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N-terminal pro-brain natriuretic peptide as an indicator of right ventricular dysfunction.

BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) are elevated in most patients with acute pulmonary embolism (APE) that results in right ventricular overload. Therefore, APE should be considered in the differential diagnosis of patients with acute dyspnea and abnormal levels of BNPs. Moreover, plasma BNPs have been proved to predict outcome in APE. METHODS AND RESULTS: Low NT-proBNP or BNP levels characterize an uneventful hospital course, and NT-proBNP levels of <500 pg/mL identify patients who could potentially be candidates for care on a complete outpatient basis. Moreover, plasma NT-proBNP and BNP reflect the degree of right ventricular overload in APE. Plasma BNPs can also be elevated in chronic precapillary pulmonary hypertension and are strongly related to total pulmonary resistance. Elevated plasma levels of BNP/NT-proBNP and especially their further increase during follow-up are a potent predictor of poor survival. CONCLUSION: Because levels of brain natriuretic peptides are elevated significantly not only in pathologic conditions that affect the left ventricle but also in clinical conditions that lead to isolated acute or chronic right ventricular overload, it could be proposed that these peptides should not be regarded as biomarkers of congestive heart failure, but as indicators of cardiovascular dyspnea.

Acute Disease↗

Evolutionary psychology of spatial representations in the hominidae.

Comparatively little is known about the inherited primate background underlying human cognition, the human cognitive "wild-type." Yet it is possible to trace the evolution of human cognitive abilities and tendencies by contrasting the skills of our nearest cousins, not just chimpanzees, but all the extant great apes, thus showing what we are likely to have inherited from the common ancestor. By looking at human infants early in cognitive development, we can also obtain insights into native cognitive biases in our species. Here, we focus on spatial memory, a central cognitive domain. We show, first, that all nonhuman great apes and 1-year-old human infants exhibit a preference for place over feature strategies for spatial memory. This suggests the common ancestor of all great apes had the same preference. We then examine 3-year-old human children and find that this preference reverses. Thus, the continuity between our species and the other great apes is masked early in human ontogeny. These findings, based on both phylogenetic and ontogenetic contrasts, open up the prospect of a systematic evolutionary psychology resting upon the cladistics of cognitive preferences.

Animals↗

Neural connectivity and cortical substrates of cognition in hominoids.

Cognitive functions and information processing recruit discrete neural systems in the cortex and white matter. We tested the idea that specific regions in the cerebrum are differentially enlarged in humans and that some of the neural reorganizational events that took place during hominoid evolution were species-specific and independent of changes in absolute brain size. We used magnetic resonance images of the living brains of 10 human and 17 ape subjects to obtain volumetric estimates of regions of interest. We parcellated the white matter in the frontal and temporal lobes into two sectors, including the white matter immediately underlying the cortex (gyral white matter) and the rest of white matter (core). We outlined the dorsal, mesial, and orbital subdivisions of the frontal lobe and analyzed the relationship between cortex and gyral white matter within each subdivision. For all regions analyzed, the observed human values are as large as expected, with the exception of the gyral white matter, which is larger than expected in humans. We found that orangutans had a relatively smaller orbital sector than any other great ape species, with no overlap in individual values. We found that the relative size of the dorsal subdivision is larger in chimpanzees than in bonobos, and that the ratio of gyral white matter to cortex stands out in Pan in comparison to Gorilla and Pongo. Individual variability, possible sex differences, and hemispheric asymmetries were present not only in humans, but in apes as well. Differences in the distribution of neural connectivity and cortical sectors were identified among great ape species that share similar absolute brain sizes. Given that these regions are part of neural systems with distinct functional attributes, we suggest that the observed differences may reflect different evolutionary pressures on regulatory mechanisms of complex cognitive functions, including social cognition.

Anatomy, Comparative↗

A fossil hominoid proximal femur from Kikorongo Crater, southwestern Uganda.

The external morphology of a fragmentary right proximal femur from southwestern Uganda is described here. Discovered in the Kikorongo Crater of Queen Elizabeth National Park in 1961, this specimen was informally assigned to Homo sapiens (although never described) and tentatively dated to the late Pleistocene. However, because aspects of the external morphology of the femur align the fossil with the African great apes, we suggest that the Kikorongo femur may be the first postcranial fossil of the genus Pan. Like the African apes, the Kikorongo specimen lacks both an obturator externus groove and an intertrochanteric line. It has a short femoral neck with a circular cross section, and a narrow and deep superior notch. Using resampling statistics and discriminant function analysis, the Kikorongo femur clustered with the genus Pan, as opposed to Gorilla or Homo. However, if the specimen is from Pan, it would be large for this taxon. Furthermore, features that clearly distinguish the external morphology of Plio-Pleistocene hominin proximal femora from African ape femora, such as the shape of the femoral neck in cross section and femoral neck length, have converged in Holocene humans and African apes. Unfortunately, the internal morphology of the femoral neck of the Kikorongo fossil was not discernable. Although we hypothesize that the Kikorongo femur is from the genus Pan, there is such variability in the proximal femora of modern humans that, although it would be an unusual human, it remains possible that this fossil represents H. sapiens.

Animals↗

Limb-size proportions in Australopithecus afarensis and Australopithecus africanus.

Previous analyses have suggested that Australopithecus africanus possessed more apelike limb proportions than Australopithecus afarensis. However, due to the errors involved in estimating limb length and body size, support for this conclusion has been limited. In this study, we use a new Monte Carlo method to (1) test the hypothesis that A. africanus had greater upper:lower limb-size proportions than A. afarensis and (2) assess the statistical significance of interspecific differences among these taxa, extant apes, and humans. Our Monte Carlo method imposes sampling constraints that reduce extant ape and human postcranial measurements to sample sizes comparable to the fossil samples. Next, composite ratios of fore- and hindlimb geometric means are calculated for resampled measurements from the fossils and comparative taxa. Mean composite ratios are statistically indistinguishable (alpha=0.05) from the actual ratios of extant individuals, indicating that this method conserves each sample's central tendency. When applied to the fossil samples, upper:lower limb-size proportions in A. afarensis are similar to those of humans (p=0.878) and are significantly different from all great ape proportions (p< or =0.034), while Australopithecus africanus is more similar to the apes (p> or =0.180) and significantly different from humans and A. afarensis (p< or =0.031). These results strongly support the hypothesis that A. africanus possessed more apelike limb-size proportions than A. afarensis, suggesting that A. africanus either evolved from a more postcranially primitive ancestor than A. afarensis or that the more apelike limb-size proportions of A. africanus were secondarily derived from an A. afarensis-like ancestor. Among the extant taxa, limb-size proportions correspond with observed levels of forelimb- and hindlimb-dominated positional behaviors. In conjunction with detailed anatomical features linked to arboreality, these results suggest that arboreal posture and locomotion may have been more important components of the A. africanus behavioral repertoire relative to that of A. afarensis.

Animals↗

The orang-utan mating system and the unflanged male: A product of increased food stress during the late Miocene and Pliocene?

The orang-utan is unique among apes in having an unusually long male developmental period and two distinct adult male morphs (flanged and unflanged), which generally, but not exclusively, employ different reproductive strategies (call-and-wait vs. sneak-and-rape). Both morphs have recently been shown to have roughly similar levels of reproductive success in the one site where such a study has been conducted. This is in stark contrast to the unimale polygynous gorilla, in which dominant males sire almost all infants. Despite this, evidence on sexual dimorphism, life history, diet, and socioecology of extant and extinct apes, as well as the ontogeny, reproductive morphology, and physiology of extant apes, all indicate that the orang-utan's present-day mating system most likely evolved from a gorilla-like base, with one dominant male guarding a harem of females. The available evidence indicates that, due chiefly to the likely onset of the El Niño Southern Oscillation (generally regarded as the trigger for mast fruiting in dipterocarps) approximately 3-5Ma, southeast Asian forests would have begun to experience longer and more severe periods of low food availability. This change in food availability would have meant that full-time gregariousness was no longer energetically tolerable and, as a result, females dispersed more widely in search of food and adult/flanged males were no longer able to effectively guard a harem of females. A niche for a quiet, quick, opportunistic "sexual predator" (i.e., the unflanged male) then became available. This finding implies that, despite being anatomically quite chimpanzee-like, the ancestral hominoid probably had a social and mating system more similar to the gorilla than any other living ape.

Animals↗

Effect of aging on intracellular distribution of abasic (AP) endonuclease 1 in the mouse liver.

The abasic (AP) endonuclease (APE1) plays a central role in the base excision repair (BER) pathway for repairing oxidatively damaged bases and abasic sites in mammalian genomes. We have investigated age-dependent changes in APE activity, contributed primarily by APE1, in total extracts as well as in nuclear, mitochondrial, and cytoplasmic compartments of mouse hepatocytes. The APE1 protein and mRNA levels did not differ significantly between the livers of 4-mo (young), 10-mo (middle-aged), and 20-mo (old) mice, and corresponds with similar APE activity. However, we observed a 2-fold increase in specific activity of APE1 in the nucleus, a 2-fold decrease in the cytoplasm, and a 6-fold increase in the mitochondrial matrix of hepatocytes of the old relative to the young animals. Surprisingly, in the middle-age animals we observed 30% increase in APE activity in the nucleus but 6-fold in the mitochondrial matrix. These results indicate age-dependent accumulation of APE1 in the nucleus and mitochondria. Such redistribution occurred early in the mitochondria during the aging process and preferential accumulation of APE in the nucleus was more gradual which may reflect distinct levels of oxidative stress in these organelles.

Aging↗

Domain specificity versus expertise: factors influencing distinct processing of faces.

To explore face specificity in visual processing, we compared the role of task-associated strategies and expertise on the N170 event-related potential (ERP) component elicited by human faces with the ERPs elicited by cars, birds, items of furniture, and ape faces. In Experiment 1, participants performed a car monitoring task and an animacy decision task. In Experiment 2, participants monitored human faces while faces of apes were the distracters. Faces elicited an equally conspicuous N170, significantly larger than the ERPs elicited by non-face categories regardless of whether they were ignored or had an equal status with other categories (Experiment 1), or were the targets (in Experiment 2). In contrast, the negative component elicited by cars during the same time range was larger if they were targets than if they were not. Furthermore, unlike the posterior-temporal distribution of the N170, the negative component elicited by cars and its modulation by task were more conspicuous at occipital sites. Faces of apes elicited an N170 that was similar in amplitude to that elicited by the human face targets, albeit peaking 10 ms later. As our participants were not ape experts, this pattern indicates that the N170 is face-specific, but not specie-specific, i.e. it is elicited by particular face features regardless of expertise. Overall, these results demonstrate the domain specificity of the visual mechanism implicated in processing faces, a mechanism which is not influenced by either task or expertise. The processing of other objects is probably accomplished by a more general visual processor, which is sensitive to strategic manipulations and attention.

Adult↗

Direct spectrophotometric determination of alkylphenol polyethoxylate nonionic surfactants in wastewater.

A new spectrophotometric method is proposed for direct determination of alkylphenol polyethoxylate, RO(CH(2)CH(2)O)(n)H (where R is alkylphenyl and n is the degree of polymerization), in wastewater. The method is based on the formation of ternary complex, Pb(II)-meso-tetra-(3,5-dibromo-4-hydrooxyphenyl)-Porphyrin (T(DBHP)P)-alkylphenol polyethoxylate (APE). Under optimum reaction conditions, T(DBHP)P reacts with lead(II) and APE to form a yellow ternary complex with the maximum absorption peak at 479 nm. The color reaction is rapidly completed and the absorbance remains stable for at least 24h under room temperature. The apparent molar absorption coefficients were 0.4-4.3 x 10(4) L mol(-1) cm(-1) for n=5-50. As little as 0.02 microg mL(-1) of APE can be detected. The effects of various substances on the determination of APE were also investigated in detail. It was found that all the studied co-existing substances, especially cationic and anionic surfactants, which always seriously interfere in some reported methods, could be tolerated in considerable amounts. The method offered the advantages of simplicity, rapidity, sensitivity and selectivity without any prior separation or extraction.

Absorption↗

BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis.

Methylating carcinogens and cytostatic drugs induce different methylation products in DNA. In cells not expressing the repair protein MGMT or expressing it at a low level, O6-methylguanine is the major genotoxic, recombinogenic, and apoptotic lesion. Genotoxicity and apoptosis triggered by O6-methylguanine require mismatch repair (MMR). In cells expressing O6-methylguanine-DNA methyl transferase (MGMT) at a high level or for agents producing low amounts of O6-methylguanine, N-alkylations become the major genotoxic lesions. N-Alkylations are repaired by base excision repair (BER). In mammalian cells, naturally occurring mutants of BER have not been detected, which points to the importance of BER for viability. In order to ascertain the role of BER in cellular defense, BER was modulated either by transfection or mutational inactivation. It has been shown that overexpression of N-methylpurine-DNA glycosylase (MPG) does not protect, but rather sensitizes cells to SN2 agents. This has been interpreted in terms of an imbalance in BER. Regarding abasic site endonuclease (APE), transient but not stable overexpression of the enzyme was achieved upon transfection in CHO cells, which indicates that unphysiologic APE levels are not tolerated by the cell. Besides the repair function, APE (alias Ref-1) exerts redox capability by which the activity of various transcription factors is modulated. Therefore, it is possible that stable overexpression of mammalian APE impairs transcriptional regulation of genes, whereas transient overexpression may exert some protective effect. DNA polymerase beta (Pol beta) transfection was ineffective in conferring resistance to methylmethane sulfonate (MMS). On the other hand, Pol beta-deficient cells proved to be highly sensitive to methylation-induced chromosomal aberrations and reproductive cell death. The dramatic hypersensitivity in the killing response is largely due to induction of apoptosis. Obviously, nonrepaired BER intermediates are clastogenic and act as a strong trigger of the apoptotic pathway. The elements of this pathway are currently under investigation.

Alkylation↗

Intravenous nitrates in the prehospital management of acute pulmonary edema.

STUDY OBJECTIVE: We sought to assess the effect of nitrates on prehospital mortality among patients with acute pulmonary edema (APE). METHODS: The study involved a retrospective evaluation of the records of prehospital outcome in 640 patients with APE rescued by the mobile CCU (MCCU) of Florence, Italy, between January 1980 and December 1991. The MCCU serves an urban environment with a population of 400,000 in a 102-sq km area. In the years 1980 through 1983, patients were treated with oxygen, morphine, furosemide, digoxin, nitrates, aminophylline, or dopamine, according to the attending physician's judgment. From 1984 through 1991, new guidelines for the use of intravenous nitrates, based on differential treatment according to blood pressure, were in use. RESULTS: Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of 640 patients). Mortality after 1984 was significantly lower than before (5.3% versus 13%, P < .01). Nitrates were effective in reducing mortality, even in hypotensive patients. Multivariate analysis showed that outcome was significantly affected by two clinical features (dyspnea and low blood pressure), treatment with nitrates, and calendar period effects (before/after 1984). CONCLUSION: Our findings suggest that the use of intravenous nitrates improves short-term prognosis in APE.

Acute Disease↗

Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?

The widespread prevalence of diet-related health problems, particularly in highly industrialized nations, suggests that many humans are not eating in a manner compatible with their biology. Anthropoids, including all great apes, take most of their diet from plants, and there is general consensus that humans come from a strongly herbivorous ancestry. Though gut proportions differ, overall gut anatomy and the pattern of digestive kinetics of extant apes and humans are very similar. Analysis of tropical forest leaves and fruits routinely consumed by wild primates shows that many of these foods are good sources of hexoses, cellulose, hemicellulose, pectic substances, vitamin C, minerals, essential fatty acids, and protein. In general, relative to body weight, the average wild monkey or ape appears to take in far higher levels of many essential nutrients each day than the average American and such nutrients (as well as other substances) are being consumed together in their natural chemical matrix. The recommendation that Americans consume more fresh fruits and vegetables in greater variety appears well supported by data on the diets of free-ranging monkeys and apes. Such data also suggest that greater attention to features of the diet and digestive physiology of non-human primates could direct attention to important areas for future research on features of human diet and health.

Animal Nutritional Physiological Phenomena↗

Micronutrient intakes of wild primates: are humans different?

Low micronutrient intake is implicated in a diversity of human health problems, ranging from problems associated with food insufficiency to those associated with food over-consumption. Humans are members of the order primates, suborder anthropoidea, and are most closely related to the great apes. Humans and apes are remarkably similar biologically. In the wild, apes and monkeys consume diets composed largely of plant foods, primarily the fruits and leaves of tropical forest trees and vines. Considerable evidence indicates that the ancestral line giving rise to humans (Homo spp.) was likewise strongly herbivorous (plant-eating). The wild plant parts consumed by apes and monkeys show moderate to high levels of many minerals and vitamins. The estimated daily intake of specific minerals, vitamin C and some other vitamins by wild primates is often quite high in comparison to intake levels of these same micronutrients recommended for humans. Are the high micronutrient intakes of wild primates simply a non-functional, unavoidable by-product of their strongly plant-based diets or might they actually be serving important as yet undetermined immunological or other beneficial functions? A better understanding of the basis for this apparent difference between humans and wild primates could help to clarify the range and proportions of micronutrients best suited for optimal human development, health and longevity.

Animal Feed↗

Learning by imitation: a hierarchical approach.

To explain social learning without invoking the cognitively complex concept of imitation, many learning mechanisms have been proposed. Borrowing an idea used routinely in cognitive psychology, we argue that most of these alternatives can be subsumed under a single process, priming, in which input increases the activation of stored internal representations. Imitation itself has generally been seen as a "special faculty." This has diverted much research towards the all-or-none question of whether an animal can imitate, with disappointingly inconclusive results. In the great apes, however, voluntary, learned behaviour is organized hierarchically. This means that imitation can occur at various levels, of which we single out two clearly distinct ones: the "action level," a rather detailed and linear specification of sequential acts, and the "program level," a broader description of subroutine structure and the hierarchical layout of a behavioural "program." Program level imitation is a high-level, constructive mechanism, adapted for the efficient learning of complex skills and thus not evident in the simple manipulations used to test for imitation in the laboratory. As examples, we describe the food-preparation techniques of wild mountain gorillas and the imitative behaviour of orangutans undergoing "rehabilitation" to the wild. Representing and manipulating relations between objects seems to be one basic building block in their hierarchical programs. There is evidence that great apes suffer from a stricter capacity limit than humans in the hierarchical depth of planning. We re-interpret some chimpanzee behaviour previously described as "emulation" and suggest that all great apes may be able to imitate at the program level. Action level imitation is seldom observed in great ape skill learning, and may have a largely social role, even in humans.

Animals↗

Contributions of an endonuclease IV homologue to DNA repair in the African swine fever virus.

We recently demonstrated that African swine fever virus DNA polymerase X (Pol X) is extremely error-prone during single-nucleotide gap-filling and that the downstream ASFV DNA ligase seals 3' mismatched nicks with high efficiency. To further assess the credence of our hypothesis that these proteins may promote viral diversification by functioning within the context of an aberrant DNA repair pathway, herein we characterize the third protein expected to function in this system, a putative AP endonuclease (APE). Assays of the purified protein using oligonucleotide substrates unequivocally establish canonical APE activity, 3'-phosphatase and 3'-phosphodiesterase activities (in the context of a single-nucleotide gap), 3' --> 5' exonuclease activity (in the context of a nick), and nucleotide incision repair activity against 5,6-dihydrothymine. The 3' --> 5' exonuclease activity is shown to be highly dependent upon the identity of the nascent 3' base pair and to be inhibited when 2-deoxyribose-5-phosphate, rather than phosphate, constitutes the 5' moiety of the nick. ASFV APE retains activity when assayed in the presence of EDTA but is inactivated by incubation with 1,10-phenanthroline in the absence of a substrate, suggesting that it is an endonuclease IV homologue possessing intrinsic metal cofactors. The activities of ASFV APE, when considered alongside those of Pol X and ASFV DNA ligase, provide an enhanced understanding of (i) the types of damage that are likely to be sustained by the viral genome and (ii) the mechanisms by which the minimalist ASFV DNA repair pathway, consisting of just these three proteins, contributes to the fitness of the virus.

African Swine Fever Virus↗

Performance in a tool-using task by common chimpanzees (Pan troglodytes), bonobos (Pan paniscus), an orangutan (Pongo pygmaeus), and capuchin monkeys (Cebus apella).

Performance by individual animals of three species of great apes (Pan troglodytes, Pan paniscus, and Pongo pygmaeus) and capuchin monkeys (Cebus apella) was assessed by presenting a food treat inside a clear tube. The subjects readily used a straight stick to obtain the food. When sticks were bundled together, the apes immediately unwrapped the bundle to obtain an individual stick, whereas capuchins attempted to insert the bundled sticks. When a misshapen stick was provided, apes, but not capuchins, showed an improvement in terms of modifying the misshapen stick before insertion. Our results indicate that all these species can solve these tasks. However, only the performance of apes is consistent with emerging comprehension of the causal relations required for the avoidance of errors in the more complex tasks.

Animals↗

Earliest known Old World monkey skull.

Similarities of the skull are commonly used to support hypotheses of ancestor-descendant relationships between fossil and living ape genera, especially between the late Miocene apes Sivapithecus and Dryopithecus from Eurasia and the living orang-utan (Pongo) from Borneo and Sumatra. Yet determining whether craniofacial traits shared by extant and Miocene apes are primitive or derived is severely hampered by the rarity of well-preserved fossil crania, particularly of early members of their closest outgroup, the Old World monkeys (Cercopithecoidea). The discovery of a complete and undistorted skull of Victoriapithecus at middle Miocene deposits from Maboko Island, Kenya, provides evidence of intact cranial-vault and basicranial morphology, brain size and craniofacial hafting for a primate from between 32 and 7 million years ago. Victoriapithecus represents a branch of Old World monkey that is intermediate between extant cercopithecids (Colobinae and Cercopithecinae) and the common ancestor they shared with apes (Hominoidea). The skull preserves traits widely thought to be derived for extant and fossil members of a proposed Sivapithecus/Pongo clade, but which now appear to be primitive features of ancestral Old World higher primates in general.

Animals↗

Lipid mediators from pollen act as chemoattractants and activators of polymorphonuclear granulocytes.

BACKGROUND: Under natural exposure conditions, pollen grains function as allergen carriers that release allergens from internal binding sites on contact with the aqueous phase of mucosa membranes. In addition, we recently demonstrated that pollen are a rich source of eicosanoid-like mediators, which are rapidly released on contact with the aqueous phase. OBJECTIVE: The current study was designed to characterize the biochemical nature of pollen-derived lipid mediators in more detail and to delineate their biologic activity on polymorphonuclear granulocytes (PMNs). METHODS: Aqueous and lipid extracts from Phleum pratense L and Betula alba L pollen were analyzed by means of HPLC. PMNs were exposed to aqueous extracts or lipid fractions from pollen or to HPLC-purified lipid mediators identified in pollen extracts. Effects on PMNs were tested with transwell migration, calcium mobilization, and surface expression of CD11b. RESULTS: Aqueous pollen extracts (APEs) contained predominantly monohydroxylated products derived of linoleic acid and linolenic acid. In chemotaxis assays PMNs displayed significant migration to APEs. Lipid extracts from pollen and the HPLC fraction containing 13-hydroxy-octadecadienoic acid/hydroxy-linoleic acid and 13-hydroxy-octadecatrienoic acid/hydroxy-linolenic acid induced migratory responses, although to a lesser degree than the APEs. In addition, APE, as well as lipid, extracts induced PMN activation, as documented by means of calcium mobilization and upregulation of CD11b. CONCLUSION: Pollen grains release mediators that recruit and activate PMNs in vitro. Similar mechanisms may be effective in vivo, suggesting that pollen-derived lipid mediators may act as adjuvants in the elicitation phase of allergic reactions.

Cell Movement↗