Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

Analysis of physical pore space characteristics of two pyrolytic biochars and potential as microhabitat

Background and Aims Biochar amendment to soil is a promising practice of enhancing productivity of agricultural systems. The positive effects on crop are often attributed to a promotion of beneficial soil microorganisms while suppressing pathogens e.g. This study aims to determine the influence of biochar feedstock on (i) spontaneous and fungi inoculated microbial colonisation of biochar particles and (ii) physical pore space characteristics of native and fungi colonised biochar particles which impact microbial habitat quality. Methods Pyrolytic biochars from mixed woods and Miscanthus were investigated towards spontaneous colonisation by classical microbiological isolation, phylogenetic identification of bacterial and fungal strains, and microbial respiration analysis. Physical pore space characteristics of biochar particles were determined by X-ray μ-CT. Subsequent 3D image analysis included porosity, surface area, connectivities, and pore size distribution. Results Microorganisms isolated from Wood biochar were more abundant and proliferated faster than those from the Miscanthus biochar. All isolated bacteria belonged to gram-positive bacteria and were feedstock specific. Respiration analysis revealed higher microbial activity for Wood biochar after water and substrate amendment while basal respiration was on the same low level for both biochars. Differences in porosity and physical surface area were detected only in interaction with biochar-specific colonisation. Miscanthus biochar was shown to have higher connectivity values in surface, volume and transmission than Wood biochars as well as larger pores as observed by pore size distribution. Differences in physical properties between colonised and non-colonised particles were larger in Miscanthus biochar than in Wood biochar. Conclusions Vigorous colonisation was found on Wood biochar compared to Miscanthus biochar. This is contrasted by our findings from physical pore space analysis which suggests better habitat quality in Miscanthus biochar than in Wood biochar. We conclude that (i) the selected feedstocks display large differences in microbial habitat quality as well as physical pore space characteristics and (ii) physical description of biochars alone does not suffice for the reliable prediction of microbial habitat quality and recommend that physical and surface chemical data should be linked for this purpose

Untangling knowledge creation and knowledge integration in enterprise wikis

A central challenge organizations face is how to build, store, and maintain knowledge over time. Enterprise wikis are community-based knowledge systems situated in an organizational context. These systems have the potential to play an important role in managing knowledge within organizations, but the motivating factors that drive individuals to contribute their knowledge to these systems is not very well understood. We theorize that enterprise wiki initiatives require two separate and distinct types of knowledge-sharing behaviors to succeed: knowledge creation (KC) and knowledge integration (KI). We examine a Wiki initiative at a major German bank to untangle the motivating factors behind KC and KI. Our results suggest KC and KI are indeed two distinct behaviors, reconcile inconsistent findings from past studies on the role of motivational factors for knowledge sharing to establish shared electronic knowledge resources in organizations, and identify factors that can be leveraged to tilt behaviors in favor of KC or KI

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

Proteolytic Processing of Nlrp1b Is Required for Inflammasome Activity

Nlrp1b is a NOD-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. Nlrp1b has two domains that promote oligomerization: a NACHT domain, which is a member of the AAA+ ATPase family, and a poorly characterized Function to Find Domain (FIIND). Here we demonstrate that proteolytic processing within the FIIND generates N-terminal and C-terminal cleavage products of Nlrp1b that remain associated in both the auto-inhibited state and in the activated state after cells have been treated with lethal toxin. Functional significance of cleavage was suggested by the finding that mutations that block processing of Nlrp1b also prevent the ability of Nlrp1b to activate pro-caspase-1. By using an uncleaved mutant of Nlrp1b, we established the importance of cleavage by inserting a heterologous TEV protease site into the FIIND and demonstrating that TEV protease processed this site and induced inflammasome activity. Proteolysis of Nlrp1b was shown to be required for the assembly of a functional inflammasome: a mutation within the FIIND that abolished cleavage had no effect on self-association of a FIIND-CARD fragment, but did reduce the recruitment of pro-caspase-1. Our work indicates that a post-translational modification enables Nlrp1b to function

Magnetoencephalography Study of Right Parietal Lobe Dysfunction of the Evoked Mirror Neuron System in Antipsychotic-Free Schizophrenia

INTRODUCTION: Patients with schizophrenia commonly exhibit deficits of non-verbal communication in social contexts, which may be related to cognitive dysfunction that impairs recognition of biological motion. Although perception of biological motion is known to be mediated by the mirror neuron system, there have been few empirical studies of this system in patients with schizophrenia. METHODS: Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement of another individual). RESULTS: Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase-locking factors and gamma-synchronization predominantly in right parietal cortex. CONCLUSIONS: Our findings demonstrate that untreated patients with schizophrenia exhibit aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization in the right parietal lobe during observation of biological motion

Deducing the Temporal Order of Cofactor Function in Ligand-Regulated Gene Transcription: Theory and Experimental Verification

Cofactors are intimately involved in steroid-regulated gene expression. Two critical questions are (1) the steps at which cofactors exert their biological activities and (2) the nature of that activity. Here we show that a new mathematical theory of steroid hormone action can be used to deduce the kinetic properties and reaction sequence position for the functioning of any two cofactors relative to a concentration limiting step (CLS) and to each other. The predictions of the theory, which can be applied using graphical methods similar to those of enzyme kinetics, are validated by obtaining internally consistent data for pair-wise analyses of three cofactors (TIF2, sSMRT, and NCoR) in U2OS cells. The analysis of TIF2 and sSMRT actions on GR-induction of an endogenous gene gave results identical to those with an exogenous reporter. Thus new tools to determine previously unobtainable information about the nature and position of cofactor action in any process displaying first-order Hill plot kinetics are now available

Human difference in the genomic era: Facilitating a socially responsible dialogue

<p>Abstract</p> <p>Background</p> <p>The study of human genetic variation has been advanced by research such as genome-wide association studies, which aim to identify variants associated with common, complex diseases and traits. Significant strides have already been made in gleaning information on susceptibility, treatment, and prevention of a number of disorders. However, as genetic researchers continue to uncover underlying differences between individuals, there is growing concern that observed population-level differences will be inappropriately generalized as inherent to particular racial or ethnic groups and potentially perpetuate negative stereotypes.</p> <p>Discussion</p> <p>We caution that imprecision of language when conveying research conclusions, compounded by the potential distortion of findings by the media, can lead to the stigmatization of racial and ethnic groups.</p> <p>Summary</p> <p>It is essential that the scientific community and with those reporting and disseminating research findings continue to foster a socially responsible dialogue about genetic variation and human difference.</p

Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

<p>Abstract</p> <p>Background</p> <p>Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR). This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR.</p> <p>Methods</p> <p>N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA).</p> <p>Results</p> <p>Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III) was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE), though AHRE-III was not identical to XRE, the conventional AhR-binding motif.</p> <p>Conclusion</p> <p>Our results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.</p