Knowledge Hidden in Nuances: From Molecules to Society

The Goal: We have discussed the theme of reintegrating biology several times at the national level over several decades (ex. A New Biology for the 21st Century, National Academy of Sciences, 2009). While these discussions are fruitful and certainly the topic may require an adaptive framework, we suggest a fundamental change in how the scientific community approaches this topic. In particular, we propose that biology can only be integrated when the structural, societal and methodological barriers to participation in biology are alleviated. A focus on the average or most prevalent approach or system - whether it is the structure of a protein, a biological process or pathway, or the average scientist - they all end up excluding observations, people, and ideas. In contrast, we propose a focus on and inclusion of nuances will enable us to examine the boundaries and rarer instances whether of topic or of people, enable us to explore, and learn from diversity that is currently unnoticed and may provide new perspectives, insights about the range of possibilities, and solutions to current challenges. By extending this paradigm to our society, including diverse perspectives and experiences may shed light on how we can learn about new ideas, tools, and resources to enhance our collective toolkits and approach solutions for problems we are addressing. The paper will compare the benefits of applying a nuanced approach at a molecular, cellular, organismal, and population levels and then extend this thinking to science and society. We think that including individuals and perspectives that are beyond the current majority/mainstream will enhance our understanding and ability to approach/address problems. Adding nuance to our understanding of science can come from better inclusion and integration. The intended audience for our Vision paper includes the National Science Foundation (NSF), academic and research institutions, and society at large. We hope that NSF has the potential to create and support opportunities for multiscale scientific explorations at the edge of the boundary (outside the averages). Knowledge derived from these observations and analyses can inspire new perspectives and/or solutions that are universally usable. Additionally, other Vision groups in the Reintegrating Biology meetings include topics that could benefit from the vision presented here (space, time, resilience, modelling, communication/signalling, networks, animal learning, biocomplexity). Academic and research institutions may utilize the proposed framework to review their institutional policies that directly or indirectly (via access to resources, opportunities etc.,) restrict collaborations based on interests and expertise. Our hope for society at large is to consider including, sharing, and respecting diverse perspectives and experiences

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed

Microclimate variables of the ambient environment deliver the actual estimates of the extrinsic incubation period of Plasmodium vivax and Plasmodium falciparum : A study from a malaria-endemic urban setting, Chennai in India

Background: Environmental factors such as temperature, relative humidity and their daily variation influence a range of mosquito life history traits and hence, malaria transmission. The standard way of characterizing environmental factors with meteorological station data need not be the actual microclimates experienced by mosquitoes within local transmission settings. Methods: A year-long study was conducted in Chennai, India to characterize local temperature and relative humidity (RH). Data loggers (Hobos) were placed in a range of probable indoor and outdoor resting sites of Anopheles stephensi. Recordings were taken hourly to estimate mean temperature and RH, together with daily temperature range (DTR) and daily relative humidity range. The temperature data were used to explore the predicted variation in extrinsic incubation period (EIP) of Plasmodium falciparum and Plasmodium vivax between microhabitats and across the year. Results: Mean daily temperatures within the indoor settings were significantly warmer than those recorded outdoors. DTR in indoor environments was observed to be modest and ranged from 2 to 6 °C. Differences in EIP between microhabitats were most notable during the hottest summer months of April-June, with parasite development predicted to be impaired for tiled houses and overhead tanks. Overall, the prevailing warm and stable conditions suggest rapid parasite development rate regardless of where mosquitoes might rest. Taking account of seasonal and local environmental variation, the predicted EIP of P. falciparum varied from a minimum of 9.1 days to a maximum of 15.3 days, while the EIP of P. vivax varied from 8.0 to 24.3 days. Conclusions: This study provides a detailed picture of the actual microclimates experienced by mosquitoes in an urban slum malaria setting. The data indicate differences between microhabitats that could impact mosquito and parasite life history traits. The predicted effects for EIP are often relatively subtle, but variation between minimum and maximum EIPs can play a role in disease transmission, depending on the time of year and where mosquitoes rest. Appropriate characterization of the local microclimate conditions would be the key to fully understand the effects of environment on local transmission ecology

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Thermodynamic examination of the pyrophosphate sensor helix in the thiamine pyrophosphate riboswitch

Riboswitches are functional mRNA that control gene expression. Thiamine pyrophosphate (TPP) binds to thi-box riboswitch RNA and allosterically inhibits genes that code for proteins involved in the biosynthesis and transport of thiamine. Thiamine binding to the pyrimidine sensor helix and pyrophosphate binding to the pyrophosphate sensor helix cause changes in RNA conformation that regulate gene expression. Here we examine the thermodynamic properties of the internal loop of the pyrophosphate binding domain by comparing the wild-type construct (RNA WT) with six modified 2 × 2 bulged RNA and one 2 × 2 bulged DNA. The wild-type construct retains five conserved bases of the pyrophosphate sensor domain, two of which are in the 2 × 2 bulge (C65 and G66). The RNA WT construct was among the most stable (ΔG°37 = −7.7 kcal/mol) in 1 M KCl at pH 7.5. Breaking the A•G mismatch of the bulge decreases the stability of the construct ∼0.5–1 kcal/mol, but does not affect magnesium binding to the RNA WT. Guanine at position 48 is important for RNA–Mg2+ interactions of the TPP-binding riboswitch at pH 7.5. In the presence of 9.5 mM magnesium at pH 5.5, the bulged RNA constructs gained an average of 1.1 kcal/mol relative to 1 M salt. Formation of a single A+•C mismatch base pair contributes about 0.5 kcal/mol at pH 5.5, whereas two tandem A+•C mismatch base pairs together contribute about 2 kcal/mol

Student perception of peer teaching and learning in pathology: A qualitative analysis of modified seminars, fishbowls, and interactive classroom activities

Context: Peer-assisted teaching and learning (PTL) is being experimented in different medical universities worldwide. It is a learner-centered approach involving students through active learning strategies. Aims: To study the student perception of PTL in methods such as group-led seminars and fishbowls, in classroom through various interactive activities; compare and find out the student acceptability and efficacy of each of these methods in learning conceptual topics such as various types of anemia. Subjects and Methods: Medical students of second-year professional course were subjected to PTL in classroom during allotted teaching hours for 10 successive sessions using group-led modified seminars, fishbowls, and different formality-level interactive activities such as street plays, prop sessions, quiz sessions, to make them understand the clinical features and presentation of different types of anemia through understanding of etio-pathogenesis. To ascertain the aspects that influenced learning, focus group discussions were conducted in small groups consisting of 14 students and one facilitator in each group. Qualitative thematic analysis was performed on transcripts of the audio recordings by authors. Results: The emerging themes from qualitative analysis of transcripts were pertaining to teacher, student, and organization. We found motivation, interest, and involvement of peer teacher, student behavior and collaboration, contact time between students and facilitator, preparation time, coherence with other curricular activities, group size and composition, suitability of topic for the kind of activity, and availability of material for preparation as few sub-aspects affecting learning. Conclusion: For PTL to be effective, adequate transfer of knowledge through good peer teacher involvement, learner receptiveness, and adequate contact time is needed. Proper preparation with suitability of topics for the type of activity, alignment of seminars with other activities, and course coherence are prerequisites for the same

Acquired aplastic anemia associated with trisomy eight converting into acute myeloid leukemia

Aplastic anemia (AA) is nowadays considered to be a clonal disorder arising from a defective hematopoietic stem cell developing after a generalized insult to bone marrow. Immunosuppressive treatment (IST) of AA causes suppression of the target dominant population of haematopoietic cells allowing the defective non targeted clones to expand. This may give rise to acute leukemia. Cytogenetic studies for chromosomal aberrations such as trisomy and monosomy may help in detecting such conversions. We present a case of acquired AA in a 60-year-old male presenting with pancytopenia and hypoplastic marrow treated with antithymocyte globulin, converting into myelodysplastic syndrome and later on acute promyelocytic leukemia after being in remission for 4 years. The patient was found to have trisomy 8 on fluorescence in situ hybridization and karyotyping

Development and quality evaluation of polyphenols enriched black carrot (Daucus carota L.) powder incorporated bread

Black carrot is a prominent source of polyphenols and the cheapest source of anthocyanins in India. In this study, an attempt has been made to examine the feasibility of black carrot powder as an ingredient in bread. Black carrot bread was prepared by incorporating different concentrations of black carrot powder (BCP) at 2.5, 5.0, 7.5 and 10 %. The developed bread samples were analyzed for physical and textural quality, proximate composition, bioactive compounds, antioxidant properties, sensory characteristics, mineral content and storage quality. The results revealed that loaf volume and specific volume decreased (1995–1254 mL, 5.25–3.28 mL/g) with the incorporation of BCP into bread. Textural analysis revealed that the addition of BCP led to increased hardness in the bread (0.110–12 0.151 N), whereas the resilience (43.64–35.10 %), cohesion and springiness (89.930–13 82.146 %) decreased significantly. The content of bioactive compounds such as total phenols, anthocyanins (29.63–112.68 mg/100 g) and flavonoids increased to exceptionally high levels in BCP-incorporated bread and showed high antioxidant activity. Incorporation of BCP up to 7.5 % showed the most acceptable sensory analysis score (7.85) with a significant increase in dietary fiber (40 %) and total mineral content (50 %), which revealed that black carrot powder could be used up to 7.5 % as an ingredient into bread with high acceptability. The present study revealed significant enhancement in bioactive compounds and mineral content of bread after the incorporation of black carrot powder, which supports its immense potential in preventing hunger and oxidative stress-induced disorders in developing countries