Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues

Since its introduction in the mid-1980s, diffusion magnetic resonance imaging (MRI), which measures the random motion of water molecules in tissues, revealing their microarchitecture, has become a pillar of modern neuroimaging. Its main clinical domain has been the diagnosis of acute brain stroke and neurogical disorders, but it is also used in the body for the detection and management of cancer lesions. It can also produce stunning maps of white matter tracks in the brain, with the potential to aid in the understanding of some psychiatric disorders. However, in order to exploit fully the potential of this method, a deeper understanding of the mechanisms that govern the diffusion of water in tissues is needed.In the mid-1980s, we showed that water diffusion in the human brain could be imaged by using magnetic resonance imaging (MRI) [1]. Since then, diffusion MRI has enjoyed a dramatic growth, with about 24,000 articles referenced in PubMed in 2014. MRI is a medical imaging technique consisting of magnetizing body atom nuclei, generally hydrogen nuclei of water molecules, using a very strong magnetic field (typically 30,000 to 60,000 times the earth’s natural magnetic field). The resulting very tiny magnetization can be manipulated in time by sending radiofrequency wave pulses at a resonant frequency. In turn, magnetized nuclei re-emit radiofrequency waves, creating a signal that is received through a coil (a kind of antenna), giving information on the nuclei magnetization properties. Magnetic field “gradient” pulses are used in addition to induce small variations of the magnetic field (and the associated radiowaves’ resonant frequency) in space, so as to spatially encode the magnetization information and create images. Magnetization varies a lot between tissues and various disease conditions, making MRI a very versatile imaging modality. However, the resolution of MRI images used for clinical practice often remains limited, typically around 1 mm (microscopic MRI is possible, but with dedicated preclinical MRI systems using ultra-high magnetic fields; see below). The concept of diffusion MRI emerged as a way to probe tissue structure at a microscopic (invisible) scale, although images are acquired at a millimetric scale: during their random, diffusion-driven displacements in the tissue, the water molecules probe the tissue structure at a microscopic scale, interacting with cell membranes, thus providing unique information on the functional architecture of tissues. Diffusion MRI has become a pillar of modern clinical imaging, used mainly to investigate neurological disorders such as acute brain ischemia, although it is now also a standard imaging method for other organs too, especially for the management of cancer patients. Indeed, diffusion MRI that does not require any tracer injection is rapidly becoming a modality of choice to detect and characterize malignant lesions. Moreover, in the brain, diffusion anisotropy in white matter can be exploited to produce stunning three-dimensional maps of brain connections, revealing faulty connections in some psychiatric disorders. More recently, diffusion MRI has been applied to monitor the dynamic changes occurring in the neural tissue structure during activation, a new approach to investigate functional neuroimaging and the mechanisms underlying neuronal activation.It is amazing that all these applications of diffusion MRI have emerged or developed while so little is known about water diffusion mechanisms in biological tissues. The relative importance of many factors governing water in tissues and their effects on the observed MRI signal are still not fully understood and are sometimes a subject of controversy.We will discuss the main applications and the outstanding issues remaining in the field in more detail below.     

The Shape of an Auxin Pulse,and What It Tells Us about the Transport Mechanism

Auxin underlies many processes in plant development and physiology, and this makes it of prime importance to understand its movements through plant tissues. In stems and coleoptiles, classic experiments showed that the peak region of a pulse of radio-labelled auxin moves at a roughly constant velocity down a stem or coleoptile segment. As the pulse moves it becomes broader, at a roughly constant rate. It is shown here that this ‘spreading rate’ is larger than can be accounted for by a single channel model, but can be explained by coupling of channels with differing polar transport rates. An extreme case is where strongly polar channels are coupled to completely apolar channels, in which case auxin in the apolar part is ‘dragged along’ by the polar part in a somewhat diffuse distribution. The behaviour of this model is explored, together with others that can account for the experimentally observed spreading rates. It is also shown that saturation of carriers involved in lateral transport can explain the characteristic shape of pulses that result from uptake of large amounts of auxin.     

What Can Cross-Cultural Correlations Teach Us about Human Nature?

Many recent evolutionary psychology and human behavioral ecology studies have tested hypotheses by examining correlations between variables measured at a group level (e.g., state, country, continent). In such analyses, variables collected for each aggregation are often taken to be representative of the individuals present within them, and relationships between such variables are presumed to reflect individual-level processes. There are multiple reasons to exercise caution when doing so, including: (1) the ecological fallacy, whereby relationships observed at the aggregate level do not accurately represent individual-level processes; (2) non-independence of data points, which violates assumptions of the inferential techniques used in null hypothesis testing; and (3) cross-cultural non-equivalence of measurement (differences in construct validity between groups). We provide examples of how each of these gives rise to problems in the context of testing evolutionary hypotheses about human behavior, and we offer some suggestions for future research.     

What a New Model of Skeletal Homologies Tells Us About Asteroid Evolution

The Extraxial-Axial Theory (EAT) is applied to the body wallhomologies of asteroids. Attempts to characterize major platesystems of asteroids as axial or extraxial, particularly thosethat are highly organized into series, can be problematic. However,the Optical Plate Rule (OPR) is instrumental in establishingthat ambulacrals and terminals are axial. It is equally clearthat the region aboral to the marginal frame is a part of theperforate extraxial body wall (with the possible exception ofthe centrodorsal, which is likely imperforate extraxial). Previouslyestablished EAT criteria, particularly those strongly rootedin the embryologically expressed boundary between axial andextraxial body wall in larvae, suggest that marginals, and perhapsadambulacrals, are extraxial in origin. We also explore theextraxial nature and phylogenetic significance of the odontophore.Our data from both juveniles and adults show that plate andtube foot addition sequences occur according to the OPR, andshed light on poorly known homologies of the asteroid mouthframe. These data indicate that the mouth angle ossicle mustat least contain the first ambulacral, although we cannot ruleout the possibility that the first adambulacral also contributesto the construction of this ossicle. The interpretations providedby the EAT for all ossicles suggest a synapomorphy scheme forsomasteroids, ophiuroids, and asteroids.     

Population Viability, Nature Reserves, and the Outlook for Gray Wolf Conservation in North America

Theoretical work on population viability and extinction probabilities, empirical data from Canis lupus (gray wolf) populations, and expert opinion provide only general and conflicting conclusions about the number of wolves and the size of areas needed for conservation of wolf populations. There is no threshold population size or proven reserve design that guarantees long-term (century or more) survival for a gray wolf population. Most theoretical analyses of population viability have assumed a single, isolated population and lack of management intervention, neither of which is likely for wolves. Data on survival of actual wolf populations suggest greater resiliency than is indicated by theory. In our view, the previous theoretical treatments of population viability have not been appropriate to wolves, have contributed little to their conservation, and have created unnecessary dilemmas for wolf recovery programs by overstating the required population size. Nonetheless, viability as commonly understood may be problematic for small populations at the fringe of or outside the contiguous species range, unless they are part of a metapopulation. The capability of existing nature reserves to support viable wolf populations appears related to a variety of in situ circumstances, including size, shape and topography of the reserve; productivity, numbers, dispersion, and seasonal movement of prey; extent of poaching inside; degree of persecution outside; exposure to enzootica; attitudes of local people; and proximity to other wolf populations. We estimate that a population of 100 or more wolves and a reserve of several thousand square kilometers may be necessary to maintain a viable population in complete isolation, although 3000 km² or even 500–1000 km² may be adequate under favorable circumstances. In most cases, management intervention is probably necessary to assure the viability of relatively small, isolated populations. Because most reserves may be inadequate by themselves to ensure the long-term survival of wolf populations, favorable human attitudes toward the species and its management must be recognized as paramount, and cooperation of neighboring management jurisdictions will be increasingly important.     

Tissue Nitrogen and Phosphorus in Seaweeds in a Tropical Eutrophic Environment: What a Long-Term Study Tells Us

Percentages of nitrogen and phosphorus in 10 species of seaweeds (6 green and 4 red algae) were monitored from 1997 to 2004 by seasonal sampling in Guanabara Bay, South-eastern Brazil. The species did not show consistent variations in tissue N, P and N:P that related to annual cycles. Throughout this study, higher percentages of tissue N and P were found in Bostrychia radicans and Grateloupia doryphora (red algae) and lower in Cladophora rupestris and Codium decorticatum (green algae). In November 1999, the Icaraí Submarine Sewage Outfall became operational, resulting in a reduction of visual pollution in the area and an improvement in the local quality of seawater for recreational use. Measurements of dissolved nutrients at the sampling site did not indicate significant changes in concentrations after the commissioning of the submarine sewage outfall; however, tissue P and N:P ratio of most of species were significantly lower than in the first two years of this survey. Variations in tissue nitrogen throughout this study were not significant, except for G. doryphora in some comparisons. Results show that seaweeds function very well as monitors of environmental changes in Guanabara Bay. Experimental data are needed to identify possible environmental processes which are promoting changes in chemical composition of the local seaweed populations.     

Organism Responses to Rapid Change: What Aquaria Tell Us About Nature

SYNOPSIS. Living corals are routinely collected and shippedto destinations thousands of miles from their point of origin.The fact that corals can survive the rigors of collecting, transport,and acclimation to totally artificial environments was consideredimpossible not long ago, but hobbyists and some researchershave persevered and have developed aquarium systems and techniquescapable of maintaining corals in apparently healthy conditionfor many years. In particular, new lighting equipment, advancesin the control of water chemistry, and new technology for simulatingwater movement have all contributed to the ability to keep coralsalive indefinitely in captivity. Despite the completely artificialconditions of most aquariums, coral extension rates and calcificationrates in some aquarium systems are close to those reported fornatural reefs, although anomalies have been observed such asdecreased skeletal density and unusual changes in colony morphology.Nonetheless, aquariums present real opportunities to culturecorals for a variety of bioassay, medicinal, and conservationpurposes. As model reef communities ("microcosms"), these systemsallow us to test hypotheses concerning the effects of rapidlychanging environmental conditions.     

G = E: What GWAS Can Tell Us about the Environment

As our understanding of genetics has improved, genome-wide association studies (GWAS) have identified numerous variants associated with lifestyle behaviours and health outcomes. However, what is sometimes overlooked is the possibility that genetic variants identified in GWAS of disease might reflect the effect of modifiable risk factors as well as direct genetic effects. We discuss this possibility with illustrative examples from tobacco and alcohol research, in which genetic variants that predict behavioural phenotypes have been seen in GWAS of diseases known to be causally related to these behaviours. This consideration has implications for the interpretation of GWAS findings.     

What Can Genome-Wide Association Studies Tell Us about the Genetics of Common Disease

The success of genome-wide association studies relies on much of the risk of common diseases being due to common genetic variants; but evidence for this is inconclusive. The results of published genome-wide association studies are examined to see what can be learnt about the distribution of disease-associated variants and how this might influence future study design. Although replicated disease-associated variants tend to be very common and frequency is inversely correlated with estimated effect size, our simulations suggest that such observations are the result of power. We find that for studies conducted to date, the frequency and effect size of significantly associated alleles are likely to be similar to those of the underlying disease alleles that they represent. Little of the genetic variation of disease has been explained so far, but current studies are only adequately powered to detect very common alleles unless they greatly increase disease risk. Thus, although the truth of the common disease / common variant hypothesis remains undecided, recent successes suggest that there are many more common genetic disease-associated variants, requiring larger studies to be identified.     

Population genomics of the inbred Scandinavian wolf

The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.     

What Cytogenetic Studies May Tell Us about Species Diversity and Speciation of Lemurs

I discuss the contribution of cytogenetic data to studies of systematics, phylogeny and speciation of several nocturnal lemurs. I examine specific distribution in Avahi and Lepilemur and propose a chromosomal mechanism involved in speciation of these two genera. I compare the contribution of cytogenetics to that of other techniques such as mitochondrial DNA sequencing. In rare situations wherein the respective systematic conclusions are contradictory, cytogenetic evidence clearly appears to be better supported.     

卧龙及草坡自然保护区大熊猫的种群与保护

卧龙和草坡自然保护区以保护大熊猫及其生态系统为主, 面积3 224 km2 , 为中国大熊猫分布区最大的保护区。自1974 年以来, 我们经过多次调查, 其栖息地由约2 500 km2 缩减到现今约800 km² 。大熊猫在该地所选择的最适生境在海拔2 800～3 100 m一带的三、四级夷平地带, 面积约4 ×104 hm² 。大熊猫的种群数量, 据1974 年调查有195 只(其中卧龙为145 只) , 1983 年冷箭竹大面积开花后种群有所下降, 而上世纪90 年代以后有所恢复, 现在约有150 只。在保护对策上, 应在4 个隔离种群间退耕还林, 控制交通流量和禁止夜间通行, 扩大保护范围到毗邻的县, 对最适的栖息地实行绝对保护, 并控制旅游规模及旅客流量。     

What Nature''s Knockout Teaches Us about GnRH Activity: Hypogonadal Mice and Neuronal Grafts

The hypogonadal mouse is one of “nature's knockouts,” bearing a specific deletion in the gene for gonadotropin-releasing hormone (GnRH), with the result that no GnRH peptide is detectable in the brain. The lack of reproductive development after birth provides an animal model that has proved fruitful in clarifying the role of GnRH in reproductive behavior and physiology. Behavioral studies with hypogonadal mice convincingly demonstrate that although GnRH may facilitate the appearance of sexual behavior, this peptide is not essential for either male or female sexual behavior in the mouse. Administration of GnRH to hypogonadal mice with regimens mimicking GnRH pulsatility initiates reproductive development. Surprisingly, continuous exposure to GnRH stimulates remarkable ovarian and uterine growth and increased FSH release, although pituitary content of LH and FSH remains unchanged. In contrast, when brain grafts of normal fetal preoptic area (POA), containing GnRH cells, are implanted in the third ventricle of adult hypogonadal mice, both pituitary and plasma gonadotropin levels increase. Grafted GnRH neurons innervate the median eminence of the host and support pulsatile LH secretion in the majority of animals with graft-associated gonadal development. Studies of hypogonadal mice with POA grafts demonstrate that distinct components of reproductive function are dissociable: hosts may demonstrate reflex but not spontaneous ovulation; others may show positive but not negative feedback. Activation of grafted GnRH cells in response to sensory input to the host, as revealed in Fos expression studies, is an example of the integration of the graft with the host brain that underlies such capabilities. A goal of these studies is to elucidate the specific connectivity underlying discrete aspects of reproductive function.     

Correlates of Mortality in an Exploited Wolf Population

Abstract We investigated the influence of habitat use on risk of death from hunting and trapping of 55 radiocollared gray wolves (Canis lupus) from an exploited insular population in Southeast Alaska, USA. We compared mortality rates for resident and nonresident wolves and used Cox proportional hazards regression to relate habitat composition within 100-m circular buffers around radiolocations to risk of death of resident and nonresident wolves. In addition, we included covariates representing distances to roads, logged stands, and lakes and streams in those analyses. We also compiled harvest data from 31 harvest units within the study area to compare densities of roads and distances from human settlements with rates of harvest. During our study 39 wolves died, of which 18 were harvested legally, 16 were killed illegally, and 5 died from natural causes. Legal and illegal harvest accounted for >87% of the mortality of radiocollared resident and nonresident wolves. Mean annual survival was 0.54 (SE = 0.17) for all wolves. Annual survival was 0.65 (SE = 0.17) for resident wolves and 0.34 (SE = 0.17) for nonresidents. Very few (19%) nonresident wolves survived to colonize vacant territories or join existing wolf packs. Roads, muskegs, and distances from lakes and streams were covariates positively associated with death of resident wolves. Clear-cuts were positively associated with risk of death of nonresident wolves. Rate of harvest increased with density of roads; however, road densities >0.9 km/km² had little additional effect on harvest rates. Harvest rates decreased with ocean distances from nearest towns or settlements. Roads clearly increased risk of death for wolves from hunting and trapping and contributed to unsustainable rates of harvest. Wildlife managers should consider effects of roads and other habitat features on harvest of wolves when developing harvest recommendations. They should expect substantial illegal harvest where wolf habitat is accessible to humans. Moreover, high rates of mortality of nonresident wolves exposed to legal and illegal harvest may reduce or delay successful dispersal, potentially affecting linkages between small disjunct wolf populations or population segments. We conclude that a combination of conservative harvest regulations and large roadless reserves likely are the most effective measures for conserving wolves where risks from human-caused mortality are high.