Preserved anatomical bypasses predict variance in language functions after stroke.

The severity of post-stroke aphasia is related to damage to white matter connections. However, neural signaling can route not only through direct connections, but also along multi-step network paths. When brain networks are damaged by stroke, paths can bypass around the damage to restore communication. The shortest network paths between regions could be the most efficient routes for mediating bypasses. We examined how shortest-path bypasses after left hemisphere strokes were related to language performance. Regions within and outside of the canonical language network could be important in aphasia recovery. Therefore, we innovated methods to measure the influence of bypasses in the whole brain. Distinguishing bypasses from all residual shortest paths is difficult without pre-stroke imaging. We identified bypasses by finding shortest paths in subjects with stroke that were longer than the most reliably observed connections in age-matched control networks. We tested whether features of those bypasses predicted scores in four orthogonal dimensions of language performance derived from a principal components analysis of a battery of language tasks. The features were the length of each bypass in steps, and how many bypasses overlapped on each individual direct connection. We related these bypass features to language factors using support vector regression, a technique that extracts robust relationships in high-dimensional data analysis. The support vector regression parameters were tuned using grid-search cross-validation. We discovered that the length of bypasses reliably predicted variance in lexical production (R2 = .576) and auditory comprehension scores (R2 = .164). Bypass overlaps reliably predicted variance in Lexical Production scores (R2 = .247). The predictive elongation features revealed that bypass efficiency along the dorsal stream and ventral stream were most related to Lexical Production and Auditory Comprehension, respectively. Among the predictive bypass overlaps, increased bypass routing through the right hemisphere putamen was negatively related to lexical production ability.

Properties of spores of Bacillus subtilis with or without a transposon that decreases spore germination and increases spore wet heat resistance.

AIMS: This work aimed to determine how genes on transposon Tn1546 slow Bacillus subtilis spore germination and increase wet heat resistance, and to clarify the transposon's 3 gene spoVA operon's role in spore properties, since the seven wild-type SpoVA proteins form a channel transporting Ca2+ -dipicolinic acid (DPA) in spore formation and germination. METHODS AND RESULTS: Deletion of the wild-type spoVA operon from a strain with Tn1546 gave spores with slightly reduced wet heat resistance but some large decreases in germination rate. Spore water content and CaDPA analyses found no significant differences in contents of either component in spores with different Tn1546 components or lacking the wild-type spoVA operon. CONCLUSIONS: This work indicates that the SpoVA channel encoded by Tn1546 functions like the wild-type SpoVA channel in CaDPA uptake into developing spores, but not as well in germination. The essentially identical CaDPA and water contents of spores with and without Tn1546 indicate that low core water content does not cause elevated wet heat resistance of spores with Tn1546. SIGNIFICANCE AND IMPACT OF THE STUDY: Since wet heat resistance of spores of Bacillus species poses problems in the food industry, understanding mechanisms of spores' wet heat resistance is of significant applied interest.

Dodecylamine rapidly kills of spores of multiple Firmicute species: properties of the killed spores and the mechanism of the killing.

AIMS: Previous work showed that Bacillus subtilis dormant spore killing and germination by dodecylamine take place by different mechanisms. This new work aimed to optimize killing of B. subtilis and other Firmicutes spores and to determine the mechanism of the killing. METHODS AND RESULTS: Spores of seven Firmicute species were killed rapidly by dodecylamine under optimal conditions and more slowly by decylamine or tetradecylamine. The killed spores were not recovered by additions to recovery media, and some of the killed spores subsequently germinated, all indicating that dodecylamine-killed spores truly are dead. Spores of two species treated with dodecylamine were more sensitive to killing by a subsequent heat treatment, and spore killing of at least one species was faster with chemically decoated spores. The cores of dodecylamine-killed spores were stained by the nucleic acid stain propidium iodide, and dodecylamine-killed wild-type and germination-deficient spores released their stores of phosphate-containing small molecules. CONCLUSIONS: This work indicates that dodecylamine is likely a universal sporicide for Firmicute species, and it kills spores by damaging their inner membrane, with attendant loss of this membrane as a permeability barrier. SIGNIFICANCE AND IMPACT OF THE STUDY: There is a significant need for agents that can effectively kill spores of a number of Firmicute species, especially in wide area decontamination. Dodecylamine appears to be a universal sporicide with a novel mechanism of action, and this or some comparable molecule could be useful in wide area spore decontamination.

Introduced and Native Parasitoid Wasps Associated With Larch Casebearer (Lepidoptera: Coleophoridae) in Western Larch.

The larch casebearer [Coleophora laricella (Hubner)], a non-native insect, continues to impact western larch (Larix occidentalis Nutt.) through defoliation events in the Pacific Northwest. Biological control programs starting in the 1960s released seven species of parasitoid wasps to control C. laricella outbreaks. However, information about current population dynamics of C. laricella and associated parasitoids remains lacking. Therefore, the goal of this study was to document the presence, current distributions, densities, and parasitism rates of introduced and native parasitoid wasps occurring on C. laricella throughout the Northwestern U.S. range of L. occidentalis. We sampled L. occidentalis trees at multiple sites in Oregon, Washington, Idaho, and Montana. C. laricella was present at all sites with average state densities ranging from 6.2 to 13.1 moths/100 buds. We recovered two introduced hymenopteran biological control agents; Agathis pumila (Ratzeburg: Braconidae) at 79% of the sites, and Chrysocharis laricinellae (Ratzeburg: Eulophidae) at 63% of the sites. Fourteen species of native parasitic wasps were also recovered. The most common species were: Bracon sp., Spilochalcis albifrons, and Mesopolobus sp. The average native species parasitism rate across the four states was 9.0%, which was higher than the introduced species Ch. laricinellae (2.9%), but not as high as A. pumila (19.3%). While survey results suggest that native species may be more important for the control of C. laricella than previously thought, A. pumila remains the major source of regional control. However, further research is needed to better understand how introduced and native parasitoids interact to control invasive pest populations.

Variability in blood oxygen level dependent (BOLD) signal in patients with stroke-induced and primary progressive aphasia.

Although fMRI is increasingly used to assess language-related brain activation in patients with aphasia, few studies have examined the hemodynamic response function (HRF) in perilesional, and contralesional areas of the brain. In addition, the relationship between HRF abnormalities and other variables such as lesion size and severity of aphasia has not been explored. The objective of this study was to investigate changes in HRF signal during language-related neural activation in patients with stroke-induced aphasia (SA). We also examined the status of the HRF in patients with aphasia due to nonvascular etiology, namely, primary progressive aphasia (PPA). Five right handed SA patients, three PPA patients, and five healthy individuals participated in the study. Structural damage was quantified with T1-weighted MR images. Functional MR imaging was performed with long trial event-related design and an overt naming task to measure BOLD signal time to peak (TTP) and percent signal change (ΔS). In SA patients, the average HRF TTP was significantly delayed in the left hemisphere regions involved in naming compared to healthy participants and PPA patients. However, ΔS was not different in SA patients compared to the other two groups. Delay in HRF TTP in the left hemisphere naming network of SA patients was correlated with lesion size and showed a negative correlation with global language function. There were no significant differences in the HRF TTP and ΔS in the right hemisphere homologues of the naming network or in the left and the right occipital control regions across the three groups. In PPA patients, HRF had a normal pattern. Our results indicate that abnormal task-related HRF is primarily found in the left hemisphere language network of SA patients and raise the possibility that abnormal physiology superimposed on structural damage may contribute to the clinical deficit. Follow-up investigations in a larger sample of age-matched healthy individuals, SA, and PPA patients will be needed to further confirm and extend our findings.

Examining the value of lexical retrieval treatment in primary progressive aphasia: two positive cases.

Individuals with primary progressive aphasia (PPA) suffer a gradual decline in communication ability as a result of neurodegenerative disease. Language treatment shows promise as a means of addressing these difficulties but much remains to be learned with regard to the potential value of treatment across variants and stages of the disorder. We present two cases, one with semantic variant of PPA and the other with logopenic PPA, each of whom underwent treatment that was unique in its focus on training self-cueing strategies to engage residual language skills. Despite differing language profiles and levels of aphasia severity, each individual benefited from treatment and showed maintenance of gains as well as generalization to untrained lexical items. These cases highlight the potential for treatment to capitalize on spared cognitive and neural systems in individuals with PPA, improving current language function as well as potentially preserving targeted skills in the face of disease progression.

An exploration of the accuracy of an invasive method for measuring the volume of specimens of Amoeba proteus.

A method is described for measuring the volume of individual specimens of Amoeba proteus which utilizes an easily constructed compressor to flatten the specimen to a known thickness. The microscopic image of the flattened specimen is captured on tape, digitized and analysed with the NIH Image software. The results from one specimen are given to illustrate the sources and magnitude of errors affecting these volume measurements.

Microtubule bending and breaking in living fibroblast cells.

Microtubules in living cells frequently bend and occasionally break, suggesting that relatively strong forces act on them. Bending implies an increase in microtubule lattice energy, which could in turn affect the kinetics and thermodynamics of microtubule-associated processes such as breaking. Here we show that the rate of microtubule breaking in fibroblast cells increases approximately 40-fold as the elastic energy stored in curved microtubules increases to > approximately 1 kT/tubulin dimer. In addition, the length-normalized breaking rate is sufficiently large (2.3 breaks x mm(-1) x minute(-1)) to infer that breaking is likely a major mechanism by which noncentrosomal microtubules are generated. Together the results suggest a physiologically important, microtubule-based mechanism for mechanochemical information processing in the cell.

Mechanisms of the selective cytotoxic actions of certain essential fatty acids.

Polyunsaturated fatty acids (PUFA) have a selective cytotoxic/cytostatic effect on a number of tumor cell lines in culture. Although this process may be enhanced by the addition of iron there is a minimum level of PUFA necessary for potentiation of cell death. Vitamin E blocks PUFA cytotoxicity when added up to 5 days after fatty acid administration. Levels of thio-barbiturate reactive material (TBARM) in the medium rise in parallel with cell death. However, they are not affected by small alterations in temperature or oxygen tension. Incubating cells with PUFA causes marked alterations in the fatty acid patterns of both neutral and phospholipid fractions. Membrane fluidity is increased and the activity of membrane-bound receptors may be influenced directly or through the actions of eicosanoids derived from the exogenous fatty acid. PUFA may be an effective way of influencing tumor growth and a safe approach for the management of human cancer.

Distribution of plasma phosphatidylcholine molecular species in rabbits fed fish oil is modulated by dietary n-6 fatty acids.

The present study examined the distribution of plasma phosphatidylcholine (PC) molecular species in rabbits fed a chow diet supplemented with fish oil (FO) in combination with either hydrogenated coconut oil or the n-6 fatty acid-rich evening primrose oil (EPO) for 4 weeks. Significant proportions of plasma PC molecular species contained long-chain n-3 fatty acids. Addition of EPO to the FO supplemented diet increased the incorporation of n-6 fatty acids into plasma PC molecules; it also raised the proportions of 16:0-18:2, n-6, 18:1-18:2, n-6, 18:2, n-6-18:2, n-6, and 16:0-20:4, n-6. The increase of n-6 fatty acid-containing PC was at the expense of n-3 fatty acid containing PC species. However, feeding n-6 fatty acids did not affect the distribution of PC molecular species based on total carbon chain length. The most interesting observation was that dietary suplementation with EPO, raised the ratio of 22:6, n-3-containing to 20:5, n-3-containing molecular species, suggesting an enhanced conversion of 20:5, n-3 to 22:6, n-3.

Hospitalizing the suicidal adolescent: an empirical investigation of decision-making criteria.

OBJECTIVE: The primary purpose of this research is to investigate the criteria used by child and adolescent clinicians in determining the appropriateness of hospitalization for suicidal adolescents. METHOD: A questionnaire containing 64 vignettes describing adolescent suicide attempters was completed by a sample of 36 child and adolescent clinicians. Six variables known to relate to lethality of attempt were systematically varied within the vignettes: gender, depression, conduct disorder/substance abuse, previous attempts, suicidal relative, and family supports. Respondents were asked to judge the appropriateness of hospitalization for each vignette. RESULTS: Hospitalization preference was found to be inversely related to professional experience and was significantly predicted by all risk factors except gender. Configural cue utilization added substantially to the efficacy of a linear model in predicting preference to hospitalize. CONCLUSIONS: Experienced clinicians use known risk factors for adolescent suicide in making recommendations to hospitalize, but results also suggest ongoing needs for education and training in adolescent suicidality.

Differences in the metabolism of 18:2n-6 and 18:3n-6 by the liver and kidney may explain the anti-hypertensive effect of 18:3n-6.

The present study examined the in vitro and in vivo metabolism of 18:2n-6 and 18:3n-6 by kidney and liver in the male adult spontaneously hypertensive (SHR) and normotensive (WKY) rats. In liver and kidney slices incubated for 1 h with either [1-14C]18:2n-6 or [1-14C]18:3n-6 (60 microM), substantial amounts of radioactivity were incorporated into triacylglycerol and phospholipid fractions. Approximately 15% of the radiolabeled 18:2n-6 was converted into 18:3n-6 in liver slices but no conversion was found in kidney slices. When incubated with radiolabeled 18:3n-6, over 40% of the radioactivity was metabolized mainly to 20:4n-6 in liver slices, but evenly to 20:3n-6 and 20:4n-6 in kidney slices. There were no differences between the results from SHR and those from WKY. In WKY rats given an oral bolus of radiolabeled 18:3n-6, most of the radioactivity was recovered in the liver and significantly less in the kidney. In both tissues, the radioactivity was associated initially only with 18:3n-6 and later with its elongation product, 20:3n-6. These findings indicated that the kidney, although unable to metabolize 18:2n-6, could metabolize 18:3n-6 taken up from the circulation. The effectiveness of 18:3n-6, compared to 18:2n-6, as an anti-hypertensive agent may result from the provision of a post-delta 6-desaturation metabolite which can be directly converted to blood pressure-regulating eicosanoids in the kidney.

Topographic measures of cerebral activity during reading of text at fast- and slow-paced rates.

Eight college level readers were given short paragraphs for reading, presented on a computer terminal in units of 2 or 3 words at a time. Two conditions were presented, a fast reading session with an inter-stimulus interval (ISI) of 1.1 seconds, and a slower session with an ISI of 1.2 seconds. EEG and ERP measures were obtained. ERP findings revealed a late central-posterior negativity which was sensitive to the effect of varying ISI by showing shorter latencies, of about 110 msec, to the smaller interval. An earlier component complex consisting of a bi-temporal-occipital negativity and frontal positivity was observed between 155 and 175 msec. This component was not observed to be sensitive to variation of ISI. Analysis of the unaveraged EEG activity by FFT and absolute power measures revealed that the activity was primarily slow wave (0-7.5 HZ), and right-sided. Findings suggested that the brain functions as an integrated whole during reading, activating a diffuse set of neural generators.

Studies on the ejection properties of asters: astral microtubule turnover influences the oscillatory behavior and positioning of mono-oriented chromosomes.

The position of a mono-oriented chromosome changes as it oscillates to and from the pole to which it is attached. Such oscillatory behavior reveals that the net force on a mono-oriented chromosome is constantly changing. Fluctuations may occur in both the polewardly directed force acting at the kinetochore and the opposing outwardly directed force associated with the aster. We have examined the ejection properties of the aster--as well as the oscillatory behavior and positioning of mono-oriented chromosomes--in relation to astral microtubule turnover. We treated cells containing monopolar spindles with drugs that affect microtubule turnover, either by promoting the depletion of dynamically unstable astral microtubules (nocodazole and colcemid) or by augmenting their numbers and stability (taxol). Both types of drugs stopped the oscillatory behavior of mono-oriented chromosomes within seconds. The final position of the chromosomes depended on how microtubule turnover was affected. In the case of nocodazole and colcemid, non-kinetochore astral microtubules were depleted first and the kinetochore-to-pole distance shortened. In these cells chromosome fragments generated by laser microsurgery were no longer expelled from the center of the aster. By contrast, with taxol the number of non-kinetochore microtubules increased and the astral ejection force became stronger as shown by the finding that the chromosomes moved away from the pole to the periphery of the monaster. Moreover, arms severed from chromosomes at the periphery of the taxol monaster failed to move further away from the aster's center. From these observations we conclude that the oscillatory movements and changing position of a mono-oriented chromosome relative to the pole are mediated by changes in the number of astral microtubules. The dynamic instability of astral microtubules that leads to a rapid turnover may contribute to the astral ejection force by allowing the continual growth of microtubules out from the aster. Growing astral microtubules may exert a pushing force that their rigidity maintains until their depolymerization.

Lysine cataboism and α-aminoadipate synthesis in Streptomyces clavuligerus.

The intracellular α-aminoadipic acid pool in Streptomyces glavuligerus mycelium growing in a starch-peptone medium decreased during the late exponential and stationary phases when cephamycin was being produced; however, the amino acid accumulated extracellularly. Although the specific activity of lysine ɛ-aminotransferase (LAT) decreased during this period, there was no indication that the extracellular α-aminoadipic acid functioned as a precursor reserve for synthesis of the ß-lactam antibiotic. Measurement of LAT activity in cultures grown in defined media with starch and various nitrogen sources indicated that the enzyme was synthesized preferentially only during early growth. In its insensitivity to induction by a precursor, and in its susceptibility to carbon catabolite repression, LAT behaved as a secondary metabolic pathway enzyme. Unexpectedly, however, the enzyme increased in specific activity when cultures were supplemented with excess phosphate. Unlike LAT, cadeverine aminotransferase was inducible by lysine or cadaverine and insensitive to phosphate; its features were consistent with a role in the catabolism of lysine by S. clavuligerus.

Effects of linoleic and gamma-linolenic acids (efamol evening primrose oil) on fatty acid-binding proteins of rat liver.

We have studied the effects of Efamol evening primrose oil (EPO) on fatty acid-binding proteins (L-FABP) of rat liver. EPO contains 72% cis-linoleic acid and 9% cis-gamma linolenic acid. EPO has been clinically used for treatment of a number of diseases in humans and animals. EPO is also known to lower cholesterol level in humans and animals. Feeding of an EPO supplemented diet to rats (n = 9) for 2 months decreases the oleate binding capacity of purified L-FABP of rat liver whereas the palmitate binding activity was increased by 38%. However, EPO feeding did not alter the L-FABP concentrations significantly as measured by using the fluorescence fatty acid probe, dansylamino undecanoic acid. Endogenous fatty acid analysis of L-FABPs revealed significant qualitative and quantitative changes in fatty acid pattern after EPO feeding. EPO feeding decreased the endogenous palmitate level by 53% and oleate level by 64% in L-FABPs and also EPO feeding decreased the total endogenous fatty acid content from 62 nanomole per mg of protein to 42 nanomole per mg of L-FABP (n = 3).

Measurement of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase activity in Streptomyces clavuligerus by high-performance liquid chromatography after precolumn derivatization with o-phthaldialdehyde.

A procedure for rapid, sensitive measurement of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) in complex cell extracts has been developed by adapting a widely used method for high-performance liquid chromatography analysis of amino acids. Samples were oxidized with performic acid and derivatized with o-phthaldialdehyde-mercaptoethanol to give the fluorescent isoindole derivative of the peptide sulfonate. The procedure was used to assay Streptomyces clavuligerus cell extracts and partially purified fractions for ACV synthetase activity and to determine some characteristics of the enzyme reaction. The presence of a second enzyme with cysteine as a substrate was also indicated.