bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing an enzyme selection tool supporting multiple hosts contexts
Authors: Camarena María , Carbonell Pablo 
Published: September 2021

AbstractEngineering biological organisms that allow the integration of alternative metabolic pathways to natural ones is one of the goals of synthetic biology. Based on this, some of the most attractive applications in terms of synthetic organisms manufacture include the production of a wide range of pharmacologically useful metabolites produced in a sustainable and environmentally friendly way. Also, the biostable molecules green-production involves different types of therapeutic processes, e.g. prostheses and grafts stabilisation. Regarding the viability of genetically modified organisms, metabolic pathways must be first properly designed, taking into consideration the type of host organism that will be involved in metabolic production, as well as its biochemical and environmental conditions. To ensure the correct growth of these synthetic organisms, the enzyme selection must guarantee both the organism survival (and proliferation) and the optimal production of the desired metabolite. Developing enzyme selection tools is essential to enhance and make cost-effective the metabolic pathways design. This technical note presents the update of Selenzyme, the enzyme selection tool which is based on organisms taxonomic compatibility and allows appropriate enzyme selection considering its amino acid sequence. The purpose of the update is to allow multiple host input, in order to perform an affinity comparison between target organisms and each host. The affinity differences will depend on which host to be considered, allowing the user to select the optimal host for the enzyme concerned.
Myosin-1b interacts with UNC45A and controls intestinal epithelial morphogenesis
Authors: Revenu Céline , Parlato Marianna , Rosello Marion , Duroure Karine , Duclaux-Loras Rémi , Nicolle Ophélie , Prospéri Marie-Thérèse , Stoufflet Julie , Vougny Juliette , Lebreton Corinne , Lépine Priscilla , Michaux Grégoire , Cerf-Benssusan Nadine , Coudrier Evelyne , Del Bene Filippo 
Published: September 2021

AbstractVesicle trafficking and the establishment of apico-basal polarity are essential processes in epithelium morphogenesis. Myosin-1b, an actin-motor able to bind membranes, regulates membrane shaping and vesicle trafficking. Here, we investigate Myosin-1b function in gut morphogenesis and congenital disorders using cell line and zebrafish larvae as well as patient biopsies. In a 3D Caco-2 cyst model, lumen formation is impaired in absence of Myosin-1b. In zebrafish, both Morpholino knock-down and genetic mutation of myo1b result in intestinal bulb epithelium folding defects associated with vesicle accumulation, reminiscent of a villous atrophy phenotype. We show that Myosin-1b interacts with the chaperone UNC45A, genetic deletion of which also results in gut folding defects in zebrafish. Loss of function mutations in UNC45A have been reported in complex hereditary syndromes, notably exhibiting intestinal disorders associated with villous atrophy. In UNC45A-depleted cells and in patient biopsies, Myosin-1b protein level is strikingly decreased. The appearance of Myosin-1b aggregates upon proteasome inhibition in cells points at a degradation mechanism of misfolded Myosin-1b in the absence of its chaperone. In conclusion, Myosin-1b plays an unexpected role in the development of the intestinal epithelium folds or villi downstream UNC45A, establishing its role in the gut defects reported in UNC45A patients.Summary statementMyosin-1b is important for intestinal epithelium folding during zebrafish development and participates in the villous atrophy clinical manifestation downstream UNC45A loss of function.
VSGs expressed during natural T. b. gambiense infection exhibit extensive sequence divergence and a subspecies-specific expression bias
Authors: So Jaime , Sudlow Sarah , Sayeed Abeer , Grudda Tanner , Deborggraeve Stijn , Ngoyi Dieudonné Mumba , Desamber Didier Kashiama , Wickstead Bill , Lejon Veerle , Mugnier Monica R. 
Published: September 2021

AbstractTrypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its Variant Surface Glycoprotein (VSG) coat through a process of antigenic variation. The serological tests which are widely used to screen for HAT use VSG as one of the target antigens. However, the VSGs expressed during human infection have not been characterized. Here we use VSG-seq to analyze the VSGs expressed in the blood of patients infected with T. b. gambiense and compared them to VSG expression in T. b. rhodesiense infections in humans as well as T. b. brucei infections in mice. The 44 VSGs expressed during T. b. gambiense infection revealed a striking bias towards expression of type B N-termini (82% of detected VSGs). This bias is specific to T. b. gambiense, which is unique among T. brucei subspecies in its chronic clinical presentation and anthroponotic nature, pointing towards a potential link between VSG expression and pathogenesis. The expressed T. b. gambiense VSGs also share very little similarity to sequences from 36 T. b. gambiense whole genome sequencing datasets, particularly in areas of the VSG protein exposed to host antibodies, suggesting that wild T. brucei VSG repertoires vary more than previously expected. Overall, this work demonstrates new features of antigenic variation in T. brucei gambiense and highlights the importance of understanding VSG repertoires in nature.Significance StatementHuman African Trypanosomiasis is a neglected tropical disease primarily caused by the extracellular parasite Trypanosoma brucei gambiense. To avoid elimination by the host, these parasites repeatedly replace their Variant Surface Glycoprotein (VSG) coat. Despite the important role of VSGs in prolonging infection, VSG expression during human infections is poorly understood. A better understanding of natural VSG gene expression dynamics can clarify the mechanisms that T. brucei uses to alter its VSG coat and improve trypanosomiasis diagnosis in humans. We analyzed the expressed VSGs detected in the blood of patients with trypanosomiasis. Our findings indicate that there are features of antigenic variation unique to human-infective T. brucei subspecies and VSGs expressed in natural infection may vary more than previously expected.
The Cortical Spectrum: a robust structural continuum in primate cerebral cortex revealed by histological staining and magnetic resonance imaging
Authors: John Yohan J. , Zikopoulos Basilis , García-Cabezas Miguel Ángel , Barbas Helen 
Published: September 2021

AbstractHigh-level characterizations of the primate cerebral cortex sit between two extremes: on one end the cortical mantle is seen as a mosaic of structurally and functionally unique areas, and on the other it is seen as a uniform six-layered structure in which functional differences are defined solely by extrinsic connections. Neither of these extremes captures the crucial neuroanatomical finding: that the cortex exhibits systematic gradations in architectonic structure. These gradations have been shown to predict cortico-cortical connectivity, which in turn suggests powerful ways to ground connectomics in anatomical structure, and by extension cortical function. A challenge to more widespread use of this concept is the labor-intensive and invasive nature of histological staining, which is the primary means of recognizing anatomical gradations. Here we show that a novel computational analysis technique can be used to derive a coarse-grained picture of cortical variation. For each of 78 cortical areas spanning the entire cortical mantle of the rhesus macaque, we created a high dimensional set of anatomical features derived from captured images of cortical tissue stained for myelin and SMI-32. The method involved semi-automated de-noising of images, and enabled comparison of brain areas without hand-labeling of features such as layer boundaries. We applied nonmetric multidimensional scaling (NMDS) to the dataset to visualize similarity among cortical areas. This analysis shows a systematic variation between weakly laminated (limbic) cortices and sharply laminated (eulaminate) cortices. We call this smooth continuum the ‘cortical spectrum’. We also show that this spectrum is visible within subsystems of the cortex: the occipital, parietal, temporal, motor, prefrontal, and insular cortices. We compared the NMDS-derived spectrum with a spectrum produced using T1- and T2-weighted magnetic resonance imaging (MRI) data derived from macaque, and found close agreement of the two coarse-graining methods. This evidence suggests that T1/T2 data, routinely obtained in human MRI studies, can be used as an effective proxy for data derived from high-resolution histological methods. More generally, this approach shows that the cortical spectrum is robust to the specific method used to compare cortical areas, and is therefore a powerful tool to understand the principles of organization of the primate cortex.
Lateral surface pressure generated by nascent ribosomal RNA suppresses growth of fibrillar centers in the nucleolus
Authors: Yamamoto Tetsuya , Yamazaki Tomohiro , Ninomiya Kensuke , Hirose Tetsuro 
Published: September 2021

ABSTRACTLiquid-liquid phase separation (LLPS) has been thought to be the biophysical principle governing the assembly of the multiphase structures of nucleoli, the site of ribosomal biogenesis. Condensates assembled through LLPS increase their sizes to minimize the surface energy as far as their components are available. However, multiple microphases, fibrillar centers (FCs), dispersed in a nucleolus are stable and their sizes do not grow unless the transcription of pre-ribosomal RNA (pre-rRNA) is inhibited. To understand the mechanism of the suppression of the FC growth, we here construct a minimal theoretical model by taking into account the nascent pre-rRNAs tethered to the FC surfaces by RNA polymerase I. Our theory predicts that nascent pre-rRNAs generate the lateral osmotic pressure that counteracts the surface tension of the FCs and this suppresses the growth of the FCs over the stable size. The stable FC size decreases with increasing the transcription rate and decreasing the RNA processing rate. This prediction is supported by our experiments showing that RNA polymerase inhibitors increase the FC size in a dose-dependent manner. This theory may provide insight into the general mechanism of the size control of nuclear bodies.Significance statementThe nucleolus, a site of pre-ribosomal RNA (pre-rRNA) production, has a characteristic multiphase structure, which has been thought to be assembled through liquid-liquid phase separation (LLPS). Although condensates assembled through LLPS grow by coarsening or coalescence as far as the components are available, the multiple inner phases, fibrillar centers (FCs), are dispersed in a nucleolus. To investigate the underlying mechanism, we constructed a minimal theoretical model by considering nascent pre-rRNAs tethered to RNA polymerase I at the FC surface. This model is supported by our experiments and explains previous experimental observations. This work shed light on the role of nascent RNAs to control the size of nuclear bodies.
Active growth signalling promotes cancer cell sensitivity to the CDK7 inhibitor ICEC0942
Authors: Wilson G.A. , Sava G. , Vuina K. , Huard C. , Meneguello L. , Coulombe-Huntington J. , Bertomeu T. , Maizels R.J. , Lauring J. , Tyers M. , Ali S. , Bertoli C. , de Bruin R.A.M. 
Published: September 2021

CDK7 has a central role in promoting cellular proliferation, through the activation of the mitotic CDKs, and by driving global gene expression, through targeting RNA polymerase II. Several recently developed CDK7 inhibitors (CDK7i) have been shown to be non-toxic and to limit tumour growth for a number of cancer cell types and are now in Phase I/II clinical trials. However, the mechanisms underlying the sensitivity of particular cancer cells to CDK7 inhibition remain largely unknown.To improve the outcome of individual patients and increase the chances of successful CDK7i approval, we assessed which fundamental cellular processes determine sensitivity to CDK7 inhibition, using the highly specific CDK7 inhibitor ICEC0942. Our data shows that selective CDK7 inhibition acutely arrests cells in the G1 phase of the cell cycle, which over time leads to senescence. Through a genome-wide CRISPR knock-out chemogenetic screen we identified active mTOR (mammalian target of rapamycin) signalling, as an important determinant of ICEC0942-induced senescence and show that a cancer-associated mutation that promotes cell growth can increase sensitivity to ICEC0942. Our work indicates that cellular growth is an important predictive marker for sensitivity to CDK7i.
Neuropsychological profile of entrepreneurs
Authors: Brenes Esteban R. , Rodríguez Gabriel , Acuña Joseph , Villalobos Yadira , Pichardo Caleb A. 
Published: September 2021

PurposeBy analyzing variables from the fields of business and neuropsychology, this document examines alternative combinations of behavioral economics and neuropsychological characteristics that would explain a successful entrepreneurial profile.Design/methodology/approachThe research is based on information gathered through a survey of 1,080 entrepreneurs. The findings offer interesting perspectives for academics, professionals and government institutions, which illustrate various neuropsychological characteristics that a person must have to be a successful entrepreneur. The method consists of a novel perspective that integrates qualitative comparative analysis (QCAs), a method based on Boolean algebra that offers a study from a configurational perspective.FindingsFrom the mixture of configurations, the paper explores following possible traits of an entrepreneurial mindset: cognitive flexibility, risk-taking, decision-making and teamwork.Originality/valueThis paper contributes to the literature on emerging attempts and approaches to understand the entrepreneurial mindset and the possible skillset that underpins successful entrepreneurship.
Supply chains and COVID-19: impacts, countermeasures and post-COVID-19 era
Authors: Butt Atif Saleem 
Published: September 2021

PurposeThis paper explores the steps/countermeasures taken by firms to address supply chain disruptions in the wake of COVID-19.Design/methodology/approachThis study employs a case study methodology and employs 46 semi-structured interviews with senior managers of the three buying firms, four distribution centres and four supplying firms based in four countries (Pakistan, Sri Lanka, China and India).FindingsResults reveal that manufacturers are refining production schedules to meet the production challenges. Distributors are working with secondary suppliers to meet the inventory shortage. Finally, supplying firms are evaluating the impact of demand, focusing on short-term demand-supply strategy, preparing for channel shifts, opening up additional channels of communication with key customers, understanding immediate customer’s demand and priorities and finally becoming more agile.Research limitations/implicationsThere are some limitations to this study. First, the results of this study cannot be generalized to a wider population. Second, this study explores the interpretations of senior managers based in four Asian countries only.Practical implicationsSupply chain firms can use these findings to understand how COVID-19 is affecting firms. Firms can also use the suggestions provided in this study to mitigate the impact of COVID-19 and make the best out of this pandemic.Originality/valueThis study contributes to the supply chain disruption literature by exploring the robust countermeasure taken by supply chain firms amid COVID-19 outbreak. In particular, it explores such countermeasures from the perspective of three different entities (buyer, supplier and distributor) based in four different countries in the South Asian region.
Is it possible to identify transformational leadership in a financial institution?
Authors: Girardi Gabriele , Rubim Sarate João Alberto 
Published: September 2021

PurposeThe aim of this study is to analyze the perception of employees of a Brazilian financial institution about transformational leadership and, subsequently, compare the results amongst the different groups of respondents.Design/methodology/approachThe authors present herein an empirical, descriptive and quantitative study, in which the survey was used as the main data collection technique. The survey was applied to a national sample composed of 603 employees (followers) operating in a financial institution. The authors utilized a few statistical techniques to analyze the data collected, namely descriptive statistics, factor analysis, variance analysis and linear regression.FindingsThe results indicate that employees have a high perception toward transformational leadership; no significant differences between the groups of respondents were found. Followers perceive their leader as a transformational agent, who inspires, encourages, considers and motivates them.Practical implicationsThe relevance of this research theme and the main findings of this research contribute to managerial practices since the leadership style under investigation is associated with positive outcomes.Originality/valueThis research sought to explore transformational leadership in an unexpected context. The originality of the study relies on the identification of a positive leadership style in the national financial system, which is usually more focused on economic criteria. There is a lack of research on leadership in Brazil, especially when it comes to quantitative studies. Not only the methodology but also the sample representing the entire Brazilian territory bring about the originality of this research.
Silicon enrichment alters functional traits in legumes depending on plant genotype and symbiosis with nitrogen‐fixing bacteria
Authors: Putra Rocky , Vandegeer Rebecca K. , Karan Shawan , Powell Jeff R. , Hartley Susan E. , Johnson Scott N. 
Published: September 2021

Abstract

Silicon (Si) uptake and deposition (silicification) in tissues is known to alleviate stresses and generally improve plant health. This is mostly studied in Si‐high accumulators, such as grasses, with comparatively less known about its effects on other plant functional groups, such as legumes. There is speculation that Si may positively impact the symbiosis between legumes and the nitrogen‐fixing bacteria (rhizobia) they associate with, but this is poorly understood. This study examined the effects of Si enrichment on legume species associated with rhizobia and the potential underlying mechanism of Si impacts.

We conducted a glasshouse experiment with lucerne Medicago sativa and barrel medic M. truncatula associated with a model rhizobial strain. Six genotypes (three per species) were either supplemented with Si (+Si) or untreated (−Si). We quantified 16 functional traits which could be classified as plant growth, physiology, elemental chemistry, nodule activity and nitrogen fixation.

The two legume species responded to Si distinctively. For example, Si supplementation increased shoot biomass by more than 10% in lucerne but growth was unaffected in barrel medic. Conversely, nitrogen‐fixing enzyme (nitrogenase) activity was promoted by more than 85% in +Si barrel medic plants but not in lucerne. Moreover, Si supplementation of lucerne increased the concentrations of Si in leaves by more than 36% but not in root nodules. Increased foliar concentrations of Si in lucerne were positively associated with increased shoot and root biomass in Sequel and Trifecta genotypes, respectively. Conversely, Si supplementation of barrel medic increased the concentration of Si in root nodules by 29% but not that in foliar tissues. Nitrogenase activity and where silicification occurred, differed between genotypes in barrel medic; nitrogenase activity was correlated with concentrations of Si in root nodules rather than that in foliar tissues in one genotype (Sephi) but the reverse was true in another (Hannaford).

This study demonstrates that two closely related legume species can respond to Si in distinct ways, depending on plant genotype and symbiosis. These results present the overlooked function of Si in legume–rhizobia interactions, which could potentially enhance productivity of this important group of plants.

A free Plain Language Summary can be found within the Supporting Information of this article.
Vernal pool wetlands respond to livestock grazing, exclusion and reintroduction
Authors: Michaels Julia S. , Tate Kenneth W. , Eviner Valerie T. 
Published: September 2021

AbstractIn disturbance‐adapted ecosystems, the removal of disturbance can lead to losses of diversity and sometimes irreversible changes in community composition. It is important to identify the thresholds at which these changes can occur, and to understand the reversibility of these shifts. We examined this question in a vernal pool ecosystem that evolved with low to moderate levels of grazing disturbance. In this system, it is not clear whether the negative effects of long‐term grazing exclusion are reversible through grazing reintroduction.We compared adjacent vernal pool wetlands in annual Mediterranean grasslands under three grazing management strategies: continuously grazed (100+ years), long‐term excluded (40+ years) and 2 years of reintroduced grazing. We also asked whether grazing treatments altered pool characteristics that are likely to influence plant community composition, and how these relationships changed with environmental conditions.Reintroducing grazing to vernal pools led to both increased diversity and native cover, but the effects on native cover were more immediate than on diversity. We identified several biotic and abiotic mechanisms related to this pattern, including changes to competitive dynamics that favour small statured native annuals and increases in hoofprint microdepressions that make soil moisture more available to plants.Synthesis and applications. Our results show that reintroduced grazing at moderate stocking rates can have significant effects on plant communities after just 2 years and can increase native cover more quickly than overall diversity. Our findings suggest that the negative effects of long‐term grazing exclusion in vernal pools may be reversible, but that land managers interested in restoring diversity should plan to monitor beyond the first two years of grazing reintroduction.