Mixed ancestry and admixture in Kauai's feral chickens: invasion of domestic genes into ancient Red Junglefowl reservoirs.

A major goal of invasion genetics is to determine how establishment histories shape non-native organisms' genotypes and phenotypes. While domesticated species commonly escape cultivation to invade feral habitats, few studies have examined how this process shapes feral gene pools and traits. We collected genomic and phenotypic data from feral chickens (Gallus gallus) on the Hawaiian island of Kauai to (i) ascertain their origins and (ii) measure standing variation in feral genomes, morphology and behaviour. Mitochondrial phylogenies (D-loop & whole Mt genome) revealed two divergent clades within our samples. The rare clade also contains sequences from Red Junglefowl (the domestic chicken's progenitor) and ancient DNA sequences from Kauai that predate European contact. This lineage appears to have been dispersed into the east Pacific by ancient Polynesian colonists. The more prevalent MtDNA clade occurs worldwide and includes domesticated breeds developed recently in Europe that are farmed within Hawaii. We hypothesize this lineage originates from recently feralized livestock and found supporting evidence for increased G. gallus density on Kauai within the last few decades. SNPs obtained from whole-genome sequencing were consistent with historic admixture between Kauai's divergent (G. gallus) lineages. Additionally, analyses of plumage, skin colour and vocalizations revealed that Kauai birds' behaviours and morphologies overlap with those of domestic chickens and Red Junglefowl, suggesting hybrid origins. Together, our data support the hypotheses that (i) Kauai's feral G. gallus descend from recent invasion(s) of domestic chickens into an ancient Red Junglefowl reservoir and (ii) feral chickens exhibit greater phenotypic diversity than candidate source populations. These findings complicate management objectives for Pacific feral chickens, while highlighting the potential of this and other feral systems for evolutionary studies of invasions.

The Atacama Rover Astrobiology Drilling Studies (ARADS) Project.

With advances in commercial space launch capabilities and reduced costs to orbit, humans may arrive on Mars within a decade. Both to preserve any signs of past (and extant) martian life and to protect the health of human crews (and Earth's biosphere), it will be necessary to assess the risk of cross-contamination on the surface, in blown dust, and into the near-subsurface (where exploration and resource-harvesting can be reasonably anticipated). Thus, evaluating for the presence of life and biosignatures may become a critical-path Mars exploration precursor in the not-so-far future, circa 2030. This Special Collection of papers from the Atacama Rover Astrobiology Drilling Studies (ARADS) project describes many of the scientific, technological, and operational issues associated with searching for and identifying biosignatures in an extreme hyperarid region in Chile's Atacama Desert, a well-studied terrestrial Mars analog environment. This paper provides an overview of the ARADS project and discusses in context the five other papers in the ARADS Special Collection, as well as prior ARADS project results.

Homogeneity assessment of the SuperCam calibration targets onboard rover perseverance.

The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 µm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 µm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 µm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work.

Psychological stress induces sodium and fluid retention in men at high risk for hypertension.

Exposure to competitive mental tasks significantly reduced the urinary sodium and fluid excreted by young men with one or two hypertensive parents or with borderline hypertension. In this high-risk group, the degree of retention was directly related to the magnitude of heart rate increase during stress, suggesting common mediation by way of the sympathetic nervous system. Thus, psychological stress appears to induce changes in renal excretory functions that may play a critical role in long-term blood pressure regulation.

Dissolved organic matter and heterotrophic microneuston in the surface microlayers of the north atlantic.

Dissolved organic carbon, carbohydrates, and adenosine triphosphate in the size fractions 0.2 to 3 micrometers and 3 to 1000 micrometers are significantly enriched in the upper 150-micrometer surface layer compared to subsurface water, mean enrichment factors being 1.6, 2.0, 2.5, and 3.1, respectively. When calculated as a 0.1-micrometer microlayer of wet surfactants, the mean concentration of organic matter was 2.9 grams per liter, of which carbohydrates accounted for 28 percent. The data for plant pigments and particulate adenosine triphosphate indicated that bacterioneuston was enriched at seven of nine stations while phagotrophic protists were enriched at five stations. Instances of enrichment and inhibition were verified by cultural data for bacteria and amoebas. The observations indicate that the surface microlayers are largely heterotrophic microcosms, which can be as rich as laboratory cultures, and that an appreciable part of the dissolved organic carbon is carbohydrate of phytoplankton origin, released and brought to the surface by migrating and excreting phagotrophic protists.

Purification of a human liver cytochrome P-450 immunochemically related to several cytochromes P-450 purified from untreated rats.

Among characterized forms of liver microsomal cytochromes P-450 in rats are four related isozymes (P-450f-i) notable for their lack of inducibility. Immunoblot analyses demonstrated that human livers microsomes contained several proteins related to these rat P-450s. A human liver P-450, termed HLx, was purified and found by immunochemical assays to resemble rat P-450g. Analysis of the NH2-terminal amino acid sequence of HLx indicates that it is related to rat P-450s f-i and human liver P-450MP. A monoclonal antibody was used to measure the amounts of HLx in 21 human liver specimens. No correlation between the levels of HLx protein in these specimens and the patients' environmental histories was observed. However, statistical analysis of the data suggests that the distribution of HLx is at least bimodal. We conclude that HLx is a member of a family of human liver P-450s that resembles in its structure, and possibly in its distribution, several liver P-450s found in other animals.

Feralisation targets different genomic loci to domestication in the chicken.

Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Island's feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population-an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.

First heart sound in Ebstein's anomaly: observations on the cause of wide splitting by echophonocardiographic studies before and after operative repair.

Preoperative echophonocardiographic study of a 31 year old woman with Ebstein's anomaly and an atrial septal defect showed wide splitting of the first heart sound with an interval of 0.08 second between mitral valve and tricuspid valve closure. After application of the anterior tricuspid leaflet and anuloplasty, the mitral and tricuspid valves closed at the same time and there was a single first heart sound. These findings suggest that delayed tricuspid valve closure in Ebstein's anomaly is due to the abnormally large size and increased excursion of the anterior tricuspid leaflet rather than associated right bundle branch block or sluggish right ventricular contraction.

Childhood traumatic infarction causing left ventricular aneurysm: diagnosis by two-dimensional echocardiography.

After being struck by an automobile, a 9 year old boy developed transient right bundle branch block followed by electrocardiographic changes of inferior wall myocardial infarction and an increase of serum cardiac enzymes. Two-dimensional echocardiography demonstrated a prominent septal aneurysm. Subsequent cardiac catheterization confirmed septal aneurysm and demonstrated an additional inferior aneurysm. Six weeks after the accident, resection of the inferior aneurysm was performed. At 1 year follow-up study, residual septal aneurysm and cardiomegaly are present, but the boy is asymptomatic.

Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.

OBJECTIVES: We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). BACKGROUND: The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. RESULTS: The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. CONCLUSIONS: Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.

Nonemergent cardiac catheterization and risk-stratified revascularization following thrombolytic therapy for acute myocardial infarction. A critical analysis of therapy in the community setting. University of North Carolina Cardiology Consortium.

We evaluated a strategy for administering thrombolytic therapy without emergent cardiac catheterization to patients with acute myocardial infarction in community hospitals. Fifty-nine patients were treated with intravenous streptokinase and heparin, and referred for elective catheterization. Angioplasty or bypass surgery was performed only in patients judged to be at risk for reinfarction. One or more predetermined criteria for infarct segment viability were present in 47 (80%) of 59 patients. Angina recurred in 24 patients and enzyme-positive reinfarction in 9 patients, but only 2 patients developed new Q waves or a creatine kinase rise to over twice the normal value. Of 18 patients judged to be at low risk for reinfarction, only 1 required urgent angioplasty or bypass surgery. Fourteen-day mortality was 7% and infarct vessel patency was 94%. These data indicate that physicians in small community hospitals with a close relationship to a referral center and with a carefully designed protocol can administer thrombolytic therapy safely and effectively. By subsequent stratification of patients according to the risk of recurrent infarction, 22% of patients eligible for revascularization were spared urgent angioplasty or bypass surgery.

Discrepancy between first-dose converting enzyme inhibition at rest and subsequent inhibition during exercise in chronic heart failure.

Low-dose angiotensin-converting enzyme inhibition is thought to completely block the renin-angiotensin system. This study examined the hemodynamic and hormonal responses to initial low- and higher dose converting-enzyme inhibitor (lisinopril or captopril) at rest compared with the response during subsequent chronic therapy while treadmill exercise testing was performed in nine patients with chronic heart failure. At rest, similar changes in systemic arterial pressure, plasma renin activity, and plasma aldosterone concentration were found with initial low and higher doses. However, after at least 4 weeks of therapy, dose-dependent increases in plasma renin activity and decreases in plasma aldosterone concentration were noted during exercise without significant differences in exercise systemic arterial pressure or heart rate. This discrepancy suggests that initial low-dose converting enzyme inhibition does completely block the enzyme, but higher dose therapy is required for complete blockade during subsequent exercise in chronic heart failure.

Clinically significant adverse effects in a Phase 1 testing program.

Twelve years' experience with a Phase I drug testing program in normal prison volunteers is reported. Involved in 805 protocol studies were 29,162 participants over 614,534 subject days. During this period there were 64 significant medical events of which 58 were adverse drug reactions and 6 were complications. One subject has residual hip changes due to an infectious complication, another on placebo died from cerebrovascular hemorrhage while asleep. There was complete recovery from all adverse drug reactions and the other 4 complications encountered. Thus a clinically significant medical event occurred once every 9,602 days subject exposure or about once every 26.3 years of individual subject participation.

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.

The apex impulse in mitral stenosis: graphic explanation of the palpable movements at the cardiac apex.

Simultaneously recorded phonocardiograms and apexcardiograms of 39 patients with mitral stenosis (MS) were retrospectively analyzed. A notch on the upstroke of the apexcardiogram coincidental with the first heart sound (S1) occurred in 18 (47%) of the patients. The notch ratio or vertical distance from the onset of the apical impulse to the notch ratio or vertical distance from the onset of the apical impulse to the notch as a percentage of the total upstroke was measured and compared with the mean mitral diastolic gradient obtained at cardiac catheterization. Statistical analysis showed a significant relation (r = 0.61; p less than 0.01) between notch ratio and the mean mitral diastolic gradient. This study reaffirms that the complex palpable movements at the cardiac apex, consisting of a "tap" representing S1 occurring perceptibly after the onset of the apex impulse itself, are a useful diagnostic sign of MS. Furthermore, a graphic measurement of the extent of delay of S1 with respect to the onset of the apical thrust can provide a rough measure of the severity of the valvular obstruction.

Racial differences in left ventricular structure in healthy young adults.

Racial differences in cardiac structure and function were evaluated in 62 black and 71 white healthy young adults. Left ventricular (LV) mass index, relative wall thickness, fractional shortening, resting cardiac index and resting systemic vascular resistance index were estimated using M-mode echocardiography. Pulsed Doppler interrogation of transmitral flow was used to characterize LV filling. Average daytime blood pressure (BP) was determined by ambulatory monitoring during a typical work or school day. Ambulatory daytime BP averaged 127 +/- 12/80 +/- 7 mm Hg in black subjects, and 127 +/- 9/80 +/- 6 mm Hg in white subjects (p = not significant). The 2 groups were also similar in resting BP, age and gender composition. Relative wall thickness was significantly greater in black than in white subjects (0.37 +/- 0.06 vs 0.34 +/- 0.05; p less than 0.01). This difference was found in both men and women. Black subjects also had a higher resting systemic vascular resistance index (2,110 +/- 570 vs 1,920 +/- 500 dynes.s.cm-5.m2; p less than 0.05) and lower resting cardiac index (3.14 +/- 0.84 vs 3.46 +/- 0.85 L/min/m2; p less than 0.05). There were no significant differences between black and white subjects in LV mass index, fractional shortening and normalized peak filling velocity. These results suggest that racial differences in LV structure and systemic hemodynamics exist even in patients without sustained hypertension. In our study population, the greater relative wall thickness in black subjects was not accompanied by significant differences in LV systolic function or diastolic filling.

History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease.

The history and physical examination were assessed in 215 patients with acute pulmonary embolism uncomplicated by preexisting cardiac or pulmonary disease. The patients had been included in the Urokinase Pulmonary Embolism Trial or the Urokinase-Streptokinase Embolism Trial. Presenting syndromes were (1) circulatory collapse with shock (10 percent) or syncope (9 percent); (2) pulmonary infarction with hemoptysis (25 percent) or pleuritic pain and no hemoptysis (41 percent); (3) uncomplicated embolism characterized by dyspnea (12 percent) or nonpleuritic pain usually with tachypnea (3 percent) or deep venous thrombosis with tachypnea (0.5 percent). The most frequent symptoms were dyspnea (84 percent), pleuritic pain (74 percent), apprehension (63 percent) and cough (50 percent). Hemoptysis occurred in only 28 percent. Dyspnea, hemoptysis or pleuritic pain occurred separately or in combination in 94 percent. All three occurred in only 22 percent. The most frequent signs were tachypnea (respiration ate 20/min or more) (85 percent), tachycardia (heart rate 100 beats/min or more) (58 percent), accentuated pulmonary component of the second heart sound (57 percent) and rales (56 percent). Signs of deep venous thrombosis were present in only 41 percent and a pleural friction rub was present in only 18 percent. Either dyspnea or tachypnea occurred in 96 percent. Dyspnea, tachypnea or deep venous thrombosis occurred in 99 percent. As a group, the identified clinical manifestations, although nonspecific, are strongly suggestive of acute pulmonary embolism. Conversely, acute pulmonary embolism was rarely identified in the absence of dyspnea, tachypnea or deep venous thrombosis.

Ethnic differences in forearm vasodilator capacity.

Previous studies have demonstrated significant ethnic differences in left ventricular structure in both normotensive and hypertensive subjects. To determine if these differences in ventricular geometry are associated with differences in vascular structure, we measured the minimum forearm vascular resistance in 30 healthy young African-American adults and in 30 whites matched for age, gender, and blood pressure. Average daytime blood pressure was determined by ambulatory monitoring during a typical work day. Minimum forearm vascular resistance was measured by plethysmography after 10 minutes of forearm ischemia. Indexed left ventricular mass and relative wall thickness were measured by 2-dimensional-directed M-mode echocardiography. The mean (+/-SD) ambulatory pressure was 126 +/- 11/79 +/- 8 mm Hg in African-Americans and 126 +/- 11/79 +/- 7 mm Hg in whites. The 2 groups were similar in body mass index and in family history of hypertension. African-Americans had a higher minimum forearm vascular resistance than did whites (2.39 +/- 0.75 vs 2.03 +/- 0.55 mm Hg, p <0.05). There was a trend toward a greater left ventricular relative wall thickness in African-Americans (0.38 +/- 0.07 vs 0.35 +/- 0.06, p=0.09). These results suggest that early vascular remodeling is present in African-Americans who do not have established hypertension, and that this ethnic difference in vascular structure is associated with a difference in ventricular geometry.

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.

Pericardial effusion was noted in 43 of 79 patients (54%) with severe primary pulmonary hypertension. Larger effusion was associated with hemodynamic and echocardiographic evidence of right heart failure, impaired exercise tolerance, and a poor 1-year prognosis.

Angled aorta ("sigmoid septum") as a cause of hypertrophic subaortic stenosis.

Review of the hearts of seven patients in whom hypertrophic obstructive cardiomyopathy had been diagnosed by the usual clinical and morphologic criteria revealed diminished angles between the interventricular septa and ascending aortas in three cases. The angles in these three hearts were 90 to 110 degrees, as compared with a mean value of 145 degrees in the other four hearts with hypertrophic obstructive cardiomyopathy and 140 +/- 14 degrees in 55 control hearts. None of the patients with hypertrophic subaortic stenoses and angled aortic roots died of the heart disease, and none had either asymmetric ventricular hypertrophy or evidence of familial cardiomyopathy. It is proposed that in patients with angled aortic roots and left ventricular hypertrophy, subaortic obstruction may develop due to narrowing of the left ventricular outflow tract, resulting in clinical and morphologic findings of hypertrophic obstructive cardiomyopathy. In hearts with angled aortic roots the top of the ventricular septum is tipped toward the mitral valve, rather than tapered toward the aorta, as in normal hearts. This configuration narrows the outflow tract of the left ventricle and can result in systolic anterior motion of the mitral valve, the illusion of asymmetric septal hypertrophy when studied by M-mode echocardiography, a subaortic pressure gradient, and a subaortic endocardial plaque. This less serious form of hypertrophic subaortic stenosis should be distinguished from other forms of hypertrophic obstructive cardiomyopathy.