Mechanisms of neuroimmune gene induction in alcoholism

RationaleAlcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual’s continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking.ObjectivesUnraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs.ResultsStudies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset.ConclusionsThe persistent and cumulative nature of alcohol on HMGB1 and TLR gene induction support their involvement in alcohol-induced long-term changes in brain function and neurodegeneration

Social Worker or Cop? Measuring the Supervision Styles of Probation & Parole Officers in Kentucky and Missouri

This study surveyed probation and parole officers in Missouri and Kentucky to determine their supervision styles along a “casework to surveillance” continuum. These self-ratings were correlated with officer self-reports of how they spend their time on the job engaged in various casework or surveillance activities. Additionally, volunteering officers were interviewed to provide clarification on their perceptions regarding the distinctions between a casework approach and a surveillance approach. Results indicate that officers spend more of their time engaged in casework activities, but perceive themselves as more surveillance oriented. Style varied significantly by sex of officer, with female officers spending significantly more time than male officers engaged in casework activities. Caseload size and type were related to style, as well. Interviews indicated that officers believe a surveillance style as necessary for community protection, but recognize the need for a balanced approach. This study has provided a way to quantify supervision styles and can be used to conduct future investigations about the impact of supervision style on client outcomes (i.e., successful reintegration or recidivism)

Supervision Styles in Probation and Parole: An Analysis of Activities

Supervision of offenders in the community remains a critical component of the correctional processes in the United States. With almost six million offenders under correctional supervision in the community, there has been relatively little attention and few resources devoted to the style and quality of supervision received by these offenders. As a result of the lack of research regarding the style of probation and parole supervision, there is a need to identify and quantify styles of casework and surveillance supervision. This article describes a research project that identifies the key functions of parole and probation officers, reports self- and peer-rating on a casework to surveillance continuum, and establishes an instrument that can be used to create baseline information regarding how probation and parole officers spend their time, and whether the functions officers perform are casework, surveillance, or a balance of the two

Development of high performance structural timver systems for non residential buildings in New Zealand and Australia

Design of structural systems for commercial and multi-residential buildings throughout most parts of the world, is currently dominated by the use of reinforced and / or prestressed concrete construction, usually supported by steel or concrete beams and frames. However, recent developments throughout the world have demonstrated the potential for timber based structural systems to be used in these types of buildings for beams and columns, roof structures and floors. The advent of engineered wood products (EWP's) such as LVL and glulam has made it possible to fabricate large section, long spanning structural members that have excellent structural properties and reliability equivalent to that of steel or concrete used in the same applications. Since 2007, significant (and related) research initiatives have been undertaken in Australia and New Zealand, investigating the performance of timber and timber hybrid systems for use in large span / medium rise commercial and industrial buildings. In 2009 a research consortium of government, industry and three Universities known as the Structural Timber Innovation Company (STIC) commenced an extensive R&D 5 year program with a total budget of $10m NZD. This paper presents an overview of each area of research, describing the focus of work to date, discussion of issues that have been identified and addressed, as well as details of expected outcomes

Relationship of VO2 Peak, Body Fat Percentage, and Power Output Measured During Repeated Bouts of a Wingate Protocol

The principle of specificity would indicate that being aerobically trained would not necessarily enhance performance in events relying principally on oxygen-independent metabolic pathways (i.e. “anaerobic” exercise). Body fatness may be associated with aerobic and anaerobic performance. VO2 Peak was determined with a graded cycle ergometry and, in a separate session 4 consecutive Wingate power tests (3 min recovery) in 31 males. Pearson correlations were calculated for VO2 Peak and Body Fat Percentage with Peak Power, Mean Power, Minimum Power, Fatigue Index, Peak Heart Rate, and Recovery Heart Rate. No significant correlations were found for VO2 Peak or Body Fat Percentage with Peak Power on any bout (p\u3e0.05). Significant correlations were found for VO2 Peak and Body Fat Percentage with Mean Power, Minimum Power, and Fatigue Index. Significant correlations were found for VO2 Peak with delta values of power performance and heart rates (peak and 3 min recovery). Results indicate that VO2 Peak is associated with repeated anaerobic performance, possibly due to greater capacity to recover between bouts. Body Fat Percentage was correlated with measures of power performance (strongest relationships existing in the earlier bouts), but is not strongly correlated with either the heart rate response to power performance or the change in performance over successive bouts

Community structure of soil fungi in a novel perennial crop monoculture, annual agriculture, and native prairie reconstruction

The use of perennial crop species in agricultural systems may increase ecosystem services and sustainability. Because soil microbial communities play a major role in many processes on which ecosystem services and sustainability depend, characterization of soil community structure in novel perennial crop systems is necessary to understand potential shifts in function and crop responses. Here, we characterized soil fungal community composition at two depths (0–10 and 10–30 cm) in replicated, long-term plots containing one of three different cropping systems: a tilled three-crop rotation of annual crops, a novel perennial crop monoculture (Intermediate wheatgrass, which produces the grain Kernza®), and a native prairie reconstruction. The overall fungal community was similar under the perennial monoculture and native vegetation, but both were distinct from those in annual agriculture. The mutualist and saprotrophic community subsets mirrored differences of the overall community, but pathogens were similar among cropping systems. Depth structured overall communities as well as each functional group subset. These results reinforce studies showing strong effects of tillage and sampling depth on soil community structure and suggest plant species diversity may play a weaker role. Similarities in the overall and functional fungal communities between the perennial monoculture and native vegetation suggest Kernza® cropping systems have the potential to mimic reconstructed natural systems

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence

Adolescent, but Not Adult, Binge Ethanol Exposure Leads to Persistent Global Reductions of Choline Acetyltransferase Expressing Neurons in Brain

During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+ IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+ IR in the basal forebrain following adolescent (P28-P48) and adult (P70-P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity