Preserved feedforward but impaired top-down processes in the vegetative state

Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an impairment of top-down processes, involved in recurrent neuronal message-passing and the generation of long-latency electrophysiological responses, might provide a more reliable correlate of consciousness in severely brain-damaged patients, than frontoparietal responses. We measured effective connectivity during a mismatch negativity paradigm and found that the only significant difference between patients in a vegetative state and controls was an impairment of backward connectivity from frontal to temporal cortices. This result emphasizes the importance of top-down projections in recurrent processing that involve high-order associative cortices for conscious perception.     

Graphoepitaxy of self-assembled block copolymers on two-dimensional periodic patterned templates

Self-assembling materials are the building blocks of bottom-up nanofabrication processes, but they need to be templated to impose long-range order and eliminate defects. In this work, the self-assembly of a thin film of a spherical-morphology block copolymer is templated using an array of nanoscale topographical elements that act as surrogates for the minority domains of the block copolymer. The orientation and periodicity of the resulting array of spherical microdomains are governed by the commensurability between the block copolymer period and the template period and is accurately described by a free-energy model. This method, which forms high-spatial-frequency arrays using a lower-spatial-frequency template, will be useful in nanolithography applications such as the formation of high-density microelectronic structures.     

TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.     

Production and dissolution rates of earthworm-secreted calcium carbonate

Earthworms secrete granules of calcium carbonate. These are potentially important in soil biogeochemical cycles and are routinely recorded in archaeological studies of Quaternary soils. Production rates of calcium carbonate granules by the earthworm Lumbricus terrestris L. were determined over 27 days in a range of soils with differing chemical properties (pH, organic matter content, water holding capacity, bulk composition, cation exchange capacity and exchangeable cations). Production rate varied between soils, lay in the range $0–0.043{\text{mmol}}_{{\text{CaCO}}_3}$ (0–4.3 mg) earthworm^?1 d^?1 with an average rate of $8\times {10}^{?3}{\text{mmol}}_{{\text{CaCO}}_3}$ (0.8 mg) earthworm^?1 d^?1 and was significantly correlated (r = 0.68, P ≤ 0.01) with soil pH. In a second experiment lasting 315 days earthworms repeatedly (over periods of 39–57 days) produced comparable masses of granules. Converting individual earthworm granule production rates into fluxes expressed on a per hectare of land per year basis depends heavily on estimates of earthworm numbers. Using values of 10–20 L. terrestris m^?2 suggests a rate of $18–3139{\text{mol}}_{{\text{CaCO}}_3}{\text{ha}}^{?1}{\text{yr}}^{?1}$. Data obtained from flow-through dissolution experiments suggest that at near neutral pH, granule geometric surface area-normalised dissolution rates are similar to those for other biogenic and inorganic calcites. Fits of the data to the dissolution relationship r = k(1 ? Ω)ⁿ where r = dissolution rate, k = a rate constant, Ω = relative saturation and n = the reaction order gave values of k = 1.72 × 10^?10 mol cm^?2 s^?1 and n = 1.8 for the geometric surface area-normalised rates and k = 3.51 × 10^?13 mol cm^?2 s^?1 and n = 1.8 for the BET surface area-normalised rates. In 196 day leaching column experiments trends in granule dissolution rate referenced to soil chemistry corresponded to predictions made by the SLIM model for dissolution of limestone in soil. If soil solution approaches saturation with respect to calcium carbonate, granule dissolution will slow or even stop and granules be preserved indefinitely. Granules have the potential to be a small but significant component of the biogeochemical cycling of C and Ca in soil.     

ADAMTS17 mutation associated with primary lens luxation is widespread among breeds

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3-15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL.     

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation‐volvulus: 84 dogs (2003–2007)

Objective – To test whether an initial plasma lactate≥6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation‐volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. Design – Retrospective study over a 5‐year period (2003–2007). Setting – Urban private referral small animal teaching hospital. Animals – Eighty‐four client‐owned dogs with a diagnosis of GDV and plasma lactate measurements. Interventions – None. Measurements and Main Results – There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate≥6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by≥50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by≥50% from the initial blood lactate. Conclusion – The results of this study indicate that an initial presenting plasma lactate concentration≥6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations≥50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome.