Phenotypic Changes in Diabetic Neuropathy Induced by a High-Fat Diet in Diabetic C57Bl/6 Mice

Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy

The Inner Ear Heat Shock Transcriptional Signature Identifies Compounds That Protect Against Aminoglycoside Ototoxicity

Mechanosensory hair cells of the inner ear transduce auditory and vestibular sensory input. Hair cells are susceptible to death from a variety of stressors, including treatment with therapeutic drugs that have ototoxic side effects. There is a need for co-therapies to mitigate drug-induced ototoxicity, and we showed previously that induction of heat shock proteins (HSPs) protects against hair cell death and hearing loss caused by aminoglycoside antibiotics in mouse. Here, we utilized the library of integrated cellular signatures (LINCS) to identify perturbagens that induce transcriptional profiles similar to that of heat shock. Massively parallel sequencing of RNA (RNA-Seq) of heat shocked and control mouse utricles provided a heat shock gene expression signature that was used in conjunction with LINCS to identify candidate perturbagens, several of which were known to protect the inner ear. Our data indicate that LINCS is a useful tool to screen for compounds that generate specific gene expression signatures in the inner ear. Forty-two LINCS-identified perturbagens were tested for otoprotection in zebrafish, and three of these were protective. These compounds also induced the heat shock gene expression signature in mouse utricles, and one compound protected against aminoglycoside-induced hair cell death in whole organ cultures of utricles from adult mice

Discovery and Characterization of Bacteriophage LuckyBarnes

Here, we report the genome sequence of LuckyBarnes, a newly isolated singleton siphovirus that infects Brevibacterium iodinum ATCC 15728 and has a 50,774-bp genome with 67 predicted genes

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain

IntroductionDiet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females.MethodsHere, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high‐capacity runners; HCR) or low endurance exercise capacity (low‐capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions.ResultsLCR female rats have reduced mechanical sensitivity, higher intraepidermal nerve fiber density and TrkA‐positive epidermal axons, increased numbers of Langerhans and mast cells in cutaneous tissues, and a higher fat content despite similar overall body weights compared to female HCR rats. Sensory and motor nerve conduction velocities, thermal sensitivity, and mRNA expression of selected genes relevant to peripheral sensation were not different.ConclusionsThese results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.These results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139060/1/brb3780.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139060/2/brb3780_am.pd

Metabolic changes of salicylic acid-elicited Catharanthus roseus cell suspension cultures monitored by NMR-based metabolomics

The effect of salicylic acid (SA) on the metabolic profile of Catharanthus roseus suspension cells throughout a time course (0, 6, 12, 24, 48 and 72 h after treatment) was investigated using NMR spectroscopy and multivariate data analysis. When compared to control cell lines, SA-treated cells showed a high level of sugars (glucose and sucrose) up to 48 h after treatment, followed by a dynamic change in amino acids, phenylpropanoids, and tryptamine. Additionally, one compound—2,5-dihydroxybenzoic-5-O-glucoside—was detected solely in SA-treated cells

Progress in customer relationship management adoption: a cross-sector study

Although customer relationship management (CRM) is widely used by organizations to capture and manage customer data, the process of implementation can be problematic. This article takes a multi-sector view of CRM implementation in three areas of the UK services sector: banking and finance; professional services; and the government/public sector. The study captures variations in CRM practice and implementation across these sectors, applying an existing framework of CRM implementation to tease out progress in relation to people (the company's staff), the company itself, the customers, and the technology. The implications for organizations that have reached different implementation stages in their CRM journey are considered

Customer Specific Transaction Risk Management in eCommerce

Increasing potential for turnover in e-commerce is inextricably linked with an increase in risk. Online retailers (e-tailers), aiming for a company-wide value orientation should manage this risk. However, current approaches to risk management either use average retail prices elevated by an overall risk premium or restrict the payment methods offered to customers. Thus, they neglect customer-specific value and risk attributes and leave turnover potentials unconsidered. To close this gap, an innovative valuation model is proposed in this contribution that integrates customer-specific risk and potential turnover. The approach presented evaluates different payment methods using their risk-turnover characteristic, provides a risk-adjusted decision basis for selecting payment methods and allows e-tailers to derive automated risk management decisions per customer and transaction without reducing turnover potential

Review of research to inform California's climate scoping plan: Agriculture and working lands

Agriculture in California contributes 8% of the state's greenhouse gas (GHG) emissions. To inform the state's policy and program strategy to meet climate targets, we review recent research on practices that can reduce emissions, sequester carbon and provide other co-benefits to producers and the environment across agriculture and rangeland systems. Importantly, the research reviewed here was conducted in California and addresses practices in our specific agricultural, socioeconomic and biophysical environment. Farmland conversion and the dairy and intensive livestock sector are the largest contributors to GHG emissions and offer the greatest opportunities for avoided emissions. We also identify a range of other opportunities including soil and nutrient management, integrated and diversified farming systems, rangeland management, and biomass-based energy generation. Additional research to replicate and quantify the emissions reduction or carbon sequestration potential of these practices will strengthen the evidence base for California climate policy