HOMING BEHAVIOR OF JUVENILE NORTHERN ELEPHANT SEALS

The aim of this study was to determine if juvenile northern elephant seals, Mirounga angustirostris , translocated from their rookery would return to it quickly and reliably. During the spring and fall of 1990 and 1991 we captured 75 seals at Año Nuevo State Reserve, CA, U. S. A. and translocated them to release sites up to 100 km away. Eighty-eight percent of the seals returned to the capture site within 4.7 ± 4.3 d. Homing rate increased with age, but even the youngest seals (8–10 mo) homed at a 73% rate. Homing rate did not vary significantly with sex, season, or year. Data from diving instruments suggested that the seals often followed direct routes home, arrived on the rookery significantly more often at night than during the day, and when released together, returned separately. Mean homing speed of 18 seals with complete diving records was 39 km/d (range 3–70 km/d). Instruments on seals had no detectable effect on homing rate or homing speed. The translocation paradigm provides a powerful tool for conducting intensive shortterm studies on free-ranging seals.     

Structural Effects of Methionine Oxidation on Isolated Subdomains of Human Fibrin D and αC Regions

Oxidation of key methionine residues on fibrin leads to altered fibrin polymerization producing severely altered fibrin gel structure and function. This is important because fibrinogen and its modification by oxidative stress have been implicated as key contributors to both pathological thrombotic and hemorrhagic diseases ranging from cardiovascular thrombosis to the acute coagulopathy of trauma. However, how oxidation leads to altered fibrin polymerization remains poorly understood at the molecular level. We have applied a powerful and novel well-tempered ensemble parallel tempering (PT-WTE) technique along with conventional molecular dynamics (MD) simulation to investigate the molecular-level consequences of selective methionine oxidation of fibrinogen. We offer new insights into molecular mechanisms of oxidation-induced changes in fibrin polymerization, while focusing on the D region knob ‘B’ and hole ‘b’ interaction and αC-domain interactions, both of which are hypothesized to contribute to the lateral aggregation mechanism of fibrin fibrils. Methionine oxidation did not alter the native state or the stability of a bound knob ‘B’ surrogate when interacting with hole ‘b’ in the D region. However, applying PT-WTE simulation to a human homology model of the bovine N-terminal subdomain fragment from the αC-domain revealed that methionine oxidation altered the conformation of the hairpin-linking region to favor open rather than closed hairpin structures. We attribute this alteration to the disruption of the hairpin-linking region''s conformation, with oxidation increasing the radius of gyration for this segment. This result is in agreement with experimental data demonstrating decreased fibrin protofibril lateral aggregation when methionine oxidation is present in the same αC-domain fragment. Therefore, single methionine oxidation within the αC-domain is a likely molecular mechanism.     

Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer

BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29–0.85; Cox regression, P = .01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36–0.99, P = .047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial.     

Alternative syntheses and reactivity of platinum(II) terpyridyl acetonitrile complexes

New direct syntheses of [Pt(trpy)(NCCH₃)](CF₃SO₃)₂2 (where trpy = 2,2′:6′,2′′-terpyridine) and [Pt(tBu₃-trpy)(NCCH₃)](CF₃SO₃)₂3 (where tBu₃-trpy = 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine) via the displacement of acetonitrile from [Pt(NCCH₃)₄](CF₃SO₃)₂ have been developed. The synthetic utility of 2 was investigated in reactions with triphenylphosphine (PPh₃), 2,6-dimethylphenyl isocyanide (CN-Xyl), 2,5-dimethyl-2,5-diisocyanohexane (TM4), and tert-butyl isocyanide (CN-tBu). Whereas the expected substitution products were observed for reactions with PPh₃, CN-Xyl, and CN-tBu, dealkylation of TM4 occurred to afford [Pt(trpy)(CN)](CF₃SO₃) 6. The structures of [Pt(trpy)L]²⁺ dications show little intermolecular interactions in the solid state, with the exception of the tBu₃-trpy complex 3 which exists as head-to-tail dimers with a Pt-Pt distance of 3.29 Å. The cyano product 6 was found to stack in infinite chains of cations with a Pt-Pt distance of 3.45 Å.     

Clinical comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy in treating renal calculi.

STUDY OBJECTIVE: To compare extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for efficacy in treating renal calculi. DESIGN: Non-randomised multicentre cohort study with 3 month follow up and 13 month data collection period. SETTING: Lithotripter centre in London, tertiary referral hospital, and urological clinics in several secondary and tertiary care centres. PATIENTS: 933 of 1001 patients treated by lithotripsy at the lithotripter centre were compared with 195 treated by nephrolithotomy. Missing patients were due to incomplete collection of data. Age and sex distributions and characteristics of the stones were similar in the two treatment groups. Two patients died in the lithotripsy group. Three month follow up was achieved in about 84% of both groups (783/933 for lithotripsy; 163/195 for nephrolithotomy). INTERVENTIONS: The nephrolithotomy group had surgical nephrolithotomy alone. In the lithotripsy group 83% (774/933) had lithotripsy alone, 11% (103/933) had combined lithotripsy and nephrolithotomy, and 6% (56/933) had lithotripsy plus ureteroscopy. Single and combined lithotripter treatments were analysed as one group and compared with nephrolithotomy. END POINT: Presence of stones three months after treatment. MEASUREMENTS AND MAIN RESULTS: Presence of residual stones was assessed by plain radiography, ultrasonography, or intravenous urography. After adjustment for age and size and position of stone for patients with single stones the likelihood of being free of stones three months after treatment was significantly greater in the nephrolithotomy group than the lithotripsy group (odds ratio 6.6; 95% confidence interval 3.0 to 14.6) and the response was particularly pronounced with staghorn calculi (62% (8/13) v 15% (141/96) patients free of stones after nephrolithotomy and lithotripsy, respectively). OTHER FINDINGS: 19%(146/775) of patients who had had lithotripsy had to be readmitted within three months after treatment compared with 14%(23/162) who had nephrolithotomy; and 64%(94/146) of readmissions after lithotripsy were for complications compared with 30%(7/23) of readmissions after nephrolithotomy. CONCLUSIONS: Nephrolithotomy may be preferable to lithotripsy for treating renal stones and it may not be wise to invest heavily in lithotripsy facilities.     

Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

Background  

Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties.     

COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.