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Introduction: Primary vitreoretinal lymphoma (PVRL) is a rare malignant tumor that typically involves the retina, vitreous, or optic nerve head. PVRL often occurs concurrently with central nervous system lymphoma. Here, we present the first report of a patient with biopsy-confirmed PVRL presenting solely with asymptomatic peripheral drusenoid lesions. Case Presentation: A woman in her 70s presented with new elevated amelanotic yellow lesions with overlying pigment in both of her eyes not previously seen prior to cataract surgery. Over the next 4 months, there was waxing and waning of lesions which resolved and first appeared in the right eye and then the left. A diagnostic vitrectomy of the left eye revealed B-cell lymphoma. The patient elected for initial treatment with radiation therapy of both orbits. A new lesion was identified in her right eye nearly 18 months after starting maintenance therapy with ibrutinib, following which systemic chemotherapy with methotrexate was initiated. Conclusion: Elevated clinical suspicion for a malignant process is needed for patients with progressive new retinal lesions in older age. Local radiation therapy to the orbits alone may not be sufficient to prevent progression despite initial presentation showing confinement of disease to the intraocular space.

Ependymal cells are ciliated-epithelial glial cells that develop from radial glia along the surface of the ventricles of the brain and the spinal canal. They play a critical role in cerebrospinal fluid (CSF) homeostasis, brain metabolism, and the clearance of waste from the brain. These cells have been implicated in disease across the lifespan including developmental disorders, cancer, and neurodegenerative disease. Despite this, ependymal cells remain largely understudied. Using single-cell RNA sequencing data extracted from publicly available datasets, we make key findings regarding the remarkable conservation of ependymal cell gene signatures across age, region, and species. Through this unbiased analysis, we have discovered that one of the most overrepresented ependymal cell functions that we observed relates to a critically understudied role in metal ion homeostasis. Our analysis also revealed distinct subtypes and states of ependymal cells across regions and ages of the nervous system. For example, neonatal ependymal cells maintained a gene signature consistent with developmental processes such as determination of left/right symmetry; while adult ventricular ependymal cells, not spinal canal ependymal cells, appeared to express genes involved in regulating cellular transport and inflammation. Together, these findings highlight underappreciated functions of ependymal cells, which will be important to investigate in order to better understand these cells in health and disease.

Dietary fat modulates neuronal health and contributes to age-related nervous system disorders. However, the complex interaction between dietary fat and supplementation and its consequences on neurotoxic pathophysiology has been sparsely explored. The indigenous Alaskan bog blueberry (BB), Vaccinum uliginosum, is known to have anti-inflammatory properties, mostly attributed to its rich polyphenolic content. Here, we evaluate the interplay between dietary fat and BB supplementation on sub-chronic manganese (Mn) exposure that inflicts neurotoxicity and behavioral impairments. In both low-fat and normal-fat diets, BB supplementation attenuated the behavioral and the molecular hallmarks of Mn-induced neurotoxicity. On the contrary, a high-fat diet was found to exacerbate these Mn-induced pathological features. Furthermore, BB supplementation failed to recover the behavioral deficits in mice subjected to a high fat diet in Mn-treated mice. Overall, our results demonstrate the importance of including a dietary regimen comprised of polyphenolic rich supplements with low-fat content in combating age-related neurodegenerative disorders.

The molecular basis of Parkinson’s disease (PD) is currently unknown. There is increasing evidence that fat metabolism is at the crossroad of key molecular pathways associated with the pathophysiology of PD. Fatty acid desaturases catalyze synthesis of saturated fatty acids from monounsaturated fatty acids thereby mediating several cellular mechanisms that are associated with diseases including cancer and metabolic disorders. The role of desaturases in modulating age-related neurodegenerative manifestations such as PD is poorly understood. Here, we investigated the effect of silencing Δ9 desaturase enzyme encoding fat-5 and fat-7 genes which are known to reduce fat content, on α-synuclein expression, neuronal morphology and dopamine-related behaviors in transgenic PD-like models of Caenorhabditis elegans(C. elegans). The silencing of the fat-5 and fat-7 genes rescued both degeneration of dopamine neurons and deficits in dopamine-dependent behaviors, including basal slowing and ethanol avoidance in worm models of PD. Similarly, silencing of these genes also decreased the formation of protein aggregates in a nematode model of PD expressing α-synuclein in the body wall muscles and rescued deficits in resistance to heat and osmotic stress. On the contrary, silencing of nhr-49 and tub-1 genes that are known to increase total fat content did not alter behavioral and pathological endpoints in the PD worm strains. Interestingly, the genetic manipulation of all four selected genes resulted in differential fat levels in the PD models without having significant effect on the lifespan, further indicating a complex fat homeostasis unique to neurodegenerative pathophysiology. Overall, we provide a comprehensive understanding of how Δ9 desaturase can alter PD-like pathology due to environmental exposures and proteotoxic stress, suggesting new avenues in deciphering the disease etiology and possible therapeutic targets.

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720–670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

Branched-chain amino acids (BCAA) found in protein are most notably known for their ability to increase protein synthesis, explaining their appeal to athletes seeking muscle hypertrophy, expedited recovery, and preservation of lean body mass. In addition to anabolic benefits, protein consumption has been implicated in the regulation of food intake, which represents an important variable in treating and preventing obesity. Protein-rich foods (such as dairy) have previously been linked to improved satiety and reduced food intake, however, there appear to be discrepancies in the effects of different protein types (for example whey versus casein) on appetite. One potential explanation for these differences is the varied amino acid composition of each protein type. Thus, one theory is that high levels of BCAA may be responsible in-part for the satiating properties of protein. Therefore, the purpose of this narrative review is to describe the effects of BCAA (both individually and in combination) on hormonal regulators of satiety including ghrelin, leptin, peptide tyrosine tyrosine (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1). This report also summarizes the effect of BCAA on food intake and subjective measures of hunger. Several reports suggest BCAA stimulate leptin activity (secretion or sensitivity) and GLP-1 levels and suppress ghrelin levels. Similarly, intake is reduced, and subjective measures of hunger are often lower following consumption of BCAA. However, inconsistencies in experimental protocols and related findings make the true effect of BCAA on satiety and food intake difficult to discern, and therefor worthy of further investigation.

Our unique multiplexed imaging assays employing FRET biosensors have previously detected that γ-secretase processes APP C99 primarily in late endosomes and lysosomes in live/intact neurons. Moreover we have shown that Aβ peptides are enriched in the same subcellular loci. Given that γ-secretase is integrated into the membrane bilayer and functionally links to lipid membrane properties in vitro, it is presumable that γ-secretase function correlates with endosome and lysosome membrane properties in live/intact cells. In the present study, we show using unique live-cell imaging and biochemical assays that the endo-lysosomal membrane in primary neurons is more disordered and, as a result, more permeable than in CHO cells. Interestingly, γ-secretase processivity is decreased in primary neurons, resulting in the predominant production of long Aβ42 instead of short Aβ38. In contrast, CHO cells favor Aβ38 over the Aβ42 generation. Our findings are consistent with the previous in vitro studies, demonstrating the functional interaction between lipid membrane properties and γ-secretase and provide further evidence that γ-secretase acts in late endosomes and lysosomes in live/intact cells.

Esse artigo apresenta uma abordagem de integração entre startups e universidade, tendo como objetivos: (i) difundir práticas gerenciais inovadoras em empresas ligadas à incubadoras de empresas, (ii) estreitar a relação entre teoria e prática no ensino da Administração sobretudo em ambiente dinâmicos, (iii) criar um ambiente propício ao desenvolvimento das competências dos alunos do curso de Administração em um enfoque de aprendizagem pela ação, ao mesmo tempo que os empresários das empresas incubadas possam refletir sobre seus processos de gestão. Tal intento é alcançado por meio de uma abordagem construtivista de aprendizagem ativa, com participação ativa dos alunos de graduação de um curso de administração, sob supervisão de um professor-facilitador e dos empresários das startups. Esse artigo apresenta resultados de casos exploratórios que visam entender problemas gerenciais de empresas incubadas na incubadora MIDI Tecnológico e propõe modelos de decisão para os empresários a partir de seus valores e preferências. Essa pesquisa apresenta inovação no aspecto gerencial, onde é apresentado o uso da abordagem Lean Startup junto ao apoio à decisão construtivista, para avaliar e criar alternativas de ações no tocante ao desenvolvimento de produto e mercado. E em adição, esse trabalho também apresenta uma abordagem de integração inovadora entre empresas incubadas e universidades, onde a primeira pode se valer de conhecimento gerenciais presentes nos cursos de administração para melhorar seu desempenho, bem como os acadêmicos podem se valer da aprendizagem vivencial para aplicar conhecimentos que precisarão ser melhor explorados durante sua vida acadêmica e profissional.