RESUMO
The 2'-5'-oligoadenylate synthetase (OAS)/RNase L pathway is an innate immune system that protects hosts against pathogenic viruses and bacteria through cleavage of exogenous single-stranded RNA; however, this system's selective targeting mechanism remains unclear. Here, we identified an mRNA quality control factor Dom34 as a novel restriction factor for a positive-sense single-stranded RNA virus. Downregulation of Dom34 and RNase L increases viral replication, as well as half-life of the viral RNA. Dom34 directly binds RNase L to form a surveillance complex to recognize and eliminate the exogenous RNA in a manner dependent on translation. Interestingly, the feature detected by the surveillance complex is not the specific sequence of the viral RNA but the 'exogenous nature' of the RNA. We propose the following model for the selective targeting of exogenous RNA; OAS3 activated by the exogenous RNA releases 2'-5'-oligoadenylates (2-5A), which in turn converts latent RNase L to an active dimer. This accelerates formation of the Dom34-RNase L surveillance complex, and its selective localization to the ribosome on the exogenous RNA, thereby promoting degradation of the RNA. Our findings reveal that the selective targeting of exogenous RNA in antiviral defense occurs via a mechanism similar to that in the degradation of aberrant transcripts in RNA quality control.
Assuntos
2',5'-Oligoadenilato Sintetase/genética , Endonucleases/metabolismo , Proteínas Nucleares/metabolismo , Transdução de Sinais/genética , Viroses/genética , Vírus/genética , Nucleotídeos de Adenina/genética , Nucleotídeos de Adenina/metabolismo , Endonucleases/genética , Endorribonucleases/genética , Regulação Viral da Expressão Gênica , Humanos , Proteínas Nucleares/genética , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Estabilidade de RNA/genética , RNA de Cadeia Dupla/genética , RNA Viral/genética , Ribossomos/genética , Ribossomos/virologia , Viroses/virologia , Replicação Viral/genética , Vírus/patogenicidadeRESUMO
Topographical disorientation (TD) in novel environments is considered to be a part of anterograde amnesia. A 56-year-old woman presented with pure TD only in novel environments following limbic encephalitis. She could not remember directions inside the hospital on weekly outpatient visits; however, her verbal and visual anterograde memories were normal. In the test of learning photographs of scenes, faces, and objects, only her scores for landscapes were worse than those in healthy controls. These findings suggested that her TD specific to landscapes and directions in novel environments was caused by category-specific memory impairment related to bilateral hippocampal and parahippocampal dysfunction.
Assuntos
Agnosia/psicologia , Amnésia Anterógrada/psicologia , Encefalite Límbica/psicologia , Agnosia/diagnóstico , Agnosia/etiologia , Amnésia Anterógrada/diagnóstico , Amnésia Anterógrada/etiologia , Feminino , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Developmental prosopagnosia (DP) is a condition that indicates the inability to recognize individuals by their faces from birth, without any history of brain damage. The assessment of face recognition ability and diagnosis of DP involve the use of face tests such as the Cambridge Face Memory Test (CFMT) and the Cambridge Face Perception Test, along with self-reported measures like the 20-Item Prosopagnosia Index (PI20). Face recognition accuracy is affected by anxiety. However, previous studies on the relationship between face recognition ability and anxiety have not used the PI20 measure. This study aimed to investigate the relationship between self-reported measures of face recognition ability and anxiety tendencies among healthy young individuals for DP diagnosis and its implications. We used a face recognition test, involving the PI20, CFMT, Visual Perception Test for Agnosia-Famous Face Test (VPTA-FFT), and State-Trait Anxiety Inventory (STAI). We assessed the performance of 116 Japanese young adults (75 females, median age of 20.7 years, with a standard deviation of 1.2). Subsequently, we conducted a statistical analysis to examine the relationship between the outcomes of the face recognition tests and STAI scores using Pearson correlation analysis and single correlation coefficients. The results showed a positive correlation between state anxiety and PI20 (r = 0.308, p = 0.007), and a weak positive correlation was also observed between trait anxiety and PI20 (r = 0.268, p = 0.04). In contrast, there was no correlation between CFMT and VPTA-FFT with respect to STAI. The results of the hierarchical multiple regression analysis also suggested that the correlation between the performance on the PI20 (self-report) and objective measures of face recognition performance (the CFMT and the VPTA-FFT) are driven by differences in anxiety. This study is the first to explore the relationship between face recognition abilities and anxiety using the PI20 self-report measure. There are implications for future research on the diagnosis of DP and the relationship between anxiety and face recognition.
Assuntos
Reconhecimento Facial , Prosopagnosia , Feminino , Adulto Jovem , Humanos , Adulto , Prosopagnosia/diagnóstico , Reconhecimento Psicológico , Ansiedade/diagnóstico , Autorrelato , Reconhecimento Visual de ModelosRESUMO
Introduction: Primary squamous cell carcinoma of the kidney is rare, with only a few cases reported to date. Case presentation: A right renal mass was detected in a 73-year-old asymptomatic man. Dynamic contrast-enhanced computed tomography showed a hypodensity mass extending from the upper pole of the kidney to the right lobe of the liver. Renal biopsy revealed that this tumor was squamous cell carcinoma. One month later, computed tomography showed rapid tumor growth. Radical nephrectomy and partial hepatic resection were performed. Pathological analysis indicated that this tumor originated from the tubular epithelium, and the patient was diagnosed with primary squamous cell carcinoma of the kidney.Following up without adjuvant therapy, he developed retroperitoneal recurrence and multiple lung metastases and expired. Conclusion: In this case, squamous cell carcinoma of the kidney invaded the liver and progressed rapidly. Considering these observations, surgical resection should be promptly performed in suspected cases.
RESUMO
Poly(A) tail metabolism contributes to post-transcriptional regulation of gene expression. Here, we present a protocol for analyzing intact mRNA poly(A) tail length using nanopore direct RNA sequencing, which excludes truncated RNAs from the measurement. We describe steps for preparing recombinant eIF4E mutant protein, purifying m7G- capped RNAs, library preparation, and sequencing. Resulting data can be used not only for expression profiling and poly(A) tail length estimation but also for detecting alternative splicing and polyadenylation events and RNA base modification. For complete details on the use and execution of this protocol, please refer to Ogami et al. (2022).1.
RESUMO
Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino-acid-rich conditions, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail-length regulation. Consistent with this, the tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. The poly(A) tail shortens under mTOR active/amino-acid-rich conditions, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino-acid-starved (AAS) conditions. An RNA-binding protein, LARP1, is indispensable for the process. LARP1 interacts with non-canonical poly(A) polymerases and induces post-transcriptional polyadenylation of the target. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tails under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS.
Assuntos
Autoantígenos , Ribonucleoproteínas , RNA Mensageiro/metabolismo , Ribonucleoproteínas/metabolismo , Autoantígenos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ribossomos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Polinucleotídeo Adenililtransferase/genética , Aminoácidos/metabolismo , Biossíntese de ProteínasRESUMO
Human color processing includes perception, naming, and knowledge of colors. These facets are dissociable from each other and appear to have discrete neuronal bases. Here, we present two cases with loss of object color knowledge but spared color perception and knowledge of object other than color. Case 1, a stroke patient with lesions in the left medial occipitotemporal lobe, is impaired in associating colors or color names with objects or object names. However, he demonstrated good color perception and well-preserved knowledge of object form, size, and functions. Case 2, another stroke patient with a lesion in the left fusiform and lingual gyri, showed anomia for colors and slight impairment in object color knowledge. Case 1 is the first subject to have complete loss of object color knowledge, including the verbal association between object and color names without impairment in object knowledge about perceptual properties other than color. These results indicate that color and object processing is comprised of numerous dissociable features with distinct neuronal bases. Further, they provide evidence supporting the critical role played by the left medial occipitotemporal region in color knowledge.
Assuntos
Percepção de Cores , Semântica , Anomia , Humanos , Conhecimento , Masculino , Lobo OccipitalRESUMO
INTRODUCTION: Although various visual function deficits have been reported in patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), vegetable freshness perception has not been thoroughly examined. OBJECTIVE: To investigate vegetable freshness perception in patients with AD and DLB and to clarify the relationship between vegetable freshness perception and various visuoperceptual functions. METHODS: We enrolled 37 patients with probable DLB, 58 patients with probable AD, and 32 age-matched healthy controls. We assessed vegetable freshness perception and visuoperceptual functions, including vegetable brightness perception, contrast sensitivity, color perception, and stereopsis. Patients with DLB showed disproportionate deficits in vegetable freshness perception and vegetable luminance perception compared to patients with AD and controls. Analyses of the groups with higher and lower vegetable freshness perceptions revealed significant differences in contrast sensitivity and visual texture recognition. RESULTS: In the vegetable freshness test, we found significant differences among the 3 groups (F = 30.029, p < 0.0001); the extent of impairment in patients with DLB was greater than that in patients with AD. In patients with DLB, the vegetable freshness judgments were significantly correlated with texture judgment scores and contrast sensitivity. CONCLUSION: Our findings revealed significantly impaired vegetable freshness perception in patients with DLB. Vegetable freshness perception may be related to visual texture recognition in patients with DLB.
RESUMO
BACKGROUND: Numerous studies have shown visuoperceptual/visuospatial deficits in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Visual texture recognition is also impaired in patients with DLB and AD. Although patients with DLB often exhibit visual misidentifications of objects, there are few studies on the relationships between visual texture recognition and viewpoints for object recognition. OBJECTIVES: The aim of this study was to clarify how viewpoints, textures, and visual cognitive functions affect object recognition and result in visual misidentifications in patients with DLB or AD. METHODS: A total of 37 patients with probable DLB and 58 with probable AD and 32 age-matched healthy controls underwent neuropsychological and visuoperceptual assessments, and performed object identification tasks under four conditions (non-canonical view + blurry texture, non-canonical view + clear texture, canonical view + blurry texture, canonical view + clear texture). The relationship between object identification and other visuoperceptual functions was analyzed. RESULTS: Patients with DLB and AD exhibited significantly impaired object recognition under non-canonical viewing with blurry texture conditions, with the DLB patients exhibiting a significantly worse performance than the AD patients. Patients with DLB and AD exhibited visual misidentifications during object identification tasks under non-canonical viewing. In patients with DLB, the number of visual misidentifications was significantly correlated with the scores of visual texture recognition. CONCLUSIONS: The present study showed that significantly impaired object recognition in patients with DLB under the influences by both viewpoint and visual texture and in those with AD under the influence by viewpoint. Visual misidentification in object recognition could be associated with impaired visual texture recognition in DLB.
Assuntos
Agnosia , Doença de Alzheimer , Doença por Corpos de Lewy , Doença de Alzheimer/complicações , Humanos , Doença por Corpos de Lewy/complicações , Testes Neuropsicológicos , Percepção VisualRESUMO
The 2'-5'-oligoadenylate synthetase (OAS)/RNase L system protects hosts against pathogenic viruses through cleavage of the exogenous single-stranded RNA. In this system, an evolutionally conserved RNA quality control factor Dom34 (known as Pelota (Pelo) in higher eukaryotes) forms a surveillance complex with RNase L to recognize and eliminate the exogenous RNA in a manner dependent on translation. Here, we newly identified that ATP-binding cassette sub-family E member 1 (ABCE1), which is also known as RNase L inhibitor (RLI), is involved in the regulation of exogenous RNA decay. ABCE1 directly binds to form a complex with RNase L and accelerates RNase L dimer formation in the absence of 2'-5' oligoadenylates (2-5A). Depletion of ABCE1 represses 2-5A-induced RNase L activation and stabilizes exogenous RNA to a level comparable to that seen in RNase L depletion. The increased half-life of the RNA by the single depletion of either protein is not significantly affected by the double depletion of both proteins, suggesting that RNase L and ABCE1 act together to eliminate exogenous RNA. Our results indicate that ABCE1 functions as a positive regulator of exogenous RNA decay rather than an inhibitor of RNase L.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Regulação da Expressão Gênica , Estabilidade de RNA , Endorribonucleases/metabolismo , Células HeLa , Humanos , Ligação ProteicaRESUMO
BACKGROUND: Neuroimaging and some clinical studies have reported that the ventral visual pathway is relevant for visual texture recognition. Although a variety of visual deficits have been reported in patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), visual material identification and texture recognition have not been thoroughly examined. OBJECTIVES: To investigate visual texture recognition in patients with AD and DLB and to clarify the relationship between visual texture recognition and various visuoperceptual functions. METHODS: Twenty-five patients with probable DLB, 53 patients with probable AD, and 32 age-matched healthy controls were included. We assessed visual texture recognition of real materials/images and visuoperceptual functions including contrast sensitivity, color perception, stereopsis, shape detection, and position in space. RESULTS: DLB patients showed disproportionate deficits in visuoperceptual functions and visual texture recognition compared with AD patients and controls, but these dysfunctions were not correlated with each other. AD patients had significantly impaired visual texture recognition but with intact visuoperceptual functions, except contrast sensitivity. Using an optimal cut-off score according to the receiver operating characteristic (ROC) curve analysis, the results from the visual texture recognition of images could differentiate DLB patients from controls with a sensitivity of 92% and a specificity of 97%. CONCLUSIONS: We demonstrated significantly impaired visual texture recognition in patients with DLB and AD, with patients with DLB performing significantly worse than patients with AD. Additionally, visual texture recognition and visuoperceptual functions are independently disturbed in DLB.