Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae

Arginine decarboxylase (ADC) is an important enzyme in the production of putrescine and polyamines in plants. It is encoded by a single or low-copy nuclear gene that lacks introns in sequences studied to date. The rate of Adc amino acid sequence evolution is similar to that of ndhF for the angiosperm family studied. Highly conserved regions provide several target sites for PCR priming and sequencing and aid in nucleotide and amino acid sequence alignment across a range of taxonomic levels, while a variable region provides an increased number of potentially informative characters relative to ndhF for the taxa surveyed. The utility of the Adc gene in plant molecular systematic studies is demonstrated by analysis of its partial nucleotide sequences obtained from 13 representatives of Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order Capparales) and 1 from the related order Malvales. Two copies of the Adc gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied to data except the basal genus Aethionema. The resulting Adc gene tree provides robust phylogenetic data regarding relationships within the complex mustard family, as well as independent support for proposed tribal realignments based on other molecular data sets such as those from chloroplast DNA.      

Tubers as fallback foods and their impact on Hadza hunter-gatherers

The Hadza are hunter-gatherers in Tanzania. Their diet can be conveniently categorized into five main categories: tubers, berries, meat, baobab, and honey. We showed the Hadza photos of these foods and asked them to rank them in order of preference. Honey was ranked the highest. Tubers, as expected from their low caloric value, were ranked lowest. Given that tubers are least preferred, we used kilograms of tubers arriving in camp across the year as a minimum estimate of their availability. Tubers fit the definition of fallback foods because they are the most continuously available but least preferred foods. Tubers are more often taken when berries are least available. We examined the impact of all foods by assessing variation in adult body mass index (BMI) and percent body fat (%BF) in relation to amount of foods arriving in camp. We found, controlling for region and season, women of reproductive age had a higher %BF in camps where more meat was acquired and a lower %BF where more tubers were taken. We discuss the implications of these results for the Hadza. We also discuss the importance of tubers in human evolution. Am J Phys Anthropol, 140:751–758, 2009. © 2009 Wiley-Liss, Inc.     

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.Cancer cells favor glycolysis over oxidative phosphorylation (OXPHOS) to meet their energy demand,¹ suggesting that they have adapted to survive and proliferate in the absence of fully functional mitochondria. Research in the last two decades demonstrates that, in addition to generation of energy, mitochondria including cancer cell mitochondria regulate multiple cellular signaling pathways encompassing cell death, proliferation, cellular redox balance, and metabolism.^{2, 3} As cancer cells possess defects in these pathways that provide an opportunity to target this organelle for therapeutic purposes. Subsequently, several agents have been developed that target cancer cell mitochondria to induce apoptosis, a cell death pathway, and eradicate cancer cells.^{4, 5} Cancer cell mitochondria harbor several proapoptotic proteins including cytochrome c, which is released from mitochondria in response to anticancer agents and activates caspases to execute apoptosis.^{5, 6} Thus, anticancer agents that induce cytochrome c release from mitochondria will be beneficial for induction of apoptosis in cancer cells. Indeed, several such agents have been developed, which include inhibitors targeting prosurvival Bcl-2 family members including Bcl-2, Bcl-xL, and Mcl-1.^{7, 8, 9} Unfortunately, cancer cells have developed multiple mechanisms to resist or overcome cytochrome c release and evade apoptosis.Although underlying mechanisms of cancer cell resistance to apoptosis are still undefined, the OXPHOS defect is known to be one of the key reasons for the attenuation of apoptosis in cancer cells.^{10, 11} Multiple lines of evidence support the notion that cancer cell survival and proliferation commonly associate with an OXPHOS defect in cancer.^{1, 12} Active OXPHOS is an efficient form of respiration but also regulates apoptosis through the OXPHOS complexes. The OXPHOS system consists of five multimeric protein complexes (I, II, III, IV, and V). The components of these complexes (except complex-II) are encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA).^{12, 13} Thus mutations, deletions, and translocations in either mtDNA or nDNA can potentially result in OXPHOS deficiency. MtDNA mutations associate with inhibition of apoptosis, induction of angiogenesis, invasion and metastasis of various types of cancer.^{3, 12, 14} Thus, mtDNA could potentially be an important target to restore cell death in cancer and attenuate cancer growth. Therefore, there is an urgent need to investigate the role of OXPHOS in the molecular mechanisms underlying cancer cell death.We investigated the effects of several anticancer agents of different classes including DNA-damaging agents (etoposide and doxorubicin), protein kinase inhibitors (staurosporine and sorafenib), mitotic inhibitor (taxol), ER stressor/inhibitor of Ca²⁺-ATPases (thapsigargin), and histone deacetylase (HDAC) inhibitor (apicidin) on mtDNA. We also determined the impact of OXPHOS defects on apoptosis induction by these agents. Although most anticancer agents induced caspase activation and apoptosis, the mtDNA level was elevated maximally by etoposide and it was not modulated by a caspase inhibitor but reduced by an autophagy inhibitor. Induction of mtDNA is associated with increased reactive oxygen species (ROS) production and elevated mitochondrial mass. Pharmacologic inhibition of OXPHOS complexes reduced the etoposide-induced elevation in mtDNA, suggesting the involvement of these complexes in etoposide-induced apoptosis. Together, we define the impact of mtDNA and OXPHOS function on mitochondrial apoptosis, which has significance in restoring cancer cell apoptosis for therapeutic purposes.     

Preferences for symmetry in human faces in two cultures: data from the UK and the Hadza, an isolated group of hunter-gatherers

Many studies show agreement within and between cultures for general judgements of facial attractiveness. Few studies, however, have examined the attractiveness of specific traits and few have examined preferences in hunter-gatherers. The current study examined preferences for symmetry in both the UK and the Hadza, a hunter-gatherer society of Tanzania. We found that symmetry was more attractive than asymmetry across both the cultures and was more strongly preferred by the Hadza than in the UK. The different ecological conditions may play a role in generating this difference. Such variation in preference may be adaptive if it reflects adaptation to local conditions. Symmetry is thought to indicate genetic quality, which may be more important among the Hadza with much higher mortality rates from birth onwards. Hadza men who were more often named as good hunters placed a greater value on symmetry in female faces. These results suggest that high quality Hadza men are more discriminating in their choice of faces. Hadza women had increased preferences for symmetry in men's faces when they were pregnant or nursing, perhaps due to their increased discrimination and sensitivity to foods and disease harmful to a foetus or nursing infant. These results imply that symmetry is an evolutionarily relevant trait and that variation in symmetry preference appears strategic both between cultures and within individuals of a single culture.     

Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow

Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.     

The 'spiteful' origins of human cooperation

We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation.     

Wealth transmission and inequality among hunter-gatherers

We report quantitative estimates of intergenerational transmission and population-wide inequality for wealth measures in a set of hunter-gatherer populations. Wealth is defined broadly as factors that contribute to individual or household well-being, ranging from embodied forms such as weight and hunting success to material forms such household goods, as well as relational wealth in exchange partners. Intergenerational wealth transmission is low to moderate in these populations, but is still expected to have measurable influence on an individual's life chances. Wealth inequality (measured with Gini coefficients) is moderate for most wealth types, matching what qualitative ethnographic research has generally indicated (if not the stereotype of hunter-gatherers as extreme egalitarians). We discuss some plausible mechanisms for these patterns, and suggest ways in which future research could resolve questions about the role of wealth in hunter-gatherer social and economic life.     

Sex differences in spatial cognition among Hadza foragers

This paper describes sex differences in spatial competencies among the Hadza, a mobile hunter–gatherer population in Tanzania. It addresses the following questions: (a) Is the usual male advantage in Euclidean spatial abilities found in this population, where both women and men are highly mobile? (b) Do Hadza women have better object location memory than men, as the gathering hypothesis predicts? (c) Do women who are nominated by others as being good at finding bushfoods excel at the object location memory task? We tested object location memory with a version of the memory game using cards of local plants and animals. This allowed us to also ask whether women and men would have better spatial memory for the plant and animal cards, respectively. We found that Hadza men were significantly better than women in three tests of spatial ability: the water-level test, targeting, and the ability to point accurately to distant locations (the latter only in the less mobile groups). There was a trend toward a male advantage at the object location memory task, in contrast to results found previously in nonforaging populations, and women's performance at the task deteriorated with age, while that of men did not. The women who were nominated by peers as being good at finding bushfoods were consistently older women. We discuss the probable hormonal causes and functional consequences of age changes in the spatial competencies of female foragers.     

Functional integrity of intravenous immunoglobulin following irradiation with a virucidal dose of gamma radiation.

Although intravenous immunoglobulins (IVIG) and other plasma therapeutics have had a relatively good safety record, improved methods for viral clearance are constantly being evaluated and incorporated into new manufacturing processes. Gamma irradiation has been used routinely to assure sterility of healthcare products and medical devices, but it has not been applied successfully as a viral inactivation method for biologics. We examine whether virucidal doses of gamma irradiation (50 kGy) can be delivered to a manufacturing intermediate form of IVIG, a fractionated plasma paste, with negligible effect on structural and functional integrity of purified IgG product. Immunoglobulins from paste were examined for radiation-induced damage by SDS-PAGE and ELISAs utilizing viral antigens specific for rubella, CMV and mumps. Fc domain integrity was assessed by immunoblotting, quantitatively comparing the binding of irradiated and non-irradiated materials to cell surface Fcgamma receptors, and by employing quantitative RT-PCR to study the kinetics of accumulation of mRNA for the immune modulatory cytokines IL-1alpha, IL-1beta, IL-4, IL-8, IFNgamma, and TNFalpha. The results demonstrate that Fab and Fc domains of IVIG remain essentially intact and functional after gamma irradiation to virucidal doses, suggesting that this method could be used to enhance the safety of IVIG products.