c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis.

A subset of CD8 T cells in normal mice, expressing high levels of activation markers such as CD44, shares many properties with antigen-specific memory CD8 T cells. Homeostasis of CD44(high) CD8 T cells depends upon cytokines such as interleukin-15 (IL-15); however, the downstream signaling pathways regulating IL-15-dependent homeostatic proliferation are poorly defined. Surprisingly, we show here that haploinsufficiency of the protooncogene c-myc leads to a highly selective decrease in CD44(high) CD8 T cells in mice. Although steady-state proliferation and survival of CD44(high) CD8 T cells appeared not to be dependent on c-Myc, homeostatic proliferation of c-myc(+/-) CD44(high) CD8 T cells in lymphopenic hosts was strongly reduced, and the residual homeostatic proliferation of these cells appeared to occur independently of IL-15. Moreover, c-myc(+/-) CD44(high) CD8 T cells responded very poorly to purified IL-15 in vitro. Backcrossing of c-myc(+/-) mice to IL-15(-/-) mice revealed that the number of CD44(high) CD8 T cells decreased in an additive fashion in mice heterozygous for c-myc and IL-15. Finally homeostatic proliferation of antigen-specific memory CD44(high) CD8 T cells was also impaired in c-myc(+/-) mice. Collectively, our data identify c-Myc as a novel downstream component of the IL-15-dependent pathway controlling homeostatic proliferation of memory CD44(high) CD8 T cells.

What is what?: A simple time-domain test of long-memory vs. structural breaks

This paper proposes a new time-domain test of a process being I(d), 0 < d = 1, under the null, against the alternative of being I(0) with deterministic components subject to structural breaks at known or unknown dates, with the goal of disentangling the existing identification issue between long-memory and structural breaks. Denoting by AB(t) the different types of structural breaks in the deterministic components of a time series considered by Perron (1989), the test statistic proposed here is based on the t-ratio (or the infimum of a sequence of t-ratios) of the estimated coefficient on yt-1 in an OLS regression of ?dyt on a simple transformation of the above-mentioned deterministic components and yt-1, possibly augmented by a suitable number of lags of ?dyt to account for serial correlation in the error terms. The case where d = 1 coincides with the Perron (1989) or the Zivot and Andrews (1992) approaches if the break date is known or unknown, respectively. The statistic is labelled as the SB-FDF (Structural Break-Fractional Dickey- Fuller) test, since it is based on the same principles as the well-known Dickey-Fuller unit root test. Both its asymptotic behavior and finite sample properties are analyzed, and two empirical applications are provided.

Food's visually perceived fat content affects discrimination speed in an orthogonal spatial task.

Choosing what to eat is a complex activity for humans. Determining a food's pleasantness requires us to combine information about what is available at a given time with knowledge of the food's palatability, texture, fat content, and other nutritional information. It has been suggested that humans may have an implicit knowledge of a food's fat content based on its appearance; Toepel et al. (Neuroimage 44:967-974, 2009) reported visual-evoked potential modulations after participants viewed images of high-energy, high-fat food (HF), as compared to viewing low-fat food (LF). In the present study, we investigated whether there are any immediate behavioural consequences of these modulations for human performance. HF, LF, or non-food (NF) images were used to exogenously direct participants' attention to either the left or the right. Next, participants made speeded elevation discrimination responses (up vs. down) to visual targets presented either above or below the midline (and at one of three stimulus onset asynchronies: 150, 300, or 450 ms). Participants responded significantly more rapidly following the presentation of a HF image than following the presentation of either LF or NF images, despite the fact that the identity of the images was entirely task-irrelevant. Similar results were found when comparing response speeds following images of high-carbohydrate (HC) food items to low-carbohydrate (LC) food items. These results support the view that people rapidly process (i.e. within a few hundred milliseconds) the fat/carbohydrate/energy value or, perhaps more generally, the pleasantness of food. Potentially as a result of HF/HC food items being more pleasant and thus having a higher incentive value, it seems as though seeing these foods results in a response readiness, or an overall alerting effect, in the human brain.

Governor's Task Force on Dependent Adults with Mental Retardation Final Report, 2009

On February 17, 2009, Governor Culver signed Executive Order No. 11 to create a Task Force on Dependent Adults with Mental Retardation. The executive order charges the Task Force with the responsibility of recommending steps to strengthen and improve state laws and regulations on the care and treatment of dependent adults with mental retardation. The Final Report includes recommendations that establish or improve systems of coordination between government entities. The report includes a series of proposals from the Department of Human Services (DHS) that redesign the adult abuse assessment process that are necessary for long-term reform. Included in them is a proposal to enhance a community’s capacity to provide a safety net of services, as well as formal and informal supports for vulnerable adults through partnerships among multiple local stakeholders.

Keep Iowa Clean and Beautiful Task Force Report, June 30, 2006

The cost to Iowa taxpayers is over $13.5 million per year for cleaning up littering and illegal dumping by others. It is estimated that the cost to the private sector is at least this high. Over thirteen million of this cost is spent on clean up efforts; less than $300,000 is spent on prevention. To have success in combating illegal dumping and littering, more effort, time, and money must be paid to prevention. The following is a summary the most recent research and work on beautification and the litter and illegal dumping problem

Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: relevance to schizophrenia.

Glutathione (GSH) metabolism dysfunction is one risk factor in schizophrenia. A transitory brain GSH deficit was induced in Wistar (WIS) and mutant (ODS; lacking ascorbic acid synthesis) rats using BSO (l-buthionine-(S,R)-sulfoximine) from post-natal days 5-16. When GSH was re-established to physiological levels, juvenile BSO-ODS rats were impaired in the water maze task. Long after treatment cessation, adult BSO-WIS/-ODS rats showed impaired place discrimination in the homing board with distributed visual or olfactory cues. Their accuracy was restored when a single cue marked the trained position. Similarly, more working memory errors were made by adult BSO-WIS in the radial maze when several olfactory cues were present. These results reveal that BSO rats did not suffer simple sensory impairment. They were selectively impaired in spatial memory when the task required the integration of multimodal or olfactory cues. These results, in part, resemble some of the reported olfactory discrimination and cognitive impairment in schizophrenia.

FRAX(®) Clinical Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

The World Health Organization fracture risk assessment tool, FRAX(®), is an advance in clinical care that can assist in clinical decision-making. However, with increasing clinical utilization, numerous questions have arisen regarding how to best estimate fracture risk in an individual patient. Recognizing the need to assist clinicians in optimal use of FRAX(®), the International Osteoporosis Foundation (IOF) in conjunction with the International Society for Clinical Densitometry (ISCD) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX(®) usage. As part of the process, the charge of the FRAX(®) Clinical Task Force was to review and synthesize data surrounding a number of recognized clinical risk factors including rheumatoid arthritis, smoking, alcohol, prior fracture, falls, bone turnover markers and glucocorticoid use. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the Clinical Task Force composition and charge is presented here.

Four functionally distinct populations of human effector-memory CD8+ T lymphocytes.

In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA-CCR7- T lymphocytes present within the circulating CD8+ T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM(1) (CD27+CD28+) and EM(4) (CD27-CD28+) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7Ralpha. EM(1) cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA-CCR7+) cells. In contrast, EM(2) (CD27+CD28-) and EM(3) (CD27-CD28-) cells express mediators characteristic of effector cells, whereby EM(3) cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA+CCR7-) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8+ T cell differentiation. Finally, memory CD8+ T cells not only include central-memory cells but also EM(1) cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.

Human memory T cells: lessons from stem cell transplantation.

Animal models have revealed the rules for the organization of mature T-cell pools. However, in humans, little is known about memory T cells, which differ in lifespan and in the number of times that the same antigen is encountered. Here, Nathalie Rufer and colleagues discuss their findings in stem-cell-transplanted patients, which provide interesting data on the human T-cell compartment.

Experimental manipulation of colony genetic diversity had no effect on short-term task efficiency in the Argentine ant Linepithema humile

Genetic diversity might increase the performance of social groups by improving task efficiency or disease resistance, but direct experimental tests of these hypotheses are rare. We manipulated the level of genetic diversity in colonies of the Argentine ant Linepithema humile, and then recorded the short-term task efficiency of these experimental colonies. The efficiency of low and high genetic diversity colonies did not differ significantly for any of the following tasks: exploring a new territory, foraging, moving to a new nest site, or removing corpses. The tests were powerful enough to detect large effects, but may have failed to detect small differences. Indeed, observed effect sizes were generally small, except for the time to create a trail during nest emigration. In addition, genetic diversity had no statistically significant impact on the number of workers, males and females produced by the colony, but these tests had low power. Higher genetic diversity also did not result in lower variance in task efficiency and productivity. In contrast to genetic diversity, colony size was positively correlated with the efficiency at performing most tasks and with colony productivity. Altogether, these results suggest that genetic diversity does not strongly improve short-term task efficiency in L. humile, but that worker number is a key factor determining the success of this invasive species.

Governor's Task Force on Efficiencies and Cost-Effectiveness in Iowa State Government,Final Report, December 1983

A special task force was formed and worked through its various committees to uncover and investigate possible areas for cutting costs and saving money in State Government operations. A total of 81 recommendations are made in this report, with potential savings of over $32 million during the next several years.

Intrahippocampal cholinergic grafts in aged rats compensate impairments in a radial maze and in a place learning task

Age-related cognitive impairments were studied in rats kept in semi-enriched conditions during their whole life, and tested during ontogeny and adult life in various classical spatial tasks. In addition, the effect of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in cholinergic neurons, was studied in some of these subjects. The rats received bilateral cell suspensions when aged 23-24 months. Starting 4 weeks after grafting, they were trained during 5 weeks in an 8-arm maze made of connected plexiglass tunnels. No age-related impairment was detected during the first eight trials, when the maze shape was that of a classical radial maze in which the rats had already been trained when young. The older rats were impaired when the task was made more difficult by rendering two arms parallel to each other. They developed an important neglect of one of the parallel tunnels resulting in a high amount of errors before completion of the task. In addition, the old rats developed a systematic response pattern of visits to adjacent arms in a sequence, which was not observed in the younger subjects. None of these behaviours were observed in the old rats with a septal transplant. Sixteen weeks after grafting, another experiment was conducted in a homing hole board task. Rats were allowed to escape from a large circular arena through one hole out of many, and to reach home via a flexible tube under the table. The escape hole was at a fixed position according to distant room cues, and olfactory cues were made irrelevant by rotating the table between the trials. An additional cue was placed on the escape position. No age-related difference in escape was observed during training. During a probe trial with no hole connected and no proximal cue present, the old untreated rats were less clearly focussed on the training sector than were either the younger or the grafted old subjects. Taken together, these experiments indicate that enriched housing conditions and spatial training during adult life do not protect against all age-related deterioration in spatial ability. However, it might be that the considerable improvement observed in the grafted subjects results from an interaction between the graft treatment and the housing conditions.

Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.

In adult mammals, neural progenitors located in the dentate gyrus retain their ability to generate neurons and glia throughout lifetime. In rodents, increased production of new granule neurons is associated with improved memory capacities, while decreased hippocampal neurogenesis results in impaired memory performance in several memory tasks. In mouse models of Alzheimer's disease, neurogenesis is impaired and the granule neurons that are generated fail to integrate existing networks. Thus, enhancing neurogenesis should improve functional plasticity in the hippocampus and restore cognitive deficits in these mice. Here, we performed a screen of transcription factors that could potentially enhance adult hippocampal neurogenesis. We identified Neurod1 as a robust neuronal determinant with the capability to direct hippocampal progenitors towards an exclusive granule neuron fate. Importantly, Neurod1 also accelerated neuronal maturation and functional integration of new neurons during the period of their maturation when they contribute to memory processes. When tested in an APPxPS1 mouse model of Alzheimer's disease, directed expression of Neurod1 in cycling hippocampal progenitors conspicuously reduced dendritic spine density deficits on new hippocampal neurons, to the same level as that observed in healthy age-matched control animals. Remarkably, this population of highly connected new neurons was sufficient to restore spatial memory in these diseased mice. Collectively our findings demonstrate that endogenous neural stem cells of the diseased brain can be manipulated to become new neurons that could allow cognitive improvement.