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Amino acid composition of human milk is not unique.

To determine whether the amino acid pattern of human milk is unique, we compared the amino acid pattern of human milk with the amino acid patterns of the milks of great apes (chimpanzee and gorilla), lower primates (baboon and rhesus monkey) and nonprimates (cow, goat, sheep, llama, pig, horse, elephant, cat and rat). Amino acid pattern was defined as the relative proportion of each amino acid (protein-bound plus free) (in mg) to the total amino acids (in g). Total amino acid concentration was lower in primate milk than in nonprimate milk. There were commonalities in the overall amino acid pattern of the milks of all species sampled; the most abundant amino acids were glutamate (plus glutamine, 20%), proline (10%) and leucine (10%). Essential amino acids were 40%, branched-chain amino acids 20%, and sulfur amino acids 4% of the total amino acids. The amino acid pattern of human milk was more similar to those of great apes than to those of lower primates. For example, cystine was higher and methionine was lower in primate milks than in nonprimate milks, and in great ape and human milks than in lower primate milks. Because the milk amino acid patterns of the human and elephant, both slow-growing species, were dissimilar, the amino acid pattern of human milk seems unrelated to growth rate.

Amino Acids↗

The critical role played by animal source foods in human (Homo) evolution.

Wild primates take most of the daily diet from plant sources, eating moderate to small amounts of animal source foods (ASF). Plant materials make up from 87% to >99% of the annual diet of great apes, the closest living relatives of modern humans (Homo sapiens sapiens). Reflecting their close genetic relationship, gut form and nutrient requirements of apes and humans (Hominoidea) are very similar, as is their pattern of digestive kinetics-one predicated on a relatively slow turnover of ingesta. In plant-eating mammals, in contrast to carnivorous mammals, greater body size is associated with lower dietary quality. Turning to ASF as a routine rather than occasional dietary component would have permitted the evolving human lineage to evade the nutritional constraints placed on body size increases in apes. Without routine access to ASF, it is highly unlikely that evolving humans could have achieved their unusually large and complex brain while simultaneously continuing their evolutionary trajectory as large, active and highly social primates. As human evolution progressed, young children in particular, with their rapidly expanding large brain and high metabolic and nutritional demands relative to adults would have benefited from volumetrically concentrated, high quality foods such as meat. Today, many humans, particularly those in high income nations, have a variety of high quality, non-ASF dietary alternatives, but such foods were not generally available to paleolithic human ancestors nor to many people today in low income nations.

Animals↗

Route of tracer administration does not affect ileal endogenous nitrogen recovery measured with the 15N-isotope dilution technique in pigs fed rapidly digestible diets.

The (15)N-isotope dilution technique ((15)N-IDT), with either pulse-dose oral administration or continuous i.v. administration of [(15)N]-l-leucine (carotid artery), both at 5 mg/(kg body weight . d), was used to measure ileal (postvalve T-cecum cannula) endogenous nitrogen recovery (ENR) in pigs (9 +/- 0.6 kg). Diets were cornstarch, enzyme-hydrolyzed casein with no (control) or high (4%) content of quebracho extract (Schinopsis spp.) rich in condensed tannins. Blood was sampled from a catheter in the external jugular vein. Mean plasma (15)N-enrichment at d 8-10 was higher (P = 0.0009) after i.v. than after oral administration [0.0356 vs. 0.0379 atom% excess (APE)]. Plasma (15)N-enrichment for i.v. infused pigs was 0.01117 APE higher (P < 0.0001) and for orally dosed pigs 0.0081 APE lower (P < 0.0001) at 11 h postprandial compared with 1 h postprandial. Apparent ileal N digestibility was higher (P < 0.0001) for the control (85.5%) than for the quebracho diet (69.5%). ENR was calculated from the ratio of (15)N-enrichment of plasma and digesta. The ENR for the quebracho diet was approximately 300% higher than for the control diet (6.03 vs. 1.94 g/kg dry matter intake, P < 0.001). The real N digestibility (92.2 +/- 0.4%) was equal for both diets (P = 0.1030) and both tracer methods (P = 0.9730). We concluded that oral administration of [(15)N]leucine provides reasonable estimates of ENR in pigs fed semipurified diets with high or low content of tannins; however, one must be careful in extrapolating this conclusion to studies with other protein sources or feeding frequencies.

Anacardiaceae↗

Fast adaptive coevolution of nuclear and mitochondrial subunits of ATP synthetase in orangutan.

Nuclear and mitochondrial genomes have to work in concert to generate a functional oxidative phosphorylation (OXPHOS) system. We have previously shown that we could restore partial OXPHOS function when chimpanzee or gorilla mitochondrial DNA (mtDNA) were introduced into human cells lacking mtDNA. However, we were unable to maintain orangutan mitochondrial DNA in a human cell. We have now produced chimpanzee, gorilla, orangutan, and baboon cells lacking mtDNA and attempted to introduce mtDNA from different apes into them. Surprisingly, we were able to maintain human mtDNA in an orangutan nuclear background, even though these cells showed severe OXPHOS abnormalities, including a complete absence of assembled ATP synthetase. Phylogenetic analysis of complex V mtDNA-encoded subunits showed that they are among the most evolutionarily divergent components of the mitochondrial genome between orangutan and the other apes. Our studies showed that adaptive coevolution of nuclear and mitochondrial components in apes can be fast and accelerate in recent branches of anthropoid primates.

Animals↗

Recent amplification of an alpha satellite DNA in humans.

A repeat sequence 682 base pairs (bp) long produced by cleavage of human DNA with Xba I restriction enzyme is composed of four tandemly arranged subunits with lengths of 171, 170, 171, and 170 bp each. The sequence organization of the 682 bp Xba I repeat bears a striking resemblance to other complex satellite DNAs of primates, including the Eco RI human alpha satellite family which also occurs as a 170 bp repeat. The Eco RI tetramer and the 682 bp Xba I repeat show a sequence divergence of 21%. The 682 bp Xba I repeat sequence is restricted to humans and is only distantly related to the previously reported 340 bp Xba human repeated DNA sequence. These finding are consistent with the concept of occasional amplifications of members or groups of members of alpha satellite DNA during human evolution. Amplifications apparently occurred after humans, apes and gibbons diverged from Old World monkeys (Eco RI satellite), after humans and apes diverged from gibbons (340 bp Xba I satellite) and after humans diverged from the great apes (682 bp Xba I satellite).

Animals↗

Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells.

Abasic (AP)-endonuclease (APE) is responsible for repair of AP sites, and single-strand DNA breaks with 3' blocking groups that are generated either spontaneously or during repair of damaged or abnormal bases via the DNA base excision repair (BER) pathway in both nucleus and mitochondria. Mammalian cells express only one nuclear APE, 36 kDa APE1, which is essential for survival. Mammalian mitochondrial (mt) BER enzymes other than mtAPE have been characterized. In order to identify and characterize mtAPE, we purified the APE activity from beef liver mitochondria to near homogeneity, and showed that the mtAPE which has 3-fold higher specific activity relative to APE1 is derived from the latter with deletion of 33 N-terminal residues which contain the nuclear localization signal. The mtAPE-sized product could be generated by incubating 35S-labeled APE1 with crude mitochondrial extract, but not with cytosolic or nuclear extract, suggesting that cleavage of APE1 by a specific mitochondria-associated N-terminal peptidase is a prerequisite for mitochondrial import. The low abundance of mtAPE, particularly in cultured cells might be the reason for its earlier lack of detection by western analysis.

Amino Acid Sequence↗

Rh gene evolution in primates: study of intron sequences.

By amplification and sequencing of RH gene intron 4 of various primates we demonstrate that an Alu-Sx-like element has been inserted in the RH gene of the common ancestor of humans, apes, Old World monkeys, and New World monkeys. The study of mouse and lemur intron 4 sequences allowed us to precisely define the insertion point of the Alu-Sx element in intron 4 of the RH gene ancestor common to Anthropoidea. Like humans, chimpanzees and gorillas possess two types of RH intron 4, characterized by the presence (human RHCE and ape RHCE-like genes) or absence (human RHD and ape RHD-like genes) of the Alu-Sx element. This led us to conclude that in the RH common ancestor of humans, chimpanzees, and gorillas, a duplication of the common ancestor gene gave rise to two genes, one differing from the other by a 654-bp deletion encompassing an Alu-Sx element. Moreover, most of chimpanzees and some gorillas posses two types of RHD-like intron 4. The introns 4 of type 1 have a length similar to that of human RHD intron 4, whereas introns 4 of type 2 display an insertion of 12 bp. The latest insertion was not found in the human genome (72 individuals tested). The study of RH intron 3 length polymorphism confirmed that, like humans, chimpanzees and gorillas possess two types of intron 3, with the RHD-type intron 3 being 289 bases shorter than the RHCE intron 3. By amplification and sequencing of regions encompassing introns 3 and 4, we demonstrated that chimpanzee and gorilla RH-like genes displayed associations of introns 3 and 4 distinct to those found in man. Altogether, the results demonstrate that, as in humans, chimpanzee and gorilla RH genes experienced intergenic exchanges.

Animals↗

Acute pulmonary edema in the emergency department: clinical and echocardiographic survey in an aged population.

BACKGROUND: This study is aimed at better defining the prevalence of left ventricular dysfunction, atrial fibrillation, and mitral regurgitation in aged patients with cardiogenic acute pulmonary edema. METHODS: One hundred and twenty-three consecutive patients with acute pulmonary edema (APE) arriving at the emergency department of a peripheral hospital who underwent Doppler echocardiography within 36 hours of admission were reviewed retrospectively. RESULTS: Left ventricular ejection fraction (LVEF) was normal or near normal (ie, LVEF > or = 40%) in 41.4% (n = 51 patients), and depressed in 58.5% (n = 72). Significant valvular dysfunction was present in 37.4%; mitral regurgitation was the most frequent (22.8%; n = 28). We found a significant positive correlation between systolic blood pressure (SBP) and LVEF (P = 0.003). Within the group of patients presenting with lower SBP (< or = 140 mm Hg), as blood pressure diminished, LVEF also diminished significantly (P = 0.008). In a logistic regression analysis, male sex and SBP of less than 120 mm Hg were found to be the strongest predictors for LVEF < or = 40%, conferring a 2.68- and 2.73-fold risk, respectively (95%CI, 1.19 to -6.00; P = 0.016 and 95%CI, 0.956-7.80; P = 0.061, respectively) compared with female sex and higher SBP groups. CONCLUSIONS: This study emphasizes that emergency departments should have clear-cut policies for diagnosing and treating acute coronary syndromes and tachyarrhythmias, as being potential treatable causes of APE. Once stabilized, patients should be examined for treatable valvular causes. A further study, of acute echocardiography done upon arrival to the emergency department in patients with APE is warranted.

Adult↗

Cognitive ornithology: the evolution of avian intelligence.

Comparative psychologists interested in the evolution of intelligence have focused their attention on social primates, whereas birds tend to be used as models of associative learning. However, corvids and parrots, which have forebrains relatively the same size as apes, live in complex social groups and have a long developmental period before becoming independent, have demonstrated ape-like intelligence. Although, ornithologists have documented thousands of hours observing birds in their natural habitat, they have focused their attention on avian behaviour and ecology, rather than intelligence. This review discusses recent studies of avian cognition contrasting two different approaches; the anthropocentric approach and the adaptive specialization approach. It is argued that the most productive method is to combine the two approaches. This is discussed with respects to recent investigations of two supposedly unique aspects of human cognition; episodic memory and theory of mind. In reviewing the evidence for avian intelligence, corvids and parrots appear to be cognitively superior to other birds and in many cases even apes. This suggests that complex cognition has evolved in species with very different brains through a process of convergent evolution rather than shared ancestry, although the notion that birds and mammals may share common neural connectivity patterns is discussed.

Animals↗

Analysis of two genomic variants of orang-utan hepadnavirus and their relationship to other primate hepatitis B-like viruses.

We recently described orang-utan hepadnavirus (OuHV) (Warren et al., Journal of Virology, 73, 7860-7865, 1999). Phylogenetic analyses indicated that the various isolates of OuHV can be divided into two genomic variants. Two representatives from each genomic cluster were analysed both molecularly and phylogenetically. Their genome organization was highly similar to other hepadnaviruses of apes and humans. The complete genome sequences of the two OuHV types had an overall 5% sequence difference. Research on 25 seropositive Bornean orang-utans showed that, of the 19 animals infected with one variant, 12 originated from East Kalimantan. Phylogenetic analysis was performed using the full-length genomes of various primate hepadnaviruses. The tree topology revealed one cluster of Old World hepadnaviruses that is divided into two subclusters, one consisting of the ape viruses, and the other comprising the human genotypes A-E. These data suggest that the great apes and gibbons have been infected with a common ancestor hepadnavirus.

Animals↗

Isolation and characterization of a chimpanzee alphaherpesvirus.

Although both beta- and gammaherpesviruses indigenous to great-ape species have been isolated, to date all alphaherpesviruses isolated from apes have proven to be human viruses [herpes simplex virus types 1 (HSV1) and 2 (HSV2) or varicella-zoster virus]. If the alphaherpesviruses have co-evolved with their host species, some if not all ape species should harbour their own alphaherpesviruses. Here, the isolation and characterization of an alphaherpesvirus from a chimpanzee (ChHV) are described. Sequencing of a number of genes throughout the ChHV genome indicates that it is collinear with that of HSV. Phylogenetic analyses place ChHV in a clade with HSV1 and HSV2, the alphaherpesviruses of Old World monkeys comprising a separate clade. Analysis of reactivity patterns of HSV2-immune human sera and ChHV-immune chimpanzee sera by competition ELISA support this relationship. Phylogenetic analyses also place ChHV rather than HSV1 as the closest relative of HSV2.

Alphaherpesvirinae↗

A preliminary solubility screen used to improve crystallization trials: crystallization and preliminary X-ray structure determination of Aeropyrum pernix flap endonuclease-1.

Crystallization of protein and protein complexes is a multi-parametric problem that involves the investigation of a vast number of physical and chemical conditions. The buffers, salts and additives used to prepare the protein will be present in every crystallization condition. It is imperative that these conditions be defined prior to crystal screening since they will have a ubiquitous involvement in the crystal-growth experiments. This study involves the crystallization and preliminary analysis of the flap endonuclease-1 (FEN-1) DNA-repair enzyme from the crenarchaeal organism Aeropyrum pernix (Ape). Ape FEN-1 protein in a standard chromatography buffer had only a modest solubility and minimal success in crystallization trials. Using an ion/pH solubility screen, it was possible to dramatically increase the maximum solubility of the protein. The solubility-optimized protein produced large diffraction-quality crystals under multiple conditions in which the non-optimized protein produced only precipitate. Only minor adjustments of the conditions were required to produce single diffraction-quality crystals. The native Ape FEN-1 crystals diffract to 1.4 A resolution and belong to space group P6(1), with unit-cell parameters a = b = 92.8, c = 80.9 A, alpha = beta = 90, gamma = 120 degrees.

Aeropyrum↗

Mechanisms for the acquisition of habitual bipedality: are there biomechanical reasons for the acquisition of upright bipedal posture?

Morphology and biomechanics are linked by causal morphogenesis ('Wolff's law') and the interplay of mutations and selection (Darwin's 'survival of the fittest'). Thus shape-based selective pressures can be determined. In both cases we need to know which biomechanical factors lead to skeletal adaptation, and which ones exert selective pressures on body shape. Each bone must be able to sustain the greatest regularly occurring loads. Smaller loads are unlikely to lead to adaptation of morphology. The highest loads occur primarily in posture and locomotion, simply because of the effect of body weight (or its multiple). In the skull, however, it is biting and chewing that result in the greatest loads. Body shape adapted for an arboreal lifestyle also smooths the way towards bipedality. Hindlimb dominance, length of the limbs in relation to the axial skeleton, grasping hands and feet, mass distribution (especially of the limb segments), thoracic shape, rib curvatures, and the position of the centre of gravity are the adaptations to arboreality that also pre-adapt for bipedality. Five divergent locomotor/morphological types have evolved from this base: arm-swinging in gibbons, forelimb-dominated slow climbing in orangutans, quadrupedalism/climbing in the African apes, an unknown mix of climbing and bipedal walking in australopithecines, and the remarkably endurant bipedal walking of humans. All other apes are also facultative bipeds, but it is the biomechanical characteristics of bipedalism in orangutans, the most arboreal great ape, which is closest to that in humans. If not evolutionary accident, what selective factor can explain why two forms adopted bipedality? Most authors tend to connect bipedal locomotion with some aspect of progressively increasing distance between trees because of climatic changes. More precise factors, in accordance with biomechanical requirements, include stone-throwing, thermoregulation or wading in shallow water. Once bipedality has been acquired, development of typical human morphology can readily be explained as adaptations for energy saving over long distances. A paper in this volume shows that load-carrying ability was enhanced from australopithecines to Homo ergaster (early African H. erectus), supporting an earlier proposition that load-carrying was an essential factor in human evolution.

Animals↗

Magnetic resonance imaging of the low rectum: defining the radiological anatomy.

Low rectal cancer provides a particular surgical challenge of local tumour control and sphincter preservation. Histopathological studies have shown that an involved circumferential resection margin (CRM) and depth of extramural invasion are independent markers of poor prognosis and correlate with high local recurrence rates due to residual microscopic disease [1]. Recent data suggests that a CRM at risk of tumour involvement can be reliably seen on the pre-operative magnetic resonance imaging (MRI) scan with good correlation with the histological specimen [2-5]. In published series, low rectal cancers have a higher incidence of involved resection margins, with rates up to 30% for abdomino-perineal excision (APE) vs 10% for low anterior resection (LAR) [6-9]. This has been attributed to narrow surgical planes deep within the pelvis as the mesorectum becomes narrowed and tapered, forming a bare muscle tube at the level of the anal sphincter complex. The challenge for the surgeon is to undertake careful removal of a cylinder of tissue beyond the rectal wall without perforating the tumour. An overall local recurrence rate of 10% after APE for all stages of rectal cancer has been reported and this low rate was attributed to the surgical technique that included a wide peri-anal dissection and lateral division of the levator ani. The abdominal dissection was stopped above the tumour, taking care to avoid separation of the tumour from the levator ani to reduce the risk of inadvertent tumour cell spillage [8]. Therefore, rates of involved surgical margins from APE specimens may be reduced when a cuff of levators is taken compared with standard resection. In this review, we will discuss how MRI of the low rectum can aid in the staging and optimization of the best treatment strategy for low rectal cancer.

Anal Canal↗

Quality of life and sexual function following surgery for rectal cancer.

The last 20 years have seen enormous strides forward in the treatment of rectal cancer with the development of improved surgical technique, tumour staging, histopathological audit and multidisciplinary team (MDT) management with emphasis on improving survival and reducing local recurrence rates. However, each rectal cancer discussed at the MDT meeting involves an individual patient. The quality of life for each patient must be taken into account when making treatment decisions, which sometimes may not fit with 'standard' treatment guidelines as the individual patient does not have a 'standard' tumour. For one patient with a tumour 5 cm above the anal verge, a low anterior resection may maintain quality of life with no incontinence and preservation of urinary and sexual function. For another with a tumour at the same level, preoperative chemo-radiotherapy may exacerbate mild incontinence and a low resection may result in a 'perineal stoma'. A decision to perform an abdomino-perineal excision (APE) must not be considered a failure of surgical treatment or be seen as a suboptimal centre by having a high APE rate. On the contrary, APE rates should represent sub-specialization and patient selection. Indeed, good function from a permanent stoma may be better than bad function from a poorly functioning coloanal pouch. Having improved tumour staging, surgical technique, oncological treatment and histopathological assessment, quality of life must not be forgotten. Both quality and quantity of life are important to all patients.

Colectomy↗

Functional analysis of the foot and ankle myology of gibbons and bonobos.

This study investigates the foot and ankle myology of gibbons and bonobos, and compares it with the human foot. Gibbons and bonobos are both highly arboreal species, yet they have a different locomotor behaviour. Gibbon locomotion is almost exclusively arboreal and is characterized by speed and mobility, whereas bonobo locomotion entails some terrestrial knuckle-walking and both mobility and stability are important. We examine if these differences in locomotion are reflected in their foot myology. Therefore, we have executed detailed dissections of the lower hind limb of two bonobo and three gibbon cadavers. We took several measurements on the isolated muscles (mass, length, physiological cross sectional area, etc.) and calculated the relative muscle masses and belly lengths of the major muscle groups to make interspecific comparisons. An extensive description of all foot and ankle muscles is given and differences between gibbons, bonobos and humans are discussed. No major differences were found between the foot and ankle musculature of both apes; however, marked differences were found between the ape and human foot. The human foot is specialized for solely one type of locomotion, whereas ape feet are extremely adaptable to a wide variety of locomotor modes. Apart from providing interesting anatomical data, this study can also be helpful for the interpretation of fossil (pre)hominids.

Animals↗

Overexpression of human copper/zinc-superoxide dismutase in transgenic animals attenuates the reduction of apurinic/apyrimidinic endonuclease expression in neurons after in vitro ischemia and after transient global cerebral ischemia.

Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Apurinic/apyrimidinic endonuclease (APE) is a multifunctional protein in the DNA base excision repair pathway which repairs apurinic/apyrimidinic sites in DNA. We investigated the involvement of oxidative stress and expression of APE in neurons after oxygen-glucose deprivation and after global cerebral ischemia. Our results suggest that overexpression of human copper/zinc-superoxide dismutase reduced oxidative stress with a subsequent decrease in APE expression. Production of oxygen free radicals and inhibition of the base excision repair pathway may play pivotal roles in the cell death pathway after ischemia.

Animals↗

Cloning and characterization of beta-carotene ketolase gene promoter in Haematococcus pluvialis.

The unicellular green alga Haematococcus pluvialis accumulates a highly valuable ketocarotenoid, astaxanthin, under various environmental stresses. beta-carotene ketolase (BKT) plays a key role in astaxanthin biosynthesis in H. pluvialis. In this paper, an approximate 700 bp 5'-flanking region of the bkt gene containing a putative promoter was cloned through walking upstream. The results of the sequence analysis showed that this bkt 5'-flanking region might have cis-acting elements such as sterol regulatory element (SRE-1)-like motifs, the C-repeat/dehydration responsive element (DRE) and al-3 proximal element (APE)-like motifs, except for typical TATA and CCAAT boxes. The results of the beta-galactosidase assay and the transient expression of lacZ driven by a series of sequential deletions revealed that a minimal promoter-like region might exist from -630 to -408 bp, and the highest promoter activity was observed to span the positions from -630 to -308 bp. The results of the site-directed mutagenesis of a C-repeat/DRE and two APE-like motifs in a promoter-like region (-630 to -308 bp) suggested that two APE-like motifs might be essential for transcriptional control of the bkt gene.

Bacterial Proteins↗