Since the early descriptions of language function based on observations of patients with language deficits by Broca and Wernicke, neurosurgeons have been focused on characterizing the anatomic regions necessary for language perception and production, and preserving these structures during surgery to minimize patient deficits post operatively. In this supplementary issue on awake intraoperative mapping, we review language processing across multiple domains, highlighting key advances in direct electrical stimulation of different cortical and subcortical regions involved in naming, repetition, reading, writing, and syntax. We then discuss different intraoperative tasks for assessing the function of a given area and avoiding injury to critical, eloquent regions.Endoscopy and robotics represent two emerging technologies within the field of spine surgery, the former an ultra-MIS approach minimizing the perioperative footprint and the latter leveraging accuracy and precision. Herein, we present the novel incorporation of robotic assistance into endoscopic laminotomy, applied to a 27-yr-old female with a large caudally migrated L4-5 disc herniation. Patient consent was obtained. Robotic guidance was deployed in (1) planning of a focussed laminotomy map, pivoting on a single skin entry point; (2) percutaneous targeting of the interlaminar window; and (3) execution of precision drilling, controlled for depth. Through this case, we illustrated the potential synergy between these 2 technologies in achieving precise bony removal tailored to the patient's unique pathoanatomy while simultaneously introducing safety mechanisms against human error and improving surgical ergonomics.1,2 The physicians consented to the publication of their images.Pre-mRNA splicing catalyzed by the spliceosome represents a critical step in the regulation of gene expression contributing to transcriptome and proteome diversity. The spliceosome consists of five small nuclear ribonucleoprotein particles (snRNPs), the biogenesis of which remains only partially understood. Here we define the evolutionarily conserved protein Ecdysoneless (Ecd) as a critical regulator of U5 snRNP assembly and Prp8 stability. Combining Drosophila genetics with proteomic approaches, we demonstrate the Ecd requirement for the maintenance of adult healthspan and lifespan and identify the Sm ring protein SmD3 as a novel interaction partner of Ecd. We show that the predominant task of Ecd is to deliver Prp8 to the emerging U5 snRNPs in the cytoplasm. Ecd deficiency, on the other hand, leads to reduced Prp8 protein levels and compromised U5 snRNP biogenesis, causing loss of splicing fidelity and transcriptome integrity. Based on our findings, we propose that Ecd chaperones Prp8 to the forming U5 snRNP allowing completion of the cytoplasmic part of the U5 snRNP biogenesis pathway necessary to meet the cellular demand for functional spliceosomes.
  The purpose of this study was to determine whether sagittal neck sitting posture subgroup membership in late adolescence was a risk factor for persistent neck pain (PNP) in young adults.
 
  There were 686 participants enrolled in the Raine Study at the 17- and 22-year follow-ups. At 17years of age, posture was measured by photographs, and 4 subgroups of sitting neck posture were determined by cluster analysis. Height and weight were measured, and exercise frequency, depression, and PNP were assessed by questionnaire. At 22years of age, participants answered questions about neck pain and occupation type.  https://www.selleckchem.com/products/Rapamycin.html  Logistic regression examined if neck posture subgroups at 17years of age were a risk factor for PNP at 22years of age, taking into account other factors.
 
  Female sex (odds ratio [OR]=1.75, 95% CI=1.16-2.65) and PNP at 17years of age (OR=3.78, 95% CI=2.57-5.57) were associated with PNP at 22years of age. In females, neck posture subgroup at 17years of age was a risk factor for PNP at 22years of age. Compared health messages to sit up straight to prevent neck pain needs rethinking.Soil microbial communities are key players of ecosystem processes and important for crop and soil health. The Humid Pampas region in Argentina concentrates 75% of the national soybean production, which is based on intensive use of agrochemicals, monocropping and no-till. A long-term field experiment under no-till management in the southeast of the Argentinean Pampas provides a unique opportunity to compare soybean under monocropping with cultivation including alternating cover crops or in a three-phase rotation. We hypothesized that cropping regimes and season affect soil microbial community composition and diversity. Amplicon sequencing of 16S rRNA genes and internal transcribed spacer fragments showed a stronger microbial seasonal dynamic in conservation regimes compared to monocropping. In addition, several bacterial (e.g. Catenulispora, Streptomyces and Bacillus) and fungal genera (e.g. Exophiala) with cropping regime-dependent differential relative abundances were identified. Despite a temporal shift in microbial and chemical parameters, this study shows that long-term cropping regimes shaped the soil microbiota. This might have important implications for soil quality and soybean performance and should therefore be considered in the development of sustainable agricultural managements.Alkylating drugs are among the most often used chemotherapeutics. While cancer cells frequently develop resistance to alkylation treatments, detailed understanding of mechanisms that lead to the resistance is limited. Here, by using genome-wide CRISPR-Cas9 based screen, we identify transcriptional Mediator complex subunit 13 (MED13) as a novel modulator of alkylation response. The alkylation exposure causes significant MED13 downregulation, while complete loss of MED13 results in reduced apoptosis and resistance to alkylating agents. Transcriptome analysis identified cyclin D1 (CCND1) as one of the highly overexpressed genes in MED13 knock-out (KO) cells, characterized by shorter G1 phase. MED13 is able to bind to CCND1 regulatory elements thus influencing the expression. The resistance of MED13 KO cells is directly dependent on the cyclin D1 overexpression, and its down-regulation is sufficient to re-sensitize the cells to alkylating agents. We further demonstrate the therapeutic potential of MED13-mediated response, by applying combinatory treatment with CDK8/19 inhibitor Senexin A.