We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, ...non-toxic concentration of MnCl2 (10mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl2 in primary somatosensory cortex. Twenty fourhours after injection in LC, Mn2+ labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn2+ labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn2+ labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn2+. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn2+ transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn2+ imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.
►We compared anterograde tracing from LC using classical and MEMRI methods. ►Major targets of LC projections were visualized using MEMRI. ►Mn2+ labeling in thalamus was below MRI delectability threshold. ►The LC functional connectivity was not predicted by anatomy.
A major goal for X‐ray free‐electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single ...macromolecular structures elucidated by XFEL radiation, since they contain one‐dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments (Escherichia coli pili, F‐actin, and amyloid fibrils), which when intersected by femtosecond X‐ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determine that F‐actin can be flow‐aligned to a disorientation of approximately 5 degrees. Using this XFEL‐based technique, we determine that gelsolin amyloids are comprised of stacked β‐strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual α‐synuclein amyloids.
The success of diffraction experiments from weakly scattering samples strongly depends on achieving an optimal signal‐to‐noise ratio. This is particularly important in single‐particle imaging ...experiments where diffraction signals are typically very weak and the experiments are often accompanied by significant background scattering. A simple way to tremendously reduce background scattering by placing an aperture downstream of the sample has been developed and its application in a single‐particle X‐ray imaging experiment at FLASH is demonstrated. Using the concept of a post‐sample aperture it was possible to reduce the background scattering levels by two orders of magnitude.
Diffraction experiments with weakly scattering samples often suffer from a low signal‐to‐noise ratio due to unwanted background scatter. Improving the signal‐to‐noise ratio for single‐particle imaging experiments is particularly important as the diffraction signal is very weak. Here, a simple way to minimize the background scattering by placing an aperture downstream of the sample is demonstrated.
Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in ...animals. We present here a novel high field, large-bore,
vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75×150×300 μm
3 and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and −2.4%, respectively. Finally, the first high-resolution (500 μm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.
Aims/hypothesis
We sought to identify minimal sets of serum peptide signatures as markers for islet autoimmunity and predictors of progression rates to clinical type 1 diabetes in a case–control ...study.
Methods
A double cross-validation approach was applied to first prioritise peptides from a shotgun proteomic approach in 45 islet autoantibody-positive and -negative children from the BABYDIAB/BABYDIET birth cohorts. Targeted proteomics for 82 discriminating peptides were then applied to samples from another 140 children from these cohorts.
Results
A total of 41 peptides (26 proteins) enriched for the functional category lipid metabolism were significantly different between islet autoantibody-positive and autoantibody-negative children. Two peptides (from apolipoprotein M and apolipoprotein C-IV) were sufficient to discriminate autoantibody-positive from autoantibody-negative children. Hepatocyte growth factor activator, complement factor H, ceruloplasmin and age predicted progression time to type 1 diabetes with a significant improvement compared with age alone.
Conclusion/interpretation
Distinct peptide signatures indicate islet autoimmunity prior to the clinical manifestation of type 1 diabetes and enable refined staging of the presymptomatic disease period.
Intellectual capital (IC) and social capital (SC), as forms of intangible value in organizations, are crucial assets in today's volatile business environment. Efforts to retain and develop these ...intangibles are becoming more deliberate and disciplined. However, organizations fail to recognize the relationship between organizational distress and the loss and/or reduction of intangible value. The loss of intangible value may potentially impact an organization with equal or greater damage than the loss of more tangible value. IC and SC generate many outcomes beneficial to the individual and the organization. These benefits are reduced when stress of employees becomes excessive and damaging. The relationship between the health of an organization and the degree of impact of distress serves as a lingering threat to organizational financial resources. Managers must build upon the growing knowledge from research and practice to help organizations account for the costs of organizational distress, translate the importance of intangible value into tangible terms, and garner support for developing IC and SC to obtain business objectives. Deliberate and disciplined effort to build collaborative capital can facilitate the growth of IC and SC which minimize the damage of organizational distress.
Self-managing work groups are a form of work design in which employees take responsibility for the group's tasks and have discretion over decisions which impact group performance. To explore the ...impact of age and work teams on job attitudes, data from 477 employees suggested that self-managed work group members differed from traditional job holders regarding perceived general job satisfaction, perceived control by supervisors, as well as a number of specific dimensions of the work environment. Moreover, while there was evidence of an age effect on attitudes toward supervisory control, there was no joint effect of age by work design on job attitudes, i.e., one's perceived general job satisfaction. Older employees who were members of self-managed work groups were however, more impacted by this form of work design in reporting more positive perceptions of their access to information essential to the performance of their work. These findings suggest that an "older" work force should not be considered a barrier to implementing a work teams approach to job design.
OBJECTIVE: Early identification of children at high risk for childhood overweight is a major challenge in fighting the obesity epidemic. We tried to identify the most powerful set of combined ...predictors for childhood overweight at school entry. RESEARCH METHODS AND PROCEDURES: A classification and regression trees analysis on risk factors for childhood overweight in 4289 children 5 to 6 years of age participating in the obligatory school entry health examination 2001/2002 in Bavaria, Germany, was performed. Parental questionnaires asked for children's weight at birth and 2 years, breastfeeding history, maternal smoking in pregnancy, parental education, parental overweight/obesity, nationality, and number of older siblings. Overweight was defined according to sex- and age-specific BMI cut-points proposed by the International Obesity Task Force. RESULTS: Prevalence of overweight was 11% among the entire study population. Although high early weight gain >10,000 grams was found in about one-half of the overweight children, its positive predictive value reached only 25%, indicating that one of four children with a high early weight gain is overweight at school entry. The best reliable set of predictors included high early weight gain and obese parents and accounted for a likelihood ratio of 3.6, with a corresponding positive predictive value of 40%, and was found in 4% of all children. DISCUSSION: A combination of predictors available at 2 years of age could improve predictability of overweight at school entry. However, corresponding low positive predictive values indicate a precision of the prediction that might be insufficient for targeting intervention programs for identified high-risk children.
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