The Cell Density Factor CMF Regulates the Chemoattractant Receptor cAR1 in Dictyostelium

Starving Dictyostelium cells aggregate by chemotaxis to cAMP when a secreted protein called conditioned medium factor (CMF) reaches a threshold concentration. Cells expressing CMF antisense mRNA fail to aggregate and do not transduce signals from the cAMP receptor. Signal transduction and aggregation are restored by adding recombinant CMF. We show here that two other cAMP-induced events, the formation of a slow dissociating form of the cAMP receptor and the loss of ligand binding, which is the first step of ligand-induced receptor sequestration, also require CMF. Vegetative cells have very few CMF and cAMP receptors, while starved cells possess ~40,000 receptors for CMF and cAMP. Transformants overexpressing the cAMP receptor gene cAR1 show a 10-fold increase of [3H]cAMP binding and a similar increase of [125I]CMF binding; disruption of the cAR1 gene abolishes both cAMP and CMF binding. In wild-type cells, downregulation of cAR1 with high levels of cAMP also downregulates CMF binding, and CMF similarly downregulates cAMP and CMF binding. This suggests that the cAMP binding and CMF binding are closely linked. Binding of ~200 molecules of CMF to starved cells affects the affinity of the majority of the cAR1 cAMP receptors within 2 min, indicating that an amplifying mechanism allows one activated CMF receptor to regulate many cARs. In cells lacking the G-protein β subunit, cAMP induces a loss of cAMP binding, but not CMF binding, while CMF induces a reduction of CMF binding without affecting cAMP binding, suggesting that the linkage of the cell density-sensing CMF receptor and the chemoattractant cAMP receptor is through a G-protein.

Institutional Effects in a Simple Model of Educational Production

This paper presents a model of educational production that tries to make sense of recent evidence on effects of institutional arrangements on student performance. In a simple principal-agent framework, students choose their learning effort to maximize their net benefits, while the government chooses educational spending to maximize its net benefits. In the jointly determined equilibrium, schooling quality is shown to depend on several institutionally determined parameters. The impact on student performance of institutions such as central examinations, centralization versus school autonomy, teachers\u27 influence, parental influence, and competition from private schools is analyzed. Furthermore, the model can rationalize why positive resource effects may be lacking in educational production

Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2.

Vertebrates produce multiple chondroitin sulfate proteoglycans that play important roles in development and tissue mechanics. In the nematode Caenorhabditis elegans, the chondroitin chains lack sulfate but nevertheless play essential roles in embryonic development and vulval morphogenesis. However, assignment of these functions to specific proteoglycans has been limited by the lack of identified core proteins. We used a combination of biochemical purification, Western blotting, and mass spectrometry to identify nine C. elegans chondroitin proteoglycan core proteins, none of which have homologues in vertebrates or other invertebrates such as Drosophila melanogaster or Hydra vulgaris. CPG-1/CEJ-1 and CPG-2 are expressed during embryonic development and bind chitin, suggesting a structural role in the egg. RNA interference (RNAi) depletion of individual CPGs had no effect on embryonic viability, but simultaneous depletion of CPG-1/CEJ-1 and CPG-2 resulted in multinucleated single-cell embryos. This embryonic lethality phenocopies RNAi depletion of the SQV-5 chondroitin synthase, suggesting that chondroitin chains on these two proteoglycans are required for cytokinesis

Microscopy with ultraviolet surface excitation for rapid slide-free histology.

Histologic examination of tissues is central to the diagnosis and management of neoplasms and many other diseases, and is a foundational technique for preclinical and basic research. However, commonly used bright-field microscopy requires prior preparation of micrometre-thick tissue sections mounted on glass slides, a process that can require hours or days, that contributes to cost, and that delays access to critical information. Here, we introduce a simple, non-destructive slide-free technique that within minutes provides high-resolution diagnostic histological images resembling those obtained from conventional haematoxylin-and-eosin-histology. The approach, which we named microscopy with ultraviolet surface excitation (MUSE), can also generate shape and colour-contrast information. MUSE relies on ~280-nm ultraviolet light to restrict the excitation of conventional fluorescent stains to tissue surfaces, and it has no significant effects on downstream molecular assays (including fluorescence in situ hybridization and RNA-seq). MUSE promises to improve the speed and efficiency of patient care in both state-of-the-art and low-resource settings, and to provide opportunities for rapid histology in research

Resting state correlates of subdimensions of anxious affect

Resting state fMRI may help identify markers of risk for affective disorder. Given the comorbidity of anxiety and depressive disorders and the heterogeneity of these disorders as defined by DSM, an important challenge is to identify alterations in resting state brain connectivity uniquely associated with distinct profiles of negative affect. The current study aimed to address this by identifying differences in brain connectivity specifically linked to cognitive and physiological profiles of anxiety, controlling for depressed affect. We adopted a two-stage multivariate approach. Hierarchical clustering was used to independently identify dimensions of negative affective style and resting state brain networks. Combining the clustering results, we examined individual differences in resting state connectivity uniquely associated with subdimensions of anxious affect, controlling for depressed affect. Physiological and cognitive subdimensions of anxious affect were identified. Physiological anxiety was associated with widespread alterations in insula connectivity, including decreased connectivity between insula subregions and between the insula and other medial frontal and subcortical networks. This is consistent with the insula facilitating communication between medial frontal and subcortical regions to enable control of physiological affective states. Meanwhile, increased connectivity within a frontoparietal-posterior cingulate cortex-precunous network was specifically associated with cognitive anxiety, potentially reflecting increased spontaneous negative cognition (e.g., worry). These findings suggest that physiological and cognitive anxiety comprise subdimensions of anxiety-related affect and reveal associated alterations in brain connectivity

Portable Emission Measurements of Yellowstone Park Snowcoaches and Snowmobiles

As part of the National Park Service’s Temporary Winter Use Plans Environmental Assessment, the University of Denver has been collecting in-use tailpipe emissions data from snowcoaches and snowmobiles in Yellowstone National Park. During the winter of 2006, using a portable emissions monitoring system, tailpipe data were collected from 10 snowcoaches and 2 four-stroke snowmobiles. These vehicles were operated over a standard route within the park, and the snowcoaches all carried identical passenger loads. These snowcoaches were newer in age with more advanced fuel management technology than those studied earlier, and average emissions were lower as a result (120, 1.7, and 11 g/mi for carbon monoxide [CO], hydrocarbons [HC], and oxides of nitrogen [NOx]). Large emissions variability was still observed despite using a standardized route and equal passenger loading. A comparison between five nearly identically equipped snow-coaches that had CO emissions ranging between 12 and 310 g/mi suggests that snow and road conditions are the most important factors behind the large emissions variability observed between modern snowcoaches. The first comprehensive emission measurements, using a portable emissions measurement system, on two snowmobiles showed that computer-controlled fuel management systems have increased fuel economy (\u3e25 mpg) and are a major reason that emissions from these winter vehicles have dropped so dramatically. Using all of the tailpipe emissions data collected to date shows that the two primary winter vehicles in Yellowstone National Park are now very similar in their per-passenger emissions

Phase Transitions in the Spin-Half J_1--J_2 Model

The coupled cluster method (CCM) is a well-known method of quantum many-body theory, and here we present an application of the CCM to the spin-half J_1--J_2 quantum spin model with nearest- and next-nearest-neighbour interactions on the linear chain and the square lattice. We present new results for ground-state expectation values of such quantities as the energy and the sublattice magnetisation. The presence of critical points in the solution of the CCM equations, which are associated with phase transitions in the real system, is investigated. Completely distinct from the investigation of the critical points, we also make a link between the expansion coefficients of the ground-state wave function in terms of an Ising basis and the CCM ket-state correlation coefficients. We are thus able to present evidence of the breakdown, at a given value of J_2/J_1, of the Marshall-Peierls sign rule which is known to be satisfied at the pure Heisenberg point (J_2 = 0) on any bipartite lattice. For the square lattice, our best estimates of the points at which the sign rule breaks down and at which the phase transition from the antiferromagnetic phase to the frustrated phase occurs are, respectively, given (to two decimal places) by J_2/J_1 = 0.26 and J_2/J_1 = 0.61.Comment: 28 pages, Latex, 2 postscript figure

The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis

Accurate chromosome segregation during cell division requires not only the establishment, but also the precise, regulated release of chromosome cohesion. Chromosome dynamics during meiosis are more complicated, because homologues separate at anaphase I whereas sister chromatids remain attached until anaphase II. How the selective release of chromosome cohesion is regulated during meiosis remains unclear. We show that the aurora-B kinase AIR-2 regulates the selective release of chromosome cohesion during Caenorhabditis elegans meiosis. AIR-2 localizes to subchromosomal regions corresponding to last points of contact between homologues in metaphase I and between sister chromatids in metaphase II. Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases, with concomitant prevention of meiotic cohesin REC-8 release from meiotic chromosomes. We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro. Interestingly, depletion of two PP1 phosphatases, CeGLC-7α and CeGLC-7β, abolishes the restricted localization pattern of AIR-2. In Ceglc-7α/β(RNAi) embryos, AIR-2 is detected on the entire bivalent. Concurrently, chromosomal REC-8 is dramatically reduced and sister chromatids are separated precociously at anaphase I in Ceglc-7α/β(RNAi) embryos. We propose that AIR-2 promotes the release of chromosome cohesion via phosphorylation of REC-8 at specific chromosomal locations and that CeGLC-7α/β, directly or indirectly, antagonize AIR-2 activity

Breast Ultrasound Following a Positive Clinical Breast Examination: Does It Have a Role in Low- and Middle-Income Countries?

Purpose: Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million new cases occurring in 2012. The majority of cases and deaths occur in low- and middle-income countries (LMICs), where population-based mammography screening is not available and countries must rely on clinical breast examination (CBE). Since ultrasound has the potential to reduce unnecessary biopsies by triaging women with palpable or focal breast findings at CBE, we searched for evidence in the literature on the effectiveness of ultrasound in detecting potential breast cancer following positive CBE findings. Methods: We reviewed the literature from 2000 to 2014 for evidence on the performance of breast ultrasound, in the absence of mammography, used to evaluate women after a positive CBE. From the studies meeting our inclusion/exclusion criteria for our analysis, we extracted data on the study design, location, ultrasound transducer parameters, patient age, method for determining positive and negative cases, and number of malignancies detected/total number of women studied. Results: We found 15 studies matching our inclusion/exclusion criteria, 9 from high-income countries and 6 from LMICs. Despite considerable variability in study design and patient populations, breast ultrasound consistently showed high sensitivity (median = 94 percent) and specificity (median = 80 percent) for detecting breast cancer and identifying normal and benign findings not requiring a biopsy. Clear patterns related to transducer frequency or income level were not discernible given the variations in patient populations and final diagnostic determinations. Conclusion: Our systematic review suggests that breast ultrasound following a positive CBE may be a powerful diagnostic test to determine those who do or do not need biopsy. We encourage further research in breast ultrasound use after a positive CBE in LMICs to assess the accuracy of ultrasound in these settings and the feasibility of widespread implementation