Repeatability of endocrine traits and dominance rank in female guinea pigs

Background Glucocorticoids (e.g. cortisol) are associated with variation in social behavior, and previous studies have linked baseline as well as challenge-induced glucocorticoid concentrations to dominance status. It is known that cortisol response to an acute challenge is repeatable and correlates to social behavior in males of many mammal species. However, it is unclear whether these patterns are also consistent for females. The aim of this study was to investigate whether baseline and response cortisol concentrations are repeatable in female guinea pigs (Cavia aperea f. porcellus) and whether dominance rank is stable and correlated to baseline cortisol concentration and/or cortisol responsiveness. Results Our results show that cortisol responsiveness (after 1 h: R = 0.635, 95% CI = 0.229, 0.927; after 2 h: R = 0.764, 95% CI = 0.433, 0.951) and dominance rank (R = 0.709, 95% CI = 0.316, 0.935) of females were significantly repeatable after six weeks but not correlated. Baseline cortisol was not repeatable (R = 0, 95% CI = 0, 0.690) and also did not correlate to dominance rank. Furthermore, the difference in repeatability estimates of baseline and response values was due to high within-individual variance of baseline cortisol concentration; the amount of between-individual variance was similar for baseline cortisol and the two measures of cortisol responsiveness. Conclusions Females occupying different dominance ranks did not have long-term differences in cortisol concentrations, and cortisol responsiveness does not seem to be significantly involved in the maintenance of dominance rank. Overall, this study reveals the remarkable stability of cortisol responsiveness and dominance rank in a female rodent, and it remains an open question whether the magnitude of cortisol responsiveness is adaptive in social contexts for females.

Multiple horizontal acquisitions of plant genes in the whitefly Bemisia tabaci

The extent to which horizontal gene transfer (HGT) has shaped eukaryote evolution remains an open question. Two recent studies reported four plant-like genes acquired through two HGT events by the whitefly Bemisia tabaci, a major agricultural pest (Lapadula et al. 2020; Xia et al. 2021). Here, we performed a systematic search for plant-to-insect HGT in B. tabaci and uncovered a total of 50 plant-like genes deriving from at least 24 independent HGT events. Most of these genes are present in three cryptic B. tabaci species, show high level of amino-acid identity to plant genes (mean = 64%), are phylogenetically nested within plant sequences, and are expressed and evolve under purifying selection. The predicted functions of these genes suggest that most of them are involved in plant-insect interactions. Thus, substantial plant-to-insect HGT may have facilitated the evolution of B. tabaci towards adaptation to a large host spectrum. Our study shows that eukaryote-to-eukaryote HGT may be relatively common in some lineages and it provides new candidate genes that may be targeted to improve current control strategies against whiteflies.

Constructing the three-qudit unextendible product bases with strong nonlocality

The unextendible product bases (UPB) are interesting members of the family of orthogonal product bases. In this paper, we investigate the construction of 3-qudit UPB with strong nonlocality. First, a UPB set in ${{C}^{3}}\otimes {{C}^{3}}\otimes {{C}^{3}}$ of size 19 is presented based on the Shifts UPB. By mapping the system to a Rubik's Cube, we provide a general method of constructing UPB in ${{C}^{d}}\otimes {{C}^{d}}\otimes {{C}^{d}}$ of size ${{\left(d-1 \right)}^{3}}+2d+5$, whose corresponding Rubik's Cube is composed of four parts. Second, for the more general case where the dimensions of parties are different, we extend the classical tile structure to the 3-qudit system and propose the Tri-tile structure. By means of this structure, a ${{C}^{4}}\otimes {{C}^{4}}\otimes {{C}^{5}}$ system of size 38 is obtained based on a ${{C}^{3}}\otimes {{C}^{3}}\otimes {{C}^{4}}$ system of size 19. Then, we generalize this approach to ${{C}^{{{d}_{1}}}}\otimes {{C}^{{{d}_{2}}}}\otimes {{C}^{{{d}_{3}}}}$ system which also consists of four parts. Our research provides a positive answer to the open question raised in [Halder, et al., PRL, 122, 040403 (2019)], indicating that there do exist UPB that can exhibit strong quantum nonlocality without entanglement.

DNA Double Strand Break Repair and Its Control by Nucleosome Remodeling

DNA double strand breaks (DSBs) are repaired in eukaryotes by one of several cellular mechanisms. The decision-making process controlling DSB repair takes place at the step of DNA end resection, the nucleolytic processing of DNA ends, which generates single-stranded DNA overhangs. Dependent on the length of the overhang, a corresponding DSB repair mechanism is engaged. Interestingly, nucleosomes—the fundamental unit of chromatin—influence the activity of resection nucleases and nucleosome remodelers have emerged as key regulators of DSB repair. Nucleosome remodelers share a common enzymatic mechanism, but for global genome organization specific remodelers have been shown to exert distinct activities. Specifically, different remodelers have been found to slide and evict, position or edit nucleosomes. It is an open question whether the same remodelers exert the same function also in the context of DSBs. Here, we will review recent advances in our understanding of nucleosome remodelers at DSBs: to what extent nucleosome sliding, eviction, positioning and editing can be observed at DSBs and how these activities affect the DSB repair decision.

The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis

DNA methylation shapes the epigenetic landscape of the genome, plays critical roles in regulating gene expression, and ensures transposon silencing. As is evidenced by the numerous defects associated with aberrant DNA methylation landscapes, establishing proper tissue-specific methylation patterns is critical. Yet, how such differences arise remains a largely open question in both plants and animals. Here we demonstrate that CLASSY1-4 (CLSY1-4), four locus-specific regulators of DNA methylation, also control tissue-specific methylation patterns, with the most striking pattern observed in ovules where CLSY3 and CLSY4 control DNA methylation at loci with a highly conserved DNA motif. On a more global scale, we demonstrate that specific clsy mutants are sufficient to shift the epigenetic landscape between tissues. Together, these findings reveal substantial epigenetic diversity between tissues and assign these changes to specific CLSY proteins, elucidating how locus-specific targeting combined with tissue-specific expression enables the CLSYs to generate epigenetic diversity during plant development.

Integrationists, Critical Europeanists and Pessimist Europeanists: Attitudinal mindsets on the EU among German students

We investigate the mindsets on the EU of students enrolled in a German university. We conducted an online survey among students of a German university (N=730) and asked them closed questions on the EU enlargement, the allocation of authority at the EU level, the way democracy works at the EU level and an open question on their wish for the future of the EU. We then ran a latent class analysis of the recoded answer categories from the open question and of our set of closed questions. Our three-class solution highlights variation in support of the EU among students. Indeed, while the vast majority of the respondents show highly supportive attitudes toward the EU, we can distinguish between “Integrationists” (in favour of pursuing the EU integration project; 68% of the sample), “Critical Europeanists” (supportive of the EU but dissatisfied with the way democracy works at the EU level; 20,50% of the sample) and “Pessimist Europeanists” (supportive of the EU but afraid of the implosion of the EU; 11% of the sample). A further analysis of the narratives provided by members of each class to the open question enables us to shed light on variation within each latent class. In particular, we find variation (1) in the dimensions and policies the EU should further integrate according to the Europeanists, (2) in the types of EU institutions to be further democratised and strategies to improve the democratisation of the EU regime according to the Critical Europeanists and (3) in strategies the EU should follow to avoid its implosion according to the Pessimist Europeanists. Our study highlights the importance of the use of non-standardised measures and mixed-methods data collection for grasping citizens´ mindset on the EU in its multidimensionality and complexity.

Current Status of Quality Assurance Scheme in Selected Undergraduate Medical Colleges of Bangladesh

This descriptive cross sectional study was carried out to determine the current status of Quality Assurance Scheme in undergraduate medical colleges of Bangladesh. This study was carried out in eight (four Government and four Non- Government) medical colleges in Bangladesh over a period from July 2015 to June 2016. The present study had an interview schedule with open question for college authority and another interview schedule with open question for head of department of medical college. Study revealed that 87.5% of college had Quality Assurance Scheme (QAS) in their college, 75% of college authority had regular meeting of academic coordination committee in their college, 50% of college had active Medical Education Unit in their college, 87.5% of college authority said positively on publication of journal in their college. In the present study researchers interviewed 53 heads of department with open question about distribution, collection of personal review form, submission with recommendation to the academic co-coordinator, and annual review meeting of faculty development. The researchers revealed from the interviews that there is total absence of this practice which is directed in national guidelines and tools for Quality Assurance Scheme (QAS) for medical colleges of Bangladesh. Bangladesh Journal of Medical Education Vol.13(1) January 2022: 33-39

Engineering Organoids for in vitro Modeling of Phenylketonuria

Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.

Ensemble learning from ensemble docking: revisiting the optimum ensemble size problem

Despite considerable advances obtained by applying machine learning approaches in protein–ligand affinity predictions, the incorporation of receptor flexibility has remained an important bottleneck. While ensemble docking has been used widely as a solution to this problem, the optimum choice of receptor conformations is still an open question considering the issues related to the computational cost and false positive pose predictions. Here, a combination of ensemble learning and ensemble docking is suggested to rank different conformations of the target protein in light of their importance for the final accuracy of the model. Available X-ray structures of cyclin-dependent kinase 2 (CDK2) in complex with different ligands are used as an initial receptor ensemble, and its redundancy is removed through a graph-based redundancy removal, which is shown to be more efficient and less subjective than clustering-based representative selection methods. A set of ligands with available experimental affinity are docked to this nonredundant receptor ensemble, and the energetic features of the best scored poses are used in an ensemble learning procedure based on the random forest method. The importance of receptors is obtained through feature selection measures, and it is shown that a few of the most important conformations are sufficient to reach 1 kcal/mol accuracy in affinity prediction with considerable improvement of the early enrichment power of the models compared to the different ensemble docking without learning strategies. A clear strategy has been provided in which machine learning selects the most important experimental conformers of the receptor among a large set of protein–ligand complexes while simultaneously maintaining the final accuracy of affinity predictions at the highest level possible for available data. Our results could be informative for future attempts to design receptor-specific docking-rescoring strategies.

Free diffusion of PI(4,5)P2 in the plasma membrane in the presence of high density effector protein complexes

The lipid phosphatidyl-D-myo-inositol-4,5-bisphosphate [PI(4,5)P2] is a master regulator of plasma membrane (PM) function. It engages effector proteins that regulate diverse traffic, transport, signaling and cytoskeletal processes that define PM structure and function. How a single class of lipid molecules independently regulate so many parallel processes remains an open question. We tested the hypothesis that spatially segregated pools of PI(4,5)P2 are associated with, and thus reserved for regulation of, different functional complexes in the PM. The mobility of PI(4,5)P2 in the membrane was measured using lipid biosensors by single particle tracking photoactivation localization microscopy (sptPALM). We found that PI(4,5)P2, and several other classes of inner PM lipids, diffuse rapidly at approximately 0.3 microns squared per second with largely Brownian motion, although they spend approximately a third of their time diffusing much more slowly. Surprisingly, areas of the PM occupied by PI(4,5)P2-dependent complexes, such endoplasmic-reticulum:PM contact sites, clathrin-coated structures, and several actin cytoskeletal elements including focal adhesions, did not cause a change in PI(4,5)P2 lateral mobility. Only the spectrin and septin cytoskeletons were observed to produce a slowing of PI(4,5)P2 diffusion. We conclude that even structures with high densities of PI(4,5)P2-engaging effector proteins, such as clathrin coated pits and focal adhesions, do not corral free PI(4,5)P2, questioning a role for spatially segregated PI(4,5)P2 pools in organizing and regulating parallel PM functions.