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.     

Smallholder experiences with dairy cattle crossbreeding in the tropics: from introduction to impact

Crossbreeding of indigenous tropical and improved western dairy cattle breeds as tool to improve dairy cattle performance on smallholder farms has been widely advocated, criticised and yet applied. The government of Ethiopia supported this technology for decades but adoption rate is low. Constraints are documented but there is little information about farm level introduction and development of crossbreeding. A total 122 smallholders with mixed crop livestock farms and at least 8 years of successful crossbreeding were interviewed using a pre-tested questionnaire in two contexts in Amhara Regional state in north-western Ethiopia. Crossbreeding initiator was either uncoordinated government extension or a coordinated development project, also implemented with governmental support. Qualitative and quantitative data on farmers’ motivations, crossbreeding introduction, initiator support, breeding adaptation and impacts at farm level were analysed. Results show that even though motives vary between contexts the underlying reason to introduce crossbreeding was economic profit. To be able to introduce crossbreeding support of initiators (e.g. extension) and other farmers was essential. The crossbreeding introduction context had some influence. Governmental actors were the main source of support and supplier of exotic genetics but the farmer network acted as safety net filling gaps of government support. Breeding strategies focused on performance increase. A lack of basic understanding of crossbreeding has been identified. A surprising, probably biased, result was general satisfaction with initiator support and with breeding services. It was challenged by the high proportion of farmers unable to follow a breeding strategy due to insufficient bull and/or semen supply. Crossbreeding changed the smallholder production system to a high input – high output system. Except for crossbred adaptation problems, challenges were ranked context specific and influenced by the initiator. Farmers perceived crossbreeding as success and recommended it. We conclude that farmers can realize income increase with crossbreeding. The complexity of this technology, high initial investment and the need for support services and external production inputs are probable reasons why crossbreeding uptake is low. Improving the availability of semen and/or bulls must be the top priority for breeding service providers to enable farmers to follow a breeding strategy and reach a suitable and sustainable herd performance. Access to investment capital, input supply, strong technical support and market linkages are crucial for successful crossbreeding.     

Synthesis,molecular docking,acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease

A series of thirty (30) thiazole analogs were prepared, characterized by ¹H NMR, ¹³C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC₅₀ value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC₅₀, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC₅₀ values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.     

A Cysteine Endopeptidase (“Dionain”) Is Involved in the Digestive Fluid of Dionaea muscipula (Venus’s Fly-trap)

The carnivorous plant Dionaea muscipula (Venus’s flytrap) secretes proteinases into the digestive fluid to digest prey proteins. In this study, we obtained evidence that the digestive fluid contains a cysteine endopeptidase, presumably belonging to the papain family, through inhibitor studies and partial amino acid sequencing of the major SDS–PAGE band protein. The name “dionain” is proposed for the enzyme.     

Radioactive labeling techniques for the identification of G antigen in the human Rh blood group system

The G antigen is one of the erythrocyte membrane Rh antigens. The amount of Rh antigen present on the red blood cell is about 10(-15) g and radioactive labeling of membrane proteins is a useful method for its identification and characterization. In this paper, we compare 4 labeling techniques. Using a human monoclonal anti-Rh(G) antibody and an immunofixation technique, we located the G antigen on a polypeptide of an average molecular weight of 28,000 Da.     

室温下有取向紫膜薄层中菌紫质的光静态

在室温条件下有取向PM薄层中的RR分子受光照可以建立多种PSS,这些PSS的建立与湿度和光照所采用的波长等因素有关。不同的PSS有不同的VCD。它们可以在设计制作分子器件时考虑使用。     

Diversity in the immune system: “Preconceived ideas” or ideas preconceived?

Two concepts of the evolution and regulation of expression of the combining site repertoire of the immune system, are compared. One view is based on the Associative Recognition Theory as formulated by the author and the other is based on the Idiotype Network Idea as conceived by Jerne. The two concepts are analyzed from the point of view of their logic, internal consistency and factual support.