Reduced MMN-indexed auditory change detection in a non-clinical high schizotypy sample.

Schizotypal traits include abnormalities in cognition, behavior, and interpersonal relationships that are similar, yet less severe than psychotic symptomology. It is estimated that approximately 5% of the general population displays psychotic symptoms and experiences that can be considered schizotypal in nature, but there is little research examining the neurological correlates of these traits. The mismatch negativity (MMN) event-related potential is an objective measure of auditory change detection derived from electroencephalography. The current study contributes to the limited body of evidence examining the neurobiological underpinnings of schizotypy in a non-clinical sample using the MMN. Participants were recruited from the general population and divided into high and low-schizotypy groups for comparison. Individuals with high schizotypal traits displayed reduced MMN amplitudes in response to frequency and location deviants, and longer MMN latencies in response to location deviants. Specific sub-traits of schizotypy were uniquely related to frequency and location amplitudes, suggesting the previously reported inconsistencies in the literature may be due to diverse samples and differing deviant tone types. Finally, impulsivity and sensation-seeking likely contributed to the slower processing seen in location deviance detection. Ultimately, the current results provide evidence that the neurobiological abnormalities seen in clinical populations of schizotypal personality disorder and psychosis also extend to non-clinical populations.

The Complex Pattern Mismatch Negativity as a Potential Indicator of Psychosis Across all Phases of Illness: A Meta-Analysis.

Over the past decade, there has been extensive research on the mismatch negativity (MMN) and its promise as a biomarker of illness in people with schizophrenia (SZ). Nevertheless, when attempting to assess the early stages of illness progression, the utility of MMN has been inconsistent. Recently, researchers have been investigating a more advanced MMN paradigm (the complex MMN [cMMN]) which is believed to index higher-order cognitive processing and has been suggested to be a more effective indicator of the early phases of SZ. The cMMN is defined as a paradigm that relies on alterations within a pre-established pattern of stimuli. In this meta-analysis, we investigated cMMN deficits in individuals with SZ, including an analysis involving those in the first 5 years of illness. Our search also included individuals with bipolar disorder who experience psychosis; however, no related papers were found and thus, no findings are reported. Our findings indicate a small/moderate effect (d = 0.47), suggesting that individuals with SZ exhibit reduced cMMN amplitudes compared to individuals without SZ. Interestingly, this effect seems to be more pronounced in individuals within the first 5 years of their illness (d = 0.58), suggesting that cMMN might be a more sensitive biomarker in the early phases of SZ compared to traditional paradigms.

Examining the Complex Mismatch Negativity in Early Phase Psychosis Using the Dual Rule Paradigm.

Using electroencephalography (EEG) to examine the simple mismatch negativity (MMN), a marker of auditory cortex function, has been of great interest in the exploration of biomarkers for psychotic illness. Despite many studies reporting MMN deficits in chronic schizophrenia, there are inconsistent reports of MMN reductions in the early phases of psychotic illness, suggesting the MMN elicited by traditional paradigms may not be a sensitive enough measure of vulnerability to be used as a biomarker. Recently, a more computationally complex measure of auditory cortex function (the complex mismatch negativity; cMMN) has been hypothesized to provide a more sensitive marker of illness vulnerability. The current study employed a novel dual rule paradigm, in which two pattern rules are established and violated, to examine the cMMN in 14 individuals with early phase psychosis (EPP, < 5 years illness) and 15 healthy controls (HC). Relationships between cMMN waveforms, symptom severity, and measures of functioning were explored. We found reductions of cMMN amplitudes at the site of maximal amplitude in EPP (p = .017) with large effect sizes (Hedges' g = 0.96). This study is an early step in the exploration of the cMMN as a biomarker for psychosis. Our results provide evidence that the dual rule cMMN paradigm shows promise as a method for cMMN elicitation that captures more subtle neurofunctional changes in the early stages of illness.

Examining the impact of schizotypal personality traits on event-related potential (ERP) indexes of sensory gating in a healthy population.

The aim of this study was to better understand the relation of schizotypy traits with sensory gating ability in a sample of community-dwelling individuals with high and low schizotypy traits. Sensory gating was assessed through the paired click paradigm and mid-latency evoked responses (i.e., P50, N100, P200), while schizotypy traits were assessed through the SPQ-BR which was used to classify participants into "high" and "low" schizotypy groups. Based on prior work, we hypothesized that those with the highest schizotypy scores would have reduced sensory gating ability. While this study does not show differences between relatively low and high schizotypy groups on sensory gating ability, it does suggest that our participants may have been experiencing deficits in attention allocation, a downstream cognitive processing measure. Scores on the SPQ-BR suggest that our sample was not close to the high end of the schizotypy traits which may help explain why no differences were found. This research shows the importance of including all levels of schizotypy ratings in clinical research as we can gain a clearer view of the impact of schizotypy on the brain and cognitive functioning in those with "high" levels of schizotypy. Additionally, this work highlights the importance of including measures of important factors such as impulsivity and sensation-seeking to better understand what aspects of schizotypy may be driving these sensory gating alterations reported in the literature.

Recent advances in genetic systems in obligate intracellular human-pathogenic bacteria.

The ability to genetically manipulate a pathogen is fundamental to discovering factors governing host-pathogen interactions at the molecular level and is critical for devising treatment and prevention strategies. While the genetic "toolbox" for many important bacterial pathogens is extensive, approaches for modifying obligate intracellular bacterial pathogens were classically limited due in part to the uniqueness of their obligatory lifestyles. Many researchers have confronted these challenges over the past two and a half decades leading to the development of multiple approaches to construct plasmid-bearing recombinant strains and chromosomal gene inactivation and deletion mutants, along with gene-silencing methods enabling the study of essential genes. This review will highlight seminal genetic achievements and recent developments (past 5 years) for Anaplasma spp., Rickettsia spp., Chlamydia spp., and Coxiella burnetii including progress being made for the still intractable Orientia tsutsugamushi. Alongside commentary of the strengths and weaknesses of the various approaches, future research directions will be discussed to include methods for C. burnetii that should have utility in the other obligate intracellular bacteria. Collectively, the future appears bright for unraveling the molecular pathogenic mechanisms of these significant pathogens.

Measuring the attention networks and quantitative-electroencephalography correlates of attention in depression.

Given the association between major depressive disorder (MDD) and cortical inefficiency related to executive control, specifically in the sense that individuals with MDD may recruit more cognitive resources to complete tasks at the same capacity as those without MDD, the current study was interested in examining the attention networks and executive functioning of those with MDD. Past research has used the Attention Network Test (ANT) to measure changes of attention in clinical vs. healthy populations; however, theoretical concerns have been raised regarding the task. The Combined Attention Systems Task (CAST) was developed to address these concerns and was used in our study in combination with quantitative-electroencephalography (QEEG) to assess both behavioural and neurophysiological changes in participants with MDD (n = 18) compared to healthy controls (HCs; n = 22). We found no behavioural differences between MDD and HC groups suggesting individuals with MDD in our sample were not experiencing the executive functioning deficits previously reported in the literature. Neurophysiological measures of attention revealed that MDD participants had greater theta and alpha1 activity relative to HCs, suggesting that although individuals with MDD do not show deficits in behavioural attention, they exhibit altered neural processing which underlies cognitive function.

An investigation of auditory processing in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.

The Periplasmic Tail-Specific Protease, Tsp, Is Essential for Secondary Differentiation in Chlamydia trachomatis.

The obligate intracellular human pathogen Chlamydia trachomatis (Ctr) undergoes a complex developmental cycle in which the bacterium differentiates between two functionally and morphologically distinct forms: the elementary body (EB) and the reticulate body (RB). The EB is the smaller, infectious, nondividing form which initiates infection of a susceptible host cell, whereas the RB is the larger, non-infectious form which replicates within a membrane-bound vesicle called an inclusion. The mechanism(s) which drives differentiation between these developmental forms is poorly understood. Bulk protein turnover is likely required for chlamydial differentiation given the significant differences in the protein repertoires and functions of the EB and RB. We hypothesize that periplasmic protein turnover is also critical for the reorganization of an RB into an EB, referred to as secondary differentiation. Ct441 is a periplasmic protease ortholog of tail-specific proteases (i.e., Tsp, Prc) and is expressed in Ctr during secondary differentiation. We investigated the effect of altering Tsp expression on developmental cycle progression. Through assessment of bacterial morphology and infectious progeny production, we found that both overexpression and CRISPR interference/dCas9 (CRISPRi)-mediated knockdown of Tsp negatively impacted chlamydial development through different mechanisms. We also confirmed that catalytic activity is required for the negative effect of overexpression and confirmed the effect of the mutation in in vitro assays. Electron microscopic assessments during knockdown experiments revealed a defect in EB morphology, directly linking Tsp function to secondary differentiation. These data implicate Ct441/Tsp as a critical factor in secondary differentiation. IMPORTANCE The human pathogen Chlamydia trachomatis is the leading cause of preventable infectious blindness and bacterial sexually transmitted infections worldwide. This pathogen has a unique developmental cycle that alternates between distinct forms. However, the key processes of chlamydial development remain obscure. Uncovering the mechanisms of differentiation between its metabolically and functionally distinct developmental forms may foster the discovery of novel Chlamydia-specific therapeutics and limit development of resistant bacterial populations derived from the clinical use of broad-spectrum antibiotics. In this study, we investigate chlamydial tail-specific protease (Tsp) and its function in chlamydial growth and development. Our work implicates Tsp as essential to chlamydial developmental cycle progression and indicates that Tsp is a potential drug target for Chlamydia infections.

Reduced duration mismatch negativity elicited by the multi-feature 'optimal' paradigm in early-phase psychosis.

BACKGROUND: MMN and P3a are EEG-derived event related potentials that are thought to be prospective biomarkers for schizophrenia and, potentially, early-phase psychosis (EPP). METHODS: EPP (n = 12) and healthy control (HC; n = 35) participants listened to a multi-feature optimal paradigm with five deviant types (gap, duration, location, intensity, and frequency). RESULTS: There was a significant amplitude difference between the EPP and HC group with duration MMN (p = .02). No significant amplitude differences between groups were found for the P3a waveform. There were several correlations for the EPP group with the BNSS, SOFAS, and PANSS-general questionnaires. Length of illness was not associated with MMN or P3a. CONCLUSIONS: The optimal paradigm is suitable for eliciting multiple deviant types within a short amount of time in both clinical and healthy populations. This study confirms duration MMN deficits within an EPP group and that MMN is related to functional outcomes and positive and negative symptomology.

Molecular Characterization of the ClpC AAA+ ATPase in the Biology of Chlamydia trachomatis.

Bacterial AAA+ unfoldases are crucial for bacterial physiology by recognizing specific substrates and, typically, unfolding them for degradation by a proteolytic component. The caseinolytic protease (Clp) system is one example where a hexameric unfoldase (e.g., ClpC) interacts with the tetradecameric proteolytic core ClpP. Unfoldases can have both ClpP-dependent and ClpP-independent roles in protein homeostasis, development, virulence, and cell differentiation. ClpC is an unfoldase predominantly found in Gram-positive bacteria and mycobacteria. Intriguingly, the obligate intracellular Gram-negative pathogen Chlamydia, an organism with a highly reduced genome, also encodes a ClpC ortholog, implying an important function for ClpC in chlamydial physiology. Here, we used a combination of in vitro and cell culture approaches to gain insight into the function of chlamydial ClpC. ClpC exhibits intrinsic ATPase and chaperone activities, with a primary role for the Walker B motif in the first nucleotide binding domain (NBD1). Furthermore, ClpC binds ClpP1P2 complexes via ClpP2 to form the functional protease ClpCP2P1 in vitro, which degraded arginine-phosphorylated ß-casein. Cell culture experiments confirmed that higher order complexes of ClpC are present in chlamydial cells. Importantly, these data further revealed severe negative effects of both overexpression and depletion of ClpC in Chlamydia as revealed by a significant reduction in chlamydial growth. Here, again, NBD1 was critical for ClpC function. Hence, we provide the first mechanistic insight into the molecular and cellular function of chlamydial ClpC, which supports its essentiality in Chlamydia. ClpC is, therefore, a potential novel target for the development of antichlamydial agents. IMPORTANCE Chlamydia trachomatis is an obligate intracellular pathogen and the world's leading cause of preventable infectious blindness and bacterial sexually transmitted infections. Due to the high prevalence of chlamydial infections along with negative effects of current broad-spectrum treatment strategies, new antichlamydial agents with novel targets are desperately needed. In this context, bacterial Clp proteases have emerged as promising new antibiotic targets, since they often play central roles in bacterial physiology and, for some bacterial species, are even essential for survival. Here, we report on the chlamydial AAA+ unfoldase ClpC, its functional reconstitution and characterization, individually and as part of the ClpCP2P1 protease, and establish an essential role for ClpC in chlamydial growth and intracellular development, thereby identifying ClpC as a potential target for antichlamydial compounds.

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

Chlamydia trachomatis (CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (e.g., ClpX). It has been shown that dihydrothiazepines can disrupt CT-ClpXP. Based on this precedent, we synthesized a dihydrothiazepine library and characterized its antichlamydial activity using a modified semi-high-throughput screening assay. Then, we demonstrated their ability to inhibit ClpX ATPase activity in vitro, supporting ClpX as a target. Further, our lead compound displayed a promising selectivity profile against CT, acceptable cytotoxicity, no mutagenic potential, and good in vitro stability. A two-dimensional quantitative structure-activity relationship (2D QSAR) model was generated as a support tool in the identification of more potent antichlamydial molecules. This study suggests dihydrothiazepines are a promising starting point for the development of new and selective antichlamydial drugs.

The structure of caseinolytic protease subunit ClpP2 reveals a functional model of the caseinolytic protease system from Chlamydia trachomatis.

Chlamydia trachomatis (ct) is the most reported bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Caseinolytic proteases (ClpP) from pathogenic bacteria are attractive antibiotic targets, particularly for bacterial species that form persister colonies with phenotypic resistance against common antibiotics. ClpP functions as a multisubunit proteolytic complex, and bacteria are eradicated when ClpP is disrupted. Although crucial for chlamydial development and the design of agents to treat chlamydia, the structures of ctClpP1 and ctClpP2 have yet to be solved. Here, we report the first crystal structure of full-length ClpP2 as an inactive homotetradecamer in a complex with a candidate antibiotic at 2.66 Å resolution. The structure details the functional domains of the ClpP2 protein subunit and includes the handle domain, which is integral to proteolytic activation. In addition, hydrogen-deuterium exchange mass spectroscopy probed the dynamics of ClpP2, and molecular modeling of ClpP1 predicted an assembly with ClpP2. By leveraging previous enzymatic experiments, we constructed a model of ClpP2 activation and its interaction with the protease subunits ClpP1 and ClpX. The structural information presented will be relevant for future rational drug design against these targets and will lead to a better understanding of ClpP complex formation and activation within this important human pathogen.

MMN and P3a Elicited by a Novelty Oddball Paradigm Are Not Reduced in Early-Phase Psychosis.

INTRODUCTION: The present study compared the mismatch negativity (MMN) and P3a waveforms among early-phase psychosis (EPP; n = 13) individuals and healthy controls (n = 30) to contribute to the research on these waveforms as potential biomarkers for schizophrenia. METHODS: MMN and P3a were elicited with a novelty paradigm using complex stimuli with electrophysiological technology. RESULTS: No significant group differences of amplitude were observed with either waveform. Increased asociality and blunted affect were associated with a reduction in both MMN and P3a waveforms indicating a relationship between these negative symptoms and cognitive deficits. Good social and occupational functioning correlated with improved MMN and P3a waveforms in the EPP group. CONCLUSIONS: This study suggests that MMN and P3a may be more appropriately used as an indicator of illness progression and symptomology rather than a biomarker in the early phase of the illness.

Impact of nutrients on the function of the chlamydial Rsb partner switching mechanism.

The obligate intracellular bacterial pathogen Chlamydia trachomatis is a leading cause of sexually transmitted infections and infectious blindness. Chlamydia undergo a biphasic developmental cycle alternating between the infectious elementary body (EB) and the replicative reticulate body (RB). The molecular mechanisms governing RB growth and RB-EB differentiation are unclear. We hypothesize that the bacterium senses host cell and bacterial energy levels and metabolites to ensure that development and growth coincide with nutrient availability. We predict that a partner switching mechanism (PSM) plays a key role in the sensing and response process acting as a molecular throttle sensitive to metabolite levels. Using purified wild type and mutant PSM proteins, we discovered that metal type impacts enzyme activity and the substrate specificity of RsbU and that RsbW prefers ATP over GTP as a phosphate donor. Immunoblotting analysis of RsbV1/V2 demonstrated the presence of both proteins beyond 20 hours post infection and we observed that an RsbV1-null strain has a developmental delay and exhibits differential growth attenuation in response to glucose levels. Collectively, our data support that the PSM regulates growth in response to metabolites and further defines biochemical features governing PSM-component interactions which could help in the development of novel PSM-targeted therapeutics.

Tag-Dependent Substrate Selection of ClpX Underlies Secondary Differentiation of Chlamydia trachomatis.

Despite having a highly reduced genome, Chlamydia trachomatis undergoes a complex developmental cycle in which the bacteria differentiate between the following two functionally and morphologically distinct forms: the infectious, nonreplicative elementary body (EB) and the noninfectious, replicative reticulate body (RB). The transitions between EBs and RBs are not mediated by division events that redistribute intracellular proteins. Rather, both primary (EB to RB) and secondary (RB to EB) differentiation likely require bulk protein turnover. One system for targeted protein degradation is the trans-translation system for ribosomal rescue, where polypeptides stalled during translation are marked with an SsrA tag encoded by a hybrid tRNA-mRNA, tmRNA. ClpX recognizes the SsrA tag, leading to ClpXP-mediated degradation. We hypothesize that ClpX functions in chlamydial differentiation through targeted protein degradation. We found that mutation of a key residue (R230A) within the specific motif in ClpX associated with the recognition of SsrA-tagged substrates resulted in abrogated secondary differentiation while not reducing chlamydial replication or developmental cycle progression as measured by transcripts. Furthermore, inhibition of trans-translation through chemical and targeted genetic approaches also impeded chlamydial development. Knockdown of tmRNA and subsequent complementation with an allele mutated in the SsrA tag closely phenocopied the overexpression of ClpXR230A, thus suggesting that ClpX recognition of SsrA-tagged substrates plays a critical function in secondary differentiation. Taken together, these data provide mechanistic insight into the requirements for transitions between chlamydial developmental forms. IMPORTANCE Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections and preventable infectious blindness. This unique organism undergoes developmental transitions between infectious, nondividing forms and noninfectious, dividing forms. Therefore, the chlamydial developmental cycle is an attractive target for Chlamydia-specific antibiotics, which would minimize effects of broad-spectrum antibiotics on the spread of antibiotic resistance in other organisms. However, the lack of knowledge about chlamydial development on a molecular level impedes the identification of specific, druggable targets. This work describes a mechanism through which both the fundamental processes of trans-translation and proteomic turnover by ClpXP contribute to chlamydial differentiation, a critical facet of chlamydial growth and survival. Given the almost universal presence of trans-translation and ClpX in eubacteria, this mechanism may be conserved in developmental cycles of other bacterial species. Additionally, this study expands the fields of trans-translation and Clp proteases by emphasizing the functional diversity of these systems throughout bacterial evolution.

Effect of caffeine on resting-state alpha activity across the human menstrual cycle.

RATIONALE: Caffeine is the most consumed stimulant worldwide, and there is great interest in understanding its neurophysiological effects. Resting-state electroencephalography (EEG) studies suggest that caffeine enhances arousal, which suppresses the spectral power of alpha frequencies associated with reduced alertness. However, it is unclear whether caffeine's neurophysiological effects vary across the human menstrual cycle. OBJECTIVE: The objective of our study was to test whether caffeine's effect on EEG activity differs across the human menstrual cycle. METHODS: Fifty-six female participants were randomly assigned to complete the experiment while in either their menstrual (n = 21), follicular (n = 19), or luteal (n = 16) phase. Each participant completed two study sessions in the same menstrual phase, approximately 1 month apart, during which they were administered either a caffeine pill (200 mg, oral) or a placebo pill in a counterbalanced order using a randomized double-blinded procedure. We measured their eyes-closed resting-state EEG approximately 30 min after pill administration and conducted a spectral power analysis at different frequency bands. RESULTS: Caffeine reduced EEG power in the alpha1 frequency band (8-10 Hz), but only for participants who self-reported higher weekly caffeine consumption. Importantly, caffeine's effects did not differ by menstrual phase. CONCLUSIONS: We conclude that when studying caffeine's effects on resting-state EEG, participants' baseline caffeine consumption is more influential than their menstrual cycle phase. This study has important implications for the inclusion of menstruating individuals in neurophysiological studies of caffeine.

MMN and P3a elicited by a novelty paradigm in healthy controls: An investigation of sex differences.

The mismatch negativity (MMN) and P3a waveforms are both markers of auditory change detection. MMN indicates deficits in performing auditory change-detection tasks, while the P3a reflects the evaluative and conscious aspect of orienting to the sound. Understanding the role biological sex has concerning these waveforms would provide insight into overall brain-based differences, but whether sex differences exist to such a degree that it can moderate the effect of auditory change detection is not certain. Thus, the purpose of this study was to examine potential sex differences in MMN and P3a elicited by a novelty paradigm in a healthy population. The results showed no significant differences between males and females. This study proves to be useful by adding to the limited literature on the topic and by providing a foundation of knowledge regarding sex differences in auditory change detection mechanisms within the population.

EEG Microstates in Early Phase Psychosis: The Effects of Acute Caffeine Consumption.

Individuals with schizophrenia use on average twice as much caffeine than the healthy population, but the underlying cortical effects of caffeine in this population are still not well understood. Using resting electroencephalography (EEG) data, we can determine recurrent configurations of the electric field potential over the cortex. These configurations, referred to as microstates, are reported to be altered in schizophrenia and can give us insight into the functional dynamics of large-scale brain networks. In the current study, we use a placebo-controlled, randomized, double-blind, repeated-measures design to examine the effects of a moderate dose of caffeine (200mg) on microstate classes A, B, C, and D in a sample of individuals within the first five years of psychosis onset compared to healthy controls. The results support the reduction of microstate class C and D, as well as the increase of microstate class A and B in schizophrenia. Further, acute caffeine administration appears to exacerbate these group differences by reducing class D, and increasing occurrences of class A and B states in the patient group only. The current results support the hypothesis of a microstate class D reduction as an endophenotypic marker for psychosis and provide the first descriptive account of how caffeine is affecting these microstate classes in an early phase psychosis sample.

Interaction of sex and cannabis in adult in vivo brain imaging studies: A systematic review.

Cannabis has been shown to cause structural and functional neurocognitive changes in heavy users. Cannabis use initiation aligns with brain development trajectories; therefore, it is imperative that the potential neurological implications of cannabis use are understood. Males and females reach neurodevelopmental milestones at different rates making it necessary to consider biological sex in all cannabis and brain-based research. Through use of a systamatic review in accordance with PRISMA guidelines, we aimed to understand the interaction between biological sex and cannabis use on brain-based markers. In total, 18 articles containing a sex-based analysis of cannabis users were identified. While the majority of studies (n = 11) reported no sex by cannabis use interactions on brain-based markers, those that reported findings (n = 8) suggest females may be more susceptible to cannabis' neurotoxic effects. Unfortunately, a large portion of the literature was excluded due to no sex-based analysis. In addition, studies that reported no sex differences often contained a reduced number of females which may result in some studies being underpowered for sex-based analyses, making it difficult to draw firm conclusions. Suggestions to improve cannabis and sex-based reseach are proposed.

Corrigendum: Genetic inactivation of Chlamydia trachomatis inclusion membrane protein CT228 alters MYPT1 recruitment, extrusion production, and longevity of infection.

[This corrects the article DOI: 10.3389/fcimb.2018.00415.].