bluuebunny/crossref_metadata_2025_split huggingface dataset:
In the neurodegenerative disease INAD, infantile neuroaxonal dystrophy, glutamate‐ and ATP‐induced Ca2+ signaling is disturbed in neurons and astrocytes, with mitochondrial dysfunction
Authors: Reiser Georg , Strokin Mikhail 
Published: November 2023

About 85% of cases of INAD (infantile neuroaxonal dystrophy, OMIM #256600), an autosom al recessive inherited degenerative disease with early onset can be associated with mutations of the PLA2G6 gene . Ca2+‐independent phospholipase A2 (VIA iPLA2) is encoded in PLA2G6 . However, connections of these mutations to disease are unclear. For the mainly phospholipid metabolizing VIA iPLA2 also so‐called non‐canonical functions were discussed and reported. These are regulation of store‐regulated Ca2+ entry in cells and change in mitochondrial Ca2+ homeostasis. In this study, we investigate glutamate‐evoked Ca2+ signals in neurons and astrocytes in co‐culture from three INAD mouse models with Pla2g6 gene mutations. The strain‐1 has a hypomorphic Pla2g6 allele with reduced transcript levels (5% of wild type), the strain‐2 has knocked‐out Pla2g6, and strain‐3 has a Pla2g6 point mutation with the VIA iPLA2 inactive. It is shown that homozygous offspring from all strains develop pathology similar to that observed in INAD patients. We demonstrate in our present study a strongly reduced glutamate‐induced Ca2+ response in mutants in astrocytes compared to control cells. When we elucidate the mechanism we find that reduced Ca2+ responses are due to about 2‐fold‐reduced Glu‐induced capacitative Ca2+ entry in astrocytes in all three mouse strains. This effect is based on the lack in VIA iPLA2 activity since we could mimic the decrease by pharmacologically inhibiting iPLA2 with the compound S‐BEL enantiomer. On the contrary, in neurons the Pla2g6 mutation completely disrupted the influence of mitochondrial Ca2+ uptake on the extracellular Glu‐induced Ca2+ influx . We see it in neurons treated with Ru360, a blocker of mitochondrial Ca2+ uniporter or treated with rotenone. The dependency of Glu‐induced Ca2+ influx on mitochondrial Ca2+ uptake was wiped out in neurons with Pla2g6 mutation, whereas a strong reduction was seen in wild‐type cells. Thus, all INAD models have comparable changes, but they are different for astrocytes and neurons, respectively, in Glu‐induced Ca2+ signaling. These modifications in Ca2+ signaling in cells with mutated Pla2g6 are critical for adequate neuron‐astrocyte communication. Thus our data help to understand molecular mechanisms of INAD pathology.Support or Funding InformationDeutsche Forschungsgemeinschaft (Re 563‐22‐1)
An LC‐MS/MS‐Based Protocol for the Absolute Quantitation of Histone Post‐Translational Modifications
Authors: Kingsley Philip John , Galligan James J. , Camarillo Jeannie M. , Marnett Lawrence J. 
Published: November 2023

Post‐translational modifications (PTMs) of histones are utilized by eukaryotic cells to modulate chromatin and effect DNA‐based cellular processes. Identification and quantification of these PTMs provides essential information on both chromatin structure and gene expression in various pathophysiological conditions. Here we report a method for (1) the isolation of core histones, (2) their digestion to single amino acid residues, and (3) the quantitative analysis of the resultant digest for both modified and unmodified amino acids.Nuclei are isolated from cultured cells or murine tissue and chromatin is isolated via high‐salt extraction. The four core histones (H2B, H4, H2A, and H3s) are purified by preparative reversed‐phase HPLC with UV detection. The histones are baseline resolved and the elution order is H2B, H4, H2A, H3.2/3, and H3.1.Isolated histones are spiked with stably labeled internal standards, proteolytically digested to their component amino acids and analyzed via LC‐MS/MS. Chromatographic separation is in the reversed‐phase mode where the ion‐pairing agent heptafluorobutyric acid facilitates retention. The analytes are detected by selected reaction monitoring in positive ion mode and quantification is achieved by stable isotope dilution with internal standards previously added to the samples.To validate this methodology, HEK293 cells were treated with the histone deacetylase inhibitor, trichostatin A, and histones were collected and subjected to the methodologies described. We observed quantitative differences in histone lysine acetylation, as expected. In addition, we quantized histone–specific alterations in lysine mono‐, di‐, and tri‐methylation, and arginine methylation.This methodology may be used to probe for novel or unanticipated PTMs with data‐dependent LC‐MS/MS acquisition methods (DDMs). Lysine and many lysine PTMs such as carboxyethyl lysine and trimethyl lysine generate a strong fragment at m/z 84 upon collisionally induced dissociation. The survey scan of a DDM can utilize this common fragment by selecting its precursors for subsequent isolation and fragmentation, potentially revealing new PTMs.Support or Funding InformationNIH: 2R01CA087819‐16
The YycFG Two‐Component System As A Regulatory Feedback Loop For The Expression Of Autolysin Activity
Authors: Keidel Victoria , Valderrama Andres , Kobir Ahasanul , Szurmant Hendrik 
Published: November 2023

The YycFG (aka WalRK) system is present in all aerobic and some aenaerobic Gram‐positive organisms of the phylum Firmicutes. This two‐component signal transduction system is essential for viability and now known to conserve a function in regulating the expression of enzymes involved in cell wall metabolism. Our previous efforts have focused on the molecular pathways that lead to activation or inhibition of the YycG kinase in Bacillus subtilis. We have identified numerous interactions of the kinase with proteins of the cell division apparatus and two dedicated inhibitory proteins YycH and YycI and have revealed some of the molecular determinants of YycG activity regulation. As a consequence of these studies the knowledge has emerged that the YycFG system serves to regulate growth dependent cell wall restructuring by coordinating autolysin expression with cell division. We present novel data that suggests that this essential signaling system also responds to the autolytic activities of enzymes under direct transcription control by the YycFG system thus providing a feedback loop to fine tune autolysin expression according to its current need. In addition, evidence has emerged suggesting that this feedback loop might be the culprit of antimicrobial activities of a class of human chemokines against Bacillus anthracis and perhaps other Gram‐positive bacteria.Support or Funding InformationSupported by grant GM106085 from the US National Institute of General Medical Sciences, National Institutes of Health
Anatomical substract of the Gluteus medius muscle myofascial trigger points: Preliminary results
Authors: Akamatsu Flávia Emi , Macaya Daniela Medina , Itezerote Ana Maria , Saleh Samir Omar , Hojaij Flávio , Andrade Mauro , Jacomo Alfredo Luiz 
Published: November 2023

Myofascial pain syndrome (MPS) is a common cause of chronic musculoskeletal pain and is characterized by myofascial trigger points (MTP), limited range of motion in joints, referred pain and local twitch response during mechanical stimulation of MTP. MTP are clinically identified by palpation of a taut band of muscle or fascia. Physiopathology of MPS remains unclear and it has been suggested that MTP occur when a nociceptor and a muscular motor endplate coincide. The gluteus medius muscle MTPs are prevalent in patellofemoral pain, back pain and can occur spontaneously gluteal pain, weakness in the lower limbs abduction and increased sensitivity. Three different MTP are clinically described for the gluteus medius muscle, but anatomical correlation is still lacking.Gluteus medius muscle from five cadavers were carefully dissected. We divided the gluteus medius muscle in four topographic áreas (I, II, III and IV) to describe the exact entry points of nerve fibers into the muscle.As these values vary with muscle size, the relative values of the insertion point was calculated from the average longitudinal (from the highest point of iliac crest to greater trochanter of the femur) and transverse dimension (the medium point of the longitudinal dimension) and categorized into four areas: I, II, III and IV. For a comparison of the number of points between the quadrants we have used generalized estimation equations with correlation matrix exchangeable between the quadrants, with marginal Poisson distribution and identity link function. For comparison of the quadrants 2 to 2 multiple Bonferroni comparisons were carried out. We observed that most of the gluteus medius muscle innervation occurred in quadrants I, II and IV of the muscle. These locations correspond to the clinically described MTP. Anatomical correlation of the MTP may be useful for a better understanding of the physiopathology of these disorders and provide basis for their treatment.
Arachidonic and Oleic Acid Exerts Distinct Effects on DNA Methylome
Authors: Silva‐Martinez Guillermo Antonio , Rodriguez‐Rios Dalia , Alvarado‐Caudillo Yolanda , Barbosa‐Sabanero Gloria , Vaquero Alejandro , Esteller Manel , Carmona F. Javier , Moran Sebastian , Nielsen Finn C. , Wickström‐Lindholm Marie , Wrobel Katarzyna , Wrobel Kazimierz , Zaina Silvio , Lund Gertrud 
Published: November 2023

Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic or oleic acid (AA and OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP‐1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hyper‐ and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA‐induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity and autism, but relatively dissimilar from OA‐induced profiles. A set of genes was identified, that display gene body hypermethylation in response to AA and in human atherosclerosis. Biochemical evidence pointed to beta‐oxidation, PPAR‐alpha and sirtuin 1 as important mediators of AA‐induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases supports and expands current diet‐based therapeutic and preventive efforts.Support or Funding InformationCONCyTEG grant no. 08‐03‐K662‐020‐A01, Mexican Council for Science and Technology (CONACyT) Basic Science (Ciencia Básica) grant no. 83401 to GL; CONACyT Sabbatical Fellowships no. 166209 to G.L. and no. 166058 to S.Z.; CONACyT Ph.D. Fellowship no. 334370 to G.A.S.‐M.; the Spanish Ministry of Ministry of Economy and Competitiveness (MINECO) grant SAF2011‐25619 to A.V.
Seaweed Supplementation Attenuates Long‐term High Fat Diet‐induced Chronic Inflammation and Insulin Resistance Regardless of Obesity in C57BL/6N Mice
Authors: Lee Yunkyoung , Oh Ji‐Hyun , Han A‐reum , Hwang Yeonji , Choi Ji‐Hey , Yang Hyoseon , Kang Sae‐im 
Published: November 2023

Antidiabetic and anti‐inflammatory effects of brown seaweeds have been reported in various experimental models, however information is scarce on their effects combined with a long‐term high fat diet. In this present study, we investigated that effects and mechanisms of seaweed supplementation (Undaria pinnatifida (UP), Laminaria japonica (LJ), Sargassum fulvellum (SF), Hizikia fusiforme (HF)) along with high‐fat (HF) diet in C57BL/6N male mice for 16 weeks. Body weight, food intake, and fasting blood glucose concentrations were measured. Insulin tolerance test was performed at week 14. Animals were sacrificed at week 16 and tissues were dissected, weighted, and snap frozen for analysis. Bone‐marrow (BM) cells were isolated from femoral and tibial BM of a representative mouse from each group. As a result, 5% seaweed supplementation did not prevent HF‐induced obesity. Although there was a trend to have less weight gain in HF+LJ and HF+HF groups compared to HF group at week 8, this trend disappeared as HF continued. In spite of being obese, mice in HF+LJ group had significantly improved insulin resistance, lowered cholesterol in plasma and liver, and increased TG in feces compared to mice in HF group that were consistent with histological observations. In addition, BM‐derived macrophages(BMDM) from mice fed HF with seaweeds showed to have less inflammatory cytokines compared to BMDM from mice fed HF only. Increased phosphorylation of insulin signaling proteins was observed in liver of the seaweed supplemented HF groups compared to the HF group. In addition, levels of TG and cholesterol excretion were altered by seaweed supplementation. Conclusively, seaweed supplementation attenuated insulin resistance and chronic inflammation induced by a long‐term HF feeding partially due to altered insulin signaling and lipogenesis in liver and muscle as well as reduced inflammation in adipose tissue regardless of obesity in C57BL/6N mice.Support or Funding InformationThis work was supported by NRF‐2013R1A1A10575730.
Weight Loss and Program Satisfaction in Response to the Weight Watchers SmartPoints Plan
Authors: Rogers Renee J , Kovacs Sara J , Byard Thomas D , Collins Katherine A , Creasy Seth A , Gomberg Monica A , McCoy Stephanie M , Peluso Anna , Raybuck Shawn D , Rupp Kristie , Jakicic John M 
Published: November 2023

BackgroundAs commercial weight loss programs adapt their approaches, it is important to evaluate the protocols for satisfaction and efficacy. This study evaluates changes in body weight and body mass index (BMI) along with program satisfaction in participants enrolled in a Weight Watchers program with the updated SmartPoints plan.MethodsParticipants (N=150; mean age: 47.3 ± 12.7 years; mean BMI: 33.9 ± 4.3 kg/m2) were enrolled in a 6‐month Weight Watchers program. The intervention was delivered by trained Weight Watchers leaders and evaluated by independent research staff that was not engaged in intervention delivery. The Weight Watchers intervention included weekly group sessions, instructions on calculating points for foods and beverages, and use of an app to log points. Assessment of body weight and BMI were completed at baseline and 6 months, attendance at group sessions was tracked weekly, and program satisfaction was reported using a survey at 6 months.ResultsOf the 150 enrolled participants, 143 (95.3%) completed the 6‐month assessment. There was a significant reduction in weight of 2.8 ± 5.0 kg (3.1 ± 5.5%) from 0 at 6 months (p<0.001). This corresponded to a reduction in BMI from 33.8 ± 4.3 kg/m2 to 32.8 ± 4.7 kg/m2 (p<0.001). A clinically meaningful threshold of 5% weight loss was achieved in 32.9% (N=47) of the sample. There was a significant correlation between attendance and weight loss (r=0.59, p<0.001) with 11.9 ± 6.4 group sessions attended. Participants who attended >75% of sessions (N=21) lost more weight (−9.4 ± 6.6%) than those who attended >50–<75% (N=52, −4.2 ± 4.5%), 25–50% (N=39, −1.5±3.3%), and <25% (N=31, −0.9 ± 3.7%) of group sessions (p<0.001); those attending >50–<75% lost significantly more weight than those attending either 25–50% or <25% of group sessions (p<0.001). There was no significant difference in weight loss between those attending 25–50% or <25% of group sessions. Weight change was significantly correlated with overall program satisfaction (r=0.52, p<0.001), satisfaction with the amount of weight lost (r=0.54, p<0.001), and with the likelihood of recommending the program to friends and colleagues (r=0.36, p<0.001).ConclusionsThe Weight Watchers SmartPoints plan appears to be effective at eliciting significant 6‐month reductions in body weight and BMI. It appears that attendance at the weekly sessions is an important component to success when participating in this commercial weight loss program.Support or Funding InformationWeight Watchers International, Inc.
Effect of Rice Cake, Seolgitteok, on Glucose, Insulin, and Satiation Response in Humans
Authors: Pottgen Ellen , Yoon Suk Hoo , Pham Tung , Seo Han‐Seok , Lee Sun‐Ok 
Published: November 2023

A research study was conducted to determine the effects of Seolgitteok (Korean rice cake) on postprandial glucose, insulin, and appetite in humans. Using a randomized‐crossover design, 23 participants consumed one of three Seolgitteok (white rice, brown rice, and mixture of equal parts white and brown rice) with a one‐week washout period. Seolgitteok contained 50 g of total starch based on rice flour analysis, and additional ingredients were consistent. Blood samples were collected intravenously at 15 minutes prior and 0, 30, 60, 90, 120, and 180 minutes after consumption and self‐reported feelings of satiety were collected at each interval using a visual analog scale (VAS). The brown rice Seolgitteok contained a significantly greater percentage of insoluble fiber (3.3±0.3%) compared to the mixed (1.6±0.3%) and white (0.8±0.3%) rice treatments (p<0.05). The brown rice cake produced the lowest glucose response at 30–120 minute intervals and the lowest insulin response at 60–180 minute intervals. Glucose incremental area under the curve (iAUC) for the brown rice Seolgitteok (1610±326 mg (~3h) dL−1) was reduced ~38% compared to the mixed rice Seolgitteok (2580±450 mg (~3h) dL−1) and ~44% compared to the white rice Seolgitteok (2871±553 mg (~3h) dL−1). Insulin iAUC for the brown rice Seolgitteok (2968±493 μU (~3h) L−1) was reduced by approximately 13 and 18 percent compared to the mixed rice (3407±607 μU (~3h) L−1) and white rice (3595±633 μU (~3h) L−1) treatments, respectively. Based on the iAUC of VAS, the brown rice cake was reportedly 10–15% more satiating over the 3 hour postprandial time period compared to the white and mixed rice Seolgitteok. These findings suggest that brown rice Seolgitteok has a potential for use as functional food to reduce postprandial glucose and insulin levels and suppress appetite.Support or Funding InformationFunding provided by Korean Food Research Institute is greatly appreciated.
Dietary Supplement Label Database (DSLD) Captures Dietary Supplements Used by Cancer Survivors: The Case of Fiber Supplements
Authors: Emenaker Nancy J , Sorkin Barbara C , Dwyer Johanna T , Rodriguez LM 
Published: November 2023

BackgroundMore than 50% of all U.S. adults consume dietary supplements (DS) contributing to an estimated $35 billion in sales in 2015. Among these are DS often recommended by oncology practitioners for the reduction of disease risks, including risk of colorectal cancer. The Dietary Supplement Label Database (DSLD) contains over 50,000 DS labels representing a large, and ever‐increasing, fraction of those sold in the U.S. Supplements touted as possessing anti‐cancer properties include multivitamins, botanical extracts, and isolated dietary components such as fiber.ObjectiveDescribe, for the specific case of dietary fiber supplements, how the oncology community (e.g., oncology health care professionals, researchers and patients) can use DSLD in assessing DS consumption hypothesized to affect cancer outcomes.DescriptionThe DSLD provides ready access to label data for dietary supplements sold in the U.S. using a web‐based interface.MethodWe searched DSLD for all products including the terms “fiber”, “colon cleanse” and “colon health” as either a product name, dietary ingredient, brand name, or label element.ResultsDSLD yielded a total of 4,873 products containing the search term “fiber” anywhere on the product label. A total of 181 products contained ingredients classified as “fiber” and 196 products contained “fiber” in the product name. 109 products contained “colon cleanse” anywhere on the product label; 58 contained “colon cleanse” on in the product name; and one contained “colon cleanse” in the dietary ingredient name. Finally, 235 products contained “colon health” anywhere on the label; and 5 contained “colon health” in the product name. DSLD can also be used in some cases to determine the type(s) of fiber claimed as present in each product, providing the potential for assessment of intake of soluble vs insoluble fiber.ConclusionDSLD serves as an online resource supplying a broad range of users, including the oncology community, with relevant DS information for research and clinical useSupport or Funding InformationOffice of Dietary Supplements and the National Library of Medicine, National Institutes of Health.
Effect of Watermelon Powder Supplementation on Colonic Aberrant Crypt Foci Formation
Authors: Kalaba Milica , Klarich DawnKylee S , Hong Mee Young 
Published: November 2023

Watermelon is a rich source of antioxidants and the amino acid L‐citrulline. L‐citrulline has been found to play a role in the treatment of various diseases such as pulmonary hypertension in infants and protected against kidney damage in type 1 diabetic mice. L‐citrulline is metabolized by the body into L‐arginine, which plays a role as a nitrogenous substrate responsible for the synthesis of nitric oxide (NO), an inorganic free radical gas at body temperature and modulator of vascular dilation. Various studies have investigated the effect of high NO levels as a cytotoxic substance towards cancer cells. Specifically, studies have examined NO in macrophage cytotoxicity. These studies state that cytokine activated rodent macrophages generate large concentrations of NO by the up‐regulation of expression of the inducible nitric oxide synthase gene (iNOS). Nitric oxide generated by this process is capable of killing different tumor cells; however, few studies have examined the role of watermelon and, consequently, L‐arginine on the progression of colon cancer. The purpose of this study was to determine the effect of watermelon powder consumption on the development of colon cancer by assessing aberrant crypt foci (ACF) formation, which are pre‐neoplastic lesions that are identifiable in the colon mucosa during the early progression of colon cancer. Thirty‐two male Sprague Dawley rats at 21 days old were administered either control, 0.36% L‐arginine, or 0.5% watermelon powder diets over a period of 9 weeks. The 0.5% watermelon powder diet provides 0.36% of L‐arginine+L‐citrulline. The rats were subcutaneously injected with azoxymethane, a carcinogenic agent, during weeks 3 and 4. Both L‐arginine and watermelon powder diets showed lower total number of ACF at 6.82 ± 0.75 and 4.73 ± 0.63 (mean ± standard error), respectively, compared to control group 26.50 ± 2.40 at P < 0.001. High multiplicity aberrant crypt foci (HMACF) (> 4 aberrant crypts/focus) were also lower in L‐arginine and watermelon powder diets at 1.09 ± 0.44 and 0.82 ± 0.23, respectively, than control group 8.10 ± 1.18 (P < 0.001). Lower total ACF and HMACF were also identified per centimeter of colon for L‐arginine and watermelon powder (P < 0.001). These results suggest that consumption of watermelon as a source for L‐arginine derived from L‐citrulline correspond with decreased ACF formation, which may reduce the risk of developing colon cancer.Support or Funding InformationThe study was funded by The US National Watermelon Promotion Board.