Fetuin A concentration in the second trimester amniotic fluid of fetuses with Trisomy 21 appears to be lower: phenotypic considerations

Objective: We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3 ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8 ng/mL). Conclusion: Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesi

Serotonin attenuates feedback excitation onto O-LM interneurons

The serotonergic system is a subcortical neuromodulatory center that controls cortical information processing in a state-dependent manner. In the hippocampus, serotonin (5-HT) is released by ascending serotonergic fibers from the midbrain raphe nuclei, thereby mediating numerous modulatory functions on various neuronal subtypes. Here, we focus on the neuromodulatory effects of 5-HT on GABAergic inhibitory oriens lacunosum-moleculare (O-LM) cells in the hippocampal area CA1 of the rat. These interneurons are thought to receive primarily local excitatory input and are, via their axonal projections to stratum lacunosum-moleculare, ideally suited to control entorhinal cortex input. We show that 5-HT reduces excitatory glutamatergic transmission onto O-LM interneurons. By means of paired recordings from synaptically connected CA1 pyramidal cells and O-LM interneurons we reveal that this synapse is modulated by 5-HT. Furthermore, we demonstrate that the reduction of glutamatergic transmission by serotonin is likely to be mediated via a decrease of calcium influx into presynaptic terminals of CA1 pyramidal cells. This modulation of excitatory synaptic transmission onto O-LM interneurons by 5-HT might be a mechanism to vary the activation of O-LM interneurons during ongoing network activity and serve as a brain state-dependent switch gating the efficiency of entorhinal cortex input to CA1 pyramidal neurons

Towards a Threat Intelligence Informed Digital Forensics Readiness Framework

Digital Forensic Readiness (DFR) has received little attention by the research community, when compared to the core digital forensic investigation processes. DFR was primarily about logging of security events to be leveraged by the forensic analysis phase. However, the increasing number of security incidents and the overwhelming volumes of data produced mandate the development of more effective and efficient DFR approaches. We propose a DFR framework focusing on the prioritisation, triaging and selection of Indicators of Compromise (IoC) to be used in investigations of security incidents. A core component of the framework is the contextualisation of the IoCs to the underlying organisation, which can be achieved with the use of clustering and classification algoriihms and a local IoC database

Improving Forensic Triage Efficiency through Cyber Threat Intelligence

The complication of information technology and the proliferation of heterogeneous security devices that produce increased volumes of data coupled with the ever-changing threat landscape challenges have an adverse impact on the efficiency of information security controls and digital forensics, as well as incident response approaches. Cyber Threat Intelligence (CTI)and forensic preparedness are the two parts of the so-called managed security services that defendants can employ to repel, mitigate or investigate security incidents. Despite their success, there is no known effort that has combined these two approaches to enhance Digital Forensic Readiness (DFR) and thus decrease the time and cost of incident response and investigation. This paper builds upon and extends a DFR model that utilises actionable CTI to improve the maturity levels of DFR. The effectiveness and applicability of this model are evaluated through a series of experiments that employ malware-related network data simulating real-world attack scenarios. To this extent, the model manages to identify the root causes of information security incidents with high accuracy (90.73%), precision (96.17%) and recall (93.61%), while managing to decrease significantly the volume of data digital forensic investigators need to examine. The contribution of this paper is twofold. First, it indicates that CTI can be employed by digital forensics processes. Second, it demonstrates and evaluates an efficient mechanism that enhances operational DFR

Actionable Threat Intelligence for Digital Forensics Readiness

The purpose of this paper is to formulate a novel model for enhancing the effectiveness of existing Digital Forensic Readiness (DFR) schemes by leveraging the benefits of cyber threat information sharing. This paper employs a quantitative methodology to identify the most popular Threat Intelligence elements and introduces a formalized procedure to correlate these elements with potential digital evidence resulting in the quick and accurate identification of patterns of malware activities. While threat intelligence exchange steadily becomes a common practice for the prevention or detection of security incidents, the proposed approach highlights its usefulness for the digital forensics domain. The proposed model can help organizations to improve their digital forensic readiness posture and thus minimize the time and cost of cybercrime incident

Formulation, characterisation and flexographic printing of novel Boger fluids to assess the effects of ink elasticity on print uniformity

Model elastic inks were formulated, rheologically characterised in shear and extension, and printed via flexography to assess the impact of ink elasticity on print uniformity. Flexography is a roll-to-roll printing process with great potential in the mass production of printed electronics for which understanding layer uniformity and the influence of rheology is of critical importance. A new set of flexo-printable Boger fluids was formulated by blending polyvinyl alcohol and high molecular weight polyacrylamide to provide inks of varying elasticity. During print trials, the phenomenon of viscous fingering was observed in all prints, with those of the Newtonian ink exhibiting a continuous striping in the printing direction. Increasing elasticity significantly influenced this continuity, disrupting it and leading to a quantifiable decrease in the overall relative size of the printed finger features. As such, ink elasticity was seen to have a profound effect on flexographic printing uniformity, showing the rheological tuning of inks may be a route to obtaining specific printed features

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer

In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids—such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001), acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001), and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p<0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p<0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients