Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated adaptor protein selectively expressed by T cells and natural killer cells.

Activation of T and natural killer (NK) cells leads to the tyrosine phosphorylation of pp36 and to its association with several signaling molecules, including phospholipase Cgamma-1 and Grb2. Microsequencing of peptides derived from purified rat pp36 protein led to the cloning, in rat and man, of cDNA encoding a T- and NK cell-specific protein with several putative Src homology 2 domain-binding motifs. A rabbit antiserum directed against a peptide sequence from the cloned rat molecule recognized tyrosine phosphorylated pp36 from pervanadate-treated rat thymocytes. When expressed in 293T human fibroblast cells and tyrosine-phosphorylated, pp36 associated with phospholipase Cgamma-1 and Grb2. Studies with GST-Grb2 fusion proteins demonstrated that the association was specific for the Src homology 2 domain of Grb-2. Molecular cloning of the gene encoding pp36 should facilitate studies examining the role of this adaptor protein in proximal signaling events during T and NK cell activation

The phenomenon of transformation from help seeking to help giving: the role of family-run organizations

The purpose of this study was to understand the lived experience of parents who staffed family-run organizations funded under System of Care (SOC) grants between1994 and 2011 in a single U.S state. For this study, I used a qualitative, interpretive phenomenological research method. The two theoretical constructs that undergird this study are empowerment theory and feminist theory. This study shows the transformative power of the family-run organization model through a gendered lens that examines the roles of class, race, and gender. In just a few years, mothers with limited resources went from feeling powerless to feeling powerful, from feeling devalued to valuable. These feelings were accompanied by actions that speak to the behavioral component of empowerment, in a manner that is reflective of the unique ways that women behave in roles of leadership and power

The role of rule-governed behavior in histrionic and compulsive personality disorders

Behavioral descriptions of the histrionic and compulsive personality disorders as well as cognitive and bio-social learning theories of these disorders appear to be consistent with the hypothesis that these disorders might be related to dysfunctional rule-governed behavior. Specifically, it was suggested that the histrionic personality disorder might be related to deficits in rule-governed behavior, while the compulsive personality disorder might be related to excesses in rule-governed behavior. It was further hypothesized that rule-governed behavior among compulsive subjects would increase in the presence of punishment contingencies. College students who showed predominantly histrionic or compulsive personality styles on the Millon Clinical Multiaxial Inventory and control subjects were trained on an operant task involving a multiple schedule in one of two rule conditions (Positive Only vs. Positive Plus Response Cost). Following training, there was an extinction phase to determine whether apparent schedule responding was actually under the control of rules

Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Direct and indirect effects of Johne's disease on farm and animal productivity in an Irish dairy herd

Johne's disease (JD) is caused by infection with the organism Mycobacterium avium spp. paratuberculosis, leading to chronic diarrhoea and ill thrift in adult cattle. JD is considered to adversely affect farm performance and profitability. This retrospective case study was undertaken on a single commercial dairy herd in the south west of Ireland. Animal production records were interrogated to assess the effect of JD on milk yield (total kg per lactation), somatic cell count (the geometric mean over the lactation), reasons for culling, cull price and changes in herd parity structure over time. JD groups were defined using clinical signs and test results. One control animal was matched to each case animal on parity number and year. Specific lactations (clinical, pre-clinical and test-positive only) from 1994 to 2004 were compared between JD case and control cows. A significantly lower milk yield (1259.3 kg/lactation) was noted from cows with clinical JD in comparison to their matched control group. Clinical animals had an average cull price of €516 less than animals culled without signs of clinical disease. In contrast, little effect was noted for sub-clinical infections. These direct effects of JD infections, in combination with increased culling for infertility and increasing replacement rates, had a negative impact on farm production. Results from this study provide preliminary information regarding the effects of JD status on both herd and animal-level performance in Ireland

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Antarctic ice sheet discharge driven by atmosphere-ocean feedbacks at the Last Glacial Termination.

Reconstructing the dynamic response of the Antarctic ice sheets to warming during the Last Glacial Termination (LGT; 18,000-11,650 yrs ago) allows us to disentangle ice-climate feedbacks that are key to improving future projections. Whilst the sequence of events during this period is reasonably well-known, relatively poor chronological control has precluded precise alignment of ice, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-sheet (AIS) dynamics, climate change and sea level. Here we present results from a highly-resolved 'horizontal ice core' from the Weddell Sea Embayment, which records millennial-scale AIS dynamics across this extensive region. Counterintuitively, we find AIS mass-loss across the full duration of the Antarctic Cold Reversal (ACR; 14,600-12,700 yrs ago), with stabilisation during the subsequent millennia of atmospheric warming. Earth-system and ice-sheet modelling suggests these contrasting trends were likely Antarctic-wide, sustained by feedbacks amplified by the delivery of Circumpolar Deep Water onto the continental shelf. Given the anti-phase relationship between inter-hemispheric climate trends across the LGT our findings demonstrate that Southern Ocean-AIS feedbacks were controlled by global atmospheric teleconnections. With increasing stratification of the Southern Ocean and intensification of mid-latitude westerly winds today, such teleconnections could amplify AIS mass loss and accelerate global sea-level rise