Successful localization of the Broca area with short-train pulses instead of ‘Penfield’ stimulation

AbstractDirect electrical stimulation of functional cortical areas is a standard procedure in epilepsy and glioma surgery. Many previous studies support that stimulation of the motor cortex with short-train pulses is a less epileptogenic alternative to the 50–60Hz ‘Penfield’ technique. However, whether the short-train stimulation is useful also in mapping of speech areas is unclear. In this case report we present a patient with oligodendroglioma near the Broca area. Extraoperative electrical stimulation via a subdural grid electrode was primarily performed to locate the speech area. The cortex was stimulated with short-train pulses (5 pulses, 0.5 pulse duration and 3ms interpulse interval) in addition to 1–3s 50Hz stimulation. The patient had speech arrest from both types of stimulation techniques during a naming task. It was however critical that the short (14.5ms) train stimulation was synchronized with the presentation of the naming objects. If not, there was no speech arrest. Despite this possible pitfall, this case has encouraged us to further try short-train stimulation in attempts to reduce stimulus-triggered seizures during mapping of eloquent areas

Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. <i>elegans</i>

Abstract Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis

A Lactobacilli diet that confers MRSA resistance causes amino acid depletion and increased antioxidant levels in the C. elegans host

Probiotic bacteria are increasingly popular as dietary supplements and have the potential as alternatives to traditional antibiotics. We have recently shown that pretreatment with Lactobacillus spp. Lb21 increases the life span of C. elegans and results in resistance toward pathogenic methicillin-resistant Staphylococcus aureus (MRSA). The Lb21-mediated MRSA resistance is dependent on the DBL-1 ligand of the TGF-β signaling pathway. However, the underlying changes at the metabolite level are not understood which limits the application of probiotic bacteria as timely alternatives to traditional antibiotics. In this study, we have performed untargeted nuclear magnetic resonance-based metabolic profiling. We report the metabolomes of Lactobacillus spp. Lb21 and control E. coli OP50 bacteria as well as the nematode-host metabolomes after feeding with these diets. We identify 48 metabolites in the bacteria samples and 51 metabolites in the nematode samples and 63 across all samples. Compared to the control diet, the Lactobacilli pretreatment significantly alters the metabolic profile of the worms. Through sparse Partial Least Squares discriminant analyses, we identify the 20 most important metabolites distinguishing probiotics from the regular OP50 food and worms fed the two different bacterial diets, respectively. Among the changed metabolites, we find lower levels of essential amino acids as well as increased levels of the antioxidants, ascorbate, and glutathione. Since the probiotic diet offers significant protection against MRSA, these metabolites could provide novel ways of combatting MRSA infections

Mining Unknown Porcine Protein Isoforms by Tissue-Based Map of Proteome Enhances the Pig Genome Annotation

A lack of the complete pig proteome has left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model. In this study, we developed a tissue-based proteome map using 34 major normal pig tissues. A total of 5841 unknown protein isoforms were identified and systematically characterized, including 2225 novel protein isoforms, 669 protein isoforms from 460 genes symbolized beginning with LOC, and 2947 protein isoforms without clear NCBI annotation in the current pig reference genome. These newly identified protein isoforms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing of the same pig tissues, further improving the genome annotation of the corresponding protein-coding genes. Combining the well-annotated genes that have parallel expression pattern and subcellular witness, we predicted the tissue-related subcellularlocations and potential functions for these unknown proteins. Finally, we mined 3081 orthologous genes for 52.7% of unknown protein isoforms across multiple species, referring to 68 KEGG pathways as well as 23 disease signaling pathways. These findings provide valuable insights and a rich resource for enhancing studies of pig genomics and biology, as well as biomedical model application to human medicine

Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile

Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemo-resistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies