Schizophrenia is a debilitating disorder with complex and unclarified etiological factors. Sex differences have been observed in humans but animal models have only focused on male subjects. In this study, we report the establishment of the neurodevelopmental MAM model of schizophrenia in mice and compare the schizotypic-like characteristics and cognitive function in both sexes. Pregnant mice were injected with 26mg/kg(i.p.) of Methylazoxy-methanol acetate (MAM) or saline (5ml/kg) on gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Behavioral, histological and electrophysiological and mass spectrometry-based comparative proteomic techniques were employed to assess the schizotypic-like characteristics and cognitive function of adult male and female offspring (MAM-or saline-treated). Female MAM-16, but not MAM-17 treated mice exhibited enhanced hyperlocomotion after acute administration of the NMDA receptor antagonist, MK-801, compared to saline treated mice. Male MAM-16, but not MAM-17 treated mice showed decreased pre-pulse inhibition of the acoustic startle reflex. Both male and female MAM-16 and MAM-17 treated mice exhibited reduced hippocampal (HPC) size and thinning of the prefrontal cortex (PFC), but only male MAM-16 treated mice showed decreased parvalbumin expression in HPC and PFC. Similarly, both male and female MAM-16 treated mice displayed impaired contextual fear memory, while only male MAM-16 treated mice exhibited deficits in the delayed alternation task. The neurophysiological mechanisms that underlie these cognitive functions were further investigated. Both male and female MAM-16 treated mice had significantly reduced long-term potentiation (LTP) in the HPC CA1 synapses, while only male MAM-16 treated mice exhibited decreased LTP in the PFC. Proteomic analyses of PFC lysates further showed significant MAM-and sex-dependent differences in regulation . CC-BY-NC-ND 4.

Schizophrenia is a debilitating disorder with complex and unclarified etiological factors. Sex differences have been observed in humans but animal models have only focused on male subjects. In this study, we report the establishment of the neurodevelopmental MAM model of schizophrenia in mice and compare the schizotypic-like characteristics and cognitive function in both sexes. Pregnant mice were injected with 26mg/kg(i.p.) of Methylazoxy-methanol acetate (MAM) or saline (5ml/kg) on gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Behavioral, histological and electrophysiological and mass spectrometry-based comparative proteomic techniques were employed to assess the schizotypic-like characteristics and cognitive function of adult male and female offspring (MAM- or saline-treated). Female MAM-16, but not MAM-17 treated mice exhibited enhanced hyperlocomotion after acute administration of the NMDA receptor antagonist, MK-801, compared to saline treated mice. Male MAM-16, but not MAM-17 treated mice showed decreased pre-pulse inhibition of the acoustic startle reflex. Both male and female MAM-16 and MAM-17 treated mice exhibited reduced hippocampal (HPC) size and thinning of the prefrontal cortex (PFC), but only male MAM-16 treated mice showed decreased parvalbumin expression in HPC and PFC. Similarly, both male and female MAM-16 treated mice displayed impaired contextual fear memory, while only male MAM-16 treated mice exhibited deficits in the delayed alternation task. The neurophysiological mechanisms that underlie these cognitive functions were further investigated. Both male and female MAM-16 treated mice had significantly reduced long-term potentiation (LTP) in the HPC CA1 synapses, while only male MAM-16 treated mice exhibited decreased LTP in the PFC. Proteomic analyses of PFC lysates further showed significant MAM- and sex-dependent differences in regulation of protein expression. Our results demonstrate that while both male and female mice, prenatally exposed to MAM on GD16, display several core schizophrenia-like deficits and impairments in the hippocampus, only male MAM-treated mice have PFC-dependent cognitive deficits.

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Malware authors are continuously evolving their code base to include counter-analysis methods that can significantly hinder their detection and blocking. While the execution of malware in a sandboxed environment may provide a lot of insightful feedback about what the malware actually does in a machine, anti-virtualisation and hooking evasion methods may allow malware to bypass such detection methods. The main objective of this work is to complement sandbox execution with the use of binary emulation frameworks. The core idea is to exploit the fact that binary emulation frameworks may quickly test samples quicker than a sandbox environment as they do not need to open a whole new virtual machine to execute the binary. While with this approach, we lose the granularity of the data that can be collected through a sandbox, due to scalability issues, one may need to simply determine whether a file is malicious or to which malware family it belongs. To this end, we record the API calls that are performed and use them to explore the efficacy of using them as features for binary and multiclass classification. Our extensive experiments with real-world malware illustrate that this approach is very accurate, achieving state-of-the art outcomes with a statistically robust set of classification experiments while simultaneously having a relatively low computational overhead compared to traditional sandbox approaches. In fact, we compare the binary analysis results with a commercial sandbox, and our classification outperforms it at the expense of the fine-grained results that a sandbox provides.