The impact of corporate governance and firm maturity on working capital management efficiency: Evidence from listed European firms

The importance of studying working capital management efficiency (WCME) springs from its effect on a firm’s profitability, value, and solvency. The board of directors together with the Chief Executive Officer formulate corporate policies including those concerning working capital levels, yet it is management’s role to continuously monitor the various working capital components to strike an optimal balance amongst them. Accordingly, this study analyses the effect of corporate governance in overseeing management handling working capital levels. In addition, this paper studies the role of firm maturity as a determinant factor of WCME. For this purpose, the paper at hand uses 583 listed European firms from 2002 till 2013. And, it employs cross section random effect panel regression models, where various working capital characteristics are used as dependent variables. And, along with the explanatory firm maturity proxy and the corporate governance variables, we control for the effect of country and multiple firm-specific characteristics. Finally, this study suggests that both corporate governance (except for ownership concentration proxy) and firm maturity are significant factors of WCME. Yet, for some of the proxies used, we did not reach conclusive results regarding the direction of impact on working capital investment

Human Deoxycytidine Kinase Is a Valuable Biocatalyst for the Synthesis of Nucleotide Analogues

Natural ribonucleoside-5’-monophosphates are building blocks for nucleic acids which are used for a number of purposes, including food additives. Their analogues, additionally, are used in pharmaceutical applications. Fludarabine-5´-monophosphate, for example, is effective in treating hematological malignancies. To date, ribonucleoside-5’-monophosphates are mainly produced by chemical synthesis, but the inherent drawbacks of this approach have led to the development of enzymatic synthesis routes. In this study, we evaluated the potential of human deoxycytidine kinase (HsdCK) as suitable biocatalyst for the synthesis of natural and modified ribonucleoside-5’-monophosphates from their corresponding nucleosides. Human dCK was heterologously expressed in E. coli and immobilized onto Nickel-nitrilotriacetic acid (Ni-NTA) superflow. A screening of the substrate spectrum of soluble and immobilized biocatalyst revealed that HsdCK accepts a wide range of natural and modified nucleosides, except for thymidine and uridine derivatives. Upon optimization of the reaction conditions, HsdCK was used for the synthesis of fludarabine-5´-monophosphate using increasing substrate concentrations. While the soluble biocatalyst revealed highest product formation with the lowest substrate concentration of 0.3 mM, the product yield increased with increasing substrate concentrations in the presence of the immobilized HsdCK. Hence, the application of immobilized HsdCK is advantageous upon using high substrate concentration which is relevant in industrial applications.DFG, 392246628, Chemo-enzymatische Synthese von Selen-modifizierten Nukleosiden, Nukleotiden und OligonukleotidenTU Berlin, Open-Access-Mittel - 201

Therapeutic potential of curcumin in a spinal cord injury model: Local application versus dietary supplement

Spinal cord injury is a debilitating disability that is characterized by a sequence of tragic events that occur following the primary impact aggravating the condition, collectively called secondary spinal cord injury. Oxidative damage and inflammatory surge are two hallmarks of the secondary spinal cord injury cascade. Curcumin is a polyphenolic compound extracted from the rhizome of Curcuma longa that has been well known to possess antioxidant and anti-inflammatory properties. The objective of this study was to evaluate the potential of curcumin as an antioxidant and anti-inflammatory agent following spinal cord injury, and to compare its therapeutic effects following local application directly to the injury versus its effect when given as a dietary supplement in a spinal cord hemisection model at T9-T10 level of the spinal cord. Female Sprague Dawley rats were randomized into a control group, injury groups (1 day and 7 days) , local treatment groups single dose of Curcuma longa extract immediately on the injury site (1 day and 7 days) and a Dietary supplement group. Crude Curcumin was added to the animals\u27 feed (10% of daily feed) one week before and week after injury. Oxidative stress parameters used for detection the effect of Curcumin before and after treatment were Malondialdehyde (MDA) by Thiobarbituric acid assay (TBA) and total antioxidant capacity (TAC). Expression of tumor necrosis factor alpha (TNF α) and interleukin 6 (IL-6) was detected using Enzyme Linked Immunosorbent Assay (ELISA). Our results show that at 7 days, although Dietary supplement was effective in increasing TAC levels and lowering TNF α expression levels, yet it did not affect MDA levels (IL-6 data not measured). Local treatment regimen has shown to be more effective on all four parameters measured as the 7 days. Our results demonstrate that local Curcumin application directly on the injury site might be more efficacious in alleviating oxidative damage and reducing inflammation following spinal cord injury. Further analysis is needed to evaluate the effect of Dietary treatment regimen on IL-6 and detect the effect of different Curcumin treatment regimens on other anti-oxidant and anti-inflammatory markers to investigate the role of curcumin in alleviating oxidation and inflammation

Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

BackgroundSchistosomiasis is one of the world's most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including for Biomphalaria pfeifferi, the most important vector for Schistosoma mansoni in Africa. We used Illumina technology to explore how field-derived B. pfeifferi, either uninfected or harboring cercariae-producing S. mansoni sporocysts, respond to a sublethal treatment of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is treated with niclosamide.Principal findingsCercariae-producing sporocysts within snails treated with niclosamide express ~68% of the genes in the S. mansoni genome, as compared to 66% expressed by intramolluscan stages of S. mansoni in snails not treated with niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. For uninfected B. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.Conclusions/significanceThis study helps define the transcriptomic responses of an important and under-studied schistosome vector to S. mansoni sporocysts, to niclosamide, and to both in combination. It suggests the response of S. mansoni sporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails

Effective teaching of science in an undergraduate course; knowledge, discipline and dedication yield scientists

AbstractEffective undergraduate teaching has always been a challenge. In 1987 Chickering & Gamson published the seven principles for good practice in undergraduate education, which was highly used and recommended by most practitioners, yet teaching basic science was still difficult. It is not easy to convey that in science negative results are as important as positive results. In fact, sometimes interpretation and troubleshooting are more important than the experiment itself. In order to make the students feel the importance of science and the importance of every experiment they are doing, the laboratory component of the course was designed as a small project through which they were taught important lessons. Every time an experiment failed, we (instructors) pointed out how it could serve the purpose of the project and how each result, whether positive or negative, leads us to another step and a better understanding of the project's goal. Other than the technical aspects of designing the course, we made sure that there's a strong bond between every student and us without compromising discipline, as it is the way to success and great achievements. Everyone had a talent and a skill that needed to be sculptured to unleash the great scientist –we believe- was in him or her. Our goal was to create an image and to set an example of how a scientist should be; manners, attitude, discipline and perseverance. By the end of the semester, the students were able to interpret, troubleshoot and report the results they collected throughout the whole semester in consolidated reports that mimicked published research papers. More importantly, they learned how to be scientists and they enjoyed learning science

The in vivo transcriptome of Schistosoma mansoni in the prominent vector species Biomphalaria pfeifferi with supporting observations from Biomphalaria glabrata.

BackgroundThe full scope of the genes expressed by schistosomes during intramolluscan development has yet to be characterized. Understanding the gene products deployed by larval schistosomes in their snail hosts will provide insights into their establishment, maintenance, asexual reproduction, ability to castrate their hosts, and their prolific production of human-infective cercariae. Using the Illumina platform, the intramolluscan transcriptome of Schistosoma mansoni was investigated in field-derived specimens of the prominent vector species Biomphalaria pfeifferi at 1 and 3 days post infection (d) and from snails shedding cercariae. These S. mansoni samples were derived from the same snails used in our complementary B. pfeifferi transcriptomic study. We supplemented this view with microarray analyses of S. mansoni from B. glabrata at 2d, 4d, 8d, 16d, and 32d to highlight robust features of S. mansoni transcription, even when a different technique and vector species was used.Principal findingsTranscripts representing at least 7,740 (66%) of known S. mansoni genes were expressed during intramolluscan development, with the greatest number expressed in snails shedding cercariae. Many transcripts were constitutively expressed throughout development featuring membrane transporters, and metabolic enzymes involved in protein and nucleic acid synthesis and cell division. Several proteases and protease inhibitors were expressed at all stages, including some proteases usually associated with cercariae. Transcripts associated with G-protein coupled receptors, germ cell perpetuation, and stress responses and defense were well represented. We noted transcripts homologous to planarian anti-bacterial factors, several neural development or neuropeptide transcripts including neuropeptide Y, and receptors that may be associated with schistosome germinal cell maintenance that could also impact host reproduction. In at least one snail the presence of larvae of another digenean species (an amphistome) was associated with repressed S. mansoni transcriptional activity.Conclusions/significanceThis in vivo study, emphasizing field-derived snails and schistosomes, but supplemented with observations from a lab model, provides a distinct view from previous studies of development of cultured intramolluscan stages from lab-maintained organisms. We found many highly represented transcripts with suspected or unknown functions, with connection to intramolluscan development yet to be elucidated

Frontline Science: Antagonism between regular and atypical Cxcr3 receptors regulates macrophage migration during infection and injury in zebrafish

The CXCR3-CXCL11 chemokine-signaling axis plays an essential role in infection and inflammation by orchestrating leukocyte trafficking in human and animal models, including zebrafish. Atypical chemokine receptors (ACKRs) play a fundamental regulatory function in signaling networks by shaping chemokine gradients through their ligand scavenging function, while being unable to signal in the classic G-protein-dependent manner. Two copies of the CXCR3 gene in zebrafish, cxcr3.2 and cxcr3.3, are expressed on macrophages and share a highly conserved ligand-binding site. However, Cxcr3.3 has structural characteristics of ACKRs indicative of a ligand-scavenging role. In contrast, we previously showed that Cxcr3.2 is an active CXCR3 receptor because it is required for macrophage motility and recruitment to sites of mycobacterial infection. In this study, we generated a cxcr3.3 CRISPR-mutant to functionally dissect the antagonistic interplay among the cxcr3 paralogs in the immune response. We observed that cxcr3.3 mutants are more susceptible to mycobacterial infection, whereas cxcr3.2 mutants are more resistant. Furthermore, macrophages in the cxcr3.3 mutant are more motile, show higher activation status, and are recruited more efficiently to sites of infection or injury. Our results suggest that Cxcr3.3 is an ACKR that regulates the activity of Cxcr3.2 by scavenging common ligands and that silencing the scavenging function of Cxcr3.3 results in an exacerbated Cxcr3.2 signaling. In human, splice variants of CXCR3 have antagonistic functions and CXCR3 ligands also interact with ACKRs. Therefore, in zebrafish, an analogous regulatory mechanism appears to have evolved after the cxcr3 gene duplication event, through diversification of conventional and atypical receptor variants

Live Imaging of Type I Collagen Assembly Dynamics in Osteoblasts Stably Expressing GFP and mCherry-Tagged Collagen Constructs

Type I collagen is the most abundant extracellular matrix protein in bone and other connective tissues and plays key roles in normal and pathological bone formation as well as in connective tissue disorders and fibrosis. Although much is known about the collagen biosynthetic pathway and its regulatory steps, the mechanisms by which it is assembled extracellularly are less clear. We have generated GFPtpz and mCherry-tagged collagen fusion constructs for live imaging of type I collagen assembly by replacing the α2(I)-procollagen N-terminal propeptide with GFPtpz or mCherry. These novel imaging probes were stably transfected into MLO-A5 osteoblast-like cells and fibronectin-null mouse embryonic fibroblasts (FN-null-MEFs) and used for imaging type I collagen assembly dynamics and its dependence on fibronectin. Both fusion proteins co-precipitated with α1(I)-collagen and remained intracellular without ascorbate but were assembled into α1(I) collagen-containing extracellular fibrils in the presence of ascorbate. Immunogold-EM confirmed their ultrastuctural localization in banded collagen fibrils. Live cell imaging in stably transfected MLO-A5 cells revealed the highly dynamic nature of collagen assembly and showed that during assembly the fibril networks are continually stretched and contracted due to the underlying cell motion. We also observed that cell-generated forces can physically reshape the collagen fibrils. Using co-cultures of mCherry- and GFPtpz-collagen expressing cells, we show that multiple cells contribute collagen to form collagen fiber bundles. Immuno-EM further showed that individual collagen fibrils can receive contributions of collagen from more than one cell. Live cell imaging in FN-null-MEFs expressing GFPtpz-collagen showed that collagen assembly was both dependent upon and dynamically integrated with fibronectin assembly. These GFP-collagen fusion constructs provide a powerful tool for imaging collagen in living cells and have revealed novel and fundamental insights into the dynamic mechanisms for the extracellular assembly of collagen

Organic Solvent Exposure and Depressive Symptoms Among Licensed Pesticide Applicators in the Agricultural Health Study

Purpose Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among farmers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers. Methods Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0–60) and dichotomous (≥16) variables. Multivariate linear and logistic regression models were used to estimate crude and adjusted associations between measures of solvent exposure and CES-D score. Results Forty-one percent of the sample reported some solvent exposure. The mean CES-D score was 6.5 (SD 6.4; median 5; range 0–44); 92% of the sample had a score below 16. After adjusting for covariates, statistically significant associations were observed between ever-use of any solvent, long duration of any solvent exposure, ever-use of gasoline, ever-use of petroleum distillates, and short duration of petroleum distillate exposure and continuous CES-D score (p \u3c 0.05). Although nearly all associations were positive, fewer statistically significant associations were observed between metrics of solvent exposure and the dichotomized CES-D variable. Conclusions Solvent exposures were associated with depressive symptoms among farmers. Efforts to limit exposure to organic solvents may reduce the risk of depressive symptoms among farmers