bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrannosaurus rex Shows Histological Evidence For Avian‐Style Cranial Kinesis
Authors: Bailleul Alida M , Horner John R , Holliday Casey M 
Published: November 2023

Modern avian cranial kinesis played a significant role in the adaptive radiation of birds as they evolved flexible skulls from their presumably less kinetic, non‐avian theropod ancestors. Avian cranial kinesis is partly mediated by novel synovial joints, which differ from those of other extant sauropsids in that they form secondary articular cartilage on dermatocranial elements. This tissue is different from the primary articular cartilage that is ubiquitous among the endochondral elements of all vertebrates. The evolutionary origin of secondary cartilage among the dinosaurian line still remains unclear, consequently limiting inferences of cranial kinesis in dinosaurs and other extinct taxa.For the first time, we investigate the presence of secondary articular cartilage in the cranial joints of a non‐avian theropod dinosaur, Tyrannosaurus rex (MOR 1125), by comparing microanatomical features of a reference synovial joint, the jaw joint, and the lesser understood otic joint, which is responsible for streptostylic movements in the avian feeding apparatus. Five extracted fragments of these joint articular surfaces from the surangular, quadrate and squamosal were microCT‐scanned, and then serially sectioned via histological techniques to identify secondary cartilage. Complementary histological data from two extant archosaurs (Anas platyrhynchos and Alligator mississippiensis) were also examined.The membranous squamosal and surangular of T. rex possess a thin layer of mineralized, secondary articular cartilage above their subchondral bone. The quadrate fragments possess primary articular cartilage, but no clear histological differences between primary and secondary cartilage were identified. These results suggest that the jaw and otic joints of T. rex were synovial and identical in structure to those of modern birds, but substantively different from those of A. mississippiensis. This study provides for the first time clear paleohistological evidence for a synovial otic joint, which bolsters hypotheses of avian‐style streptostyly in a theropod dinosaur, and that birds inherited this tissue from their dinosaurian ancestors. This study has significant implications for our understanding of the origins of avian cranial kinesis, for inferences of kinesis in theropod dinosaurs, and increases our knowledge of the evolution of cranial skeletal tissues in vertebrates.Support or Funding InformationThis study was funded by: NSF‐IOS 1457319; Department of Pathology and Anatomical Sciences.
Antibiotics from the microbial dark matter
Authors: Lewis Kim 
Published: November 2023

Our ability to discover novel compounds has diminished, and pathogens acquire and spread resistance largely unchecked, leading to a human health crisis. The main source of antibiotics – soil actinomycetes – has been overmined. The problem is compounded by the presence of dormant persister cells tolerant to killing by all antibiotics. As a result, chronic osteomyelitis or infections of patients with cystic fibrosis can be untreatable. There are then two main problems facing the field of antibiotic discovery – resistance; and tolerance. Ideally, we need compounds free of resistance; and antimicrobials capable of killing dormant cells with inactive targets.We reasoned that antibiotic producers face similar problems that we do, and evolved anti‐persister compounds. We considered an old abandoned antimicrobial acyldepsipeptide (ADEP) as a possible anti‐persister antibiotic. The compound targets the ClpP/A,C,X protease which normally degrades misfolded peptides with the aid of its ATP‐dependent chaperones. In the presence of ADEP the chaperones are no longer needed. We found that ADEP causes massive degradation of mature proteins in S. aureus by the disregulated ClpP protease, killing persisters both in vitro and in a biofilm model of infection in a mouse.In search of new antibiotics, we decided to target uncultured microorganisms, which make up 99% of the total diversity. We developed approaches to grow uncultured bacteria and find that this “microbial dark matter” harbors novel antimicrobials. Lassomycin produced by soil actinomycetes kills persisters of Mycobacteria by forcing the ClpC1 chaperone to hydrolyze ATP. Teixobactin, made by a β‐proteobacterium, is essentially free of resistance. It binds two immutable targets, lipid II and lipid III. These examples suggest that natural products that can address the dual problem of resistance and tolerance were evolved by producing microorganisms, and mining uncultured bacteria holds the promise of reviving the field of antibiotic discovery.Support or Funding InformationT‐RO1 AI085585, Bill & Melinda Gates Foundation
Radical strategies for biological methylation
Authors: Booker Squire J. 
Published: November 2023

A new and menacing mechanism for antibiotic resistance is on the rise, involving the C8 methylation of adenosine 2503 of 23S rRNA of the bacterial ribosome. Indeed, this seemingly minor addition, installed by the radical SAM protein, Cfr, impedes the binding of over five classes of antibiotics to their targets. Considering that one‐half of all antibiotics currently in use target the bacterial ribosome, this emerging mechanism of resistance has the potential to reduce the effectiveness of the world's current arsenal of antibiotics severely. Interestingly, C8 of adenosine is chemically resistant to biological methylation by all currently accepted mechanisms, which usually involves the attack of a nucleophile onto an electrophilic methylating agent. This lecture will detail a new and novel strategy for the biological methylation of sp2‐hybridized carbon centers, which involves radical intermediates generated via the reductive cleavage of S‐adenosylmethionine and the participation of five essential cysteinyl residues.Support or Funding InformationNIH GM 101957
Nature's Imitation Game: Decipher the Combinatorial CTD Code for Eukaryotic Transcription
Authors: Zhang Y. Jessie 
Published: November 2023

In eukaryotes, the C‐terminal domain of RNA polymerase II (CTD) orchestrates the temporal and spatial control of transcription and is involved in the epigenetic regulation of gene expression. Errors in CTD regulation can result in cell death, cancer and severe developmental defects. The CTD executes its function as a transcription template to recruite transcription regulators through various post‐translational modifications on its heptad repeats. Recently, novel modifications on CTD have been identified, setting the stage for the possibility of combinatorial mechanisms for transcription regulation. We focused on the eukaryotic phosphatases in the CTD regulation and how they affect the function of CTD binding proteins. Determination of the structures of these CTD phosphatases guide our structure‐function investigation. Using a collection of chemical biology techniques including analytical chemistry, spectroscopy, enzymology and structural biology, we dissect the multiple layers of regulation in CTD‐mediated transcription. In particular, we developed an innovative method of mass spectromety, Ultraviolet photodissociation (UVPD), to map the site of modification in S. cerevisiae and Drosophila CTDs. Overall, we probe how the identities and phosphorylation states of individual residues in the consensus heptad repeats of CTD result in differentiated post‐translational modification states within CTD that lead to various transcription outcomes.Support or Funding InformationThe work is funded by National Institute for Health, Welch Foundation and Alzheimer's Drug Discovery Foundation.
Desire to Eat and Intake of Sweet and Savory, High‐ and Low‐Calorie Foods in Male and Female Adolescents
Authors: Singh Jaishree , Papantoni Afroditi , Carnell Susan 
Published: November 2023

Highly palatable, energy‐dense (ED), sweet and savory foods may contribute to the obesity epidemic by triggering desire to eat, experienced by some as an addiction‐like response. However, individual differences in appetitive responses, and their relationships with hunger level or food intake, are not well understood. Fifty‐nine 14–18 year‐olds (10 overweight M, 13 overweight F, 23 lean M, 13 lean F) from the Baltimore, MD area, attended two study visits, both of which involved consuming a meal‐replacement drink (474 ml, 480 kcal) or water (474 ml, 0 kcal) and then undergoing an fMRI scan 38±12 min later, during which they viewed pictures of different foods and reported their desire to eat each one. Following the scan, participants were allowed to eat ad libitum from a multi‐item dinner meal. Examples of high‐ED food pictures and buffet items were: chips (savory) and ice cream (sweet); examples of low‐ED food pictures and buffet items were: vegetable pieces (savory) and fruit (sweet). Analyses revealed that males reported desiring high‐ED, both sweet and savory, foods more than did females, in the fed condition only, with no sex differences emerging for high‐ED foods in the fasted condition, or for low‐ED foods in either condition. Males and females consumed equal amounts of high‐ED, sweet and savory, foods in both conditions. In both conditions, overweight adolescents reported desiring high‐ED, both sweet and savory, foods less than did lean adolescents, with no weight group differences for low‐ED foods. Lean and overweight adolescents consumed equal amounts of high‐ED, sweet and savory, foods across both conditions. Participants reported desiring high‐ED, both sweet and savory, and low‐ED, savory only, foods more when fasted than when fed. Participants consumed more high‐ED, both sweet and savory, foods when fasted than when fed, and consumed more low‐ED, both sweet and savory, foods when fed than when fasted. There were no sex differences in modulation of intake by fasted/fed condition. Males' desire to eat savory high‐ED foods was negatively correlated with savory high‐ED food intake (r=−.504, p=.009), but only in the fasted condition (r=−.537, p=.005); there were no correlations between desire and intake emerging for the other food categories in either condition. Our results suggest that adolescent reports of desire to eat certain foods and/or subsequent food intake depend on hunger state consistently across sex and weight groups. However, overweight and female participants may under‐report desire to eat certain foods due to social desirability bias. Further research should explore potential sex differences in appetitive responses and how they translate into actual intake.Support or Funding InformationResearch was funded by an R00 National Institute of Diabetes & Digestion & Kidney Disease grant.
Does the Recent Chilean Regulation on Food Labelling Improve Chilean Population Knowledge on Nutritional Facts? A longitudinal comparison between 2012 and 2016
Authors: Gregori Dario , Gafare Claudia Elena , Lorenzoni Giulia 
Published: November 2023

Obesity epidemic is concerning worldwide, both in developed and newly industrialized countries. It represents a severe public health issue, since obese subjects are prone to develop metabolic, cardiovascular, and orthopaedic diseases. In recent years, several public health interventions have been developed in order to fight such epidemic. Several governments worldwide have implemented interventions for obesity prevention by regulating food labelling. Particularly, the Chilean government has recently approved a regulation (law 20606/2012), aimed at improving consumers' knowledge on the content of food products' nutrients, by including front‐of‐packages labelling in products high in sodium, total sugar, satured fat, and energy.The aim of the present study is to assess knowledge about nutritional facts of Chilean population before and after the approval of the Chilean law on food labelling.In 2012, a “Computer Assisted Telephone Interview” (CATI) was conducted on a Chilean population‐based sample. The survey's questionnaire consisted of four main sections (participants socio‐demographic characteristics; attitudes towards the concepts of nutrition and obesity; understanding of nutritional facts; attitude towards the potential development of a new front‐of‐pack labelling). The survey was undertaken on a sample of 1280 Chilean subjects, selected using random digital dialling. The same survey is now taking place (on the same sample of subjects interviewed in 2012) in order to asses if the awareness of Chilean population on nutritional facts has improved, after the recent introduction of the regulation.Results of the 2012 survey revealed a concerning lack of knowledge about nutritional facts (most of subjects interviewed did not read the labels and reported a low interest in paying an additional fee for additional information about nutritional facts). Preliminary results of the survey, currently ongoing and planned to be over by early December, are based on 24% of the sample, and showed no improvements in labeling knowledge after 4 years with an increase about 0.97% (95% C.I 0.3%–1.7%).Evaluation of effectiveness of policies need longitudinal information and definition of sensitive targets. Improving knowledge of consumers is showing, on the basis of this preliminary results, to be a target not being caught by current Chilean regulation.Support or Funding InformationStudy has been done with a unrestricted grant from Prochild ONLUS, an Italian based ONG
The Efficacy of Silibinin to Reduce the Impact of Obesity on Invasive Prostate Cancer
Authors: Sherman Blaine , Hernandez Ana R , Alani Maraim F , Price Ramona S 
Published: November 2023

IntroductionObesity is a risk factor for therapeutic resistance, disease progression, and metastasis in prostate cancer (PCa) patients. Further, obesity results in a state of chronic inflammation, which has been linked, to several types of cancer including the prostate. Previously, we have shown that obesity‐related systemic factors promoted an invasive prostate cancer phenotype, in vitro. Specifically, interleukin‐6 (IL‐6) has been identified as a pro‐inflammatory cytokine, which may mediate obesity‐induced prostate cancer progression. Interestingly, silibinin, a polyphenol found in milk thistle seed, reduces inflammation and may have anti‐tumorigenic properties. The mechanisms involved in obesity‐induced PCa progression are not completely understood, therefore limiting the development of effective interventions to inhibit or reverse the tumor promoting effects of obesity. Therefore, we hypothesize that silibinin may be used to reduce or reverse the impact of obesity on invasive prostate cancer by using an in vitro approach of obesity and cancer.MethodsTo investigate the efficacy of silibinin to reduce obesity‐induced invasive prostate cancer, a novel in vitro model of obesity and human sera was used. Male human sera from each body mass index (BMI) category (n=5) of normal weight <25 (NW), overweight BMI 25–29.9 (OW), and obese BMI >30 (OB). The prostate cancer cell lines used for this study were PacMetUT1, 22RV1, and DU145. Matrigel chambers were used to measure the invasive capacity of prostate cancer cells. MTT was used to assess cell viability. Immunofluorescence was used to visualize the localization of e‐cadherin. Western blot analysis was used to detect IL‐6, phospho‐Androgen Receptor, total Androgen Receptor and COX‐2. qRT‐PCR was used to evaluate differences in gene expression of IL‐6, phospho‐Androgen, and COX‐2. Student's t‐testResultsPacMetUT1, and 22RV1 cells exposed to serum from obese and overweight sera increased cell viability while silibinin inhibited cell viability. DU145 cell did not differ in cell viability upon exposure to sera from obese, overweight or normal weight with and without silibinin. Silibinin inhibited obesity‐induced invasion in 22RV1, DU145 and PacMetUT1 cells. At the time of the conference, qRT‐PCR and western data analyses will be presented on gene and protein expression of IL‐6, phospho‐Androgen, and COX‐2. Immunofluorescence was used to visualize localization of Ecadherin. In prostate cancer cells exposed to sera from obese sera resulted in dispersion of Ecadherin compared to normal and overweight sera which was modified by exposure to silibinin.ConclusionIn summary, silibinin modulates several characteristics from the hallmarks of cancer. Silibinin was effective in selectively inhibiting obesity induced invasion, and suppressed proliferation in several prostate cancer cell lines. Future studies are needed to identify strategies to reverse the impact of obesity on prostate cancer progression.
Evenly Re‐distributing Daily Dietary Protein Intake Does Not Augment Changes in Body Composition and Cardio‐metabolic Health Indexes
Authors: Hudson Joshua L. , Kim Jung Eun , Paddon‐Jones Douglas , Campbell Wayne W. 
Published: November 2023

Limited, inconsistent research suggests that re‐distributing total protein intake from one very high‐protein meal daily, to multiple moderately‐high protein meals, improves 24 h muscle protein synthesis and over‐time, and may promote positive changes in indexes of body composition and cardio‐metabolic health. We sought to assess the effects of within‐day protein intake distribution on dietary energy restriction and resistance training‐induced changes in body composition, including skeletal muscle size, and cardio‐metabolic health indexes. In a randomized, parallel‐design study, 41 men and women (mean ± SEM; age: 35 ± 2 y; BMI: 31.5 ± 0.5 kg/m2) performed resistance training 3 times/wk for 16 wk concurrent with consuming a controlled, energy‐restricted (750 kcal/d below estimated energy requirements) diet. Subjects consumed 90 g protein/day in either a skewed (10 g breakfast, 20 g lunch, 60 g dinner; n=20) or even (30 g each at breakfast, lunch, and dinner; n=21) distribution pattern. Consuming an energy‐restricted diet resulted in reductions of fasting state body mass (LSmean ± SE; −7.9 ± 0.6 kg), lean mass (−1.0 ± 0.2 kg), fat mass (−6.9 ± 0.5 kg), serum glucose (−2.9 ± 1.2 mg/dL), HOMA‐IR (−1.3 ± 0.2), total cholesterol (−21 ± 4 mg/dL), and triglycerides (−26 ± 7 mg/dL). However, right mid‐thigh muscle area (cm2) did not change over time. Collectively, the within‐day distribution of protein intake did not differentially affect body composition, muscle size, or cardio‐metabolic health index responses over time. Consuming an equivalent amount of protein daily distributed evenly (30‐30‐30 g/meal) versus skewed (10‐20‐60 g/meal) during dietary energy‐restriction combined with resistance training does not confer additional benefits to fat loss, lean mass retention or cardio‐metabolic health outcomes in young adults with overweight or obesity.Support or Funding InformationPork Checkoff; American Egg Board‐Egg Nutrition Center; National Dairy Council; Beef Checkoff; and the National Institutes of Health, Indiana Clinical and Translational Sciences Institute, Clinical Research Center, Grant # UL1TR001108.
A class of models to estimate energy requirements
Authors: Plucker Andrew , Powell Michael , Broskey Nick , Martin Corby K , Heymsfield Steven B , Schoeller Dale , Thomas Diana , Redman Leanne 
Published: November 2023

BackgroundAccurately estimating energy requirements represents a standard activity for developing effective diet and exercise interventions. Mathematical models that predict energy requirements as a product of physical activity level (PAL) and a resting energy expenditure (REE) formula is a commonly applied method to provide a first pass estimate. These estimates require knowledge of an individual's PAL and an accurate prediction of REE. Access to different anthropometric data or body composition and even REE measurements can improve and personalize predictions without making assumptions involving PAL.MethodsTotal energy expenditure measured by DLW and metabolic chamber from 733 subjects obtained from compiled study database of baseline measurements measured at Pennington Biomedical Research Center was applied as two different output variables. The DLW measures were applied to develop free‐living energy requirement models and the chamber data was applied to develop in‐residence energy requirement models. Twenty‐eight different linear regression models were developed that included different combinations of input variables that may be accessible to investigators and clinicians. The input variables were age, height, gender, weight, waist circumference, fat mass, fat free mass, and REE. The simplest model predicting DLW measured energy expenditures was validated on the Institute of Medicine DLW database (N=473) and compared to the product of 1.6 and the Mifflin St. Jeor prediction of REE.ResultsThe adjusted R2 values for the models predicting free‐living energy requirements in males ranged from 0.65 with minimal covariates of age, height, and weight to 0.73 in models that included body composition or REE. For females adjusted R2 ranged from 0.68 to 0.74. The adjusted R2 values for the models predicting in‐residence energy requirements were lower (males 0.43–0.45, females (0.32–0.33). The bias in the newly developed models was −95±461 kcal/d while the bias obtained from using 1.6 times REE predicted by Mifflin St. Jeor yielded a bias of −315±444 kcal/d.ConclusionsThe newly developed class of models offers an improved alternative to estimating a PAL value and energy requirements using REE formulas. Additionally, when available, the models include additional covariates that improve predictions even further.