Cis-regulatory modules contain multiple transcription factor (TF)-binding sites and integrate the effects of each TF to control gene expression in specific cellular contexts. Transposable elements (TEs) are uniquely equipped to deposit their regulatory sequences across a genome, which could also contain cis-regulatory modules that coordinate the control of multiple genes with the same regulatory logic. We provide the first evidence of mouse-specific TEs that encode a module of TF-binding sites in mouse embryonic stem cells (ESCs). The majority (77%) of the individual TEs tested exhibited enhancer activity in mouse ESCs. By mutating individual TF-binding sites within the TE, we identified a module of TF-binding motifs that cooperatively enhanced gene expression. Interestingly, we also observed the same motif module in the in silico constructed ancestral TE that also acted cooperatively to enhance gene expression. Our results suggest that ancestral TE insertions might have brought in cis-regulatory modules into the mouse genome.

The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3D and 2D objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER. Performance of rats with crossed lesions was compared with that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We found that rats with contralateral PER-POR lesions were impaired in object-context recognition but not in contextual FC. Therefore, interaction between the POR and PER is necessary for context-guided exploratory behavior but not for associating fear with context. Our results provide evidence for the hypothesis that the POR relies on object and pattern information from the PER to encode representations of context. The association of fear with a context, however, may be supported by alternate cortical and/or subcortical pathways when PER-POR interaction is not available. Our results suggest that contextual FC may represent a special case of context-guided behavior. Representations of context are important for perception, memory, decision making, and other cognitive processes. Moreover, there is extensive evidence that the use of contextual representations to guide appropriate behavior is disrupted in neuropsychiatric and neurological disorders including developmental disorders, schizophrenia, affective disorders, and Alzheimer's disease. Many of these disorders are accompanied by changes in parahippocampal and hippocampal structures. Understanding how context is represented in the brain and how parahippocampal structures are involved will enhance our understanding and treatment of the cognitive and behavioral symptoms associated with neurological disorders and neuropsychiatric disease.

BACKGROUND Vestibular schwannomas (VS) are benign tumors derived from Schwann cells ensheathing the vestibulocochlear nerve. The retrosigmoid (RS) surgical approach is useful to resect tumors of multiple sizes while affording the possibility of preserving postoperative hearing. OBJECTIVE To conduct a systematic review of published literature investigating hearing preservation rates in patients who underwent the RS approach for VS treatment. METHODS The PubMed, Scopus, and Embase databases were surveyed for studies that reported preoperative and postoperative hearing grades on VS patients who underwent RS treatment. Hearing preservation rates were calculated, and additional patient demographic data were extracted. Tumor size data were stratified to compare hearing preservation rates after surgery for intracanalicular, small (0-20 mm), and large (>20 mm) tumors. RESULTS Of 383 deduplicated articles, 26 studies (6.8%) met eligibility criteria for a total of 2034 patients with serviceable preoperative hearing, for whom postoperative hearing status was evaluated. Aggregate hearing preservation was 31% and 35% under a fixed and random effects model, respectively. A mixed effects model was used to determine hearing preservation rates depending on tumor size, which were determined to be 57%, 37%, and 12% for intracanalicular, small, and large tumors, respectively. Significant cross-study heterogeneity was found (I2 = 93%, τ2 = .964, P < .01; Q = 287.80, P = < .001), with rates of hearing preservation ranging from 0% to 100%. CONCLUSION Tumor size may have an effect on hearing preservation rates, but multiple factors should be considered. Discussion of a patient's expectations for hearing preservation is critical when deciding on VS treatment plans.

BACKGROUND External ventricular drain (EVD) placement is essential for the management of many neurocritical care patients. However, ventriculostomy-related infection (VRI) is a serious complication, and there remains no well-established protocol guiding use of perioperative or extended antibiotic prophylaxis to minimize risk of VRI. OBJECTIVE To analyze published evidence on the efficacy of extended prophylactic antimicrobial therapy and antibiotic-coated external ventricular drains (ac-EVDs) in reducing VRI incidence. METHODS We searched PubMed for studies related to VRIs and antimicrobial prophylaxis. Eligible articles reported VRI incidence in control and treatment cohorts evaluating prophylaxis with either extended systemic antibiotics (&gt; 24 hr) or ac-EVD. Risk ratios and VRI incidence were aggregated by prophylactic strategy, and pooled estimates were determined via random or mixed effects models. Study heterogeneity was quantified using I2 and Cochran's Q statistics. Rigorous assessment of study bias was performed, and PRISMA guidelines were followed throughout. RESULTS Across 604 articles, 19 studies (3%) met eligibility criteria, reporting 5242 ventriculostomy outcomes. Extended IV and ac-EVD prophylaxis were associated with risk ratios of 0.36 [0.14, 0.93] and 0.39 [0.21, 0.73], respectively. Mixed effects analysis yielded expected VRI incidence of 13% to 38% with no prophylaxis, 7% to 18% with perioperative IV prophylaxis, 3% to 9% with either extended IV or ac-EVD prophylaxis as monotherapies, and as low as 0.8% to 2% with extended IV and ac-EVD dual prophylaxis. CONCLUSION Management with both extended systemic antibiotics and ac-EVDs could lower VRI risk in ventriculostomy patients, but the impact on associated morbidity and mortality, healthcare costs, and length of stay remain unclear.