Uncovering the Neoproterozoic carbon cycle.

Interpretations of major climatic and biological events in Earth history are, in large part, derived from the stable carbon isotope records of carbonate rocks and sedimentary organic matter. Neoproterozoic carbonate records contain unusual and large negative isotopic anomalies within long periods (10-100 million years) characterized by δ(13)C in carbonate (δ(13)C(carb)) enriched to more than +5 per mil. Classically, δ(13)C(carb) is interpreted as a metric of the relative fraction of carbon buried as organic matter in marine sediments, which can be linked to oxygen accumulation through the stoichiometry of primary production. If a change in the isotopic composition of marine dissolved inorganic carbon is responsible for these excursions, it is expected that records of δ(13)C(carb) and δ(13)C in organic carbon (δ(13)C(org)) will covary, offset by the fractionation imparted by primary production. The documentation of several Neoproterozoic δ(13)C(carb) excursions that are decoupled from δ(13)C(org), however, indicates that other mechanisms may account for these excursions. Here we present δ(13)C data from Mongolia, northwest Canada and Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon isotope anomalies, and use these data in a new quantitative mixing model to examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate and organic carbon isotope data from Mongolia and Canada are tightly coupled through multiple δ(13)C(carb) excursions, quantitatively ruling out previously suggested alternative explanations, such as diagenesis or the presence and terminal oxidation of a large marine dissolved organic carbon reservoir. Our data from Namibia, which do not record isotopic covariance, can be explained by simple mixing with a detrital flux of organic matter. We thus interpret δ(13)C(carb) anomalies as recording a primary perturbation to the surface carbon cycle. This interpretation requires the revisiting of models linking drastic isotope excursions to deep ocean oxygenation and the opening of environments capable of supporting animals.

Did the breakout of laurentia turn gondwanaland inside-out?

Comparative geology suggests that the continents adjacent to northern, western, southern, and eastern Laurentia in the Late Proterozoic were Siberia, Australia-Antarctica, southern Africa, and Amazonia-Baltica, respectively. Late Proterozoic fragmentation of the supercontinent centered on Laurentia would then have been followed by rapid fan-like collapse of the (present) southern continents and eventual consolidation of East and West Gondwanaland. In this scenario, a pole of rotation near the Weddell Sea would explain the observed dominance of wrench tectonics in (present) east-west trending Pan-African mobile belts and subduction-accretion tectonics in north-south trending belts. In the process of fragmentation, rifts originating in the interior of the Late Proterozoic supercontinent became the external margins of Paleozoic Gondwanaland; exterior margins of the Late Proterozoic supercontinent became landlocked within the interior of Gondwanaland.

Cryoconite pans on Snowball Earth: supraglacial oases for Cryogenian eukaryotes?

Geochemical, paleomagnetic, and geochronological data increasingly support the Snowball Earth hypothesis for Cryogenian glaciations. Yet, the fossil record reveals no clear-cut evolutionary bottleneck. Climate models and the modern cryobiosphere offer insights on this paradox. Recent modeling implies that Snowball continents never lacked ice-free areas. Wind-blown dust from these areas plus volcanic ash were trapped by snow on ice sheets and sea ice. At a Snowball onset, sea ice was too thin to flow and ablative ice was too cold for dust retention. After a few millenia, sea ice reached 100 s of meters in thickness and began to flow as a 'sea glacier' toward an equatorial ablation zone. At first, dust advected to the ablative surface was recycled by winds, but as the surface warmed with rising CO2 , dust aka cryoconite began to accumulate. As a sea glacier has no terminus, cryoconite saturated the surface. It absorbed solar radiation, supported cyanobacterial growth, and sank to an equilibrium depth forming holes and decameter-scale pans of meltwater. As meltwater production rose, drainages developed, connecting pans to moulins, where meltwater was flushed into the subglacial ocean. Flushing cleansed the surface, creating a stabilizing feedback. If the dust flux rose, cryoconite was removed; if the dust flux waned, cryoconite accumulated. In addition to cyanobacteria, modern cryoconite holes are inhabited by green algae, fungi, protists, and certain metazoans. On Snowball Earth, cryoconite pans provided stable interconnected habitats for eukaryotes tolerant of fresh to brackish cold water on an ablation surface 60 million km2 in area. Flushing and burial of organic matter was a potential source of atmospheric oxygen. Dominance of green algae among Ediacaran eukaryotic primary producers is a possible legacy of Cryogenian cryoconite pans, but a schizohaline ocean-supraglacial freshwater and subglacial brine-may have exerted selective stress on early metazoans, or impeded their evolution.

Carbocyclic nucleosides as inhibitors of human tumor necrosis factor-alpha production: effects of the stereoisomers of (3-hydroxycyclopentyl)adenines.

A series of four structurally related carbocyclic nucleosides (6a, 6b, 10a, and 10b) were synthesized and evaluated for their ability to inhibit tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) production from human primary macrophages. These compounds had little effect on the production of IL-1 beta and IL-6. It was determined that compound 10a was the most potent inhibitor of TNF-alpha production (IC50 = 10 microM), having 2-5-fold more activity compared to its enantiomer 10b or its diastereomers 6a and 6b. In addition, these compounds were also tested for their ability to protect mice against lethal challenges of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Compound 10a showed superior protective effects (100% protection) compared to its enantiomer 10b or its diastereomers 6a and 6b when it was administered to mice which were challenged with 3 times the LD100 dose of LPS.

Orally active cephalosporins and penicillins.

A number of orally active cephalosporins and penicillins with interesting biological activity were synthesized. Two of these, 7-[[[3,4-(methylenedioxy)phenyl]glycyl]amino]deacetoxycephalosporanic acid and 7-[[2-(2,3-dihydro-5-benzofuranyl)glycyl]amino]deacetoxycephalosporanic acid were considerably more active than cephalexin both in vitro and in vivo against staphylococcal and streptococcal infections.

A sensitive bioassay for teicoplanin in serum in the presence or absence of other antibiotics.

A teicoplanin bioassay has been developed that is accurate, sensitive, and reliable. A linear relationship is obtained between the diameter of the zone of inhibition and log10 teicoplanin concentration in human serum over the range of 0.15 or 1.25 to 96 micrograms/ml using wells or paper filter disks, respectively. The assay medium devised consists of 50 g BBL Mueller-Hinton II Agar, 30 g NaCl, 8 g CaCl2, and 1.0 g citric acid (monohydrate) per liter of deionized water (resulting pH 5.1 +/- 0.1) and the assay organism Bacillus subtilis ATCC 6633. This system allows the assay of teicoplanin in the presence of commonly used aminoglycosides and in the presence of beta-lactams after inactivation by beta-lactamase. Additionally, it has the potential to be used in the presence of rifampin by using a rifampin-resistant strain of B. subtilis.

In vitro and in vivo evaluation of MDL 19,592, an oral cephalosporin.

MDL 19,592 is a new semisynthetic cephalosporin with a good therapeutic potential against Gram-positive bacterial infections when administered orally or parenterally. In the oral treatment of benzylpenicillin-resistant Staphylococcus aureus infections in mice, MDL 19,592 was superior to cephalexin, cephradine, cefaclor, cefadroxil and cefroxadine. These in vivo results reflect the in vitro superiority expressed by MDL 19,592 over the other oral cephalosporins against staphylococci. Additionally, MDL 19,592 orally was superior to cefazolin and cephalothin administered subcutaneously and to a number of penicillinase-resistant penicillins given orally or subcutaneously in the treatment of S. aureus mouse infections. MDL 19,592 killed S. aureus cells at the same or faster rate than did cephalexin or cephradine. As compared to cephalexin, MDL 19,592 was marginally superior in vitro against Streptococcus pyogenes and Streptococcus pneumoniae. In vivo, MDL 19,592 was significantly the more effective of the two against S. pyogenes and marginally more effective against S. pneumoniae. Against Gram-negative organisms, with the exception of Haemophilus influenzae, cephalexin was the more potent of the two antibiotics both in vitro and in vivo. Administered orally to mice, MDL 19,592 was absorbed as rapidly as cephalexin with both drugs attaining similar concentrations in the blood. MDL 19,592, like cephalexin, was minimally bound by mouse serum.

beta-lactam antibiotics derived from nitrogen heterocyclic acetic acids. 2. Cephalosporin derivatives.

Three cephalosporin derivatives were prepared from 1,4-dihydro-4-oxypyridine-1-acetic acid. These were the 7-aminocephalosporanic acid (7-ACA) derivative and the compounds with 5-methyl-1,3,4-thiadiazol-2-thiol and 1-methyl-1,2,3,4-tetrazole-5-thiol at C-3 of the cephalosporin nucleus. The antibacterial activity of the 7-ACA derivative was comparable to cephalothin, and that of the other two derivatives was comparable to cefazolin. The 7-ACA derivative, compared to cephalothin, was significantly less metabolized, was less protein bound, and had a longer half life.

A sick child day care unit in a military hospital.

Sick child day care units have been developed to provide care for children who are excluded from day care because of illness. We implemented a sick child day care unit at a military hospital. In the first year of operation, 526 children were admitted to the unit, with a daily average of 1.9 children and a range of 0-9 children. The most common admission diagnoses were: otitis media (21.3%), upper respiratory infection (19.4%), gastroenteritis (10.6%), and viral syndrome (10.5%). A sick child day care unit in a military hospital can provide a useful service to dependent children, their parents, and the military.

Ambulatory care teams: the dehassling of Air Force medicine.

Lack of complete outpatient medical records is a chronic problem. Most facilities are only able to find 60% to 70% of records for appointments. Many records have incomplete laboratory and x-ray information. A program utilizing Ambulatory Care Teams (ACTS) was tested at the Air Force hospital at Carswell AFB. Records were pulled 48 hours prior to appointments, and the day prior to the appointment clinics endeavored to locate 100% of the records and reports. During a 1-year test period the staff at Carswell was able to produce or account for 98.2% of all medical records for more than 102,000 scheduled appointments.

Suicidal ingestion of isoniazid: an uncommon cause of metabolic acidosis and seizures.

Despite the widespread use of isoniazid, suicidal ingestion is rare. Two patients are presented who ingested 5 gm and 12 gm respectively, both having seizures within two hours and severe metabolic adisosis. They were treated successfully with intravenous administration of diazepam and bicarbonate, and forced diuresis. Both patients showed a mild rise in levels of serum glutamic oxaloacetic transaminase and lactic acid dehydrogenase. Physicians should be alerted to the possibility of isoniazid ingestion in patients with an unexplained severe metabolic acidosis and seizures.