Antisaccadic eye movements in middle-aged individuals with a family history of Alzheimer's disease

BackgroundAntisaccade is closely associated with cognitive ability in Alzheimer's disease (AD). However, studies regarding antisaccade in the early stages of AD are scarce. Considering that first-degree family history is a well-established risk factor for AD, we explored the influence of family history on the performance of antisaccade tasks in individuals with normal cognition.MethodsIn total, 44 participants (aged 50–66 years) with a family history of AD (FH+) and 44 age-, gender-, and educational level-matched controls (FH-) were enrolled in our study. After cognitive assessment using the Montreal Cognitive Assessment and Mini-mental State Examination, participants underwent antisaccade trials, and all parameters were recorded using an eye tracker.ResultsWhile the average velocity was relatively lower in FH+ individuals than in FH− individuals (107.9 ± 14.3°/s vs. 132.9 ± 23.7°/s, p < 0.001), FH+ individuals surprisingly showed relatively fewer uninhibited reflexive saccades (44.7 ± 26.0% vs. 56.2 ± 24.7%, p = 0.037) than the control group. They also required a relatively shorter time to detect and correct false saccades (121.6 ± 40.7 ms vs. 143.9 ± 37.0 ms, p = 0.023).ConclusionsThis study showed that family history is associated with alterations in antisaccadic parameters, suggesting that eye tracking can be used to assess oculomotor control and executive function in individuals at risk of developing dementia

The Splicing Factor RBM4 Controls Apoptosis, Proliferation, and Migration to Suppress Tumor Progression

Splicing dysregulation is one of the molecular hallmarks of cancer. However, the underlying molecular mechanisms remain poorly defined. Here we report the splicing factor RBM4 suppresses proliferation and migration of various cancer cells by specifically controlling cancer-related splicing. Particularly, RBM4 regulates Bcl-x splicing to induce apoptosis, and co-expression of Bcl-xL partially reverses the RBM4-mediated tumor suppression. Moreover, RBM4 antagonizes an oncogenic splicing factor, SRSF1, to inhibit mTOR activation. Strikingly, RBM4 expression is dramatically decreased in cancer patients, and RBM4 level is positively correlated with improved survival. In addition to providing mechanistic insights of cancer-related splicing dysregulation, this study establishes RBM4 as a tumor suppressor with therapeutic potentials and clinical values as a prognostic factor

Spatial lifecourse epidemiology and infectious disease research

Spatial lifecourse epidemiology aims to utilize advanced spatial, location-aware, and artificial intelligence technologies to investigate long-term effects of measurable biological, environmental, behavioral, and psychosocial factors on individual risk for chronic diseases. It could also further the research on infectious disease dynamics, risks, and consequences across the life course

Data_Sheet_1_Antisaccadic eye movements in middle-aged individuals with a family history of Alzheimer's disease.docx

BackgroundAntisaccade is closely associated with cognitive ability in Alzheimer's disease (AD). However, studies regarding antisaccade in the early stages of AD are scarce. Considering that first-degree family history is a well-established risk factor for AD, we explored the influence of family history on the performance of antisaccade tasks in individuals with normal cognition.MethodsIn total, 44 participants (aged 50–66 years) with a family history of AD (FH+) and 44 age-, gender-, and educational level-matched controls (FH-) were enrolled in our study. After cognitive assessment using the Montreal Cognitive Assessment and Mini-mental State Examination, participants underwent antisaccade trials, and all parameters were recorded using an eye tracker.ResultsWhile the average velocity was relatively lower in FH+ individuals than in FH− individuals (107.9 ± 14.3°/s vs. 132.9 ± 23.7°/s, p ConclusionsThis study showed that family history is associated with alterations in antisaccadic parameters, suggesting that eye tracking can be used to assess oculomotor control and executive function in individuals at risk of developing dementia.</p

Hepatitis E virus infection in acute non-traumatic neuropathy: A large prospective case-control study in ChinaResearch in context

Neurological manifestations are potentially associated with hepatitis E virus (HEV) infection in Europe, mainly attributed to genotype (GT) 3 HEV infection. In this study, we determined the frequency and causal relationship of HEV in patients with non-traumatic neurological disorders in China, where GT4 HEV is prevalent. 1117 consecutive patients diagnosed with neurological illnesses in a hospital of eastern China and 1475 healthy controls who took routine examination in the same hospital were tested for HEV by serology and molecular methods. Anti-HEV IgM antibodies were detectable in 6 (0.54%) of the patients and 10 (0.68%) of the healthy controls (P = 0.651). Serum HEV RNA was detected in all of the 16 individuals with positive anti-HEV IgM. The six patients with HEV infection included two viral encephalitis, two posterior circulation ischemia, one peripheral neuropathy and one Guillian-Barré syndrome. They had no symptoms of acute viral hepatitis except two patients of viral encephalitis that showed mildly transaminitis. Additional, 39.51% patients and 35.63% controls without acute HEV infection were positive for anti-HEV IgG (P = 0.144). Anti-HEV IgG positivity was more frequent in male and elderly in both the patients and control groups, but unrelated to the incidence of any non-traumatic neurological illness, hospital stay or treatment outcome, except linking to better outcome of hemorrhagic stroke disease. These data demonstrated that HEV appears not to contribute to acute neurological disorders in China. Nevertheless, we cannot exclude a possible causative role, suggesting that testing HEV in this population, especially in situations of unexplained deregulated liver function would be warranted. Keywords: Hepatitis E virus (HEV), Neurological disorder, Genotypes, Viral encephaliti

Reprogramming One-Carbon Metabolic Pathways To Decouple l‑Serine Catabolism from Cell Growth in <i>Corynebacterium glutamicum</i>

l-Serine, the principal one-carbon source for DNA biosynthesis, is difficult for microorganisms to accumulate due to the coupling of l-serine catabolism and microbial growth. Here, we reprogrammed the one-carbon unit metabolic pathways in <i>Corynebacterium glutamicum</i> to decouple l-serine catabolism from cell growth. <i>In silico</i> model-based simulation showed a negative influence on <i>glyA</i>-encoding serine hydroxymethyltransferase flux with l-serine productivity. Attenuation of <i>glyA</i> transcription resulted in increased l-serine accumulation, and a decrease in purine pools, poor growth and longer cell shapes. The <i>gcvTHP</i>-encoded glycine cleavage (Gcv) system from <i>Escherichia coli</i> was introduced into <i>C. glutamicum</i>, allowing glycine-derived ¹³CH₂ to be assimilated into intracellular purine synthesis, which resulted in an increased amount of one-carbon units. Gcv introduction not only restored cell viability and morphology but also increased l-serine accumulation. Moreover, comparative proteomic analysis indicated that abundance changes of the enzymes involved in one-carbon unit cycles might be responsible for maintaining one-carbon unit homeostasis. Reprogramming of the one-carbon metabolic pathways allowed cells to reach a comparable growth rate to accumulate 13.21 g/L l-serine by fed-batch fermentation in minimal medium. This novel strategy provides new insights into the regulation of cellular properties and essential metabolite accumulation by introducing an extrinsic pathway