Dissociation of Immune Responses from Pathogen Colonization Supports Pattern Recognition in C. elegans

Caenorhabditis elegans has been used for over a decade to characterize signaling cascades controlling innate immune responses. However, what initiates these responses in the worm has remained elusive. To gain a better understanding of the initiating events we delineated genome-wide immune responses to the bacterial pathogen Pseudomonas aeruginosa in worms heavily-colonized by the pathogen versus worms visibly not colonized. We found that infection responses in both groups were identical, suggesting that immune responses were not correlated with colonization and its associated damage. Quantitative RT-PCR measurements further showed that pathogen secreted factors were not able to induce an immune response, but exposure to a non-pathogenic Pseudomonas species was. These findings raise the possibility that the C.elegans immune response is initiated by recognition of microbe-associated molecular patterns. In the absence of orthologs of known pattern recognition receptors, C. elegans may rely on novel mechanisms, thus holding the potential to advance our understanding of evolutionarily conserved strategies for pathogen recognition

Achieving Long-term Fairness in Submodular Maximization through Randomization

Submodular function optimization has numerous applications in machine learning and data analysis, including data summarization which aims to identify a concise and diverse set of data points from a large dataset. It is important to implement fairness-aware algorithms when dealing with data items that may contain sensitive attributes like race or gender, to prevent biases that could lead to unequal representation of different groups. With this in mind, we investigate the problem of maximizing a monotone submodular function while meeting group fairness constraints. Unlike previous studies in this area, we allow for randomized solutions, with the objective being to calculate a distribution over feasible sets such that the expected number of items selected from each group is subject to constraints in the form of upper and lower thresholds, ensuring that the representation of each group remains balanced in the long term. Here a set is considered feasible if its size does not exceed a constant value of $b$. Our research includes the development of a series of approximation algorithms for this problem.Comment: This paper has been accepted to 19th Cologne-Twente Workshop on Graphs and Combinatorial Optimizatio

Assessment of financial control practices in Polytechnics in Ghana. A case study of Sunyani Polytechnic

The study sought to assess the financial Control systems of Polytechnics in Ghana and suggest ways of improving them. Financial control systems exist to help organizations meet their goals and objectives, promote efficiency, reduce the risk of loss, and help ensure financial statement reliability and compliance with laws and regulations. The study adopts the case study design using Sunyani Polytechnic in the Brong Ahafo region, Ghana. A sample size of 50 staff members was selected for the study using the convenience sampling. The sources of data for the study were both primary and secondary data. The study found out that three (3) major financial control systems, namely, preventive, directive and detective control systems are in existence in the Sunyani Polytechnic. Effectively, realistic budgets are established and results are actively monitored. It was discovered from the findings that there was existence of internal financial controls regulated by Financial Administration, Procurement, Internal Audit Agency Acts and indirect application of Committee of Sponsoring Organizations of the Treadway Commission (COSO). It was revealed that the level of compliance was high and this is very commendable and must be encouraged. It was also discovered there was a fair amount of compliance but sanctions are rarely given to a person who does not comply with the laws and conventions of internal financial control. It was recommended that pre-audit should be done for all transactions and seriousness need to be attached to it. It was recommended that audit units need to be strengthened in the Polytechnics. It was recommended that review of internal control needs to be done from time to time, so that new standards can be embraced for performance and improvement. Regular training programmes should be organized for workers on the financial management and control of the Polytechnic activities for its sustainability and growth. There should be in-depth investigations into the accounting system to eliminate all identified weaknesses

Assessment of financial control practices in Polytechnics in Ghana. A case study of Sunyani Polytechnic

The study sought to assess the financial Control systems of Polytechnics in Ghana and suggest ways of improving them. Financial control systems exist to help organizations meet their goals and objectives, promote efficiency, reduce the risk of loss, and help ensure financial statement reliability and compliance with laws and regulations. The study adopts the case study design using Sunyani Polytechnic in the Brong Ahafo region, Ghana. A sample size of 50 staff members was selected for the study using the convenience sampling. The sources of data for the study were both primary and secondary data. The study found out that three (3) major financial control systems, namely, preventive, directive and detective control systems are in existence in the Sunyani Polytechnic. Effectively, realistic budgets are established and results are actively monitored. It was discovered from the findings that there was existence of internal financial controls regulated by Financial Administration, Procurement, Internal Audit Agency Acts and indirect application of Committee of Sponsoring Organizations of the Treadway Commission (COSO). It was revealed that the level of compliance was high and this is very commendable and must be encouraged. It was also discovered there was a fair amount of compliance but sanctions are rarely given to a person who does not comply with the laws and conventions of internal financial control. It was recommended that pre-audit should be done for all transactions and seriousness need to be attached to it. It was recommended that audit units need to be strengthened in the Polytechnics. It was recommended that review of internal control needs to be done from time to time, so that new standards can be embraced for performance and improvement. Regular training programmes should be organized for workers on the financial management and control of the Polytechnic activities for its sustainability and growth. There should be in-depth investigations into the accounting system to eliminate all identified weaknesses

“Whom you know” and labour market outcomes: An empirical investigation in Ghana.

The relevance of social networks sometimes referred to in Ghana as “whom you know” in the job acquisition process and its effect on labour market outcomes (wages, job satisfaction and job tenure) have been highlighted by a number of studies. Most of these studies have concentrated largely on monetary post-hire outcomes with limited research on non-pecuniary aspects. Using a cox proportional hazard model to analyse a survey of 150 formal sector workers in the services sector in Accra, the study observes that first, jobs acquired through the help of workers’ friends and relatives did not last long. The first jobs could be a stepping-stone for better jobs. This effect is however not statistically significant after controlling for individual and firm-level covariates. Conclusions are however made with caution due to the small sample size and the nature of respondents’ majority of whom are highly educated and relatively younger. Future research can explore further social networks and labour markets particularly in Africa where familiarity and identical ethnic bonds are visible and stronger

The paf gene product modulates asexual development in Penicillium chrysogenum

Penicillium chrysogenum secretes a low molecular weight, cationic and cysteine-rich protein (PAF). It has growth inhibitory activity against the model organism Aspergillus nidulans and numerous zoo- and phytopathogenic fungi but shows only minimal conditional antifungal activity against the producing organism itself

Trypacidin, a Spore-Borne Toxin from Aspergillus fumigatus, Is Cytotoxic to Lung Cells

Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC50 close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H2O2). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported

Transcriptional and Proteomic Analysis of the Aspergillus fumigatus ΔprtT Protease-Deficient Mutant

Aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. The fungus invades the lungs and other organs, causing severe damage. Penetration of the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases to degrade the host structural barriers. The A. fumigatus transcription factor PrtT controls the expression of multiple secreted proteases. PrtT shows similarity to the fungal Gal4-type Zn(2)-Cys(6) DNA-binding domain of several transcription factors. In this work, we further investigate the function of this transcription factor by performing a transcriptional and a proteomic analysis of the ΔprtT mutant. Unexpectedly, microarray analysis revealed that in addition to the expected decrease in protease expression, expression of genes involved in iron uptake and ergosterol synthesis was dramatically decreased in the ΔprtT mutant. A second finding of interest is that deletion of prtT resulted in the upregulation of four secondary metabolite clusters, including genes for the biosynthesis of toxic pseurotin A. Proteomic analysis identified reduced levels of three secreted proteases (ALP1 protease, TppA, AFUA_2G01250) and increased levels of three secreted polysaccharide-degrading enzymes in the ΔprtT mutant possibly in response to its inability to derive sufficient nourishment from protein breakdown. This report highlights the complexity of gene regulation by PrtT, and suggests a potential novel link between the regulation of protease secretion and the control of iron uptake, ergosterol biosynthesis and secondary metabolite production in A. fumigatus

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level. To ensure highly reproducible growth conditions, an oxygen-controlled, glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane proteins led to the identification of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions. Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and amino acid metabolism. Consistently, the cellular contents in heme, iron, copper, and zinc increased. Furthermore, hypoxia induced biosynthesis of the secondary metabolite pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the proteins so far not implicated in hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated proteins which indicates a link between hypoxia and the generation of nitrosative stress in A. fumigatus