bluuebunny/crossref_metadata_2025 huggingface dataset:
Programming Effects of Infant Diet on Cholesterol/Bile Acid Synthesis and Absorption in Piglets
Authors: Mercer Kelly E , Diaz‐Rubio Maria Elena , Bhattacharyya Sudeepa , Sharma Neha , Yeruva Laxmi
Published: June 2021

Unlike breast milk, infant milk formula contains little cholesterol, and requirements necessary for normal growth and development are met through increased endogenous cholesterol synthesis in the liver. Human studies looking at the long‐term metabolic implications of manipulating cholesterol homeostasis during infancy have reported lower circulating cholesterol and triglycerides in adults that were breast fed when compared those that received formula. To determine the molecular etiology of diet‐associated changes in early‐life cholesterol metabolism, we employed a neonatal piglet feeding model to investigate differences in cholesterol homeostasis between two infant diets (sow's milk and a cow's milk‐based formula). Male and female piglets (n=12) were breast fed and compared to piglets (n=12) receiving a commercially available milk‐based formula from postnatal day 2 to day 21. As expected, we observed a significant up‐regulation of liver transcripts associated with hepatic cholesterol synthesis, including 3‐hydroxy‐3‐methylglutaryl‐Co‐A synthase (HMGCS1) and reductase (HMGR) in formula fed piglets. Using a non‐targeted metabolomic approach in the liver, we identified 47 significant features that differed between breast fed and formula fed piglets. Pathway analysis identified taurine metabolism and bile acid metabolism among the top pathways elevated in formula fed piglets compared to those breast fed. Presently, we have confirmed increases in hepatic taurine (p=0.02), taurochenodeoxycholic acid (p=0.002) and glycoursodexoycholic acid, (p=0.002) and a decrease in taurocholic acid (p=0.01) in the formula fed group compared to breast fed piglets. Consistent with these data, in formula fed males and females we also observed a significant increase in cholesterol 7α‐hydroxylase (CYP7A1) mRNA and protein expression (p<0.05), indicating excessive bile acid production. In the liver farnesoid X receptor (FXR) regulation of bile acid synthesis and export were intact. We observed a significant decrease in CYP8B1 mRNA expression, with 2‐fold increases in mRNA expression of the bile acid export pump (BSEP) and multidrug resistance protein 2 (MDR2), p<0.05. In females, intestinal mRNA expression of the cholesterol pathway regulator fibroblast factor 19 (FGF 19) was reduced by 4‐fold in response to the formula diet (p<0.05), suggesting that loss of intestinal FGF19 signaling is responsible for the increase in CYP7A1 expression. In conclusion, formula feeding elicits profound metabolic programming effects on hepatic and intestinal regulation of cholesterol/bile acid metabolism in a neonatal piglet model of human infant nutrition.

Support or Funding Information

This work was funded by USDA‐ARS Project 6026‐5100‐010‐05S.
Comparison of Morphology and Bending Mechanics of Femora in Response to Chronic Exercise in Three Strains of Mice
Authors: Middleton Kevin M , Peacock Sarah J , Coats Brittney R , Kirkland J Kyle , Garland Theodore
Published: June 2021

Analyses of bone cross‐sectional geometry are frequently used to predict the loading histories of past populations. We investigated the interplay between genetic background and exercise, as well as the relationship between bone cross‐sectional geometry and bending mechanics, in three mouse strains: high bone density (C3H/He), low bone density (C57BL/6), and a high‐runner strain homozygous for the Myh4Minimsc allele (MM). Each strain was divided into exercise (wheel) or control (no wheel) treatment groups. After seven weeks, morphometric and mechanical loading analyses were conducted on dissected femora. Comparisons of exercise versus control treatments revealed no significant differences within any strain, although exercising MM mice ran significantly more than their C3H/He and C57BL/6 counterparts (P < 0.001). Thus, predictions that exercise would alter bone phenotype were not supported in this sample. Results of cross‐sectional geometry predicted that MM femora would be most resistant to bending forces and C3H/He femora least resistant. Mechanical tests, however, showed that C3H/He mice had significantly stiffer bones than both MM (P < 0.001) and C57BL/6 (P < 0.001) mice. Thus, predictions of low bending strength in C3H/He femora, made without factoring in their high mineral content, were not supported. Overall, we did not find the expected associations between exercise, cross‐sectional geometry, and mechanical properties. Accordingly, our results suggest that predicting loading response from cross‐sectional geometry alone only partially informs such hypotheses. Our study questions common paleoanthropological conventions in which bone mineral composition is assumed to be constant, and differences in cross‐sectional geometry are interpreted as indicative of differential loading regimes.

Support or Funding Information

This project was supported by an EARDA award from National Institutes of Health National Institute of Arthritis and Musculoskeletal Diseases (KMM), the University of Missouri Department of Pathology and Anatomical Sciences (SJP, KMM), the University of Missouri Bond Life Sciences Fellowship program (SJP), the California State University, San Bernardino Department of Biology (BRC, KMM), Associated Students Incorporated of California State University, San Bernardino (BRC), the University of Missouri School of Medicine (JKK), and the National Science Foundation (TG, Jr.; IOB‐0543429).
Gastrointestinal Microbial Changes Following Whole Grain Barley and Oat Consumption in Healthy Men and Women
Authors: Thompson Sharon V. , Swanson Kelly S. , Novotny Janet A. , Baer David J. , Holscher Hannah D.
Published: June 2021

Background

Whole grain fiber consumption is a promising approach to positively alter the human gastrointestinal (GI) microbiome. The Dietary Guidelines for Americans recommends half of all grain servings be consumed as whole grains to minimize chronic disease risk. However, little is known about the effects of whole grain barley and oat consumption in their whole food forms on GI microbial profiles in healthy individuals.

Objective

We aimed to assess the impact of whole grain barley and oat consumption on the GI microbiota in healthy men and women and determine whether effects of whole grain consumption on the GI microbiota are associated with metabolic and immunological improvements.

Methods

A 6‐week randomized, double‐blinded, parallel‐arm, controlled‐feeding intervention was undertaken in healthy adults (n=68) fed at weight maintenance. Male and female participants were randomly assigned to 1 of 3 treatments: 1) a control diet containing 0.8 daily servings of whole grain/1800 kcal, 2) a diet containing 4.4 daily servings of whole grain barley/1800 kcal or 3) a diet containing 4.4 daily servings of whole grain oats/1800 kcal. Blood, urine, and fecal samples were collected at baseline and at the end of the intervention period for metabolic, immunologic, and microbial analyses. Bacterial, fungal, and archaeal sequences were generated using an Illumina MiSeq and analyzed with QIIME 1.8. Data were analyzed using SAS 9.4.

Results

Prior to treatments, associations between bacterial taxa and host metabolism were observed. The Bacteriodes:Firmicutes ratio was negatively correlated with BMI (r=−0.31, p=0.009). The abundance of Bifidobacterium was negatively correlated with age (r=−0.40, p=0.0008). Alternatively, Collinsella was positively correlated with age (r=0.26, p=0.03), LDL cholesterol (r=0.21, p=0.09), and triglycerides (r=0.23, p=0.06). Microbial community structure was affected by whole grain barley and oat consumption. Total species richness was higher in participants consuming oats compared with control (p=0.01). Principal coordinates analysis (PCoA) of UniFrac distances between samples based on their 97% OTU composition and abundances indicated that the microbiota of participants within a treatment were more similar than between treatments (p=0.03).

Conclusions

Our findings are congruent with previous research demonstrating associations between the GI microbiota, weight status, age, and serum lipids. Ecological analyses revealed that whole grain barley and oats induced changes in the microbial community structure of the Gl microbiota. Additional study is ongoing to delineate the microbial taxa driving these shifts and the interrelationships among changes in the GI microbiota and metabolic improvements.

Support or Funding Information

This study was funded by USDA and the Kellogg Company.
Parents of Preschoolers: Weight‐Related Cognitions and Behaviors
Authors: Martin‐Biggers Jennifer T , Quick Virginia , Povis‐Alleman Gayle , Hongu Nobuko , Worobey John , Byrd‐Bredbenner Carol
Published: June 2021

Parents are gatekeepers of the home environment; their weight‐related cognitions and behaviors have a strong likelihood of affecting child growth, development, and body fatness. The purpose of this study was to benchmark weight‐related (diet, physical activity [PA], and sleep) cognitions and behaviors of 702 parents of preschool children (ages 2 to 5 years) at the outset of their participation in the HomeStyles childhood obesity prevention randomized controlled trial via survey. Participants were 92% female, 58% white, aged 32.40±5.78SD years. Analysis of parent dietary behaviors showed limited fruit/vegetable intake (21.51±8.44SD on a 0–56 point scale); intake from sugar sweetened beverages was 101.77±117.03SD calories/day and percent calories from fat was 37.07±6.18. Parents reported eating family meals 12.82±4.84SD times/week (most frequently dinner followed by breakfast) with most meals (4.83±2.35 days/week) eaten at a dining table, but were ambivalent about planning family meals (3.45±1.03SD) and expending effort to prepare meals (3.55±0.90SD). An examination of diet‐related cognitions using 5‐point scales revealed that parents felt family meals were important (4.38±0.70SD), rated their family meals as calm (4.02±0.90SD), were fairly neutral about the importance of modeling healthy eating to their children (3.63±0.78SD), and tended to not pressure children to eat (2.33±1.00SD) or use food to reward children for desired behavior (2.43±0.79SD). Parent PA behaviors were low, averaging 15.9±9.99SD on a 0–42 point scale with 85% of parents exceeding the 2 hour recommended daily screentime limit. With regard to PA cognitions, 5‐point scale results indicated that parents felt it was important to model PA to children (3.92±0.83SD) but scored lower on actually modeling PA behavior (3.25±1.27SD) and engaging in PA with children (3.69±1.84SD) despite reporting fairly good access to PA opportunities in and around their homes (3.59±0.63SD) and strongly agreeing there were many health benefits to exercising (4.43±0.60SD). Results indicate that parents barely met minimum recommendations for sleep (7.08+1.27SD hours/night) and reported only moderate sleep quality (3.21+0.91SD; 5‐point scale). Parents tended to disagree that they were concerned about their children's risk for becoming overweight (2.07±1.06SD). Parents’ weight‐related cognitions and behaviors coupled with their limited concern about overweight risk in children indicate important opportunities for promoting simple changes in the home environment that may help protect family health and well‐being.

Support or Funding Information

USDA NIFA #2011‐68001‐30170
HomeStyles: Recruitment Strategies for a Childhood Obesity Prevention Randomized Controlled Trial
Authors: Martin‐Biggers Jennifer T , Delaney Colleen , Koenings Mallory , Byrd‐Bredbenner Carol
Published: June 2021

Participant recruitment is one of the biggest challenges when conducting research. HomeStyles is an online 18‐month childhood obesity prevention randomized control trial with intervention families receiving weight‐related diet, activity, and sleep instructional guides and control families receiving home safety guides. A literature review of recruitment strategies was conducted and a systematic plan for recruitment was created and iteratively refined to be responsive to emerging and receding opportunities. All methods used program branded printed materials, uniform scripted communications on cash stipends and nonfinancial benefits of participation, and brief study description to establish credibility. The following recruitment efforts were used: 1) emails posted to listservs of workplaces, philanthropic, community, preschools/day care centers, professional associations, extracurricular activity groups sent ≥3 times over 16 month recruitment period; 2) postings to websites, such as online community newspapers, local businesses, parent blogs, and HealthyHomeStyles.com intervention site; 3) social media, including project Facebook and Pinterest pages; 4) printed newspapers and child cooking magazine articles (i.e., ChopChop); 5) face‐to‐face recruitment at community events, parent resource centers, WIC offices, farm markets; 6) community partners who distributed program branded printed informational flyers at their sites (e.g., community centers, pediatrician offices, fitness centers, schools and preschool/day care centers); 7) radio and Spanish‐speaking television interviews; 8) personal contact with colleagues, family, friends, neighbors, and professional listservs. Follow‐up phone calls to partners and personal contacts were made ≥twice to confirm receipt of program information and answer questions. Materials created for recruitment in English and Spanish included: flyers of varying reading levels, bookmarks, posters, and brief informational videos for dietitians, pediatricians, and educators. Families successfully recruited into the program reported learning about HomeStyles from their child's school, preschool, or daycare; a family member or friend; Facebook ad; or their doctor (16.2%, 15.2%, 9% and 0.4%, respectively). Most learned about HomeStyles through other sources (44.5%), including electronic listserv notices, workplace presentations, and marketing survey company (41%). The results coupled with the extend recruitment period (16 months) indicates a need for intensive, varied recruitment strategies.

Support or Funding Information

USDA NIFA #2011‐68001‐30170
The Impact of Nutrition Label Usage on Food Selection and Consumption in a University Dining Setting
Authors: Christoph Mary Jane , Ellison Brenna D
Published: June 2021

Background

Although adding nutrition labels at the point of purchase is commonly recommended to improve food choice, most studies have relied on self‐reported dietary intake or have inferred usage based on sales data without examining actual food selection and consumption of label users and non‐users. In this study, we combine survey and plate photo data to compare food selection and consumption of label users and non‐users in a university dining hall setting.

Methods

We surveyed n=606 diners in two university dining halls in the Fall 2014 semester. Food selections were recorded, and pre‐ and post‐meal photos were taken of each diner's plate. Photos were coded to identify the presence, servings, and consumption of MyPlate food categories. We compared the plates of self‐reported label users (those who agreed they used nutrition labels to make their food choices at the meal surveyed) and non‐users.

Results

Across the entire sample, the most commonly selected categories were protein (86.1% of diners selected protein items), refined grains (79.0%), and vegetables (70.6%); whole grains (5.3%), beans (14.0%), and low‐fat dairy (15.4%) were the least commonly selected categories. Label users were more likely to select vegetables and beans and less likely to select potatoes (all P<0.05) than non‐users. Serving sizes only differed between label users and non‐users for the vegetables, beans, potatoes, and refined grains categories. On average, label users selected 0.53 ± 0.51 cups vegetables versus 0.38 ± 0.40 cups for non‐users (P=0.0001), and 0.18 ± 0.46 ounces beans versus 0.09 ± 0.28 ounces for non‐users (P=0.0055). Users selected an average of 0.22 ± 0.27 cups potatoes while non‐users selected 0.31 ± 0.31 cups (P=0.0024). For refined grains, label users served themselves 1.35 ± 1.2 ounces on average, whereas non‐users selected 1.59 ± 1.31 ounces (P=0.0485). Net consumption, calculated by multiplying serving size by the percentage consumed, showed label users consumed 1/10 cup more vegetables (p=0.0538) and 1/5 ounce fewer refined grains (p=0.0320) compared to non‐users.

Conclusions

Label users behave differently than label non‐users in selecting and consuming food. Further, since our results suggest both groups must improve significantly to meet current dietary guidelines, educational efforts beyond nutrition labeling may be needed.

Support or Funding Information

This research was supported by the Agriculture and Food Research Initiative of the USDA National Institute of Food and Agriculture as part of the AFRI Childhood Obesity Prevention Challenge (2011‐67001‐30101) to the Division of Nutritional Sciences at the University of Illinois Funding began on 02/01/2011.
Intermittent Leucine Pulses during Continuous Feeding Alters Novel Components Involved in Skeletal Muscle Growth of Neonatal Pigs
Authors: Suryawan Agus , Boutry Claire , Manjarín Rodrigo , Cánovas Angela , Islas‐Trejo Alma , Medrano Juan F , Nguyen Hanh , Fiorotto Marta L. , Davis Teresa A.
Published: June 2021

Extra‐uterine growth restriction in low‐birth‐weight (LBW) infants is associated with the development of chronic metabolic derangements, and emphasizes the need for improved nutritional protocols to optimize growth. Supplementation with intermittent pulses of leucine in continuously fed neonatal pigs enhanced skeletal muscle protein synthesis through the upregulation of mammalian target of rapamycin signaling. Piglets (n = 23, 7‐d‐old) were continuously fed a milk formula via orogastric tube for 21 d, with an additional parenteral infusion of either leucine (800 μmol·kg−1·h−1, LEU) or alanine (CON) for 1 h every 4 h. To identify novel genes by which LEU may promote neonatal muscle growth, we performed RNA‐Seq analysis of longissimus dorsi muscle from 4 pigs per group, followed by gene ontology (GO) analysis of differentially expressed genes (DEG). In addition, protein abundance/activation of DEG products involved in both muscle protein anabolic or catabolic pathways was assessed by immunoblots. RNA‐Seq was performed on a HiSeq2000 sequencer analyzer. Reads were analyzed using CLCBio Genomics workbench software, assembled against the porcine reference genome, and normalized by a threshold of ‘reads per kilo base per million mapped reads’ (RPKM) ≥ 0.2. A total of 465 genes were differentially expressed between LEU and CON groups (RPKM P < 0.05). GO analyses showed developmental processes, cell junction assembly, regulation of cellular process and organ development as the terms most significantly enriched among the 465 genes. Applying more stringent parameters (RPKM P < 0.01 + >2 fold change), 18 differential expressed genes were identified between CON and LEU pigs, of which tumor necrosis factor receptor‐associated factor 6 (TRAF6) and mammalian Ste20‐like kinase 1 (MST1), both negative regulators of muscle growth, were decreased by > 2‐fold (P < 0.01) in LEU compared to CON. Western blot analysis also showed a downregulation of MST1 and TRAF6 abundance in LEU animals (P < 0.01) compared to CON. Together, these findings suggest that intermittent leucine pulses in continuously fed neonate pigs lead to downregulation in the gene and protein expression of signaling components that limit muscle growth.

Support or Funding Information

NIH AR444474, NIHHD072891, USDA NIFA 2013‐67015‐20438, and USDA/ARS 6250‐51000‐055
A Conceptual Framework for the Core Concept of Cell‐Cell Communications
Authors: Michael Joel , Cliff William , McFarland Jenny , Wright Ann , Modell Harold , Martinkova Patricia
Published: June 2021

Physiology faculty regard Cell‐Cell Communications as one of the core concepts their students should understand and be able to apply. This concept has been summarized as follows: the function of the organism requires that cells pass information to one another to coordinate their activities. We have developed a conceptual framework that describes the core concept of Cell‐Cell Communications and have begun the process of validating its content.

This framework consists of 51 items, descriptions of physiological phenomena, which are arranged in as many as four hierarchical levels under the core concept: critical components (e.g. binding of the messenger molecule to its receptor gives rise to signal transduction), constituent ideas (e.g. there are two basic mechanisms for transduction), elaborations (e.g., the speed of the response of the two systems is different), and amplifications (e.g.the speed of response in a second‐messenger system . . .).

Thirty‐seven faculty were surveyed about the importance of each of the 51 items (5=Essential, 4=Important, 3=Moderately Important, 2=Slightly Important, 1=NOT Important). Written feedback about the items was also solicited from the respondents.

Respondents teach at 2‐year colleges, 4‐year colleges offering only bachelors degrees, 4‐year colleges offering some masters degrees, research universities, and professional schools.

Mean responses over all 51 items ranged from 4.92 (slightly less than Essential) to 3.46 (between Important and Moderately Important). No more than 2 respondents rated any item as Not Important, and all items were rated as Essential by at least 2 respondents. We conclude that our respondents found the framework as a whole to be important for students to understand. Written feedback did point to one item that needed to be re‐written to conform with current understanding of the phenomenon referred to in the framework.

There seems to be strong and linear dependence of importance on level of hierarchy, with items on the main level being deemed the most important and with lower importance for items at lower levels.

Although our respondents teach at different educational levels, analyses support the conclusion that there are no differences in the ratings based on the different categories of institutions.

The generation of a validated conceptual framework is the first step in the process of writing a concept inventory to be used to assess student understanding of this core concept.

Support or Funding Information

Supported by NSF grant DUE‐104344
Indications for Lumbar Fusion in the Skeletally Mature Adolescent: How to Address Oblique Takeoff and Limb Length Discrepancy
Authors: Li Ying , Fletcher Nicholas D.
Published: June 2021

Background:

Indications for posterior spinal fusion (PSF) with segmental spinal instrumentation (SSI) of a scoliotic deformity in a skeletally mature individual are based on the balance between the anticipated benefit of stopping future curve progression and the potential downside of loss of spinal mobility. The dilemma regarding PSF with SSI in the adolescent population is exacerbated by the patient’s participation in athletics requiring flexibility and motion of the spine, the location of the curve, the presence of pelvic obliquity, and the impact of a limb length discrepancy. The purpose of this review is to discuss the potential advantages and disadvantages of PSF with SSI in a hypothetical skeletally mature adolescent with a 45-degree lumbar curve, pelvic obliquity, and limb length discrepancy.

Discussion:

Natural history studies of untreated adolescent idiopathic scoliosis (AIS) have shown that slow curve progression throughout adulthood is likely. Adults with untreated AIS may also have more back pain and dissatisfaction with their appearance. Although the clinical and radiographic outcomes of PSF with SSI are excellent, patients should be counseled about the impact of fusing the lumbar spine on back pain, decreased spinal mobility, and potential inability to return to athletics at the same level. Adults who undergo surgery for AIS have greater operative morbidity and number of levels fused compared with adolescents.

Conclusion:

These factors should be presented when discussing observation versus PSF with SSI with patients and families. Delaying surgery until formal athletic participation is complete should be considered.
Streamlining Postoperative Care After Pediatric Supracondylar Humerus Fractures: Is Follow-up After Pin Removal Routinely Needed?
Authors: Patel Harshadkumar A. , Chaudhry Sonia , Lee Mark C. , Solomito Matthew
Published: June 2021

Background:

Closed reduction and percutaneous pinning is the standard of care for displaced supracondylar humerus fractures (SCHFs). Although the operative management of SCHFs has achieved good consensus with low complication rates, there remains a paucity of literature on postoperative management. We hypothesized that routine office visits after pin removal can safely be avoided in uncomplicated SCHFs without compromising patient care.

Method:

A retrospective review was conducted to query the electronic medical record for SCHFs, treated with closed reduction and percutaneous pinning. Patients with complicated SCHFs were excluded. Patients were divided into 2 cohorts: follow-up (FU) and nonfollow-up (NFU), depending on the presence or absence of after-pin removal (APR) FU visits. Demographics, surgical variables, number of x-rays, referrals for physical therapy, total FU visits, complications, and clinical events after pin removal up to 3 months were compared. Subgroup analysis was performed according to Gartland fracture types.

Results:

A total of 179 patients were included in the study, 111 in the FU group and 68 in the NFU group. There were no significant differences found in demographics between the 2 groups. There were no significant differences in complications and APR clinical events between 2 groups (P>0.05). An average of 1.98 additional x-rays were taken APR in FU group. None of the NFU group patients required physical therapy. Excluding patients with pin site infections, 15/108 (13.9%) of FU group patients had >1 APR visits.

For operatively managed uncomplicated SCHFs, patients who do not have routinely scheduled FU APR have no greater incidence of clinical events APR than patients with a scheduled FU. With a detailed discussion including expectations, timeframe for resuming activities, home exercises, and reassurance of the ease of FU if desired, routine FU APR can be safely eliminated after uncomplicated SCHFs in order to streamline postoperative care.

Level of Evidence:

Level III.
Estimated SARS-CoV-2 Seroprevalence in Healthy Children and Those with Chronic Illnesses in the Washington Metropolitan Area as of October 2020
Authors: Bahar Burak , Simpson Joelle N. , Biddle Cara , Campbell Andrew , Dome Jeffrey S. , DeBiasi Roberta L. , Mowbray Catriona , Marguilies Stefanie , Sherman Adrienne , Reuben Jacqueline , Delaney Meghan
Published: June 2021

The estimated severe acute respiratory syndrome coronavirus 2 seroprevalence in children was found to be 9.46% for the Washington Metropolitan area. Hispanic/Latinx individuals were found to have higher odds of seropositivity. While chronic medical conditions were not associated with having antibodies, previous fever and body aches were predictive symptoms.
Olfactory Dysfunction in Neurodegenerative Disease
Authors: Saramago Israel , Franceschi Ana M.
Published: June 2021

Familiarity with the physiology of smell allows a deeper understanding of olfactory dysfunction in dementia and neurodegenerative disease. This manuscript reviews the characteristic clinical and advanced imaging findings in patients with neurodegenerative disorders presenting with olfactory dysfunction.
‘Cooperative game’ inspired approach for multi-area power system security management taking advantage of grid flexibilities
Authors: Karangelos Efthymios , Panciatici Patrick
Published: June 2021

This paper advocates for a progressive rethinking of the day-ahead/intra-day power system security management practice in the low-carbon energy transition era. As a starting point, the need for coordination between multi-area transmission system operators in order to efficiently exploit the value of grid flexibility towards operating the low-carbon, multi-area power system securely and economically is emphasized. On this basis, the core proposal of this paper is the adoption of a new approach to day-ahead/intra-day multi-area power system security management, inspired by the principles of cooperative game theory. The proposed approach relies on counterfactual analysis to evaluate the (positive and/or negative) impact of each distinctive control area to the common security of the multi-area system, thus providing clear economic incentives to achieve the required coordination. This proposal is not a marginal approach and notably facilitates the integration of more detailed physical modelling (including the non-convexities of the power system) in the inter-TSO settlement of the multi-area interconnected system security management cost. The proposed framework allows some level of subsidiarity and the definition of hedging products to cover ex-post costs. Further from the blueprint of the proposed approach, the paper presents a demonstrative implementation in the context of static N-1 security management and discusses prominent research and development pathways in order to progressively put such vision into practice.

This article is part of the theme issue ‘The mathematics of energy systems’.
On incorporating forecasts into linear state space model Markov decision processes
Authors: de Chalendar Jacques A. , Glynn Peter W.
Published: June 2021

Weather forecast information will very likely find increasing application in the control of future energy systems. In this paper, we introduce an augmented state space model formulation with linear dynamics, within which one can incorporate forecast information that is dynamically revealed alongside the evolution of the underlying state variable. We use the martingale model for forecast evolution (MMFE) to enforce the necessary consistency properties that must govern the joint evolution of forecasts with the underlying state. The formulation also generates jointly Markovian dynamics that give rise to Markov decision processes (MDPs) that remain computationally tractable. This paper is the first to enforce MMFE consistency requirements within an MDP formulation that preserves tractability.

This article is part of the theme issue ‘The mathematics of energy systems’.
An econometric model for intraday electricity trading
Authors: Kremer Marcel , Kiesel Rüdiger , Paraschiv Florentina
Published: June 2021

This paper develops an econometric price model with fundamental impacts for intraday electricity markets of 15-min contracts. A unique dataset of intradaily updated forecasts of renewable power generation is analysed. We use a threshold regression model to examine how 15-min intraday trading depends on the slope of the merit order curve. Our estimation results reveal strong evidence of mean reversion in the price formation mechanism of 15-min contracts. Additionally, prices of neighbouring contracts exhibit strong explanatory power and a positive impact on prices of a given contract. We observe an asymmetric effect of renewable forecast changes on intraday prices depending on the merit-order-curve slope. In general, renewable forecasts have a higher explanatory power at noon than in the morning and evening, but price information is the main driver of 15-min intraday trading.

This article is part of the theme issue ‘The mathematics of energy systems’.
Evolutionary tracking of cancer haplotypes at single-cell resolution
Authors: Williams Marc J , Funnell Tyler , O’Flanagan Ciara H , McPherson Andrew , Salehi Sohrab , Vázquez-García Ignacio , Kabeer Farhia , Lee Hakwoo , Masud Tehmina , Eirew Peter , Yap Damian , Wang Beixi , Brimhall Jazmine , Biele Justina , Ting Jerome , Beatty Sean , Lai Daniel , Pham Jenifer , Grewal Diljot , Abrams Douglas , Havasov Eliyahu , Leung Samantha , Bojilova Viktoria , Weiner Adam C , Rusk Nicole , Uhlitz Florian , Ceglia Nicholas ,   IMAXT consortium, Aparicio Samuel , Shah Sohrab P.
Published: June 2021

Cancer genomes exhibit extensive chromosomal copy number changes and structural variation, yet how allele specific alterations drive cancer genome evolution remains unclear. Here, through application of a new computational approach we report allele specific copy number alterations in 11,097 single cell whole genomes from genetically engineered mammary epithelial cells and 21,852 cells from high grade serous ovarian and triple negative breast cancers. Resolving single cell copy number profiles to individual alleles uncovered genomic background distributions of gains, losses and loss of heterozygosity, yielding evidence of positive selection of specific chromosomal alterations. In addition specific genomic loci in maternal and paternal alleles were commonly found to be altered in parallel with convergent phenotypic transcriptional effects. Finally we show that haplotype specific alterations trace the cyclical etiology of high level amplifications and reveal clonal haplotype decomposition of complex structures. Together, our results illuminate how allele and haplotype specific alterations, here determined across thousands of single cell cancer genomes, impact the etiology and evolution of structural variations in human tumours.
Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells
Authors: Oelen Roy , de Vries Dylan H. , Brugge Harm , Gordon Gracie , Vochteloo Martijn ,   BIOS Consortium, Ye Chun J. , Westra Harm-Jan , Franke Lude , van der Wijst Monique G.P.
Published: June 2021

Gene expression and its regulation can be context-dependent. To dissect this, using samples from 120 individuals, we single-cell RNA-sequenced 1.3M peripheral blood mononuclear cells exposed to three different pathogens at two time points or left unexposed. This revealed thousands of cell type-specific expression changes (eQTLs) and pathogen-induced expression changes (response QTLs) that are influenced by genetic variation. In monocytes, the strongest responder to pathogen stimulations, genetics also affected co-expression of 71.4% of these eQTL genes. For example, the pathogen recognition receptor CLEC12A showed many such co-expression interactions, but only in monocytes after 3h pathogen stimulation. Further analysis linked this to interferon-regulating transcription factors, a finding that we recapitulated in an independent cohort of patients with systemic lupus erythematosus, a condition characterized by increased interferon activity. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.
Differentiation of Peritubular Myoid-Like Cells from Human Induced Pluripotent Stem Cells
Authors: Robinson Meghan , Witherspoon Luke , Willerth Stephanie , Flannigan Ryan
Published: June 2021

Spermatogenesis is a complex process requiring intricate cellular interactions between multiple cell types to produce viable sperm. Peritubular myoid cells (PTMs) are smooth muscle cells that line the seminiferous tubules and play a critical role in sperm production by providing mechanical support and molecular signaling factors. In vitro investigation of their contribution to spermatogenesis and their dysfunction in infertility is currently limited by the rare accessibility of human testicular tissue for research. Therefore, this study set forth to generate an alternative source of PTMs using human induced pluripotent stem cells (hiPSCs) - adult cells that have been reprogrammed into a pluripotent state, making them capable of indefinite expansion and the regeneration of any cell type in the body. PTMs and Leydig cells arise from a common progenitor, so we hypothesized that PTMs could be derived by modifying an existing differentiation protocol for Leydig cell differentiation from hiPSCs. These hiPSC-derived cells, or hPTMs, were characterized and compared to hiPSC-derived Leydig cells (hLCs) and human primary Sertoli cells as a negative control. Our findings show that the substitution of the molecular patterning factor Platelet-Derived Growth Factor Subunit B (PDGF-BB) for Platelet-Derived Growth Factor Subunit A (PDGF-AA) in a molecule-based differentiation protocol for deriving Leydig-like cells, is sufficient to derive peritubular myoid-like cells. This study describes a method for generating PTM-like cells from hiPSCs. These cells will allow for ongoing understanding of the cellular interactions required for normal spermatogenesis in an in vitro setting.
Self-reported adaptability among postgraduate dental learners and their instructors: accelerated change induced by COVID-19
Authors: Otaki Farah , Amir-Rad Fatemeh , Al-Halabi Manal , Baqain Zaid , Zary Nabil
Published: June 2021

It is forecasted that the skills and competencies necessary for post-pandemic success in higher education need to be founded upon adaptability, coping, and Self-regulated Learning (SRL). It is worth investigating how stakeholders perceived their adaptability and coping with the accelerated change accompanying COVID-19. Accordingly, the purpose of this study was to assess the self-reported adaptability of postgraduate dental learners and their instructors in the context of abrupt transition to distance learning induced by the pandemic.

This study utilized a convergent mixed methods study design. The qualitative and quantitative data were concurrently collected from instructors and learners. The datasets were analyzed independently, and the generated information was integrated using a joint model analysis.

The percentage of average of self-reported adaptability of both groups was 81.15%. The instructors, with a mean of satisfaction of 17.94 (±1.76), rated their adaptability significantly higher than the learners, with a mean of satisfaction of 15.66 (±2.77) (p=0.002). The thematic analysis resulted in two interrelated themes: Self and Environment. Within the Self theme, three subthemes surfaced: Cognitions, Emotions, Behaviors. As for the Environment theme, it encapsulated two subthemes: Enablers and Impediments.

The stakeholders perceived themselves to have adapted well to the transition, and SRL appeared as a cornerstone in the adaptation to the accelerated change (accompanying COVID-19). There appeared to be an interplay between the cognitions, emotions, and behaviors on the level of the self as part of the adaptation process. Also, building upon existent models of SRL, this study uncovered that the stakeholders considered the environment to play a crucial role in their adaptation process. This highlights the importance of developing a climate that remains, despite external pressures, conducive to attaining learning and teaching goals. It is also crucial for university-level mental health promotion activities to proactively foster, among learners and instructors, adaptability, building ‘academic resilience’.
Epitope-Based Peptide prediction of vaccine against European bat lyssaviruses type 2 Glycoprotein G with Immunoinformatic Approach
Authors: Gumaa Manal A. , Idris Abeer Babiker , Bashir H. , Dawoud Enas dk. , Lina Elhassn. , Hassan Mohamed A.
Published: June 2021

Objective

European bat lyssaviruses (EBLV) type 2 is present in many European countries. Infection is usually seen in bats, the primary reservoirs of the viruses. Human deaths have been documented within few days following bat exposures. So, it is very useful to design an insilco peptide vaccine for European bat lyssaviruses type 2 virus using glycoprotein G as an immunogen to stimulate protective immune response

Results

B cell tests were conducted for Bepipred with 15 conserved epitopes, Emini surface accessibility prediction with 7 conserved epitopes in the surface and Kolaskar and Tongaonkar antigenicity tested with three conserved epitopes being antigenic. 357 conserved epitopes were predicted to interact with different MHC-1 alleles with (IC50) ≤500 while 282 conserved epitopes found to interact with MHC-II alleles with IC50≤ 1000. Among all tested epitopes for world population coverage the epitope VFSYMELKV binding to MHC11 alleles was 97.94% and it found to bind 10 different alleles that indicate strong potential to formulate peptide vaccine for lyssaviruses type 2 virus. To the best of our knowledge this is the first study to propose peptide vaccine for European bat lyssavirus type 2.
Postnatal lymph node expansion of stromal progenitors towards reticular and CD34+stromal cell subsets is determined by distinct transcriptional programs
Authors: Pezoldt Joern , Wiechers Carolin , Litovchenko Maria , Biocanin Marjan , Zou Mangge , Sitnik Katarzyna , Beckstette Michael , Chen Wanze , Gardeux Vincent , Floess Stefan , Ebel Maria , Russeil Julie , Arampatzi Panagiota , Vafardanejad Ehsan , Saliba Antoine-Emmanuel , Deplancke Bart , Huehn Jochen
Published: June 2021

Gut-draining mesenteric lymph nodes (mLN) provide the framework and microenvironment to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in composition and immuno-modulatory function of SCs.

Here, we dissect the tissue-specific epigenomic DNA accessibility and CpG methylation landscape of LN non-endothelial SCs and identify a microbiota-independent core epigenomic signature of LN SCs. By combined analysis of transcription factor (TF) binding sites together with the gene expression profiles of non-endothelial SCs, we delineated TFs poising skin-draining peripheral LN (pLN) SCs for pro-inflammatory responses. Furthermore, using scRNA-seq, we dissected the developmental trajectory of mLN SCs derived from postnatal to aged mice, identifying two distinct putative progenitors, namely CD34+SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid postnatal LN expansion. Finally, we identifiedIrf3as a key differentiation TF inferred from the epigenomic signature of mLN SCs that is dynamically expressed along the differentiation trajectories of FRCs, and validatedIrf3as a regulator of Cxcl9+FRC differentiation.

Together, our data constitute a comprehensive transcriptional and epigenomic map of mLN development and dissect location-specific, microbiota-independent properties of mLN non-endothelial SCs. As such, our findings represent a valuable resource to identify core transcriptional regulators that impinge on the developing mLN early in life, thereby shaping long-lasting intestinal adaptive immune responses.
In-depth sequence-function characterization reveals multiple paths to enhance phenylalanine ammonia-lyase (PAL) activity
Authors: Trivedi Vikas D. , Chappell Todd C. , Krishna Naveen B. , Shetty Anuj , Sigamani Gladstone G. , Mohan Karishma , Ramesh Athreya , R. Pravin Kumar , Nair Nikhil U.
Published: June 2021

Phenylalanine ammonia-lyases (PALs) deaminate L-phenylalanine to trans-cinnamic acid and ammonium and have idespread application in chemo-enzymatic synthesis, agriculture, and medicine. In particular, the PAL from Anabaena variabilis (Trichormus variabilis) has garnered significant attention as the active ingredient in Pegvaliase®, the only FDA-approved drug treating classical phenylketonuria (PKU). Although an extensive body of literature exists on structure, substrate-specificity, and catalytic mechanism, protein-wide sequence determinants of function remain unknown, which limits the ability to rationally engineer these enzymes. Previously, we developed a high-throughput screen (HTS) for PAL, and here, we leverage it to create a detailed sequence-function landscape of PAL by performing deep mutational scanning (DMS). Our method revealed 79 hotspots that affected a positive change in enzyme fitness, many of which have not been reported previously. Using fitness values and structure-function analysis, we picked a subset of residues for comprehensive single- and multi-site saturation mutagenesis to improve the catalytic activity of PAL and identified combinations of mutations that led to improvement in reaction kinetics in cell-free and cellular contexts. To understand the mechanistic role of the most beneficial mutations, we performed QM/MM and MD and observed that different mutants confer improved catalytic activity via different mechanisms, including stabilizing first transition and intermediate states and improving substrate diffusion into the active site, and decreased product inhibition. Thus, this work provides a comprehensive sequence-function relationship for PAL, identifies positions that improve PAL activity when mutated and assesses their mechanisms of action.
Linking parasitism to network centrality and the impact of sampling bias in its interpretation
Authors: Xu Zhihong , MacIntosh Andrew J. J. , Castellano-Navarro Alba , Macanás-Martínez Emilio , Suzumura Takafumi , Duboscq Julie
Published: June 2021

Abstract

Group living is beneficial for individuals, but also comes with costs. One such cost is the increased possibility of pathogen transmission because increased numbers or frequencies of social contacts are often associated with increased parasite abundance or diversity. The social structure of a group or population is paramount to patterns of infection and transmission. Yet, for various reasons, studies investigating the links between sociality and parasitism in animals, especially in primates, have only accounted for parts of the group (e.g., only adults), which is likely to impact the interpretation of results. Here, we investigated the relationship between social network centrality and an estimate of gastrointestinal helminth infection intensity in a whole group of Japanese macaques (Macaca fuscata). We then tested the impact of omitting parts of the group on this relationship. We aimed to test: (1) whether social network centrality – in terms of the number of partners (degree), frequency of interactions (strength), and level of social integration (eigenvector) – was linked to parasite infection intensity (estimated by eggs per gram of faeces, EPG); and, (2) to what extent excluding portions of individuals within the group might influence the observed relationship. We conducted social network analysis on data collected from one group of Japanese macaques over three months on Koshima Island, Japan. We then ran a series of knock-out simulations. General linear mixed models showed that, at the whole-group level, network centrality was positively associated with geohelminth infection intensity. However, in partial networks with only adult females, only juveniles, or random subsets of the group, the strength of this relationship - albeit still generally positive - lost statistical significance. Furthermore, knock-out simulations where individuals were removed but network metrics were retained from the original whole-group network showed that these changes are partly a power issue and partly an effect of sampling the incomplete network. Our study indicates that sampling bias can thus hamper our ability to detect real network effects involving social interaction and parasitism. In addition to supporting earlier results linking geohelminth infection to Japanese macaque social networks, this work introduces important methodological considerations for research into the dynamics of social transmission, with implications for infectious disease epidemiology, population management, and health interventions.