Neural systems for speech and song in autism

Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal–posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls

Visual search performance in infants associates with later ASD diagnosis

An enhanced ability to detect visual targets amongst distractors, known as visual search (VS), has often been documented in Autism Spectrum Disorders (ASD). Yet, it is unclear when this behaviour emerges in development and if it is specific to ASD. We followed up infants at high and low familial risk for ASD to investigate how early VS abilities links to later ASD diagnosis, the potential underlying mechanisms of this association and the specificity of superior VS to ASD. Clinical diagnosis of ASD as well as dimensional measures of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were ascertained at 3 years. At 9 and 15 months, but not at age 2 years, high-risk children who later met clinical criteria for ASD (HR-ASD) had better VS performance than those without later diagnosis and low-risk controls. Although HR-ASD children were also more attentive to the task at 9 months, this did not explain search performance. Superior VS specifically predicted 3 year-old ASD but not ADHD or anxiety symptoms. Our results demonstrate that atypical perception and core ASD symptoms of social interaction and communication are closely and selectively associated during early development, and suggest causal links between perceptual and social features of ASD

Impact of drought stress on growth and quality of miscanthus for biofuel production

Miscanthus has a high potential as a biomass feedstock for biofuel production. Drought tolerance is an important breeding goal in miscanthus as water deficit is a common abiotic stress and crop irrigation is in most cases uneconomical. Drought may not only severely reduce biomass yields, but also affect biomass quality for biofuel production as cell wall remodeling is a common plant response to abiotic stresses. The quality and plant weight of 50 diverse miscanthus genotypes were evaluated under control and drought conditions (28 days no water) in a glasshouse experiment. Overall, drought treatment decreased plant weight by 45%. Drought tolerance - as defined by maintenance of plant weight - varied extensively among the tested miscanthus genotypes and ranged from 30% to 110%. Biomass composition was drastically altered due to drought stress, with large reductions in cell wall and cellulose content and a substantial increase in hemicellulosic polysaccharides. Stress had only a small effect on lignin content. Cell wall structural rigidity was also affected by drought conditions; substantially higher cellulose conversion rates were observed upon enzymatic saccharification of drought-treated samples with respect to controls. Both cell wall composition and the extent of cell wall plasticity under drought varied extensively among all genotypes, but only weak correlations were found with the level of drought tolerance, suggesting their independent genetic control. High drought tolerance and biomass quality can thus potentially be advanced simultaneously. The extensive genotypic variation found for most traits in the evaluated miscanthus germplasm provides ample scope for breeding of drought-tolerant varieties that are able to produce substantial yields of high-quality biomass under water deficit conditions. The higher degradability of drought-treated samples makes miscanthus an interesting crop for the production of second-generation biofuels in marginal soils

Southern San Andreas-San Jacinto fault system slip rates estimated from earthquake cycle models constrained by GPS and interferometric synthetic aperture radar observations

We use ground geodetic and interferometric synthetic aperture radar satellite observations across the southern San Andreas (SAF)-San Jacinto (SJF) fault systems to constrain their slip rates and the viscosity structure of the lower crust and upper mantle on the basis of periodic earthquake cycle, Maxwell viscoelastic, finite element models. Key questions for this system are the SAF and SJF slip rates, the slip partitioning between the two main branches of the SJF, and the dip of the SAF. The best-fitting models generally have a high-viscosity lower crust (η = 10^(21) Pa s) overlying a lower-viscosity upper mantle (η = 10^(19) Pa s). We find considerable trade-offs between the relative time into the current earthquake cycle of the San Jacinto fault and the upper mantle viscosity. With reasonable assumptions for the relative time in the earthquake cycle, the partition of slip is fairly robust at around 24–26 mm/a for the San Jacinto fault system and 16–18 mm/a for the San Andreas fault. Models for two subprofiles across the SAF-SJF systems suggest that slip may transfer from the western (Coyote Creek) branch to the eastern (Clark-Superstition hills) branch of the SJF from NW to SE. Across the entire system our best-fitting model gives slip rates of 2 ± 3, 12 ± 9, 12 ± 9, and 17 ± 3 mm/a for the Elsinore, Coyote Creek, Clark, and San Andreas faults, respectively, where the large uncertainties in the slip rates for the SJF branches reflect the large uncertainty in the slip rate partitioning within the SJF system

Large‐scale hydraulic conductivities inferred from three‐dimensional groundwater flow and 4 He transport modeling in the Carrizo aquifer, Texas

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94983/1/jgrb14187.pd

Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing MAPK activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some patients with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we show that LCH-ND is caused by myeloid cells that are clonal with peripheral LCH cells. We discovered that circulating BRAF V600E $^{+}$ myeloid cells cause the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiate into senescent, inflammatory CD11a $^{+}$ macrophages that accumulate in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent novel and targetable mechanisms of ND

Distribution and projection pattern of motoneurons that innervate hindlimb muscles in the quail

We characterized the motoneuron pool positions and projection patterns in the embryonic quail hindlimb and compared them to those in the chick to determine the degree of similarity and to form a baseline for future chimeric experiments. We find that the most similar parameters of pool position correlate with the major axonal pathway choices. First, the medial-lateral pool position, which is highly conserved among birds and mammals, is identical in the quail and chick and correlates with the dorsal-ventral pathway choice, the first and least plastic of the choices within the limb. Second, although quail pools were known to be compressed into seven rather than eight segments, we show that the map of pools is compressed about a central point (segment three) that preserves the spatial relationships between anterior pools and the crural plexus, and between posterior pools and the sciatic plexus. Access to guidance cues that are restricted to each plexus region is thus maintained between species. Third, pool position along the anterior-posterior axis is the least similar parameter between species. In fact, the entire lumbosacral motor complex may shift by ± half a segment in individual quail. Despite the consequent differences in segmental projections, the specific projection pattern within each quail hindlimb is identical to that in the chick. There is no need to preserve the exact segmental pattern either phylogenetically or during development, because motoneurons accommodate to modest variations in their position along the anterior-posterior axis by sorting out at the limb base. The contrast between variable segmental and constant limb projections also demonstrates that neither the specification nor the precise projection of motoneurons is dependent upon the specification or development of somites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50047/1/902980404_ftp.pd

Rye kernel breakfast increases satiety in the afternoon - an effect of food structure

<p>Abstract</p> <p>Background</p> <p>The structure of whole grain cereals is maintained to varying degrees during processing and preparation of foods. Food structure can influence metabolism, including perceived hunger and satiety. A diet that enhances satiety per calorie may help to prevent excessive calorie intake. The objective of this work was to compare subjective appetite ratings after consumption of intact and milled rye kernels.</p> <p>Methods</p> <p>Two studies were performed using a randomized, cross-over design. Ratings for appetite (hunger, satiety and desire to eat) were registered during an 8-h period after consumption of whole and milled rye kernels prepared as breads (study 1, n = 24) and porridges (study 2, n = 20). Sifted wheat bread was used as reference in both study parts and the products were eaten in iso-caloric portions with standardized additional breakfast foods. Breads and porridges were analyzed to determine whether structure (whole vs. milled kernels) effected dietary fibre content and composition after preparation of the products. Statistical evaluation of the appetite ratings after intake of the different breakfasts was done by paired t-tests for morning and afternoon ratings separately, with subjects as random effect and type of breakfast and time points as fixed effects.</p> <p>Results</p> <p>All rye breakfasts resulted in higher satiety ratings in the morning and afternoon compared with the iso-caloric reference breakfast with sifted wheat bread. Rye bread with milled or whole kernels affected appetite equally, so no effect of structure was observed. In contrast, after consumption of the rye kernel breakfast, satiety was increased and hunger suppressed in the afternoon compared with the milled rye kernel porridge breakfast. This effect could be related to structural differences alone, because the products were equal in nutritional content including dietary fibre content and composition.</p> <p>Conclusions</p> <p>The study demonstrates that small changes in diet composition such as cereal grain structure have the potential to effect feelings of hunger and satiety.</p> <p>Trial registration</p> <p>This trial was registered at clinicaltrials.gov as <a href="http://www.clinicaltrials.gov/ct2/show/NCT01042418">NCT01042418</a>.</p

Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance