Hominin brain evolution--new century, new directions

The study of hominin brain evolution focuses on the interiors of fossilized braincases. Applications of recent three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) techniques for visualizing and measuring >virtual endocasts< from braincases in combination with advances in computer graphics and software for acquiring relevant data are transforming the way in which fossil skulls are analyzed, and improving the quality of paleoneurological investigations. Although CT imaging is preferred for fossil skulls, a novel method that combines high-resolution MRI of physical endocasts, electronic reconstruction of their missing parts, and warping of the resulting virtual endocasts is currently being developed and has great potential for future studies of hominin brain evolution. Applications of CT and MR techniques have already resulted in surprising new findings, which are briefly outlined. Exciting revelations about hominin brain evolution are expected as the 21st century unfolds.     

Evolution of genitalia: theories,evidence, and new directions

Many hypotheses have been proposed to explain why male intromittent genitalia consistently tend to diverge more rapidly than other body traits of the same individuals in a wide range of animal taxa. Currently the two most popular involve sexual selection: sexually antagonistic coevolution (SAC) and cryptic female choice (CFC). A review of the most extensive attempts to discriminate between these two hypotheses indicates that SAC is not likely to have played a major role in explaining this pattern of genital evolution. Promising lines for future, more direct tests of CFC include experimental modification of male genital form and female sensory abilities, analysis of possible male–female dialogues during copulation, and direct observations of genital behavior.     

Mesenchymal stromal cells: new directions

Research into mesenchymal stromal/stem cells (MSCs) has been particularly exciting in the past five years. Our understanding of mechanisms of MSC-mediated tissue regeneration has undergone considerable evolution. Recent investigation of the primary in situ counterpart of cultured MSCs has led to fresh insights into MSC physiology and its role in the immune system. At the same time, the clinical application of MSCs continues to increase markedly. Taken together, a reappraisal of the definition of MSCs, a review of current research directions, and a reassessment of the approach to clinical investigation are timely and prudent.     

Cell-free oxygen carriers: scientific foundations, clinical development, and new directions

The most significant hurdle to the development of a safe and effective hemoglobin-based oxygen carrier ("blood substitute") is generally thought to be its propensity to cause vasoconstriction in the microcirculation and hypertension. Two theories for this effect are currently being studied: in one, scavenging NO by hemoglobin reduces vasorelaxation; in the other, cell-free hemoglobin oversupplies O2 (a known vasoconstrictor) to vascular walls by facilitated diffusion. While both mechanisms might lead to reduction of local NO concentration, the important distinction between the two is that if the NO scavenging theory is correct, it greatly diminishes the prospects to develop any solution based on free hemoglobin. However, if the O2-oversupply theory is correct, modifications to the hemoglobin molecule can be envisioned that can prevent oversupply and reduce toxicity. This review summarizes the development of Hemospan, a novel modification of human hemoglobin whose design is based on the O2-oversupply theory. Because of its low P50 and increased molecular size, the release of O2 in resistance vessels (arterioles) by Hemospan is restricted, and vasoconstriction is greatly reduced.     

Modernization, stress, and blood pressure: new directions in research.

The relationship between modernization and blood pressure has been formally examined in anthropology for some 3 decades. A prominent hypothesis to account for the increase in blood pressure in more modernized (or economically developed) communities is the stressful nature of cultural and social change. Research has progressed from hypothesizing that culture change is stressful to trying to operationalize theoretical models of what it is about culture change that is stressful and in turn relating those more precise variables to blood pressure variability within and between communities. Here, I selectively review the literature on modernization and blood pressure, especially the research literature that explicitly uses models of the stress process to guide that research. The most interesting results have been obtained when the use of the stress model has been informed by careful ethnographic work. This has enabled researchers to adapt models of the stress process to be culturally appropriate in local populations. In addition, incorporating an explicit model of culture, especially one that is sensitive to intracultural diversity, has led to new hypotheses regarding the modification of the effects of stressors by social and cultural context. I conclude with a discussion of recent innovations in ethnographic methods, specifically the cultural consensus model, and the use of those methods in operationalizing relevant variables in culturally appropriate and sensitive ways. The utility of combining these methods in the study of modernization and blood pressure is illustrated by recent research in Brazil.     

Double-mutant cycles: new directions and applications

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The defense hypothesis of elemental hyperaccumulation: status,challenges and new directions

Elemental hyperaccumulation may have several functions, including plant defense against natural enemies. A total of 34 studies, including 72 experimental tests, have been conducted to date. At least some tests have demonstrated defense by hyperaccumulated As, Cd, Ni, Se and Zn, but relatively few plant taxa and natural enemies have been investigated. Defense by hyperaccumulated Ni has been shown for most leaf/root chewing herbivores and pathogens tested (20 of 26 tests) but not for herbivores of other feeding modes (1 of 8 tests). Most tests (5 of 6) using Ni concentrations below accumulator levels found no defensive effect, and the single test using plants in the accumulator range also found no effect. For Zn, mixed results have been reported for both hyperaccumulator (3 of 6 tests showed defense) and accumulator levels (3 of 4 tests showed defense). These tests have focused exclusively on leaf chewing/scraping herbivores: no herbivores of other feeding modes, or pathogens, have been tested. Both hyperaccumulator and accumulator concentrations of Se generally have shown defensive effects (12 of 14 tests). Most (75%) of these positive results used plants with accumulator Se concentrations. The three tests of Cd showed defensive effects in two cases, one for hyperaccumulator and one for sub-accumulator Cd concentrations. Arsenic has been tested only once, and was found effective against a leaf-chewing herbivore at a concentration much less than the hyperaccumulator level. Defense studies have used a variety of experimental approaches, including choice and no-choice experiments as well as experiments that use artificial diet or growth media. Investigations of hyperaccumulation as a defense against natural enemies have led to two emerging questions. First, what is the minimum concentration of an element sufficient for defense? Evidence suggests that plants other than hyperaccumulators (such as accumulators) may be defended by elements against some natural enemies. Second, do the effects of an element combine with the effects of organic defensive compounds in plants to produce enhanced joint defensive effects? Recent investigation of this “joint effects hypothesis,” using Ni and secondary plant compounds in artificial insect diet, has demonstrated joint effects. Initial answers to both these questions suggest that defensive effects of elements in plants are more widespread than previously believed. These results also suggest an evolutionary pathway by which elemental hyperaccumulation may have evolved from accumulation. In this “defensive enhancement” scenario, defensive benefits of elevated levels of elements may have led to stepwise increases in element concentrations that further magnified these benefits. This series of steps could have led to increased accumulation, and ultimately hyperaccumulation, of elements by plants.     

Protection during peptide synthesis: Some new directions

Methods available for the protection of the functional groups of amino acids during peptide synthesis are discussed, and attention is drawn to the advantages of side-chain protection of the 4-pyridylmethyl type, having increased acid stability and cleaved by mild reductive procedures in the presence of sulfur. The use of S-diphenyl-4-pyridylmethyl-cysteine and N^im-diphenyl-4-pyridylmethyl-histidine is described.     

TNF family members and malaria: Old observations, new insights and future directions

Tumor necrosis factor (TNF) has long been recognized to promote malaria parasite killing, but also to contribute to the development of severe malaria disease. The precise molecular mechanisms that influence these different outcomes in malaria patients are not well understood, but the virulence and drug-resistance phenotype of malaria parasites and the genetic background and age of patients are likely to be important determinants. In the past few years, important roles for other TNF family members in host immune responses to malaria parasites and the induction of disease pathology have been discovered. In this review, we will summarize these more recent findings and highlight major gaps in our current knowledge. We will also discuss future research strategies that may allow us to better understand the sometimes subtle and intricate effects of TNF family molecules during malaria infection.     

Beyond EBM: new directions for evidence-based public health

Public health researchers, policy makers, and practitioners agree that health is the outcome of interactions between biological, behavioral, and social determinants. Nonetheless, institutional patterns of research funding and practice remain obstacles to generating research at and between each of these levels. These practices are embedded in historic assumptions about the nature of reality and how it can best be understood. Current debates over the criteria for evaluating public health research have centered on the applicability of the clinical evidence-based medicine (EBM) model to the field of public health. The EBM hierarchy, which is based on traditional scientific assumptions about causality, is insufficient and potentially harmful as the basis for evaluating research on the determinants of health. Yet those who have put forward a critique of EBM have failed to develop a plausible alternative. Critical realism, based on the philosophy of Roy Bhaskar, may provide a way out of the current stalemate, enabling public health researchers from various disciplines and research paradigms to work together, bringing the full weight of scientific knowledge to bear on increasingly complex and global public health problems.     

Fruit development: new directions for an old pathway

A recent study investigating the molecular mechanisms of seed pod shattering has shown that the basic helix-loop-helix (bHLH) proteins INDEHISCENT and?ALCATRAZ appear to regulate fruit patterning through gibberellic acid (GA)-DELLA signalling, revealing a central role for bHLH family members in GA?response specificity.     

Avian cooperative breeding: Old hypotheses and new directions

In cooperatively breeding birds, individuals that appear capable of reproducing on their own may instead assist others with their breeding efforts. Research into avian cooperative breeding has attempted to reconcile the apparent altruism of this behaviour with maximization of inclusive fitness. Most explanations of cooperative breeding have suggested that philopatry is enforced by ecological constraints, such as a shortage of resources critical to breeding. Non-dispersers may then benefit both directly and indirectly from contributing at the nest. Recent research has shown that such benefits may be sufficient to promote philopatry, without the need for ecological constraints, and emphasizes that consideration of both costs and benefits of philopatry is essential for a comprehensive approach to the problem. The growing body of data from long-term studies of different species should combine with an improved phylogenetic perspective on cooperative breeding, to provide a useful base for future comparative analyses and experimentation.