Downregulation of CDKN2A and suppression of cyclin D1 gene expressions in malignant gliomas

<p>Abstract</p> <p>Background</p> <p>Malignant gliomas are the most common in central nervous system cancer. Genome-wide association study identifies that CDKN2A was a susceptibility loci for glioma. The CDKN2A/cyclin-dependent kinase 4, 6/Retinoblastoma protein (Rb) pathway is thought to play a crucial role in malignant gliomas pathogenesis. We have investigated the expression of CDKN2A for potential correlations with malignant gliomas grade and potential role of CDKN2A on malignant gliomas pathogenesis.</p> <p>Methods</p> <p>Tumour tissue samples from 61 patients suffering from malignant gliomas were investigated. The expression levels of CDKN2A were detected using immunohistochemical staining and western blot. Overexpression and knockdown of CDKN2A were performed in human glioma cell lines. Subsequently, colony formation, growth curves and CDKN2A-Cyclin-Rb pathway were analyzed.</p> <p>Results</p> <p>Here we show that a lower expression of CDKN2A and a higher expression of cyclin D1 in the patients with high-grade malignant gliomas than low-grade gliomas, respectively. Moreover, overexpression of CDKN2A inhibits growth of glioma cell lines by suppression of cyclin D1 gene expression.</p> <p>Conclusions</p> <p>Our study suggests that CDKN2A as a malignant gliomas suppressor gene, appears to be useful for predicting behaviour of high-grade malignant gliomas. CDKN2A-Cyclin-Rb pathway plays a key role on malignant gliomas formation and that therapeutic targeting of this pathway may be useful in malignant gliomas treatment.</p

Mitigating Biased Activation in Weakly-supervised Object Localization via Counterfactual Learning

In this paper, we focus on an under-explored issue of biased activation in prior weakly-supervised object localization methods based on Class Activation Mapping (CAM). We analyze the cause of this problem from a causal view and attribute it to the co-occurring background confounders. Following this insight, we propose a novel Counterfactual Co-occurring Learning (CCL) paradigm to synthesize the counterfactual representations via coupling constant foreground and unrealized backgrounds in order to cut off their co-occurring relationship. Specifically, we design a new network structure called Counterfactual-CAM, which embeds the counterfactual representation perturbation mechanism into the vanilla CAM-based model. This mechanism is responsible for decoupling foreground as well as background and synthesizing the counterfactual representations. By training the detection model with these synthesized representations, we compel the model to focus on the constant foreground content while minimizing the influence of distracting co-occurring background. To our best knowledge, it is the first attempt in this direction. Extensive experiments on several benchmarks demonstrate that Counterfactual-CAM successfully mitigates the biased activation problem, achieving improved object localization accuracy.Comment: 13 pages, 5 figures, 4 table

Therapeutic potential of traditional Chinese medicine on heat stroke

As global warming progresses, heat waves are becoming increasingly frequent and intense, meanwhile the incidence of heat stroke (HS) has increased sharply during the past decades. HS is typically associated with significant morbidity and mortality, and there is an urgent need for further research to solve this difficult issue. There currently exists difficulties regarding on-site emergency treatment methods and limited in-hospital treatment approaches, and better treatments are required as soon as possible. Theories and therapies from various traditional Chinese medicine (TCM) academic groups have been widely reported. Therefore, an exploration of prevention and protection methods should consider TCM experiences as an alternative. This article primarily reviews TCM herbal therapies and external therapies that have been described in various clinical reports and demonstrated in relevant studies. Herbal therapies, including herbal formulas, Chinese patent medicines (CPMs), single Chinese herbs, and associated extracts or monomers, are summarized based on the shared perspectives of the underlying mechanisms from TCM. In addition, external therapies including acupuncture, bloodletting, cupping, Gua sha and Tui na that have rarely been rarely mentioned and considered in most cases, are introduced and discussed to offer a unique perspective in the search for novel interventions for HS. In summary, TCM may provide abundant potential clinical benefits and research directions in the fight against HS

Jump-seq: Genome-Wide Capture and Amplification of 5-Hydroxymethylcytosine Sites

5-Hydroxymethylcytosine (5hmC) arises from the oxidation of 5-methylcytosine (5mC) by Fe2+ and 2-oxoglutarate-dependent 10–11 translocation (TET) family proteins. Substantial levels of 5hmC accumulate in many mammalian tissues, especially in neurons and embryonic stem cells, suggesting a potential active role for 5hmC in epigenetic regulation beyond being simply an intermediate of active DNA demethylation. 5mC and 5hmC undergo dynamic changes during embryogenesis, neurogenesis, hematopoietic development, and oncogenesis. While methods have been developed to map 5hmC, more efficient approaches to detect 5hmC at base resolution are still highly desirable. Herein, we present a new method, Jump-seq, to capture and amplify 5hmC in genomic DNA. The principle of this method is to label 5hmC by the 6-N3-glucose moiety and connect a hairpin DNA oligonucleotide carrying an alkyne group to the azide-modified 5hmC via Huisgen cycloaddition (click) chemistry. Primer extension starts from the hairpin motif to the modified 5hmC site and then continues to “land” on genomic DNA. 5hmC sites are inferred from genomic DNA sequences immediately spanning the 5-prime junction. This technology was validated, and its utility in 5hmC identification was confirmed

Modality- and task-specific brain regions involved in Chinese lexical processing

fMRI was used to examine lexical processing in native adult Chinese speakers. A 2 task (semantics and phonology) x 2 modality (visual and auditory) within-subject design was adopted. The semantic task involved a meaning association judgment and the phonological task involved a rhyming judgment to two sequentially presented words. The overall effect across tasks and modalities was used to identify seven ROIs, including the left fusiform gyrus (FG), the left superior temporal gyrus (STG), the left ventral inferior frontal gyrus (VIFG), the left middle temporal gyrus (MTG), the left dorsal inferior frontal gyrus (DIFG), the left inferior parietal lobule (IPL), and the left middle frontal gyrus (MFG). ROI analyses revealed two modality-specific areas, FG for visual and STG for auditory, and three task-specific areas, IPL and DIFG for phonology and VIFG for semantics. Greater DIFG activation was associated with conflicting tonal information between words for the auditory rhyming task, suggesting this region&#39;s role in strategic phonological processing, and greater VIFG activation was correlated with lower association between words for both the auditory and the visual meaning task, suggesting this region&#39;s role in retrieval and selection of semantic representations. The modality- and task-specific effects in Chinese revealed by this study are similar to those found in alphabetical languages. Unlike English, we found that MFG was both modality- and task-specific, suggesting that MFG may be responsible for the visuospatial analysis of Chinese characters and orthography-to-phonology integration at a syllabic level