12,971 research outputs found
Expression Profiling and Functional Validation of MicroRNAs Involved in Schizophrenia and Bipolar Disorder
MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression at both the mRNA and protein levels. MiRNAs have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. We investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N =35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain-specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. Given that miRNAs can bind to their targets with imperfect complementarity, computational prediction of true miRNA:mRNA interactions has been difficult and therefore, functional validation of miRNA:mRNA interactions has been relatively sparse. Thus, it was the goal of this study to demonstrate biological functionality of miRNAs on their targets by evaluating transcriptional and translational levels of gene expression(real-time PCR, western blot) as well as determining miRNA target-site specificity (luciferase reporter gene assays). We investigated two miRNAs, miR-132 and miR-137, both of which have been shown to regulate neuronal function and development, and are believed to be associated with schizophrenia from two distinct avenues of research, miR-132 from expression studies and miR-137 from genetic studies. We demonstrated miR-132 down-regulates NTF3, DISC1, and GRIK5 at the transcript level and down-regulates GRIK5 at the protein level as well. Furthermore, we demonstrated miR-137 down-regulates TCF4, CACNA1C, CDK6, ANK3, and ZNF804A at the transcript level, and down-regulates TCF4, CACNA1C, and CDK6 at the protein level. Going further, we also demonstrated miR-137 binds specifically to target sites in the 3\u27-UTR of CACNA1C, TCF4, and CDK6, suggesting repression of these genes is directly mediated by miR-137. In total, this study provides strong evidence that miRNA dysregulation may contribute to schizophrenia pathogenesis
Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma
BACKGROUND: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent
METHODS: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on
RESULTS: A total of 29 new and 60 recurrent
CONCLUSIONS: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS fo
Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases
BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.
METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.
RESULTS: Ninety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure.
CONCLUSIONS: LITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients
Search for Boosted Dark Matter at ProtoDUNE
We propose the first experimental test of the inelastic boosted dark matter
hypothesis, capitalizing on the new physics potential with the imminent data
taking of the ProtoDUNE detectors. More specifically, we explore various
experimental signatures at the cosmic frontier, arising in boosted dark matter
scenarios, i.e., relativistic, inelastic scattering of boosted dark matter
often created by the annihilation of its heavier component which usually
comprises of the dominant relic abundance. Although features are unique enough
to isolate signal events from potential backgrounds, vetoing a vast amount of
cosmic background is rather challenging as the detectors are located on the
ground. We argue, with a careful estimate, that such backgrounds nevertheless
can be well under control by performing dedicated analyses after data
acquisition. We then discuss some phenomenological studies which can be
achieved with ProtoDUNE, employing a dark photon scenario as our benchmark
dark-sector model.Comment: Supplemental material include
TERT, a promoter of CNS malignancies
As cells replicate their DNA during mitosis, telomeres are shortened due to the inherent limitations of the DNA replication process. Maintenance of telomere length is critical for cancer cells to overcome cellular senescence induced by telomere shortening. Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, an RNA-dependent DNA polymerase that lengthens telomeric DNA to maintain telomere homeostasis
Phase ordering on small-world networks with nearest-neighbor edges
We investigate global phase coherence in a system of coupled oscillators on a
small-world networks constructed from a ring with nearest-neighbor edges. The
effects of both thermal noise and quenched randomness on phase ordering are
examined and compared with the global coherence in the corresponding \xy model
without quenched randomness. It is found that in the appropriate regime phase
ordering emerges at finite temperatures, even for a tiny fraction of shortcuts.
Nature of the phase transition is also discussed.Comment: 5 pages, 4 figures, Phys. Rev. E (in press
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