Multiomic Metabolic Enrichment Network Analysis Reveals Metabolite–Protein Physical Interaction Subnetworks Altered in Cancer

Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings.     

Highly specialized Cretaceous beetle parasitoids (Ripiphoridae) identified with optimized visualization of microstructures

Extremely miniaturized longipedes insects (body length c. 0.3 mm) embedded in two pieces of Cretaceous amber from Myanmar are described and interpreted. Using inverted fluorescence and light microscopy for detailed analysis of microstructures, the inclusions were identified as primary larvae of the beetle family Ripiphoridae, subfamily Ripidiinae. While the structure of thoracic and abdominal segments including appendages corresponds well with the groundplan known in recent members of Ripidiinae, a curved prosternal ridge with prominent spines (each c. 5 μm), the reduced condition of stemmata and antennae and the lack of sharp mandibles are unique features within the entire family, apparently apomorphies of the longipedes larvae. A sinuate prosternal edge with a dense row of spines (prosternoctenidium) might be homologous with ‘head ctenidia’ in some previously described miniaturized conicocephalate larvae, but further investigation is needed. The morphological differences between the head of longipedes larvae and extant Ripidiinae are interpreted as adaptations to different groups of hosts and life strategies. Palaeoethology of the longipedes larvae is briefly discussed. In addition, the systematic placement of conicocephalate larvae from Canadian, Myanmar and Russian Cretaceous ambers, already interpreted by various authors as primary instars within Coleopterida (assigned to either Strepsiptera or to the coleopteran Tenebrionoidea: Ripiphoridae), is discussed.     

Prevalence of Post-Stroke Cognitive Impairment in China: A Community-Based,Cross-Sectional Study

International hospital-based studies have indicated a high risk of cognitive impairment after stroke, evidence from community-based studies in China is scarce. To determine the prevalence of post-stroke cognitive impairment (PSCI) and its subtypes in stroke survivors residing in selected rural and urban Chinese communities, we conducted a community-based, cross-sectional study in 599 patients accounting for 48% of all stroke survivors registered in the 4 communities, who had suffered confirmed strokes and had undergone cognitive assessments via the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Hachinski Ischemia Scale (HIS). Detection of PSCI was based on scores in these neuropsychological scales. Factors potentially impacting on occurrence of PSCI were explored by comparing demographic characteristics, stroke features, and cardiovascular risk factors between patients with and without PSCI. The overall prevalence of PSCI was 80.97% (95%CI: 77.82%-84.11%), while that of non-dementia PSCI (PSCI-ND) and post-stroke vascular dementia (PSD) was 48.91% (95%CI: 44.91%-52.92%) and 32.05% (95%CI: 28.32%-35.79%), respectively. Prior stroke and complications during the acute phase were independent risk factors for PSCI. The risk of recurrent stroke survivors having PSCI was 2.7 times higher than for first-episode survivors, and it was 3 times higher for those with complications during the acute phase than for those without. The higher prevalence of PSCI in this study compared with previous Chinese studies was possibly due to the combined effects of including rural stroke survivors, a longer period from stroke onset, and different assessment methods. There is an urgent need to recognize and prevent PSCI in stroke patients, especially those with recurrent stroke and complications during the acute phase.     

Mediator structure and conformation change

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Application of automated DNA sizing technology for genotyping microsatellite loci.

Highly polymorphic microsatellite loci offer great promise for gene mapping studies, but fulfillment of this potential will require substantial improvements in methods for accurate and efficient genotyping. Here, we report a genotyping method based on fluorescently labeled PCR primers and size characterization of PCR products using an automated DNA fragment analyzer. We capitalize on the availability of three distinct fluorescent dyes to label uniquely loci that overlap in size, and this innovation increases by threefold the number of loci that can be analyzed simultaneously. We label size standards with a fourth dye and combine these with the microsatellite PCR products in each gel lane. Computer programs provide very rapid and accurate sizing of microsatellite alleles and efficient data management. In addition, fluorescence signals are linear over a much greater range of intensity than conventional autoradiography. This facilitates multiplexing of loci (since signal intensities often vary greatly) and helps distinguish major peaks from artifacts, thereby improving genotyping accuracy.     

微波辐射对小鼠脑内乙酰胆碱含量及胆碱乙酸转移酶活性的影响

用频率为2450MHz功率密度为10mW/Cm~2(WBASAR约11.4W/kg)的微波(连续波)对置于微波暗室内的昆明种雄性小鼠急性全身照射1小时后,立即按常规方法断头,取脑,制成样品,然后用放射免疫测定法测量小鼠脑内乙酰胆碱(ACh)含量及胆碱乙酰转移酶(ChAT)活性。结果表明:照射组的ACh含量为11.6±1.4pmol/mg(脑鲜重),ChAT活性为45.4±8.7pmolACh/min.mg(脑鲜重);而对照组的分别为16.0±2.1pmol/mg和61.0±13.8pmolACh/min.mg。证明微波照射后可引起动物脑内ACh水平和ChAT活性下降,提示微波辐射对中枢胆碱能系统确有不利影响。     

Binding inhibition by monoclonal antibodies of ovine placental lactogen to growth hormone receptors in human liver

In the radioreceptor assay for growth hormone (RRA-GH) using [125I]iodo-hGH, hGH and human liver membrane particulate fractions as tracer, hormone standard and receptors, respectively, ovine placental lactogen (oPL) is capable of inhibiting the binding of [125I]iodo-hGH in a parallel manner with hGH and in equipotency. Similarly, in the RRA-GH by employing [125I]iodo-oPL, oPL and human liver membrane particulate fractions as tracer, hormone standard and receptors, respectively, hGH is also equipotent as oPL in inhibiting the binding of [125I]iodo-oPL in a parallel fashion. The addition of monoclonal antibodies against oPL in the assay was effective in inhibiting the binding of [125I] iodo-oPL to human liver, but could not, however, inhibit the binding of [125I]iodo-hGH to human liver. Furthermore, the addition of the monoclonal antibodies in the RRA-GH did not affect the parallelism of the oPL standard but lowered the total binding of oPL. Our studies indicate that the structure of the binding sequence in oPL which binds to the GH receptor of human liver is not identical to the equivalent sequence of hGH and that the monoclonal antibodies compete with GH receptors in human liver for the binding of oPL.