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.     

人粒细胞集落刺激因子（hG－CSF）cDNA3′－UTR对其表达的影响

利用人粒细胞集落刺激因子（ｈＧ－ＣＳＦ）ｃＤＮＡ３′端非翻译区（３′－ＵＴＲ）中存在的ＤｒａⅠ酶切位点,通过部分酶切与完全酶切,删除３′－ＵＴＲ不同长度,构建了四种ｈＧ－ＣＳＦｃＤＮＡ瞬时重组表达质粒。转染ＣＯＳ－７细胞后,生物活性测定结果提示,ｈＧ－ＣＳＦｃＤＮＡ３′－ＵＴＲ对其表达起负调控作用,其关键性序列位于紧接终止密码子ＴＧＡ下游的６５ｂｐ范围内,３′－ＵＴＲ对ｈＧ－ＣＳＦｃＤＮＡ表达的影响与转录水平的差别有一定关系。     

Factors underpinning Iranian farmers’ intention to conserve biodiversity at the farm level

The depletion of biodiversity is a major environmental challenge of the present time, with the agricultural sector being a significant contributor to the loss. Therefore, farmers' decisions and practices are pivotal in safeguarding biodiversity at the farm level. Accordingly, this study aimed to unravel the key factors influencing farmers' intention to conserve biodiversity (ICB), and in doing so, it adopted the protection motivation theory (PMT) as the theoretical framework. The study's statistical population comprised 412 farmers residing in Bavi County in the southwestern region of Iran. The research employed a questionnaire as the data collection instrument, and the research hypotheses were tested using structural equation modeling (SEM). The findings indicated that the respondents held a perception of high costs associated with implementing biodiversity conservation behaviors. They believed that such measures would not be easy to implement, and they would incur both monetary and non-monetary costs. Furthermore, the findings of the study revealed that the variables of SE and ICB among the studied farmers were lower than the theoretical median of 3, indicating that farmers may not have a strong desire and self-efficacy to engage in biodiversity conservation practices. Through the application of SEM, the study determined that the PMT accounts for 65.2% of farmers’ ICB. Additionally, perceived severity and self-efficacy were found to have the strongest effects on farmers’ ICB (as the first and second determinants), highlighting the importance of these variables in predicting farmers’ conservation behaviors. Overall, it can be concluded that these results have significant implications for policymakers in the agricultural sector, providing valuable insights into how to promote biodiversity conservation practices among farmers.