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Olfactory neuroblastoma, or esthesioneuroblastoma, is an uncommon malignant tumor originating from the neural crest that commonly occurs in the upper nasal cavity. Its ectopic origin is extremely rare, especially when located in the optical pathways. This paper reports the case of a giant ectopic esthesioneuroblastoma of the optic pathways that were surgically treated through a cranio-orbital-zygomatic (COZ) craniotomy with extensive resection, in addition to a literature review. The patient is a 46-year-old female presenting with a 4-month history of visual loss in the left eye. Since she was previously blind in the right eye from a traumatic injury, it was evolving to loss of bilateral vision. Imaging depicted an expansive infiltrating lesion involving the entire path of the right optic nerve, extending to the optic chiasm, cisternal portion of the left optic nerve, bilateral optic tract, and hypothalamus. Investigation of pituitary function was unremarkable. Esthesioneuroblastoma is a rare tumor with poorly defined standard clinical management. Its ectopic presentation makes the diagnosis even more challenging, making it difficult to manage these cases properly. Surgeons should be aware of this rare possibility, as early aggressive treatment is likely to be associated with better results.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

A obesidade é atualmente assunto de interesse universal. É considerada uma doença crônica, multifatorial, caracterizada pelo acúmulo excessivo de tecido adiposo no organismo. Do ponto de vista emocional pode ser causadora de sofrimento, depressão e de comportamentos de esquiva social que prejudicam a qualidade de vida.Uma vez estabelecida a obesidade, os problemas advindos desta poderão trazer também dificuldades em realizar o ato sexual, seja pelas restrições físicas propriamente ditas ou pela diminuição do poder de atração que pode ocorrer por uma baixa auto-estima, conseqüente as inúmeras cobranças sócio - culturais relacionados a padrões estéticos. O objetivo desta pesquisa bibliográfica é o de abordar diferentes visões sobre a dificuldade da aceitação do próprio corpo, vivida pela pessoa obesa, sua dinâmica intrapsíquica, e a relação entre a obesidade e a sexualidade.

Background The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number of experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, such as the Illumina NovaSeq 6000, enables this demand to be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer sequencing technologies, such as index-hopping, and their ability to generate high quality data has yet to be systematically evaluated. Results Here, we engineered a dual-indexed library structure, called TruDrop, on top of the inDrop scRNA-seq platform to solve these compatibility challenges, such that TruDrop libraries and standard Illumina libraries can be sequenced alongside each other on the NovaSeq. On scRNA-seq libraries, we implemented a previously-documented countermeasure to the well-described problem of index-hopping, demonstrated significant improvements in base-calling accuracy on the NovaSeq, and provided an example of multiplexing twenty-four scRNA-seq libraries simultaneously. We showed favorable comparisons in transcriptional diversity of TruDrop compared with prior inDrop libraries. Conclusions Our approach enables cost-effective, high throughput generation of sequencing data with high quality, which should enable more routine use of scRNA-seq technologies.

Additional file 2: Supplementary Table 1. Cost of Sequencing for inDrop. Supplementary Table 2. Evaluation of two TruDrop libraries’ raw yield and quality in low-throughput sequencing run on the iSeq 100. Supplementary Table 3. 24 TruDrop libraries raw data yield and quality in combined high-throughput sequencing run on the NovaSeq. Supplementary Table 4. 37 inDrop library quality scores from TruDrop on NovaSeq and V2 on NextSeq. Supplementary Table 5. inDrop library alignment metrics from TruDrop on NovaSeq and V2 on NextSeq. Supplementary Table 6. Diversity of UMI’s and genes expressed for cells sequenced with the TruDrop structure.

Additional file 5: Supplementary file 3.

Additional file 1: Supplementary Figure 1. Comparison of amplification of TruDrop and inDrop V2 primers during library preparation. (A) Diagnostic qPCR amplification curves comparing performance of all TruDrop primer pairs to V2 primers, all performed on the same sample. (B) Ct values of A. Supplementary Figure 2. Comparison of the library size distributions for TruDrop and inDrop V2 structured libraries during library preparation. (A) A BioAnalyzer profile of the size distribution of a V2 structured library. The spikes at 35 bp and 10,380 bp are controls. The numbers above the profile indicate the timepoints at which the various peaks were measured. (B) A BioAnalyzer profile of the size distribution of a TruDrop structured library. The spikes at 35 bp and 10,380 bp are controls. The numbers above the profile indicate the timepoints at which the various peaks were measured. (C) Plot of the average library size as determined via a BioAnalyzer for inDrop V2 libraries and TruDrop libraries. The median value is marked with a dotted line and a 95% confidence interval for the median is shown. Supplementary Figure 3. Comparison of sequence alignment metrics of inDrop V2 on NextSeq and TruDrop on NovaSeq. (A) Plot of the percent of reads with Valid Barcodes in 11 inDrop V2 mouse libraries and 23 TruDrop mouse libraries. The Median value is marked with a dotted line and a 95% confidence interval for the median is shown. (B) Plot of the percent of reads that uniquely align to a section of the mouse genome for inDrop V2 libraries and TruDrop libraries. The median value is marked with a dotted line and a 95% confidence interval for the median is shown. (C) Plot of the percent of reads that contain valid cell barcodes and a transcript that uniquely aligns to a section of the mouse genome for inDrop V2 libraries and TruDrop libraries. The median value is marked with a dotted line and a 95% confidence interval for the median is shown. Supplementary Figure 4. Another comparison of cell types identified between inDrop V2 on NextSeq and TruDrop on NovaSeq. (A) t-SNE and (B) sc-UniFrac analysis as performed in Fig. 5.

In vitro selection of RNA libraries constructed by randomization of RNA structural scaffolds from known ribozymes and riboswitches led to the identification of aptamers that were readily translated into functional biosensors in cells. Allosteric RNA devices are increasingly being viewed as important tools capable of monitoring enzyme evolution, optimizing engineered metabolic pathways, facilitating gene discovery and regulators of nucleic acid–based therapeutics. A key bottleneck in the development of these platforms is the availability of small-molecule-binding RNA aptamers that robustly function in the cellular environment. Although aptamers can be raised against nearly any desired target through in vitro selection, many cannot easily be integrated into devices or do not reliably function in a cellular context. Here, we describe a new approach using secondary- and tertiary-structural scaffolds derived from biologically active riboswitches and small ribozymes. When applied to the neurotransmitter precursors 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, this approach yielded easily identifiable and characterizable aptamers predisposed for coupling to readout domains to allow engineering of nucleic acid–sensory devices that function in vitro and in the cellular context.

The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number of experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, such as the Illumina NovaSeq 6000, enables this demand to be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer sequencing technologies, such as index-hopping, and their ability to generate high quality data has yet to be systematically evaluated. Here, we engineered a new dual-indexed library structure, called TruDrop, on top of the inDrop scRNA-seq platform to solve these compatibility challenges, such that TruDrop libraries and standard Illumina libraries can be sequenced alongside each other on the NovaSeq. We overcame the index-hopping issue, demonstrated significant improvements in base-calling accuracy, and provided an example of multiplexing twenty-four scRNA-seq libraries simultaneously. We showed favorable comparisons in transcriptional diversity of TruDrop compared with prior library structures. Our approach enables cost-effective, high throughput generation of sequencing data with high quality, which should enable more routine use of scRNA-seq technologies.

Background: The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ⩾70 years and 60 years.

A prevalent means of regulating gene expression in bacteria is by riboswitches found within mRNA leader sequences. Like protein repressors, these RNA elements must bind an effector molecule with high specificity against a background of other cellular metabolites of similar chemical structure to elicit the appropriate regulatory response. Current crystal structures of the lysine riboswitch do not provide a complete understanding of selectivity as recognition is substantially mediated through main-chain atoms of the amino acid. Using a directed set of lysine analogs and other amino acids, we have determined the relative contributions of the polar functional groups to binding affinity and the regulatory response. Our results reveal that the lysine riboswitch has >1000-fold specificity for lysine over other amino acids. The aptamer is highly sensitive to the precise placement of the e-amino group and relatively tolerant of alterations to the main-chain functional groups in order to achieve this specificity. At low nucleotide triphosphate (NTP) concentrations, we observe good agreement between the half-maximal regulatory activity (T(50)) and the affinity of the receptor for lysine (K(d)), as well as many of its analogs. However, above 400 μM [NTP], the concentration of lysine required to elicit transcription termination rises, moving into the riboswitch into a kinetic control regime. These data demonstrate that, under physiologically relevant conditions, riboswitches can integrate both effector and NTP concentrations to generate a regulatory response appropriate for global metabolic state of the cell.

Over the past decade the purine riboswitch, and in particular its nucleobase-binding aptamer domain, has emerged as an important model system for exploring various aspects of RNA structure and function. Its relatively small size, structural simplicity and readily observable activity enable application of a wide variety of experimental approaches towards the study of this RNA. These analyses have yielded important insights into small molecule recognition, co-transcriptional folding and secondary structural switching, and conformational dynamics that serve as a paradigm for other RNAs. In this article, the current state of understanding of the purine riboswitch family and how this growing knowledge base is starting to be exploited in the creation of novel RNA devices are examined. This article is part of a Special Issue entitled: Riboswitches.