BackgroundMycobacterium leprae transcriptomic and human host immune gene expression signatures that demonstrate a plausible association with type I (T1R) and type II reactions (T2R) aid in early... Show moreBackgroundMycobacterium leprae transcriptomic and human host immune gene expression signatures that demonstrate a plausible association with type I (T1R) and type II reactions (T2R) aid in early diagnosis, prevention of nerve damage and consequent demyelinating neuropathy in leprosy. The aim of the study is to identify M. leprae and host-associated gene-expression signatures that are associated with reactional states in leprosy. MethodsThe differentially expressed genes from the whole transcriptome of M. leprae were determined using genome-wide hybridization arrays with RNA extracted from skin biopsies of 20 T1R, 20 T2R and 20 non reactional controls (NR). Additionally, human immune gene-expressions were profiled using RT2-PCR profiler arrays and real-time qPCRs. ResultsThe RNA quality was optimal in 16 NR, 18 T1R and 19 T2R samples. Whole transcriptome expression array of these samples revealed significant upregulation of the genes that encode integral and intrinsic membrane proteins, hydrolases and oxidoreductases. In T1R lesional skin biopsy specimens, the top 10 significantly upregulated genes are ML2064, ML1271, ML1960, ML1220, ML2498, ML1996, ML2388, ML0429, ML2030 and ML0224 in comparison to NR. In T2R, genes ML2498, ML1526, ML0394, ML1960, ML2388, ML0429, ML0281, ML1847, ML1618 and ML1271 were significantly upregulated. We noted ML2664 was significantly upregulated in T1R and repressed in T2R. Conversely, we have not noted any genes upregulated in T2R and repressed in T1R. In both T1R and T2R, ML2388 was significantly upregulated. This gene encodes a probable membrane protein and epitope prediction using Bepipred-2.0 revealed a distinct B-cell epitope. Overexpression of ML2388 was noted consistently across the reaction samples. From the host immune gene expression profiles, genes for CXCL9, CXCL10, CXCL2, CD40LG, IL17A and CXCL11 were upregulated in T1R when compared to the NR. In T2R, CXCL10, CXCL11, CXCL9, CXCL2 and CD40LG were upregulated when compared to the NR group. ConclusionA gene set signature involving bacterial genes ML2388, ML2664, and host immune genes CXCL10 and IL-17A can be transcriptomic markers for reactional states in leprosy. Show less
Haastrecht, M. van; Golpur, G.; Tzismadia, G.; Kab, R.; Priboi, C.; David, D.; ... ; Spruit, M. 2022
Small- and medium-sized enterprises (SMEs) frequently experience cyberattacks, but often do not have the means to counter these attacks. Therefore, cybersecurity researchers and practitioners need... Show moreSmall- and medium-sized enterprises (SMEs) frequently experience cyberattacks, but often do not have the means to counter these attacks. Therefore, cybersecurity researchers and practitioners need to aid SMEs in their defence against cyber threats. Research has shown that SMEs require solutions that are automated and adapted to their context. In recent years, we have seen a surge in initiatives to share cyber threat intelligence (CTI) to improve collective cybersecurity resilience. Shared CTI has the potential to answer the SME call for automated and adaptable solutions. Sadly, as we demonstrate in this paper, current shared intelligence approaches scarcely address SME needs. We must investigate how shared CTI can be used to improve SME cybersecurity resilience. In this paper, we tackle this challenge using a systematic review to discover current state-of-the-art approaches to using shared CTI. We find that threat intelligence sharing platforms such as MISP have the potential to address SME needs, provided that the shared intelligence is turned into actionable insights. Based on this observation, we developed a prototype application that processes MISP data automatically, prioritises cybersecurity threats for SMEs, and provides SMEs with actionable recommendations tailored to their context. Subsequent evaluations in operational environments will help to improve our application, such that SMEs are enabled to thwart cyberattacks in future. Show less
Small- and medium-sized enterprises (SMEs) frequently experience cyberattacks, but often do not have the means to counter these attacks. Therefore, cybersecurity researchers and practitioners need... Show moreSmall- and medium-sized enterprises (SMEs) frequently experience cyberattacks, but often do not have the means to counter these attacks. Therefore, cybersecurity researchers and practitioners need to aid SMEs in their defence against cyber threats. Research has shown that SMEs require solutions that are automated and adapted to their context. In recent years, we have seen a surge in initiatives to share cyber threat intelligence (CTI) to improve collective cybersecurity resilience. Shared CTI has the potential to answer the SME call for automated and adaptable solutions. Sadly, as we demonstrate in this paper, current shared intelligence approaches scarcely address SME needs. We must investigate how shared CTI can be used to improve SME cybersecurity resilience. In this paper, we tackle this challenge using a systematic review to discover current state-of-the-art approaches to using shared CTI. We find that threat intelligence sharing platforms such as MISP have the potential to address SME needs, provided that the shared intelligence is turned into actionable insights. Based on this observation, we developed a prototype application that processes MISP data automatically, prioritises cybersecurity threats for SMEs, and provides SMEs with actionable recommendations tailored to their context. Subsequent evaluations in operational environments will help to improve our application, such that SMEs are enabled to thwart cyberattacks in future. Show less
