Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Types of Bacillus subtilis tetA(L) Deletion Strains Reveal the Physiological Importance of TetA(L) in K+ Acquisition as well as in Na+, Alkali, and Tetracycline Resistance

ABSTRACT The chromosomally encoded TetA(L) protein of Bacillus subtilis is a multifunctional tetracycline-metal/H+antiporter that also exhibits monovalent cation/H+ antiport activity and a net K+ uptake mode. In this study, B. subtilis mutant strains JC112 and JC112C were found to be representative of two phenotypic types of tetA(L) deletion strains that are generated in the same selection. Both strains exhibited increased sensitivity to low tetracycline concentrations as expected. The mutants also had significantly reduced ability to grow in media containing low concentrations of K+, indicating that the net K+ uptake mode is of physiological consequence; the deficit in JC112 was greater than in JC112C. JC112 also exhibited (i) greater impairment of Na+- or K+-dependent growth at pH 8.3 than JC112C and (ii) a greater degree of Co+2 as well as Na+ sensitivity. Studies were initiated to explore the possibility of two different patterns of compensatory changes in other ion-translocating transporters in these mutants. Increased expression of two loci has thus far been shown. Increased expression of czcD-trkA, a locus with a proposed involvement in K+ uptake, occurred in both mutants. The increase was highest in the presence of Co2+ and was higher in JC112 than in JC112C. Deletion of czcD-trkA resulted in diminished growth of the wild-type and both mutant strains at low [K+], supporting a significant role for this locus in K+ uptake. Expression of yheL, which is a homologue of the Na+/H+ antiporter-encodingnhaC gene from Bacillus firmus OF4, was also increased in both tetA(L) deletion strains, again with higher up-regulation in JC112. The phenotypes resulting from deletion of yheL were consistent with a modest role for YheL in Na+-dependent pH homeostasis in the wild type. No major role for YheL was indicated in the mutants in spite of the overexpression. The studies underscore the multiple physiological functions of TetA(L), including tetracycline, Na+, and alkali resistance and K+ acquisition. The studies also reveal and begin to detail the complexity of the response to mutational loss of these functions.
The social networks of unaccompanied asylum seeking young people in the transition to adulthood

The number of children seeking asylum alone in the UK and across Europe is increasing. Previous research has focused on the support unaccompanied children receive within children’s services, and highlighted their vulnerability and isolation. Limited research exists that considers their transition to adulthood, at which time the process of leaving local authority care may coincide with a need to re-engage with the immigration system in an attempt to achieve the right to remain in the UK permanently. This thesis therefore focuses on unaccompanied young people as they transition to adulthood. Focusing holistically on the social networks of the young people, this study is concerned with understanding the process of transition and its impact on the social worlds of the young people. Taking the life-course approach as iits conceptual framework, issues of time, space, structure and agency are emphasised. Based on interviews with both unaccompanied young people and professionals (accessed through statutory and voluntary services in one large urban local authority in the north of England) the findings suggest that unaccompanied young people’s social networks are active, complex and diverse, yet may be negatively impacted by uncertain and temporary immigration statuses. The findings illuminate previously unexplored aspects of unaccompanied young people’s social networks, including their continued embeddedness in multi-sited family networks. The findings also challenge current constructions of unaccompanied young people as vulnerable recipients of support, and repositions them as young people who provide care and support to others as they begin to develop adult identities.
MNCs entering an emerging industry: The choice of governance mode under high uncertainty

Abstract This paper provides insights into the choice of governance mode among relatively similar multinational companies (MNCs) entering into an emerging industry characterised by high uncertainty related to technology, market and policy framework. The study utilises a multiple case study methodology, including interviews with members of five MNCs and the perspective of their investees. The case companies are global leaders in related industries (such as hydropower and wind energy), and they have all chosen to enter the tidal energy industry with a similar technology. Based on their choice of governance mode, the case companies are divided into two groups: “Flexibility” and “Control”. The study elaborates on how the two groups’ governance mode choices are driven by “real options” (RO) and “transaction cost economics” (TCE) logic when assessing the high uncertainty related to the technology, the emerging industry and the relationships with potential firms to be invested in.
Group secret key generation over broadcast erasure channels

We consider a group of m trusted nodes that aim to create a shared secret key K over a wireless channel in the presence an eavesdropper Eve. We assume an erasure broadcast channel from one of the honest nodes to the rest of them including Eve. All of the trusted nodes can also discuss over a cost-free public channel which is observed by Eve. For this setup we characterize the secret key generation capacity and propose an achievability scheme that is computationally efficient and employs techniques from network coding. Surprisingly, whether we have m = 2 nodes, or an arbitrary number m of nodes, we can establish a shared secret key among them at the same rate, independently of m.1
Intellectual capital and firm performance in India: a comparative study between original and modified value added intellectual coefficient model

With the dawn of a knowledge economy, the role of intellectual capital in value creation and sustainable competitive advantage became evident. With increasing importance of intellectual capital, the emphasis on its management and measurement increased manifolds. The Pulic's value added intellectual coefficient (VAIC) model is one such method that has been widely used for measuring intellectual capital and examining the link between IC and firm performance. However, this model has been criticised because of its inefficiency to capture the structural capital of a firm. The present study is a modest attempt to modify Pulic's VAIC model with the primary intention of dealing with the structural capital measurement deficiency. Employing panel data and quantile regression on Indian firms for a period of 15 years from 2000-2001 to 2013-2014, the study finds that both original VAIC model and the modified model advocate in favour of the positive influence of IC and its components on firm performance. With respect to structural capital, the study reveals that the modified VAIC model to some extend captures the structural capital efficiency of a firm more efficiently than the original model.
Resistance to sulphadrug‐based antifolate therapy in malaria: are we looking in the right place?

Sulphadrug treatment failure in malaria therapy cannot solely be ascribed to the build‐up of genetic resistance within the parasitic genome. Although numerous in vitro studies have tried to determine the exact genetic markers that could predict treatment outcome in patients, this research has not been conclusive. Sulphadrugs work by competitive inhibition with pABA at one point of the pathway to de novo folate synthesis. However, evidence suggests that the malaria parasite is capable of overcoming this competitive inhibition by switching over to other metabolic pathways, like direct folate salvage from a person's bloodstream. In other words, increased folic acid administration, via diet or supplementation, may have reduced the effectiveness of sulphadrugs more than genetic mutations. Although in vitro studies are valuable for understanding disease mechanisms, we should not forget that the human being is infinitely more complex than any laboratory model.
Analysis of acute traumatic axonal injury using diffusion tensor imaging

Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity following traumatic brain injury (TBI), but is poorly characterized by conventional imaging techniques. Diffusion tensor imaging (DTI) may provide better detection as well as insights into the mechanisms of white matter injury. DTI data from 33 patients with moderate-to-severe TBI, acquired at a median of 32 h postinjury, were compared with data from 28 age-matched controls. The global burden of whole brain white matter injury (GBWMI) was quantified by measuring the proportion of voxels that lay below a critical fractional anisotropy (FA) threshold, identified from control data. Mechanisms of change in FA maps were explored using an Eigenvalue analysis of the diffusion tensor. When compared with controls, patients showed significantly reduced mean FA (p < 0.001) and increased apparent diffusion coefficient (ADC; p = 0.017). GBWMI was significantly greater in patients than in controls (p < 0.01), but did not distinguish patients with obvious white matter lesions seen on structural imaging. It predicted classification of DTI images as head injury with a high degree of accuracy. Eigenvalue analysis showed that reductions in FA were predominantly the result of increases in radial diffusivity (p < 0.001). DTI may help quantify the overall burden of white matter injury in TBI and provide insights into underlying pathophysiology. Eigenvalue analysis suggests that the early imaging changes seen in white matter are consistent with axonal swelling rather than axonal truncation. This technique holds promise for examining disease progression, and may help define therapeutic windows for the treatment of diffuse brain injury.
Clustering of Nuclei in Multinucleated Hyphae Is Prevented by Dynein-Driven Bidirectional Nuclear Movements and Microtubule Growth Control in Ashbya gossypii

ABSTRACT During filamentous fungus development, multinucleated hyphae employ a system for long-range nuclear migration to maintain an equal nuclear density. A decade ago the microtubule motor dynein was shown to play a central role in this process. Previous studies with Ashbya gossypii revealed extensive bidirectional movements and bypassings of nuclei, an autonomous cytoplasmic microtubule (cMT) cytoskeleton emanating from each nucleus, and pulling of nuclei by sliding of cMTs along the cortex. Here, we show that dynein is the sole motor for bidirectional movements and bypassing because these movements are concomitantly decreased in mutants carrying truncations of the dynein heavy-chain DYN1 promoter. The dynactin component Jnm1, the accessory proteins Dyn2 and Ndl1, and the potential dynein cortical anchor Num1 are also involved in the dynamic distribution of nuclei. In their absence, nuclei aggregate to different degrees, whereby the mutants with dense nuclear clusters grow extremely long cMTs. As in budding yeast, we found that dynein is delivered to cMT plus ends, and its activity or processivity is probably controlled by dynactin and Num1. Together with its role in powering nuclear movements, we propose that dynein also plays (directly or indirectly) a role in the control of cMT length. Those combined dynein actions prevent nuclear clustering in A. gossypii and thus reveal a novel cellular role for dynein.
Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process

Background: During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neovessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, and wound healing, tumors, and placenta, as well. Methods: Based on protein expression levels of common endothelial markers using flow cytometry, 3 subpopulations of endothelial cells could be identified among VE-Cadherin+ and CD45– cells. Results: Lineage tracing by using Cdh5cre ERt2/Rosa-YFP reporter strategy demonstrated that the CD31–/loVEGFR2lo/intracellular endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2lo/intracellular transit amplifying (TA) and a definitive differentiated (D) CD31hiVEGFR2hi/extracellular population. EVP cells arose from vascular-resident beds that could not be transferred by bone marrow transplantation. Furthermore, EVP displayed progenitor-like status with a high proportion of cells in a quiescent cell cycle phase as assessed in wounds, tumors, and aorta. Only EVP cells and not TA and D cells had self-renewal capacity as demonstrated by colony-forming capacity in limiting dilution and by transplantation in Matrigel plugs in recipient mice. RNA sequencing revealed prominent gene expression differences between EVP and D cells. In particular, EVP cells highly expressed genes related to progenitor function including Sox9, Il33, Egfr, and Pdfgr&agr;. Conversely, D cells highly expressed genes related to differentiated endothelium including Ets1&2, Gata2, Cd31, Vwf, and Notch. The RNA sequencing also pointed to an essential role of the Sox18 transcription factor. The role of SOX18 in the differentiation process was validated by using lineage-tracing experiments based on Sox18CreERt2/Rosa-YFP mice. Besides, in the absence of functional SOX18/SOXF, EVP progenitors were still present, but TA and D populations were significantly reduced. Conclusions: Our findings support an entirely novel endothelial hierarchy, from EVP to TA to D, as defined by self-renewal, differentiation, and molecular profiling of an endothelial progenitor. This paradigm shift in our understanding of vascular-resident endothelial progenitors in tissue regeneration opens new avenues for better understanding of cardiovascular biology.
A Screen for Nigericin-Resistant Yeast Mutants Revealed Genes Controlling Mitochondrial Volume and Mitochondrial Cation Homeostasis

Little is known about the regulation of ion transport across the inner mitochondrial membrane in Saccharomyces cerevisiae. To approach this problem, we devised a screening procedure for facilitating the identification of proteins involved in mitochondrial ion homeostasis. Taking advantage of the growth inhibition of yeast cells by electroneutral K+/H+ ionophore nigericin, we screened for genetic mutations that would render cells tolerant to this drug when grown on a nonfermentable carbon source and identified several candidate genes including MDM31, MDM32, NDI1, YMR088C (VBA1), CSR2, RSA1, YLR024C, and YNL136W (EAF7). Direct examination of intact cells by electron microscopy indicated that mutants lacking MDM31 and/or MDM32 genes contain dramatically enlarged, spherical mitochondria and that these morphological abnormalities can be alleviated by nigericin. Mitochondria isolated from the Δmdm31 and Δmdm32 mutants exhibited limited swelling in an isotonic solution of potassium acetate even in the presence of an exogenous K+/H+ antiport. In addition, growth of the mutants was inhibited on ethanol-containing media in the presence of high concentrations of salts (KCl, NaCl, or MgSO4) and their mitochondria exhibited two- (Δmdm31 and Δmdm32) to threefold (Δmdm31Δmdm32) elevation in magnesium content. Taken together, these data indicate that Mdm31p and Mdm32p control mitochondrial morphology through regulation of mitochondrial cation homeostasis and the maintenance of proper matrix osmolarity.
Intracellular zidovudine (ZDV) and ZDV phosphates as measured by a validated combined high-pressure liquid chromatography-radioimmunoassay procedure

In vitro studies of zidovudine (ZDV) phosphorylation may not accurately reflect the in vivo dose-response relationship, which is crucial to determining the relationship between ZDV exposure, efficacy, and toxicity. However, measurement of ZDV phosphorylated anabolites in peripheral blood mononuclear cells (PBMCs) from ZDV-treated human immunodeficiency virus (HIV)-infected patients would be extremely useful in the more appropriate utilization of ZDV in the treatment of HIV infection. We developed a specific and sensitive combined high-pressure liquid chromatography (HPLC)-radioimmunoassay (RIA) procedure for the determination of ZDV, ZDV-monophosphate, ZDV-diphosphate, and ZDV-triphosphate in PBMCs taken from ZDV-treated HIV-infected patients. ZDV and its anabolites were extracted from washed, Ficoll-Paque-isolated PBMCs and then separated by HPLC using a strong anion-exchange column. The anabolites were then hydrolyzed to ZDV with acid phosphatase. ZDV was then measured by using a modified commercially available RIA protocol. Our method was validated by measuring [3H]ZDV anabolites generated in Molt-4 cells radioisotopically and simultaneously by the combined HPLC-RIA procedure. The ZDV determinations correlated well (r2 = 0.97) over the range of 0.037 to 5.2 pmol (10 to 1,400 pg) per assay tube. Furthermore, we defined the stability of ZDV anabolites during ficoll isolation and the recovery after extraction and cleanup. We then measured intracellular parent ZDV and its phosphorylated anabolites in PBMCs from six ZDV-treated HIV-infected patients (PBMCs were taken 2 h after a 300-mg oral dose). The mean concentrations ( +/- standard deviations) of parent and of mono-, di-, and triphosphates were 0.15 +/- 0.08, 1.4 +/-, 0.082 +/- 0.02, and 0.081 +/- 0.03 pmol/10(6) PBMC, respectively (one pmol/10(6) PBMC represents a concentration of approximately 1 microm). Concurrent serum ZDV concentrations were between 1.3 and 7.1 microm. This method should provide a useful tool for evaluating in vivo pharmacokinetics of ZDV anabolites in PBMCs and possibly other cell types, even at the low doses of ZDV currently administered therapeutically.
Abscisic Acid Plays an Important Role in the Regulation of Strawberry Fruit Ripening1[W][OA]

The plant hormone abscisic acid (ABA) has been suggested to play a role in fruit development, but supporting genetic evidence has been lacking. Here, we report that ABA promotes strawberry (Fragaria ananassa) fruit ripening. Using a newly established Tobacco rattle virus-induced gene silencing technique in strawberry fruit, the expression of a 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1), which is key to ABA biosynthesis, was down-regulated, resulting in a significant decrease in ABA levels and uncolored fruits. Interestingly, a similar uncolored phenotype was observed in the transgenic RNA interference (RNAi) fruits, in which the expression of a putative ABA receptor gene encoding the magnesium chelatase H subunit (FaCHLH/ABAR) was down-regulated by virus-induced gene silencing. More importantly, the uncolored phenotype of the FaNCED1-down-regulated RNAi fruits could be rescued by exogenous ABA, but the ABA treatment could not reverse the uncolored phenotype of the FaCHLH/ABAR-down-regulated RNAi fruits. We observed that down-regulation of the FaCHLH/ABAR gene in the RNAi fruit altered both ABA levels and sugar content as well as a set of ABA- and/or sugar-responsive genes. Additionally, we showed that exogenous sugars, particularly sucrose, can significantly promote ripening while stimulating ABA accumulation. These data provide evidence that ABA is a signal molecule that promotes strawberry ripening and that the putative ABA receptor, FaCHLH/ABAR, is a positive regulator of ripening in response to ABA.
Candida albicans responds to glycostructure damage by Ace2‐mediated feedback regulation of Cek1 signaling

Candida albicans uses the Cek1 MAPK pathway to restore cells from damage of its cell wall glycostructures. Defective protein N‐ or O‐glycosylation activates Cek1 and the transcription factor Ace2 as its downstream target, to upregulate genes encoding protein O‐mannosyltransferases (Pmt proteins). In unstressed cells, Cek1‐Ace2 activity blocks expression of PMT1, which is de‐repressed by tunicamycin. Genomic binding targets of Ace2 included ZCF21, which was upregulated by Ace2 and found to repress PMT1 transcription in unstressed cells. Surprisingly, genes encoding components of the Cek1 pathway including MSB2, CST20, HST7, CEK1 and ACE2 were also identified as Ace2 targets indicating Ace2‐mediated transcriptional amplification of pathway genes under N‐glycosylation stress. In this condition, physical interaction of the Ace2 protein with the upstream MAPKKK Cst20 was detected. Cst20‐GFP showed stress‐induced import from the cytoplasm into the nucleus and phosphorylation of Ace2. Interestingly, forced nuclear localization of Cst20 inhibited Cek1‐Ace2 signaling, while forced cytoplasmic localization of Cst20 retained full signaling activity, suggesting that nuclear Cst20 downregulates the Cek1 pathway. Collectively, the results indicate that Ace2 is a versatile multifunctional transcriptional regulator, which activates glycostress responses of C. albicans by both positive forward and negative feedback regulation of Cek1 signaling.
Knowledge Acquisition in Production Networks: Effective Strategies for System Integrators and Component Specialists

ABSTRACT This study provides new insight into the effectiveness of different knowledge acquisition strategies for organizations at different positions in a production network. Component specialists and systems integrators require a different knowledge repertoire in terms of knowledge depth and knowledge breadth. We show that a greater reliance on inter-organizational partnering than on intra-organizational acquiring is effective in the acquisition of knowledge breadth rather than knowledge depth. And the positive effect of a greater reliance on inter-organizational partnering on knowledge breadth is particularly strong for system integrators.
Downward Nominal Wage Rigidity Meets the Zero Lower Bound

We add downward nominal wage rigidity to a standard New Keynesian model with sticky prices and wages, where the zero lower bound on nominal interest rates is allowed to bind. We find that wage rigidity not only reduces the frequency of zero bound episodes but also mitigates the severity of corresponding recessions. As a result, previous studies abstracting from the presence of wage rigidity may have overemphasized the need for increasing the inflation target to offset the costs associated with hitting the zero bound. Moreover, our findings add to the recent debate on the presumed benefits of wage flexibility that has arisen in the aftermath of the Great Recession.