bluuebunny/crossref_metadata_2025_split huggingface dataset:
Processing Human Milk to Increase Nutrient Density for Preterm Infants
Authors: Ulus Hande Z. , Watkins Ruth H. , Allen Jonathan C 
Published: June 2021

Breast milk is the optimal food for infants. It is tailor‐made for each species and each birth. Preterm birth can cause problems with initiation of lactation especially if it is the first pregnancy of the mother, and infants may have inadequate suckling reflexes. In this situation direct intragastric feeding can use donor breast milk from a milk bank, infant formula, or a combination. Concerns regarding the choice of feed are catch‐up growth and health effects. Formula might cause necrotizing enterocolitis and negative long term health effects but has faster catch‐up growth. Preterm infants have better tolerance for human milk, but lower caloric density of term mothers' milk or donor milk might not meet preterm infant growth needs. Preterm infants have higher needs for calories and protein and have a very limited stomach capacity.Aims of this study were to concentrate donor breast milk to have a higher caloric density and protein, but at the same time avoiding side effects of higher lactose concentration and hyperosmolarity by precipitating lactose at low temperature.Donor breast milk was obtained from WakeMed Mothers' Milk Bank. For preliminary results 10 human milk samples of 50 mL were concentrated by evaporation (Rotavap Buchi R‐300) to different concentration levels, held at 0°C overnight, followed by refrigerated centrifugation for lactose removal. Measurement of lactose was performed with enzymatic analysis via Roche Lactose/D‐Galactose kit on skim milk supernate and remixed skim milk.Preliminary data found that low temperature removal of lactose from unprocessed human milk was minimal. Therefore milk was concentrated to varying extents prior to freezing. Volume reductions were 63%, 48%, 40%, 30% and 28%. Macronutrients were concentrated in the milks during the evaporation procedure in proportion to the amount of water removed, so caloric density was higher. Volume reduction (%) vs. Lactose concentration (g/L) yielded a linear relationship (Lactose =1.25 * volume‐reduction +3.50, r2=.77, p<0.05). Lactose was not consistently precipitated at the lower levels of volume reduction.Water can be effectively removed from human milk by low pressure evaporation at temperatures that are unlikely to denature bioactive substances. Regression analysis found that every percent of concentration increased 1.2 g/L of lactose in milk, but the effectiveness of low temperature lactose precipitation was not statistically significant. Similar concentration should be true for protein and other bioactive factors. Additional research is needed to devise techniques to further reduce the osmotic activity in the donor milk concentrate generated by the increased lactose concentration.Support or Funding InformationUSDA HatchProject NC02435; Fulbright Foundation Scholarship to HZU.
Evo‐Devo, epigenetics, niche construction and the Extended Evolutionary Synthesis: crucial implications for anatomical and medical sciences in the 21st century
Authors: Diogo Rui 
Published: June 2021

It is a puzzling paradox that eco‐morphological mismatches occur so frequently in an evolutionary process that often leads to macroevolutionary trends and in which organisms are said to be ‘designed’ for the habitats they inhabit. Here I present a new framework ‐ Organic Nonoptimal Constrained Evolution (ONCE) ‐ to address this paradox, and to explain why organisms look as they look: organisms themselves, and in particular their behavior, are the major active players of evolution. That is, within this framework, internal factors can both decrease and increase plasticity/hidden variation and therefore, together with epigenetic factors influenced by the external environment, can allows organisms to shift their behavior, for instance as a response to environmental changes. Importantly, due to behavioral persistence related to behavioral/ecological inheritance, organisms as diverse as bacteria, plants and animals help to construct their own niches, thus being crucial to direct evolution. Darwinian natural (external) selection then comes into play as a secondary ‐ but still crucial ‐ player. That is, due to organismal behavioral persistence, the random mutations/epigenetic factors that happen to be advantageous within the niches constructed by the organisms will be selected, further directing evolution and increasing the match between behavior, phenotype, and environment. This process can extend for long periods of time, leading to macroevolutionary trends and further increasing this match, potentially resulting in successful phenotypic overspecialization. However, behavioral persistence, loss of plasticity due to natural selection, genetic drift, overspecialization, and internal constraints can often make it difficult for the organisms to respond behaviorally and/or anatomically to new environmental changes, resulting in potential mismatches between behavior, ecology and form, and eventually in extinction. This new framework therefore bridges the gap between ideas that have been long considered to be opposing views of biology since Aristotle, including internalism and externalism, Cuvier's vs. Geoffroy's take on form and function, Darwinism and Lamarkism, the ideas of Baldwin, Waddington and Goldschmidt, and current Evo‐Devo ideas such as a physicalist framework, niche construction and epigenetic plasticity. This talk therefore covers ‐ and aims to link ‐ areas as diverse as evolutionary developmental biology, paleontology, evolutionary biology, comparative anatomy, ecomorphology, functional anatomy, ecology, ethology, biological anthropology, evolutionary medicine and history and philosophy of biology.Support or Funding InformationSupport from NSF (1516557) and American Association of Anatomists Innovations Program
A Race‐Specific Interaction Between Vitamin K Status and Statin Use During Warfarin Therapy Initiation
Authors: Kelly Jennifer M , Harshman Stephanie G , Brensinger Colleen M , Barger Kathryn , Kimmel Stephen E , Booth Sarah L 
Published: June 2021

Vitamin K (VK) is required for the post‐translational modification of several clotting factors. Warfarin is a vitamin K antagonist and anticoagulant. The most common dietary and circulating form of VK is phylloquinone (PK). PK is lipid soluble, carried by triglyceride‐rich lipoproteins, and shares a metabolic pathway with cholesterol. Thus, there is biological plausibility for an interaction between serum PK and lipid‐lowering medications (statins) in warfarin therapy.The objective of this study was to examine if serum PK and/or statin treatment was associated with anticoagulation control in African Americans and Caucasians initiating warfarin therapy. Warfarin sensitivity differs between African Americans and Caucasians, so analyses were race‐specific.Cox proportional hazards and linear regression models were used in a cross‐sectional analysis of the 2009–2013 International Normalized Ratio Adherence and Genetics II cohort of African Americans (n=331; 40% female) and Caucasians (n=140; 36% female) initiating warfarin therapy. Primary exposures included serum PK (categorized as quartiles 1: PK<0.6, 2: 0.6≤PK≤1.0, 3: 1.0<PK≤1.7, 4: PK>1.7nmol/L) and statin use. Outcomes included number of days to maintenance dose and percent time in the therapeutic range (PTTR). Covariates included age, sex, smoking status, serum triglycerides, BMI, and clinic site.A significant interaction between serum PK quartile and statin use with respect to days to maintenance was detected in Caucasians (p=0.04), but not African Americans (p=0.81). In Caucasians taking statins (n=60), the rate to reach maintenance was 88% (HR=0.12, 95%CI 0.04–0.39) and 81% (HR=0.19, 5%CI 0.06–0.53) slower for those in the second and third serum PK quartiles, respectively, compared to those in the lowest quartile. The rate to reach maintenance did not differ between the highest and lowest serum PK quartiles (HR=0.84, 95% CI 0.26–2.70) or between any quartiles among Caucasians not taking statins (n=80, p=0.67). In African Americans, serum PK was not associated with the rate to reach maintenance whether they used statins (n=140, p=0.98) or not (n=191, p=0.23). Serum PK and statin use were not associated significantly with PTTR in either race.Statin use appears to slow the rate to establish maintenance warfarin dose among Caucasians with moderate serum PK. This apparent drug‐drug‐nutrient interaction suggests PK status and lipid‐lowering medication may influence anticoagulation for Caucasians during warfarin therapy initiation. The role of vitamin K with statin use in anticoagulation therapy in different races requires further examination.Support or Funding InformationSupported by: USDA, Agricultural Research Service under Cooperative Agreements No. 58‐1950‐7‐707 and NIH‐NHLBI R01HL06617606A1.
Dietary cranberry alleviated colonic inflammation and altered gut microbiota in mice
Authors: Cai Xiaokun , Gu Min , Song Mingyue , Li Zhengze , Li Fang , Goulette Timothy , You Xiaomeng , Sela David A. , Xiao Hang 
Published: June 2021

Increased consumption of fruits such as cranberry may decrease the risk of several chronic diseases such as inflammatory bowel disease (IBD). However, the exact mechanism of actions of dietary cranberry is unknown. In this study, we determined the effects of whole cranberry powder on IBD as well as the structure of gut microbiota in a mouse model of IBD induced by dextran sodium sulfate (DSS). Our results showed that dietary cranberry treatment significantly decreased the severity of IBD in DSS‐treated mice, evidenced by that cranberry treatment significantly increased colon length, and decreased disease activity and histologic score of IBD in DSS‐treated mice compared to the positive control group (p < 0.05). Moreover, the colonic levels of pro‐inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) were significantly reduced by cranberry treatment (p<0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels reveled that DSS treatment significantly altered the microbial structure of fecal microbiota in mice, and dietary cranberry treatment partially reversed these alterations. Our results also demonstrated that DSS treatment significantly increased the relative abundance of Akkermansia and Sutterella, and decreased the abundance of Bifidobacterium and Lactobacillus in the mouse feces, which was associated with the development of IBD. Importantly, dietary cranberry treatment inhibited Akkermansia and Sutterella, and promoted Bifidobacterium and Lactobacillus in DSS‐treated mice. Overall, our results for the first time suggested that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of IBD.Support or Funding InformationThis study was partially supported by fund from USDA and Cranberry Institute.
Oral administration of curcumin and salsalate attenuates high fat diet‐induced up‐regulation of pro‐inflammatory colonic cytokines and suppresses Akt/NFκB signaling in azoxymethane‐treated mice
Authors: Wu Xian , Pfalzer Anna C , Koh Gar Yee , Crott Jimmy W , Tang Sanyuan , Thomas Michael J , Meydani Mohsen , Mason Joel B 
Published: June 2021

BackgroundObesity, a robust risk factor for colorectal cancer (CRC), is known to elevate the concentrations of pro‐inflammatory cytokines in the murine colon. Also, signaling through the Akt pathway, which is known to be activated by pro‐inflammatory cytokines, is thought to play a role in colorectal carcinogenesis, in part by enhancing NFκB signaling. Further, we have previously demonstrated that high fat diets (HFD) and excess adiposity each alter the expression of the regulators of colonic Akt signaling in a pattern suggestive of Akt activation.ObjectiveWe sought to determine whether the combination of a pharmacologic agent and a dietary component that each possesses anti‐inflammatory properties might suppress obesity‐induced elevations in colonic cytokines and Akt/NFκB signaling, with the ultimate intent of mitigating the cancer‐promoting effect of obesity.MethodsCurcumin (CUR), a natural polyphenol in turmeric, and salsalate (SAL) a non‐steroidal anti‐inflammatory drug (NSAID) that lacks the gastrointestinal toxicity of other NSAIDs, were tested alone and in combination in the azoxymethane (AOM) model of colonic carcinogenesis in 110 A/J mice, randomized to five groups including a control group receiving a low‐fat diet. AOM (7 mg/kg body weight, 4 weekly injections) in combination with a HFD that contained 60% kcals as fat was used induce a pro‐tumorigenic milieu in the colons of mice.ResultsThe results showed that HFD‐mice had 30.4% greater fat mass and a lower lean mass than did low‐fat diet (10% kcal fat, LFD, p<0.005)‐mice. In the colonic mucosa of the obese mice addition of CUR and SAL (0.2% and 0.15% w/w, respectively) to the diet significantly diminished concentrations of IL‐1β and IL‐6 (p<0.015). Moreover, CUR/SAL co‐treatments also profoundly suppressed phosphorylation of Akt (p<0.044) and concurrently suppressed NF‐κB p65 signaling (p<0.042).ConclusionsOur results demonstrate, for the first time, that co‐administration of CUR and SAL in very low, well‐tolerated, concentrations attenuates inflammatory cytokine levels, Akt activation, and NFkB signaling in the colons of AOM/HFD mice, providing a scientific rationale for using this combination as a chemopreventive regimen to mitigate the risk of obesity‐associated colon cancer.Support or Funding InformationTufts Collaborates Grant; United States Department of Agriculture, Cooperative Agreements #58‐1950‐0‐014 and #58‐1950‐4‐003
Quantitative Real Time PCR (qRT‐PCR) Evaluation of Pig Mitochondrial DNA Damage
Authors: Barr Johnny L , Thomas Theo W , Gibson Ruby S , Dubick Michael A , Bowman Phillip D 
Published: June 2021

Mitochondrial DNA (MtDNA) damage has generated much interest in recent years as a potential biomarker after ischemia/reperfusion and traumatic injury and in critical illness. MtDNA is particularly susceptible to damage due to is close proximity to the source of generation of reactive oxygen species during metabolism and its relatively low ability to repair DNA damage compared to nuclear repair mechanisms. Reduction in MtDNA damage appears to be a good indicator of a successful intervention. QRT‐PCR has been shown to be the most sensitive and accurate method to evaluate mtDNA damage requiring only nanogram amounts of DNA. While validated primer pairs for mtDNA damage for human and rodent mtDNA damage are available, comparable sets for pig have not previously been described, yet many studies in trauma and critical illness have utilized swine models. To select primer pairs for pigs, we aligned the pig mitochondrial DNA sequence to the pig genome in the UCSC Genome Browser and primers for regions not exhibiting overlap with the nuclear genome were selected with NCBI Primer3. Using the bleomycin injury model, porcine pulmonary artery endothelial cells obtained from Cell Biologics and cultivated in MCDB 131 medium were treated for 1 hr with bleomycin (10 μg/ml). Short and long sequences were tested with pig total DNA and demonstrated that one set detected specific induction of DNA lesions. The assay was able to detect 11 lesions per 10,000 base pairs. The short primer pairs also accurately predicted mitochondrial copy number DNA as corroborated for mtDNA by published results for the pig ND4 gene. We are currently employing this assay to detect mtDNA damage in a swine model of hemorrhagic shock.Support or Funding InformationFunded by US Army Medical Research Materiel Command
Phylogenetic Analysis of RuBIsCO: An Active Learning Strategy for Teaching Plant Evolution
Authors: Van Stry Melanie 
Published: June 2021

Lane College is a small historically black college located in Jackson, TN. The majority of the students are underserved African Americans from areas of high poverty. General Biology at Lane College is a foundational survey course required for Biology majors and Physical Education majors. Topics covered in the second semester of the course include natural selection, evolution, biodiversity, and ecology. This course is especially challenging for students given the large amount of information that they are typically required to memorize. We are currently implementing a peer‐led team learning strategy to enable students to actively engage in learning core concepts outlined in Vision and Change. The learning goal for the exercise presented here is to explore the evolutionary relatedness of different plant species. The learning objectives for this exercise are for students to understand plant taxonomy and to analyze the DNA evidence for the origin of the chloroplast through a phylogenetic comparison of the ribulose‐1,5 bisphosphate carboxylase/oxidase large subunit (rbcl) gene and to understand plant taxonomy. Prior to coming to class, the students are given a reading assignment for the Land Plants chapter in their textbook. During the first class meeting, at the beginning of the exercise, the students are divided into teams of four. Each team is assigned a set of four unknown DNA sequences from closely related plant or algal species, and each student chooses a sequence. Each student then uses the standard Basic Alignment Search Tool (BLAST) to identify the gene and their plant species for their sequence. The students then answer specific questions about their plant or algal species regarding taxonomic classification. Next, each student creates a sequence alignment of the entire class set of sequences and constructs a phylogenetic tree using CLUSTAL Omega. They then compare their phylogenetic tree with the one from their textbook and discuss the similarities and differences between the trees. At the next class meeting, each group presents a short summary of the characteristics for their assigned plant clade.Support or Funding InformationNational Science Foundation: HRD 1623340
Experiences of Undergraduate Students Identifying Proteins of Unknown Function As Part of a Teaching Laboratory in a Biochemistry Course
Authors: Daubner Susan Colette , Beckman John , Gastelum Jazmin Beltran , Mallet Sarah , Vogt Ellysa 
Published: June 2021

In the laboratory section of Biochemistry II at St. Mary's University, we are performing a series of experiments involving authentic scientific inquiry. The experiments' goal is to identify the functions of a handful of unknown proteins. The curriculum relies heavily on both in silico and in vitro biochemistry techniques. Faculty and students pick the proteins by looking through the PDB list of crystallized proteins that have no known function. Since these proteins have been crystallized, they have already been cloned and purified; we know we are likely to be able to isolate suitable quantities of the proteins for work. We ascertain ahead of time that their coding vectors are available to us from sources such as DNASU or AddGene. We analyze the sequences of potential proteins using internet programs such as Pfam, Dali, BLAST, and HHPred. Good alignment with characterized proteins allows us to make hypotheses for the function of the unknown ones. We use the PyMol plug‐in ProMol to look for arrangements of active site residues common to certain categories of enzymes. For example, we used the triad of serine, histidine, and aspartate from chymotrypsin to identify possible hydrolases. We use the three‐dimensional alignment function of the program Chimera to see whether our unknown proteins resemble the known proteins that are thought to be similar. We overexpress the unknown proteins in E. coli, and purify the enzymes taking advantage of their engineered tags. The spring 2016 class focused on and was successful in broadly identifying four unknown hydrolases. Of these, three were lipases and one was a nuclease. We are extending that success by purifying and assaying additional hydrolases in spring 2017. After every lab in the pilot semester students reported on their experiences, and they presented posters at a University research symposium. The student authors of this poster will either have performed the pilot semester (SM) or be involved in the second round of the curriculum (JB, JB, and EV). They will report on their experiences, their experiments, their findings and whether this innovative teaching lab affected their attitudes toward the inquiry process.Support or Funding InformationThis work is funded by NSF DUE‐1502720.
Architecture of the Nucleosome Remodeling and Deacetylase (NuRD) Complex
Authors: Low Jason K.K. , Silva Ana P.G. , Sharifitabar Medhi , Torrado Mario , Schmidberger Jason , Webb Sarah R. , Saathoff Hinnerk , Parker Benjamin L. , Paudel Bishnu , van Oijen Antoine , Landsberg Michael J , Shepherd Nicholas E. , Mackay Joel P. 
Published: June 2021

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a ~1‐MDa 10‐subunit transcriptional co‐regulator that plays essential roles in hematopoietic development, stem cell renewal and DNA repair, and is emerging as a central player in diseases ranging from cancer to thalassemia.Despite the importance of this complex, little is known about its structure and biochemical activity. Hence, knowledge of NuRD structure and function will provide broad insight into mechanisms of eukaryotic gene regulation.To address this deficit, we are using a barrage of biochemical and biophysical approaches. We recently showed that the NuRD complex can exist as a separate stable entity (without CHD4) dubbed the NuDe (Nucleosome Deacetylase) complex — disrupting the architectural paradigm that CHD4 is an integrated core component of the complex (1). In addition, a combination of mass spectrometry and single‐particle electron microscopy has allowed us to piece together the architecture of NuRD through its subcomplexes at (quite) low resolution (2). Last but not least, we are now utilising single‐molecule fluorescence to observe the remodeling activity of individual NuRD complexes in real time. This could reveal the biochemical mechanism by which this complex remodels chromatin during gene transcription and DNA repair.Support or Funding InformationAustralian Research Council (DE120102857) Australian National Health and Medical Research Council (APP1012161 and 571099)