonstrating the importance of placing diabetes in a broader context of metabolism beyond glucose.
Rise of escitalopram and the fall of citalopram
Authors: Cavanah Luke R. , Ray Parita , Goldhirsh Jessica L. , Huey Leighton Y. , Piper Brian J. 
Published: May 2023

AbstractIntroductionCitalopram and escitalopram are among the most used medications and are key treatments for many psychiatric disorders. Previous findings suggest citalopram and escitalopram prescription rates are changing because of the patent for citalopram ending as opposed to evidence of a clear therapeutic advantage, which is called evergreening. This retrospective study focuses on characterizing the chronologic and geographic variation in the use of citalopram and escitalopram among US Medicaid and Medicare patients. We hypothesized that prescription rates of citalopram will decrease with a concurrent increase in escitalopram, consistent with evergreening.MethodsCitalopram and escitalopram prescription rates and costs per state were obtained from the Medicaid State Drug Utilization Database and Medicare Provider Utilization and Payment Data. Annual prescription rates outside a 95% confidence interval were considered significantly different from the average.ResultsOverall, a decreasing trend for citalopram and an increasing trend for escitalopram prescription rates were noted in both Medicare and Medicaid patients. Cost differences between generic and brand were noted for both drugs, with generic forms being cheaper compared to the brand-name version.DiscussionDespite limited evidence suggesting that citalopram and escitalopram have any meaningful differences in therapeutic or adverse effects, there exists a noticeable decline in the use of citalopram that cooccurred with an increase in escitalopram prescribing, consistent with our hypothesis. Moreover, among these general pharmacoepidemiologic trends exists significant geographic variability. There was disproportionate spending (relative to their use) on the brand versions of these medicines compared to their generic forms.
Mobilizing faith-based COVID-19 health ambassadors to address COVID-19 health disparities among African American older adults in under-resourced communities: A hybrid, community-based participatory intervention
Authors: Adinkrah Edward K. , Bazargan Shahrzad , Cobb Sharon , Kibe Lucy W. , Vargas Roberto , Waller Joe , Sanchez Humberto , Bazargan Mohsen 
Published: May 2023

AbstractThe COVID-19 pandemic disproportionately affected older adults, particularly those with pre-existing chronic health conditions. To address the health disparity gap and challenges faced by under-resourced African American older adults in South Los Angeles during this period, we implemented a hybrid (virtual/in-person), pre-post, community-based participatory intervention research project utilizing a faith-based lay health advisor model (COVID-19 Health Ambassador Program (CHAP)). We recruited COVID-19 Health Ambassadors (CHAs) and African American older adults (participants) from faith-based organizations who partook in CHA-led meetings and follow-ups that educated and supported the participants. This paper seeks to evaluate this intervention’s implementation using the Consolidated Framework for Implementation Research (CFIR) as a reporting tool with an emphasis on fidelity, challenges, and adaptations based on data collected via stakeholder interviews and surveys. Results: CHAP was delivered to 152 participants by 19 CHAs from 17 faith-based organizations. CHAs assisted with chronic disease management, resolved medication-related challenges, encouraged COVID-19 vaccination, reduced psychological stress and addressed healthcare avoidance behaviors such as COVID-19 vaccine hesitancy among the participants. Challenges encountered include ensuring participant engagement and retention in the virtual format and addressing technological barriers for CHAs and participants. Adaptations made to better suit the needs of participants included providing communication tools and additional training to CHAs to improve their proficiency in using virtual platforms in addition to adapting scientific/educational materials to suit our participants’ diverse cultural and linguistic needs. Conclusion: The community-centered hybrid approach in addition to our partnership with faith-based organizations and their respective COVID-19 health ambassadors proved to be essential in assisting underserved African American older adults manage chronic health conditions and address community-wide health disparities during the COVID-19 pandemic. Adaptability, cultural sensitivity, and teamwork are key to implementing health interventions especially in underserved populations.
Rectal and vaginal challenge with mpox virus increases virus dissemination and contact transmission compared to skin challenge in the multimammate rat (Mastomys natalensis)
Authors: Port Julia R. , Riopelle Jade C. , Smith Samuel G. , Myers Lara , Lewis Matthew C. , Gallogly Shane , Okumura Atsushi , Schulz Jonathan E. , Rosenke Rebecca , Prado-Smith Jessica , Carmody Aaron , Bane Sidy , Smith Brian J. , Saturday Greg , Feldmann Heinz , Rosenke Kyle , Munster Vincent J. 
Published: May 2023

AbstractThe 2022 mpox virus outbreak was sustained by efficient human-to-human transmission and spread predominantly through sexual networks of men who have sex with men (MSM). It is currently unclear what combination of factors resulted in the enhanced transmission. To investigate this, we established the peridomestic African rodentMastomys natalensisas a new rodent model susceptible to infection after intraperitoneal, rectal, vaginal, and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Route-dependent shedding and tissue replication occurred in the presence of self-resolving localized skin, reproductive tract, or rectal lesions. Mucosal inoculation via both the rectal and vaginal route led to increased shedding compared to skin inoculation, and increased replication and a proinflammatory T-cell profile. Contact transmission was higher in rectally inoculated animals. This suggests that the spread in MSM communities may have been enhanced by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.
Lack of paternal silencing and ecotype-specific expression in head and body lice hybrids
Authors: Marshall Hollie , de la Filia Andrés G. , Cavalieri Ross , Mallon Eamonn B. , Clark John M. , Ross Laura 
Published: May 2023

AbstractPaternal genome elimination (PGE) is a non-Mendelian inheritance system in which males develop from fertilised eggs but their paternally-inherited chromosomes are eliminated before or during spermatogenesis. Therefore, PGE males only transmit their maternally inherited set of chromosomes to their offspring. PGE has been described in numerous arthropod species, many of which are pests or parasites, posing a severe economic burden on crop production and/or with implications for human health. In order to understand how PGE has evolved on the molecular level, to potentially develop novel control strategies, we need to examine species which display basal forms of PGE. The human louse, Pediculus humanus, represents an ideal model system to understand the molecular underpinnings of PGE. In this study we analysed parent-of-origin allele specific expression patterns in male offspring of crosses between head and body lice ecotypes. We have shown that hybrid adult males of P. humanus display biparental gene expression, which constitutes the first known case of a species with PGE in which genetic activity of paternal chromosomes in the soma is not affected by embryonic heterochromatinization or (partial or complete) elimination. We have also identified maternally-biased genes (potentially imprinted genes) which may be involved in the elimination of paternal chromosomes during spermatogenesis. Finally, we have identified genes which show ecotype-specific expression bias. Given the low genetic diversity between ecotypes this is suggestive for a role of epigenetic processes in ecotype differences. These findings have implications for models of pediculicide resistance in human lice and for the development of novel epigenetic-mediated control strategies.
Immunomodulatory Effects of Atractylodes Lancea in Healthy Volunteers with Dosage Prediction for Cholangiocarcinoma Therapy: a modelling approach
Authors: Sae-heng Teerachat , Karbwang Juntra , Na-Bangchang Kesara 
Published: May 2023

AbstractBackgroundA recent study on the immunomodulatory activity ofAtractylodes Lancea(Thunb.) DC. (AL) in healthy Thai subjects revealed that a once daily dose of 1,000 mg AL administered for 21 days significantly inhibited the production of key pro-inflammatory cytokines, while stimulating the production of immune cells. There is however, no reported maximum tolerated dose (MTD) and suggested phase 2A dosage regimens in the literature.ObjectiveThis study aimed to evaluate the immunomodulatory effectsof Atractylodes Lancea(Thunb.) DC. (AL) in healthy subjects, and to recommend optimal dose regimens for intrahepatic cholangiocarcinoma (iCCA) based on toxicity criteria.MethodsA physiologically-based pharmacokinetic (PBPK) model, combined with the toxicological approach and the immunomodulatory effect, was used for a dose-finding. The safety and efficacy of each AL regimen were evaluated based on the previous study. At least, a daily OD dose of 1,000 mg AL significantly suppressed the production of all proinflammatory cytokines while significantly increasing the number of peripheral immune cells.ResultsThe developed PBPK model well predicted clinical observed data. No significant differences in SII index values were found, but a difference in the lymphocyte-monocyte ratio was found on day 4. The dosage regimens for phase 2A are BID doses of 1,000 or 2,000 mg or OD doses of 2,000 mg. Preliminary results in phase 2A revealed that a once-daily dose of 2,000 mg had a significantly higher median overall survival, progression-free survival, disease control rate, and inhibition of increased tumor size without toxicities compared with a once-daily dose of 1,000 mg and standard supportive care.ConclusionA PBPK model, in conjunction with a toxicological approach, could assist in finding the potential dosage regimens for a clinical study, including herbal medicine.
Shear force enhances adhesion ofPseudomonas aeruginosaby counteracting pilus-driven surface departure
Authors: Palalay Jessica-Jae S. , Simsek Ahmet N. , Sabass Benedikt , Sanfilippo Joseph E. 
Published: May 2023

AbstractFluid flow is thought to prevent bacterial adhesion, but some bacteria use adhesins with catch bond properties to enhance adhesion under high shear forces. However, many studies on bacterial adhesion either neglect the influence of shear force or use shear forces that are not typically found in natural systems. In this study, we use microfluidics and single-cell imaging to examine how the human pathogenPseudomonas aeruginosainteracts with surfaces when exposed to shear forces typically found in the human body (0.1 pN to 10 pN). Through cell tracking, we demonstrate that the angle between the cell and the surface predicts if a cell will depart the surface. We discover that at lower shear forces, type IV pilus retraction tilts cells away from the surface, promoting surface departure. Conversely, we show that higher shear forces counterintuitively enhance adhesion by counteracting type IV pilus retraction-dependent cell tilting. Thus, our results reveal thatP. aeruginosaexhibits behavior reminiscent of a catch bond, without having a specific adhesin that is enhanced by force. Instead,P. aeruginosacouples type IV pilus dynamics and cell geometry to tune adhesion to its mechanical environment, which likely provides a benefit in dynamic host environments.
A Cryo-to-Liquid Phase Correlative Light Electron Microscopy Workflow for the Visualization of Biological Processes in Graphene Liquid Cells
Authors: Rutten Luco , Joosten Ben , Schaart Judith , de Beer Marit , Roverts Rona , Gräber Steffen , Jahnen-Dechent Willi , Akiva Anat , Macías-Sánchez Elena , Sommerdijk Nico 
Published: May 2023

AbstractLiquid phase electron microscopy (LP-EM) has emerged as a powerful technique forin-situobservation of material formation in liquid. However, monitoring these processes requires the repeated interaction of the electron beam with the aqueous environment leading to the decomposition of water molecules (radiolysis), which affects the formation processes under investigation. Graphene’s ultra-conductive properties have made it an efficient way to mitigate this problem, as it acts as an electron scavenger when used as a window material. Using the strategy, the process of interest is initiated when the graphene liquid cells (GLCs) are sealed. This means that the process cannot be imaged at early time points since microscope preparation and initiation of image acquisition at the region of interest are time-consuming.Here we report a novel cryogenic/liquid phase correlative light/electron microscopy workflow that addresses the most significant limitations of the graphene liquid cells, while combining the advantages of fluorescence and electron microscopy. This workflow allows imaging to be initiated at a predetermined space and time by vitrifying and thawing at a selected time point. We demonstrate the workflow first by observing multiple day crystallization processes and highlight its potential by observing a biological process: the complexation of calciprotein particles. With this observation, we show the exciting possibilities for LP-EM in biology.
Site-Specific Introduction of Alanines for the NMR Investigation of Low-Complexity Regions and Large Biomolecular Assemblies
Authors: Elena-Real Carlos A. , Urbanek Annika , Imbert Lionel , Morató Anna , Fournet Aurélie , Allemand Frédéric , Sibille Nathalie , Boisbouvier Jerome , Bernadó Pau 
Published: May 2023

AbstractNMR studies of large biomolecular machines and highly repetitive proteins remain challenging due to the difficulty of assigning signals to individual nuclei. Here, we present an efficient strategy to address this challenge by engineering aPyrococcus horikoshiitRNA/alanyl-tRNA synthetase pair that enables the incorporation of up to three isotopically labeled alanine residues in a site-specific manner usingin vitroprotein expression. We have demonstrated the general applicability of this approach for NMR assignment by introducing isotopically labeled alanines into four proteins, including the 300-kDa molecular chaperone ClpP and the alanine-rich Phox2B transcription factor. For large protein assemblies, our labeling approach enables unambiguous assignments, while avoiding potential artefacts induced by site-specific mutations. When applied to Phox2B, which contains two poly-alanine tracts of nine and twenty alanines, we observe that the helical stability is strongly dependent on the homorepeat length, demonstrating structural cooperativity. The capacity to selectively introduce alanines with distinct labeling patterns is a powerful tool to probe structure and dynamics of biomolecular systems that are out of the reach of traditional structural biology methods.
O antigen biogenesis sensitisesEscherichia coliK-12 to bile salts, a likely cause for how it lost its O antigen
Authors: Qin Jilong , Hong Yaoqin , Morona Renato , Totsika Makrina 
Published: May 2023

AbstractEscherichia coliK-12 is a model organism for bacteriology and has served as a workhorse for molecular biology and biochemistry for over a century since its first isolation in 1922. However,Escherichia coliK-12 strains are phenotypically devoid of an O antigen (OAg) since early reports in the scientific literature. Recent studies reported the presence of independent mutations that abolish OAg biogenesis inE. coliK-12 strains from the same original source, suggesting unknown evolutionary forces have selected for loss of OAg during the early propagation of K-12. Here, we show for the first time that restoration of OAg inE. coliK-12 strain MG1655 synergistically sensitises bacteria to vancomycin with bile salts (VBS). Suppressor mutants surviving lethal doses of VBS mostly contained disruptions in OAg biogenesis. We present data supporting a model where the transient presence and accumulation of lipid-carried OAg intermediates in the bacterial periplasm interfere with peptidoglycan synthesis, causing growth defects that are synergistically enhanced by bile salts. Lastly, we demonstrate that continuous bile salt exposure of OAg-producing MG1655 in the laboratory, can recreate a scenario where OAg disruption is selected for. Hence our work provides a likely explanation for the long-held mystery of howE. coliK-12 lost its OAg production and opens new avenues for exploring long-standing questions on the intricate network coordinating the synthesis of different cell envelope components in Gram-negative bacteria.Significance statementEscherichia coliK-12 is the most studied microorganism, widely used in laboratories for studying bacteriology and as a tool for molecular biology. The reason why it is devoid of O antigen remains a long-standing question. Our work has uncovered a previously unknown selection pressure of bile salts on bacterial O antigen biogenesis, which provides a plausible scenario for how the early propagation ofE. coliK-12 strains in bile salt containing media could have led to loss of O antigen in K-12. Our results also suggest that the accumulation of O antigen intermediates in the bacterial periplasm may interfere with bacterial cell wall synthesis, which paves a new research direction into the interplay of different cell envelope component synthesis pathways.
CTCF barrier breaking by ZFP661 promotes protocadherin diversity in mammalian brains
Authors: Jin Jinpu , Ralls Sherry , Wu Elaine , Wolf Gernot , Sun Ming-An , Springer Danielle A. , Cosby Rachel L. , Senft Anna D. , Macfarlan Todd S. 
Published: May 2023

AbstractMammalian brains are larger and more densely packed with neurons than reptiles, but the genetic mechanisms underlying the increased connection complexity amongst neurons are unclear. The expression diversity of clustered protocadherins (Pcdhs), which is controlled by CTCF and cohesin, is crucial for proper dendritic arborization and cortical connectivity in vertebrates. Here, we identify a highly-conserved and mammalian-restricted protein, ZFP661, that binds antagonistically at CTCF barriers at thePcdhlocus, preventing CTCF from trapping cohesin. ZFP661 balances the usage of Pcdh isoforms and increases Pcdh expression diversity. Loss ofZfp661causes cortical dendritic arborization defects and autism-like social deficits in mice. Our study reveals both a novel mechanism that regulates the trapping of cohesin by CTCF and a mammalian adaptation that promoted Pcdh expression diversity to accompany the expanded mammalian brain.One sentence summaryZFP661 blocks cohesin trapping by CTCF and increases protocadherin diversity for proper cortical dendritic arborization.