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

Insulin Receptor Substrate 2 Expression and Involvement in Neuronal Insulin Resistance in Diabetic Neuropathy

Insulin signaling depends on tyrosine phosphorylation of insulin receptor substrates (IRSs) to mediate downstream effects; however, elevated serine phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS protein expression patterns in dorsal root ganglia (DRG) of mice and whether their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in DRG; however, IRS2 appears to be the prevalent isoform and is expressed by many DRG neuronal subtypes. Phosphorylation of Ser(731)IRS2 was significantly elevated in DRG neurons from type 1 and type 2 diabetic mice. Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice. These results suggest that DRG neurons express IRS proteins that are altered by diabetes similar to other peripheral tissues, and insulin signaling downstream of the insulin receptor may be impaired in sensory neurons and contribute to the pathogenesis of diabetic neuropathy

Attitudes and behaviours of key account managers:Are they really any different to senior sales professionals?

This study investigates the range of attitudes and behaviours exhibited by Key Account Managers (KAMs) in their roles as customer relationship managers. Specifically, we test whether KAMs exhibit different behaviours and attitudes towards relationship management compared to other sales professionals based on a range of assumptions currently theorized but untested in the Key Account Management (KAM) literature. Utilizing the existing theoretical models of a KAM role we identify six major areas of relational behaviour assumed in the literature to separate the KAM from the sales professional. Drawing on a cross sectional quantitative study of 10 organizations and 409 key account managers, sales managers, and senior sales executives we explore goal orientation, planning, customer embeddedness, strategic prioritization, adaptability and internal management behaviours of our groups and find that, in certain managerial tasks, KAMs do indeed exhibit many of the different behaviours and attitudes predicted in the literature. However, in many customer-facing, goal orientated and revenue generating activities, contrary to expectations, they display similar attitudes and behaviours to those in senior sales roles. This challenges the way that the KAM role has previously been conceptualized. Our findings raise a potential issue for senior managers, since KAMs' unexpectedly short term orientation may lead to insufficient consideration of the strategic consequences of their decisions for these key customer relationships

An ecosystems analysis of how sales managers develop salespeople

Purpose The purpose of this study is to identify and explain how leadership behaviors of sales managers can enhance the development of salespeople within the context of those interpersonal connections and interactions that is the sales ecosystem. Design/methodology/approach The authors collected and analyzed qualitative data from in-depth interviews with a sample of 36 sales professionals. Over 47 hours of interviews were transcribed and analyzed via NVivo. The statements were labeled as particular leader behaviors using the Miles and Huberman (1994) coding system. Findings The study identifies coaching, customer engaging, collaborating and championing as the four key leader behaviors that are relevant to the sales ecosystem. Specifically, coaching and customer engaging enhance the individual microsystems of salespeople; and collaborating and championing enhance the corresponding mesosystems. Analysis of the interview statements further revealed that trust, confidence, optimism and resilience are four relational elements that tend to coexist with these leader behaviors in the sales ecosystem. Practical implications This study provides a structure for sales organizations to strengthen their sales ecosystem through targeted interventions and training for those that manage salespeople. Past research finds that sales organizations too often neglect this type of managerial training. Originality/value This is the first study to examine sales leadership through the lens of Bronfenbrenner’s (1979) ecological systems theory. Further, the qualitative methodology, which is relatively unique in sales research, provides rich data that is particularly useful for exploring how and why things have happened

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

A qualitative study of leader behaviors perceived to enable salesperson performance

This study builds on and extends previous sales leadership research by exploring sales professionals’ perceptions of effective leadership behaviors. Semistructured interviews with both sales leaders and salespeople working in a global enterprise software company were examined through a qualitative analysis. Results indicated that participants believed sales leadership played an important role in influencing sales performance. When asked to describe specific sales leader behaviors that best enable salesperson performance, sales professionals – both sales leaders and salespeople – overwhelmingly referenced coaching, followed by collaborating, championing, and customer engaging. We define and describe these four key sales leader behaviors and identify four potential mediating variables (trust, confidence, optimism, and resilience), from which emerges a conceptual framework of sales leader behaviors perceived to enable salesperson performance. We examine these four key sales leader behaviors and mediators in the broader context of leadership theory, particularly transformational, servant, authentic, and adaptive leadership theories. The key contribution of this study is the identification of a set of leader behaviors that are likely to be especially effective in modern sales organizations given that they originated from the perceptions of sales professionals themselves