The potential for carbon dioxide removal by enhanced rock weathering in the tropics: An evaluation of Costa Rica.

Tropical environments show great potential to sequester CO2 by enhanced rock weathering (ERW) of powdered mafic rocks applied to agricultural fields. This study seeks to assess carbon dioxide reduction (CDR) potential in the humid tropics (1) by experimental weathering of mafic rock powders in conditions simulating humid tropical soils, and (2) from weathering rates determined from a Holocene tropical soil chronosequence where parent material is andesitic sediments. Experimentally determined weathering rates by leaching of basaltic andesites from Costa Rica (Arenal and Barva) for 50 t ha-1 applications indicate potential sequestration of 2.4 to 4.5 t CO2 ha-1 yr-1, whereas the USGS basalt standard BHVO-1 yields a rate of 11.9 t ha-1 yr-1 (influenced by more mafic composition and finer particle size). The chronosequence indicates a rate of 1.7 t CO2 ha-1 yr-1. The weathering experiment consisted of 0.6 mm of powdered rock applied atop 12 mm of Ultisol at 35 °C. To simulate a tropical soil solution, 100-mL aliquots of a dilute solution of oxalic acid in carbonated DI water were rained onto soils over a 14-day period to simulate soil moisture in the humid tropics. Solutions were collected and analyzed by ICPMS for concentrations of leached cations. A potential ERW scenario for Costa Rica was assessed assuming that one-half of lowland agricultural kaolinitic soils (mainly Ultisols, common crop and pasture soils, excluding protected areas) were to receive 50 t ha-1 of annual or biennial applications of powdered mafic rock. With an experimentally determined humid tropical CDR rate for basaltic andesite (3.5 t ha-1 yr-1) and allowances for carbon costs (e.g. emissions from processing and delivery) that reduce CDR to a net 3.2 t ha-1 yr-1, potential annual CDR of this tropical nation is ∼2-4 million tons, amounting to ∼25-50 % of annual CO2 emissions (mainly from transportation in Costa Rica).

Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart disease.

RATIONALE: Cardiomyocytes cultured in a mechanically active 3-dimensional configuration can be used for studies that correlate contractile performance to cellular physiology. Current engineered cardiac tissue (ECT) models use cells derived from either rat or chick hearts. Development of a murine ECT would provide access to many existing models of cardiac disease and open the possibility of performing targeted genetic manipulation with the ability to directly assess contractile and molecular variables. OBJECTIVE: To generate, characterize, and validate mouse ECT with a physiologically relevant model of hypertrophic cardiomyopathy. METHODS AND RESULTS: We generated mechanically integrated ECT using isolated neonatal mouse cardiac cells derived from both wild-type and myosin-binding protein C (cMyBP-C)-null mouse hearts. The murine ECTs produced consistent contractile forces that followed the Frank-Starling law and accepted physiological pacing. cMyBP-C-null ECTs showed characteristic acceleration of contraction kinetics. Adenovirus-mediated expression of human cMyBP-C in murine cMyBP-C-null ECT restored contractile properties to levels indistinguishable from those of wild-type ECT. Importantly, the cardiomyocytes used to construct the cMyBP-C(-/-) ECT had yet to undergo the significant hypertrophic remodeling that occurs in vivo. Thus, this murine ECT model reveals a contractile phenotype that is specific to the genetic mutation rather than to secondary remodeling events. CONCLUSIONS: Data presented here show mouse ECT to be an efficient and cost-effective platform to study the primary effects of genetic manipulation on cardiac contractile function. This model provides a previously unavailable tool to study specific sarcomeric protein mutations in an intact mammalian muscle system.

Mutations in the murine homologue of the Menkes gene in dappled and blotchy mice.

The murine homologue of the Menkes disease gene (MNK) was isolated from cDNA libraries, using human cDNA clones as probes, and by PCR. The predicted amino acid sequence shows a high level of identity (89.9%) with the human protein, and the predicted functional domains in the human protein are present. Using probes to the mouse Mnk gene, we found that the mottled dappled mutation was caused by alteration in the Mnk locus and lack of expression of Mnk RNA. Tissues of the blotchy mouse contained two larger sizes of MNK mRNA demonstrating a likely defect in RNA splicing. Thus, the mottled locus is homologous to the human MNK locus and dappled and blotchy are allelic mutations in this gene.

Isolation of a partial candidate gene for Menkes disease by positional cloning.

Menkes disease is an X-linked recessive disorder of copper metabolism resulting in death in early infancy. The gene has been mapped to band Xq13 based, in part, on a translocation breakpoint in a female with the disease, which was found to lie within 300 kilobases (kb) of the PGK-1 locus, allowing the isolation of a YAC clone spanning the breakpoint. Phage subclones from the breakpoint region were isolated and used to screen cDNA libraries. cDNA clones were found which detect an 8 kb transcript from normal individuals but show diminished or absent hybridization in Menkes disease patients. Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene.

The outflow tract of the heart in fishes: anatomy, genes and evolution.

A large number of congenital heart defects associated with mortality in humans are those that affect the cardiac outflow tract, and this provides a strong imperative to understand its development during embryogenesis. While there is wide phylogenetic variation in adult vertebrate heart morphology, recent work has demonstrated evolutionary conservation in the early processes of cardiogenesis, including that of the outflow tract. This, along with the utility and high reproductive potential of fish species such as Danio rerio, Oryzias latipes etc., suggests that fishes may provide ideal comparative biological models to facilitate a better understanding of this poorly understood region of the heart. In this review, the authors present the current understanding of both phylogeny and ontogeny of the cardiac outflow tract in fishes and examine how new molecular studies are informing the phylogenetic relationships and evolutionary trajectories that have been proposed. The authors also attempt to address some of the issues of nomenclature that confuse this area of research.

The effects of technology use in feedlot production systems on feedlot performance and carcass characteristics.

The objectives of this study were to examine the effects of feedlot production systems with and without the use of a ß-adrenergic agonist compared to an all-natural production program on feedlot performance and carcass characteristics. Crossbred beef steers ( = 336; initial BW = 379 ± 8 kg) were randomized to 1 of 3 treatments in a randomized complete block design (RCBD; 14 steers/pen; 8 pens/treatment). Treatments consisted of an all-natural treatment (NAT), a conventional treatment (CONV), and a conventional treatment with a ß-agonist (CONV-Z). All treatments were fed the same basal diet with NAT cattle receiving no growth promoting technologies. The CONV and CONV-Z cattle were implanted with 40 mg of estradiol and 200 mg of trenbolone acetate (TBA) on d 0 and were fed 33 and 9 mg/kg of monensin and tylosin daily, respectively. The CONV-Z cattle were fed zilpaterol hydrochloride (ZH) at 6.76 mg/kg (90% DM basis) for the last 20 days on feed (DOF) There was no effect of treatment on DMI ( = 0.83); however, CONV-Z steers gained 3.8% faster (1.64 vs. 1.58 kg/d; < 0.01) and were 5.3% more efficient (0.160 vs. 0.152; < 0.01) than CONV steers, and CONV steers gained 32.8% faster (1.58 vs. 1.19 kg/d; < 0.01) and were 26.7% more efficient (0.152 vs. 0.120; < 0.01) than NAT steers. There was a 35.7% improvement in estimated carcass gain (1.29 vs. 0.95 kg/d; < 0.01) and a 32.6% improvement in carcass efficiency (0.126 vs. 0.095; < 0.01) for CONV-Z steers compared to NAT steers. Hot carcass weight was increased by 8 kg for CONV-Z steers compared to CONV steers (394 vs. 386 kg; = 0.05) and 46 kg compared to NAT steers (394 vs. 348 kg; < 0.01). Longissimus muscle area was increased by 3.6 cm for CONV-Z steers compared to CONV steers (92.29 vs. 88.67 cm; = 0.02) and 12.1 cm for CONV-Z steers compared to NAT steers (92.29 vs. 80.16 cm; < 0.01), resulting in a 9.6% unit increase in USDA yield grade (YG) 1 (15.14 vs. 5.52%; < 0.05) and a 21.6% unit reduction in USDA YG 3 for CONV-Z steers compared to CONV steers (30.70 vs. 52.32%; < 0.05). The CONV-Z steers had a lower marbling score compared to the other treatments (432; 0.01), resulting in an 11.7% unit increase (20.70 vs. 9.03%; < 0.05) in USDA Select carcasses compared to CONV steers. The results of this experiment show that CONV-Z and CONV production results in a significant improvement in feedlot performance and USDA YG compared to NAT.

Auditory brainstem responses in pervasive developmental disorders.

Several studies have reported prolonged neural transmission times on auditory brainstem responses (ABRs) measured in autistic children, a finding which implicates CNS dysfunction at the level of the brainstem in autistic conditions. This study measured ABRs in 25 children and adults with pervasive developmental disorders (PDDs), including autism, and 25 age- and sex-matched normal controls. Subjects were carefully evaluated audiometrically and neurologically and artifact was controlled to produce highly reliable measures. Prolonged transmission times were seen in only one PDD subject and in one normal control, while shortened transmission times were seen in four PDD subjects. The majority of PDD subjects showed normal ABRs. Previous reports of a significant incidence of prolonged transmission times among autistic and autisticlike subjects, thus, were not replicated. Possible reasons for this discrepancy are discussed.

Isolation of a human ceruloplasmin cDNA clone that includes the N-terminal leader sequence.

A number of cDNA clones encoding human ceruloplasmin were identified using two mixed oligonucleotide probes. One of these clones was shown by DNA sequence analysis to span from the complete N-terminal leader sequence to 114 amino acids short of the C-terminus. The leader sequence consists of 19 primarily hydrophobic amino acids. Northern blot analysis of RNA from human liver showed two species of ceruloplasmin mRNA; a minor species of 3600 nucleotides and a major one of 4400 nucleotides.

Expression of the Menkes gene homologue in mouse tissues lack of effect of copper on the mRNA levels.

The expression of the homologue of the Menkes disease gene (Mnk) in mice was studied using RNA blots. The highest level of expression of the 8.0 kb mRNA was found in placenta, substantial expression was noted in lung, heart, brain, testis and kidney and gut mucosa, but very low levels were found in spleen and adult liver. In fetal liver, the amount of Mnk mRNA is similar to that found in kidney, however, it declines soon after birth. Results with copper-loaded normal mice and mutant mice with genetic defects in copper transport suggested that Mnk mRNA levels are not regulated by tissue copper concentrations.

Auditory brain-stem responses in adrenomyeloneuropathy.

We studied three patients with adrenomyeloneuropathy. Complete audiologic assessment was obtained: two patients showed unimpaired peripheral hearing and one showed a mild high-frequency hearing loss. Auditory brain-stem responses were abnormal in both ears of all subjects, with one subject showing no response above wave I, and the other two having significant wave I to III and wave III to V interval prolongations. We concluded that auditory brain-stem response testing provides a simple, valid, reliable method for demonstrating neurologic abnormality in adrenomyeloneuropathy even prior to evidence of clinical signs.

Divided attention, as measured by dichotic speech performance, in dementia of the Alzheimer type.

To determine if impaired dichotic performance in patients with dementia of the Alzheimer type is due to the inability to divide attention or the inability to perceive degraded auditory stimuli, we measured performance on tasks of both dichotic and degraded monotic speech materials. We also examined whether perception of degraded speech stimuli presented monaurally is related to abnormalities of temporal lobe anatomy and physiology, as we have shown for dichotic performance. Although the patients were impaired on both dichotic and monotic tests, significantly greater impairment was seen on the dichotic test. Our earlier finding of a significant relation between dichotic performance and measures of anterior temporal lobe atrophy and reduced glucose metabolism was replicated, but no significant relation was found between monotic tests and measures to temporal lobe integrity. We conclude that the inability to divide attention, rather than abnormal processing of degraded stimuli per se, is reflected in poor dichotic performance in patients with dementia of the Alzheimer type, and that dichotic performance, unlike degraded monotic perception, depends directly on the integrity of temporal cortex in these patients.

Central auditory function in Alzheimer's disease.

The central auditory (dichotic) function of 38 patients with Alzheimer's disease was found to be significantly impaired when compared with a control group. Significant relationships were observed between dichotic scores and intelligence quotient, cortical atrophy in the temporal lobes, and cerebral glucose metabolism in the left temporal lobe. Comparing atrophy and glucose metabolism in the temporal lobes, we observed contralateral ear effects in dichotic performance as well as an interaction of asymmetry of atrophy with dichotic performance, consistent with previous models of dichotic listening in other forms of temporal lobe pathology.

beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations.

An infant, born to parents who were first cousins had multiple physical malformations. An associated biochemical abnormality was suggested by the urinary excretion of cysteine and cysteamine conjugates of methacrylic acid. The coenzyme A (CoA) ester of this compound is an intermediate in the pathway of valine oxidation. Subsequent investigation revealed a deficiency of beta-hydroxyisobutyryl-CoA deacylase, an enzyme unique to valine metabolism. The enzyme defect results in accumulation of methacrylyl-CoA, a highly reactive compound, which readily undergoes addition reactions with free sulfhydryl groups. Tissue damage due to reactions between methacrylyl-CoA and important sulfhydryl-containing enzymes and cofactors may account for the teratogenic effects seen in this patient.

Prospective, randomized study of ventilator-associated pneumonia in patients with one versus three ventilator circuit changes per week.

OBJECTIVE: To assess the effect on the rate of ventilator-associated pneumonia (VAP) of decreasing the frequency of ventilator circuit changes from three times to once per week. DESIGN: Prospective, randomized trial. SETTING: Medical intensive care unit (MICU), a 12-bed, critical-care internal medicine unit, and neurosciences intensive care unit (NICU), a 21-bed, predominantly adult neurosurgical unit, of an urban university hospital. PATIENTS: All 447 patients requiring mechanical ventilation during October 1992 through June 1993. INTERVENTION: Patients were allocated randomly on the basis of permanent medical record numbers: those with odd numbers had circuits changed three times per week, those with even numbers once per week. Intensive-care-unit surveillance was conducted in accordance with definitions and methods of the National Nosocomial Infections Surveillance System. RESULTS: In the MICU, the one-change-per-week group had a VAP rate of 7.3 per 1,000 ventilator days, versus 5.9 for the three-per-week group (P = .6). In the NICU, the one-change-per-week group had a rate of 12.2 per 1,000 ventilator days, versus 12.6 for the three-per-week group (P = .9). Considering patients in both units ventilated for no more than 7 days, the one-change-per-week group had a VAP rate of 5.9 per 1,000 ventilator days, versus 9.0 per 1,000 for the three-changes-per-week group (odds ratio [OR], 0.65; 95% confidence interval [CI95], 0.25 to 1.69). Including patients in the two units maintained on mechanical ventilation for more than 7 days, the one-change-per-week group had a VAP rate of 13.2 per 1,000 ventilator days, versus 9.6 per 1,000 for the three-changes-per-week group (OR, 1.37; CI95, 0.71 to 2.65). CONCLUSIONS: Decreasing the frequency of ventilator circuit changes from three times to once per week had no adverse effect on the overall rate of VAP. Less frequent ventilator circuit changes may decrease the incidence of VAP among patients ventilated for no more than 1 week. However, the incidence of VAP may be higher among patients with once weekly circuit changes ventilated for more than 1 week.

Alterations in auditory processing of speech stimuli during aging in healthy subjects.

Studies of auditory processing during aging in man have not provided a consensus on whether aging affects the ability to process speech stimuli. To evaluate the relationship between speech recognition tasks and age, we examined 36 male subjects between the ages of 21 and 83 years, who were screened for the absence of disease, particularly in the cardiovascular and neurologic systems. Measures were obtained on the following tests: pure tone thresholds, speech reception threshold, speech discrimination, low-pass filtered speech, and binaural fusion. A statistically significant correlation was found between pure tone thresholds and age for all frequencies. When the effect of peripheral hearing loss was taken into account, speech measures did not correlate with age, with the exception of low-pass filtered speech in the left ear. Our findings suggest that the aging process in healthy man is not necessarily accompanied by deficits in the processing of speech stimuli beyond those which are due to peripheral hearing loss.

The effect of UVB irradiation on ferritin subunit synthesis, ferritin assembly and Fe metabolism in cultured canine lens epithelial cells.

Ferritin is a multimeric protein consisting of heavy and light chains assembled in different tissue-specific ratios, which can protect cells from oxidative stress by storing reactive iron (Fe). Because the lens is constantly exposed to UV irradiation, we studied its effects on ferritin synthesis and Fe metabolism in cultured lens epithelial cells with and without ascorbic acid (Asc). UVB caused a large increase in accumulation of newly synthesized ferritin chains; this increase was additive to that induced by Asc. In contrast to the Asc-induced increase in Fe storage, Fe storage in ferritin was unaltered by UVB. Although UVB increased accumulation of newly synthesized ferritin chains, total ferritin levels were unaltered. In contrast, Asc, which induced a quantitatively similar increase in accumulation of newly synthesized ferritin chains, doubled the total amount of ferritin. Because UVB did not change Fe storage in ferritin or the size of the labile Fe pool, it was hypothesized and then determined that these newly synthesized chains did not assemble into functional holoferritin. Numerous studies detail the effects of various treatments on de novo ferritin synthesis; however, this study provides a cautionary note regarding the conclusions of such studies in the absence of data indicating assembly of functional ferritin molecules.

The effect of D-penicillamine on metallothionein mRNA levels and copper distribution in mouse hepatocytes.

Penicillamine increases the levels of metallothionein (MT) mRNA in a time and concentration dependent manner without altering either the rate of copper uptake or the amount of copper within the cell. The effect is dependent on the presence of intracellular copper, however, since depletion of copper by chelators blocks the effect, and does not alter the ability of dexamethasone to stimulate mRNA production. Penicillamine did not alter the distribution of 64Cu in the hepatocytes, as measured by fast protein liquid chromatography (FPLC), although the pattern may be affected by the amount of MT present. The data indicates that penicillamine removes copper from some intermediary ligand, thereby making it available to induce metallothionein. It is possible that this is part of the therapeutic action of the chelator in the treatment of Wilson's disease.

Clinical signs of acute ocular inflammatory response to endotoxin are not altered by increasing antioxidant potency of intraocular fluids.

Plasma antioxidant activity is due in large part to the ferroxidase activity of the copper (Cu) transport protein, ceruloplasmin. Implantation of osmotic pumps containing copper into rabbits resulted in a doubling of Cu concentration, ferroxidase activity, and antioxidant activity in plasma. Blood-ocular barriers essentially prevent the entry of large molecules such as proteins from plasma into the intraocular fluid compartments. However, during ocular inflammation, when these barriers are disrupted, plasma proteins can enter. Twenty-four hours after the induction of ocular inflammation by intraocular injection of endotoxin, the Cu concentration and antioxidant activity of intraocular fluids from the Cu pump animals was twice that of control groups, reflecting the differences in plasma levels. This is the first direct demonstration that alterations in plasma levels of ceruloplasmin can influence the antioxidant potency of the extracellular fluids. Increased intraocular fluid antioxidant activity did not affect the acute anterior segment response to endotoxin. However, it is possible that the time course and resolution of the response is altered by changes in extracellular fluid antioxidant activity. This possibility is currently under investigation.

Informed consent and neuroanatomic correlates of intentionality and voluntariness among psychiatric patients.

The authors examine the less-studied components of patients' autonomous decision making, or decisional autonomy, in the light of current research in psychiatry and neuropsychology and developments in the construct of informed consent. The three components of decisional autonomy-understanding, intentionality, and noncontrol or voluntariness-are related to clinical constructs in psychiatry and neuropsychology, in particular to executive control functions. The authors review studies that examine deficits in prefrontal cerebral function in schizophrenia, depression, and some anxiety disorders that are related to intentionality and voluntariness. Assessment of decisional autonomy should encompass evaluation of impaired intentionality and voluntariness, not simply impaired understanding. The main response to finding such impairments should be to provide treatment to ameliorate them. New strategies for psychiatric care should be developed to address the clinical challenges of an increasingly complex view of decisional autonomy.