The Human Connectome Project of adolescent anxiety and depression dataset.

This article describes primary data and resources available from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, a novel arm of the Human Connectome Project (HCP). Data were collected from 215 adolescents (14-17 years old), 152 of whom had current diagnoses of anxiety and/or depressive disorders at study intake. Data include cross-sectional structural (T1- and T2-weighted), functional (resting state and three tasks), and diffusion-weighted magnetic resonance images. Both unprocessed and HCP minimally-preprocessed imaging data are available within the data release packages. Adolescent and parent clinical interview data, as well as cognitive and neuropsychological data are also included within these packages. Release packages additionally provide data collected from self-report measures assessing key features of adolescent psychopathology, including: anxious and depressive symptom dimensions, behavioral inhibition/activation, exposure to stressful life events, and risk behaviors. Finally, the release packages include 6- and 12-month longitudinal data acquired from clinical measures. Data are publicly accessible through the National Institute of Mental Health Data Archive (ID: #2505).

Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.

Brain function and clinical characterization in the Boston adolescent neuroimaging of depression and anxiety study.

We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14-17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and longitudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource.

Vesicle shrinkage in hydrous phonolitic melt during cooling.

The ascent of hydrous magma prior to volcanic eruptions is largely driven by the formation of H2O vesicles and their subsequent growth upon further decompression. Porosity controls buoyancy as well as vesicle coalescence and percolation, and is important when identifying the differences between equilibrium or disequilibrium degassing from textural analysis of eruptive products. Decompression experiments are routinely used to simulate magma ascent. Samples exposed to high temperature (T) and pressure (P) are decompressed and rapidly cooled to ambient T for analysis. During cooling, fluid vesicles may shrink due to decrease of the molar volume of H2O and by resorption of H2O back into the melt driven by solubility increase with decreasing T at P < 300 MPa. Here, we quantify the extent to which vesicles shrink during cooling, using a series of decompression experiments with hydrous phonolitic melt (5.3-3.3 wt% H2O, T between 1323 and 1373 K, decompressed from 200 to 110-20 MPa). Most samples degassed at near-equilibrium conditions during decompression. However, the porosities of quenched samples are significantly lower than expected equilibrium porosities prior to cooling. At a cooling rate of 44 K·s-1, the fictive temperature T f, where vesicle shrinkage stops, is up to 200 K above the glass transition temperature (T g), Furthermore, decreasing cooling rate enhances vesicles shrinkage. We assess the implications of these findings on previous experimental degassing studies using phonolitic melt, and highlight the importance of correctly interpreting experimental porosity data, before any comparison to natural volcanic ejecta can be attempted.

From State-to-Trait Meditation: Reconfiguration of Central Executive and Default Mode Networks.

While brain default mode network (DMN) activation in human subjects has been associated with mind wandering, meditation practice has been found to suppress it and to increase psychological well-being. In addition to DMN activity reduction, experienced meditators (EMs) during meditation practice show an increased connectivity between the DMN and the central executive network (CEN). However, the gradual change between DMN and CEN configuration from pre-meditation, during meditation, and post-meditation is unknown. Here, we investigated the change in DMN and CEN configuration by means of brain activity and functional connectivity (FC) analyses in EMs across three back-to-back functional magnetic resonance imaging (fMRI) scans: pre-meditation baseline (trait), meditation (state), and post-meditation (state-to-trait). Pre-meditation baseline group comparison was also performed between EMs and healthy controls (HCs). Meditation trait was characterized by a significant reduction in activity and FC within DMN and increased anticorrelations between DMN and CEN. Conversely, meditation state and meditation state-to-trait periods showed increased activity and FC within the DMN and between DMN and CEN. However, the latter anticorrelations were only present in EMs with limited practice. The interactions between networks during these states by means of positive diametric activity (PDA) of the fractional amplitude of low-frequency fluctuations (fALFFs) defined as [Formula: see text] revealed no trait differences but significant increases during meditation state that persisted in meditation state-to-trait. The gradual reconfiguration in DMN and CEN suggest a neural mechanism by which the CEN negatively regulates the DMN and is probably responsible for the long-term trait changes seen in meditators and reported psychological well-being.

Child overweight and obesity are associated with reduced executive cognitive performance and brain alterations: a magnetic resonance imaging study in Mexican children.

BACKGROUND: Overweight and obesity in childhood is associated with negative physical and psychological effects. It has been proposed that obesity increase the risk for developing cognitive deficits, dementia and Alzheimer's disease and that it may be associated with marked differences in specific brain structure volumes. OBJECTIVE: The purpose of this study was a neurobiopsychological approach to examine the association between overweight and obesity, brain structure and a paediatric neuropsychological assessment in Mexican children between 6 and 8 years of age. METHODS: We investigated the relation between the body mass index (BMI), brain volumetric segmentation of subcortical gray and white matter regions obtained with magnetic resonance imaging and the Neuropsychological Assessment of Children standardized for Latin America. Thirty-three healthy Mexican children between 6 and 8 years of age, divided into normal weight (18 children) and overweight/obese (15 children) groups. RESULTS: Overweight/obese children showed reduced executive cognitive performance on neuropsychological evaluations (i.e. verbal fluidity, P = 0.03) and presented differences in brain structures related to learning and memory (reduced left hippocampal volumes, P = 0.04) and executive functions (larger white matter volumes in the left cerebellum, P = 0.04 and mid-posterior corpus callosum, P = 0.03). Additionally, we found a positive correlation between BMI and left globulus pallidus (P = 0.012, ρ = 0.43) volume and a negative correlation between BMI and neuropsychological evaluation scores (P = 0.033, ρ = -0.37). CONCLUSIONS: The findings contribute to the idea that there is a relationship between BMI, executive cognitive performance and brain structure that may underlie the causal chain that leads to obesity in adulthood.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development.

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.

Abnormal functioning of the thalamocortical system underlies the conscious awareness of the phantom limb phenomenon.

Phantom limb (PL), a phenomenon experienced by most patients after amputation, has mostly served as a paradigm to study experiences that appear to be associated with neural plasticity within the CNS. However, the subjective nature of PL experiences has had no definitive means of reliable assessment other than using patients' direct reports, nor was there a way to study the neural mechanisms involved in the conscious awareness of this mental phenomenon. Here we obtained patients' indirect responses to PL experiences for an objective evaluation using functional magnetic resonance imaging (fMRI). Six control subjects and six lower limb (LL) amputees participated in a motor imagery task for both the intact and the particular phantom toes. While all subjects shared neural processing of distinctive regional cerebral activations during motor imagery of the intact toes (prefrontal (PF), supplementary motor area (SMA), primary motor cortex (M1), superior temporal gyrus (STG)), it was only during motor imagery of the amputated toes in amputees that we observed an increased blood oxygen level-dependent (BOLD) signal in the contralateral basal ganglia at the medial globus pallidus (MGP), substantia nigra (SN), and thalamus. This increased BOLD signal in the basal ganglia-thalamus-cortex pathway during imaginary movement of the phantom toes may reflect an abnormal open loop functioning of the thalamocortical system underlying the conscious awareness of the phantom phenomenon. We suggest that the reduction in afferent information contributes to and coalesces with the higher-level reorganization resulting in the subjective conscious awareness of the phantom limb.

Prevalence of Panton-Valentine leukocidin genes in methicillin-resistant Staphylococcus aureus isolates phenotypically consistent with community-acquired MRSA, 1999-2007, Vienna General Hospital.

The purpose of this study was to investigate methicillin-resistant Staphylococcus aureus (MRSA) isolates with antibiotic resistance restricted to beta-lactam antibiotics and variable resistance to fusidic acid for the presence of Panton-Valentine leukocidin (PVL) genes. Our data show that the selected resistance pattern is found rarely among MRSA isolates in our hospital, but it appears that this phenotype consistent with typical community-acquired (ca) MRSA is indicative of PVL-positive MRSA.

Hypoxic modulation of ca(2+) signaling in human venous and arterial endothelial cells.

Our understanding of vascular endothelial cell physiology is based on studies of endothelial cells cultured from various vascular beds of different species for varying periods of time. Systematic analysis of the properties of endothelial cells from different parts of the vasculature is lacking. Here, we compare Ca(2+) homeostasis in primary cultures of endothelial cells from human internal mammary artery and saphenous vein and how this is modified by hypoxia, an inevitable consequence of bypass grafting (2.5% O(2), 24 h). Basal [Ca(2+)]( i ) and store depletion-mediated Ca(2+) entry were significantly different between the two cell types, yet agonist (ATP)-mediated mobilization from endoplasmic reticulum stores was similar. Hypoxia potentiated agonist-evoked responses in arterial, but not venous, cells but augmented store depletion-mediated Ca(2+) entry only in venous cells. Clearly, Ca(2+) signaling and its remodeling by hypoxia are strikingly different in arterial vs. venous endothelial cells. Our data have important implications for the interpretation of data obtained from endothelial cells of varying sources.

Differential assembly of alpha- and gamma-filagenins into thick filaments in Caenorhabditis elegans.

Muscle thick filaments are highly organized supramolecular assemblies of myosin and associated proteins with lengths, diameters and flexural rigidities characteristic of their source. The cores of body wall muscle thick filaments of the nematode Caenorhabditis elegans are tubular structures of paramyosin sub-filaments coupled by filagenins and have been proposed to serve as templates for the assembly of native thick filaments. We have characterized alpha- and gamma-filagenins, two novel proteins of the cores with calculated molecular masses of 30,043 and 19,601 and isoelectric points of 10.52 and 11.49, respectively. Western blot and immunoelectron microscopy using affinity-purified antibodies confirmed that the two proteins are core components. Immunoelectron microscopy of the cores revealed that they assemble with different periodicities. Immunofluorescence microscopy showed that alpha-filagenin is localized in the medial regions of the A-bands of body wall muscle cells whereas gamma-filagenin is localized in the flanking regions, and that alpha-filagenin is expressed in 1.5-twofold embryos while gamma-filagenin becomes detectable only in late vermiform embryos. The expression of both proteins continues throughout later stages of development. C. elegans body wall muscle thick filaments of these developmental stages have distinct lengths. Our results suggest that the differential assembly of alpha- and gamma-filagenins into thick filaments of distinct lengths may be developmentally regulated.

Unc-45 mutations in Caenorhabditis elegans implicate a CRO1/She4p-like domain in myosin assembly.

The Caenorhabditis elegans unc-45 locus has been proposed to encode a protein machine for myosin assembly. The UNC-45 protein is predicted to contain an NH2-terminal domain with three tetratricopeptide repeat motifs, a unique central region, and a COOH-terminal domain homologous to CRO1 and She4p. CRO1 and She4p are fungal proteins required for the segregation of other molecules in budding, endocytosis, and septation. Three mutations that lead to temperature-sensitive (ts) alleles have been localized to conserved residues within the CRO1/She4p-like domain, and two lethal alleles were found to result from stop codon mutations in the central region that would prevent translation of the COOH-terminal domain. Electron microscopy shows that thick filament accumulation in vivo is decreased by approximately 50% in the CB286 ts mutant grown at the restrictive temperature. The thick filaments that assemble have abnormal structure. Immunofluorescence and immunoelectron microscopy show that myosins A and B are scrambled, in contrast to their assembly into distinct regions at the permissive temperature and in wild type. This abnormal structure correlates with the high degree of instability of the filaments in vitro as reflected by their extremely low yields and shortened lengths upon isolation. These results implicate the UNC-45 CRO1/She4p-like region in the assembly of myosin isoforms in C. elegans and suggest a possible common mechanism for the function of this UCS (UNC-45/CRO1/She4p) protein family.

beta-Filagenin, a newly identified protein coassembling with myosin and paramyosin in Caenorhabditis elegans.

Muscle thick filaments are stable assemblies of myosin and associated proteins whose dimensions are precisely regulated. The mechanisms underlying the stability and regulation of the assembly are not understood. As an approach to these problems, we have studied the core proteins that, together with paramyosin, form the core structure of the thick filament backbone in the nematode Caenorhabditis elegans. We obtained partial peptide sequences from one of the core proteins, beta-filagenin, and then identified a gene that encodes a novel protein of 201-amino acid residues from databases using these sequences. beta-Filagenin has a calculated isoelectric point at 10.61 and a high percentage of aromatic amino acids. Secondary structure algorithms predict that it consists of four beta-strands but no alpha-helices. Western blotting using an affinity-purified antibody showed that beta-filagenin was associated with the cores. beta-Filagenin was localized by immunofluorescence microscopy to the A bands of body-wall muscles, but not the pharynx. beta-filagenin assembled with the myosin homologue paramyosin into the tubular cores of wild-type nematodes at a periodicity matching the 72-nm repeats of paramyosin, as revealed by immunoelectron microscopy. In CB1214 mutants where paramyosin is absent, beta-filagenin assembled with myosin to form abnormal tubular filaments with a periodicity identical to wild type. These results verify that beta-filagenin is a core protein that coassembles with either myosin or paramyosin in C. elegans to form tubular filaments.

Suppression of heterocyst differentiation in Anabaena PCC 7120 by a cosmid carrying wild-type genes encoding enzymes for fatty acid synthesis.

A cosmid containing a wild-type Anabaena PCC 7120 DNA fragment was found to suppress heterocyst differentiation, creating a Het phenotype in an otherwise wild-type strain. Curing of the cosmid restored the full wild-type Het+ Nif+ phenotype. The cosmid contains at least four genes encoding proteins with significant sequence similarity to enzymes involved in the synthesis of fatty acids. Selection for Nif+ revertants of the suppressed strain yielded modified cosmids, one of which contained a 10.2-kb transposon, Tas1, inserted into the promoter region of a gene encoding a protein with acyl carrier and beta-keto reductase domains. This gene, called hetN, was shown previously by Black and Wolk (J. Bacteriol. (1994) 176, 2282-2292) to inhibit heterocyst differentiation when present alone on a plasmid. Oddly, hetN gene transcription is detected later than 6 h into heterocyst differentiation.

Assemblases and coupling proteins in thick filament assembly.

Thick filaments are stable assemblies of myosin that are characteristic of specific muscle types from both vertebrates and invertebrates. In general, their structure and assembly require remarkably precise determination of lengths and diameters, structural differentiation and nonequivalence of myosins, a high degree of inelasticity and rigidity, and dynamic regulation of assembly and disassembly in response to both extracellular and intracellular signals. Directed assembly of myosin in which additional proteins function in key roles, therefore, is more likely to be significant than the simple self assembly of myosin into thick filaments. The nematode Caenorhabditis elegans permits a wide spectrum of biochemical, genetic, molecular and structural approaches to be applied to the experimental testing of this hypothesis. Biochemical analysis of C. elegans thick filaments reveals that paramyosin, a homologue of the myosin rod that is the unique product of a single genetic locus, exists as two populations which differ by post-translational modification. The major paramyosin species interacts with the two genetically specified myosin heavy chain isoforms. The minor paramyosin species is organized within the cores of the thick filaments, where it is associated stoichiometrically with three recently identified proteins P20, P28 and P30. These proteins have now been characterized molecularly and contain unique, novel amino acid sequences. Structural analysis of the core shows that seven paramyosin subfilaments are crosslinked by additional internal proteins into a highly rigid tubule. P20, P28 and P30 are proposed to couple the paramyosin subfilaments together into the core tubule during filament assembly. Mutants that affect paramyosin assembly are being characterized for alterations in the core proteins. A fourth protein has been identified recently as the product of the unc-45 gene. Computational analysis of this gene's DNA suggests that the predicted protein may exhibit protein phosphatase and chaperone activities. Genetic analysis shows that three classes of specific unc-45 mutant proteins differentially interact with the two myosins during thick filament assembly. The unc-45 protein is proposed to be a myosin assemblase, a protein catalyst of thick filament assembly.

Vectors for determining the differential expression of genes in heterocysts and vegetative cells of Anabaena sp. strain PCC 7120.

Plasmid vectors were constructed to study promoters of the cyanobacterium Anabaena sp. strain PCC 7120. Plasmid pCCBSelect contains the promoterless reporter genes in the order cat-nifHDK. In pCCBSelect/a, the nifHDK operon precedes the cat gene. Putative promoter sequences were cloned into a polylinker region upstream of the reporter genes. Activity in heterocysts was determined by complementation of a strain containing a deletion of the nifH gene. Activity in vegetative cells was determined by measuring resistance to chloramphenicol. The promoter of the nifHDK operon was active only in heterocysts; the promoter of the nifJ gene was active only in iron-depleted medium; and the promoters of the psbB gene, the ntcA gene, and a newly found transcription factor gene were all active in both cell types.

A short-filament mutant of Anabaena sp. strain PCC 7120 that fragments in nitrogen-deficient medium.

Strain 129 is a fragmentation mutant of the filamentous cyanobacterium Anabaena sp. strain PCC 7120. Growing with fixed nitrogen, this mutant forms filaments that are much shorter than wild-type filaments. Following starvation for fixed nitrogen, strain 129 becomes nearly unicellular and forms few heterocysts, although electron microscopy suggests that proheterocysts form while fragmentation occurs. Starvation for sulfate, phosphate, iron, and calcium does not cause this fragmentation. The affected gene in strain 129, fraC, was cloned by complementation and characterized. It encodes a unique 179-amino-acid protein rich in phenylalanine. Insertional inactivation of the chromosomal copy of fraC results in a phenotype identical to that of strain 129, while complementation using a truncated version of FraC results in only partial complementation of the original mutant. Heterocysts could be induced to form in N-replete cultures of strain 129, as in wild-type cells, by supplying extra copies of the hetR gene on a plasmid. Thus, FraC is required for the integrity of cell junctions in general but is apparently not directly involved in normal differentiation and nitrogen fixation.

Growth of the cyanobacterium Anabaena on molecular nitrogen: NifJ is required when iron is limited.

The nifJ gene of Klebsiella pneumoniae encodes an oxidoreductase required for the transfer of electrons from pyruvate to flavodoxin, which reduces nitrogenase. The nifJ gene of Anabaena 7120, isolated from a cosmid bank, was found to contain an open reading frame encoding a 1197-aa protein. The deduced amino acid sequence shows 50% identity to the Klebsiella homolog. The nifJ gene in Anabaena 7120 was inactivated by chromosomal interruption. The resulting mutant was unable to grow on medium depleted of both iron and combined nitrogen but grew normally, fixing nitrogen, when iron was present. NifJ transcripts of 2.7 and 4.3 kb are induced by iron depletion irrespective of nitrogen status. One particular stretch of the Anabaena 7120 nifJ gene encodes 12 aa with no complementary matches in the Klebsiella protein. This insert contains five tandem repeats of the heptamer CCCCAGT. These heptamers, as well as heptamers and octamers of other related sequences, have been located in a number of cyanobacterial genomes but are usually not found within the coding region of a gene. The site of the Anabaena 7120 heptamers in the nifJ genes of other filamentous cyanobacteria contains a surprising diversity of repeated sequences, both octamers and heptamers. The corresponding protein inserts range in length from 1 to 21 aa, relative to Klebsiella NifJ.