The Alkaloid Compound Harmane Increases the Lifespan of Caenorhabditis elegans during Bacterial Infection,by Modulating the Nematode’s Innate Immune Response

The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.     

Erratum to: Immune maintenance in glaucoma: boosting the body’s own neuroprotective potential

Glaucoma, a slow progressive neurodegenerative disorder associated with death of retinal ganglion cells and degeneration of their connected optic nerve fibers, has been classically linked to high intraocular pressure. Regardless of the primary risk factor, degeneration may continue, resulting in further loss of neurons and subsequent glaucomatous damage. During the past decade, scientists and clinicians began to accept that, in addition or as an alternative to fighting off the primary risk factor(s), there is a need to protect the tissue from the ongoing spread of damage—an approach collectively termed “neuroprotection.” We found that the immune system, the body’s own defense mechanism, plays a key role in the ability of the optic nerve and the retina to withstand glaucomatous conditions. This defense involves recruitment of both innate and adaptive immune cells that together create a protective niche and thereby halt disease progression. The spontaneous immune response might not be sufficient, and therefore, we suggest boosting it by immunization (with the appropriate antigen, at specific timing and predetermined optimal dosing) which may be developed into a suitable therapeutic vaccination to treat glaucoma. This view of immune system involvement in glaucoma will raise new challenges in glaucoma research, changing the way in which clinicians perceive the disease and the approach to therapy.     

Mango introduction in Florida and the ’haden’ cultivar’s significance to the modern industry

Mango (Mangifera indica L.) introductions to Florida began in 1861 with the importation of ’No. 11’, a polyembryonic, seed-propagated (nucellar) cultivarfrom Cuba. In the 1880s a collection of Cuban mangos was established near Bradenton. One resulting popular cultivar was ’Turpentine’, now widely used as a rootstock. The U. S. Department of Agriculture introduced ’Mulgoba’, an improved cultivarfrom India, in 1889. Other mangos were later brought from India, Vietnam, the Philippines, Thailand, Israel, Australia and Kenya. Related Mangifera species were collected in East Malaysian Borneo in 1990. Inasmuch as the breeding system of Mangifera favors outcrossing, the proximity of numerous genotypes of disparate geographic origin in Florida has made that state a secondary center of diversity for the mango and enabled it to make a unique contribution to the fruit industry.     

Widespread Shortening of 3’ Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection

The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform diversity after infection. In response to both bacteria, we found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3’ UTRs, with near-universal shifts towards usage of more upstream polyadenylation sites. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Following infection, we identify candidate RNA processing factors whose expression is associated with individual-specific variation in isoform abundance. Finally, by profiling microRNA levels, we show that 3’ UTRs with reduced abundance after infection are significantly enriched for target sites for particular miRNAs. These results suggest that the pervasive usage of shorter 3’ UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results suggest that dynamic changes in RNA processing may play key roles in the regulation of innate immune responses.     

A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O₂/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na⁺/K⁺ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K⁺]_o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.     

Leptin Signaling in the Arcuate Nucleus Reduces Insulin’s Capacity to Suppress Hepatic Glucose Production in Obese Mice

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Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sj?gren’s Syndrome in a Mouse Model

Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren’s syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues.     

Persistent and novel threats to the biodiversity of Kazakhstan’s steppes and semi-deserts

Temperate grasslands have suffered disproportionally from conversion to cropland, degradation and fragmentation. A large proportion of the world’s remaining near-natural grassland is situated in Kazakhstan. We aimed to assess current and emerging threats to steppe and semi-desert biodiversity in Kazakhstan and evaluate conservation research priorities. We conducted a horizon-scanning exercise among conservationists from academia and practice. We first compiled a list of 45 potential threats. These were then ranked by the survey participants according to their perceived severity, the need for research on them, and their novelty. The highest-ranked threats were related to changes in land use (leading to habitat loss and deterioration), direct persecution of wildlife, and rapid infrastructure development due to economic and population growth. Research needs were identified largely in the same areas, and the mean scores of threat severity and research need were highly correlated. Novel threats comprised habitat loss by photovoltaic and wind power stations, climate change and changes in agriculture such as the introduction of biofuels. However, novelty was not correlated with threat severity or research priority, suggesting that the most severe threats are the established ones. Important goals towards more effective steppe and semi-desert conservation in Kazakhstan include more cross-sector collaboration (e.g. by involving stakeholders in conservation and agriculture), greater allocation of funds to under-staffed areas (e.g. protected area management), better representativeness and complementarity in the protected area system and enhanced data collection for wildlife monitoring and threat assessments (including the use of citizen-science databases).     

Evolution’s past and future: an introduction and partial précis to Stephen Jay Gould’s The Structure of Evolutionary Theory

In The Structure of Evolutionary Theory, his last and largest book on evolution, Stephen Jay Gould conceives of the structure of evolutionary theory since Darwin as comprising three major propositions. First, natural selection is the most important direction-giving force in evolution. Second, it operates at the level of the individual organism. Third, selection can be extrapolated smoothly from its actions on individuals in living species throughout geologic time, to produce the gradual divergence of species and adaptations that characterizes the history of life. Challenges to each of these major propositions, according to Gould, can be of three kinds of severity. The most severe challenges, if true, would nullify one of the major propositions entirely, thus destroying the integration of the theory (and perhaps the logic and support of its other propositions). Other, less severe challenges would revise, modify, and expand the content and scope of one or another of the propositions, but not destroy any of them or the theory in toto. Still other, even less severe challenges add to what is known and extend the scope and possibilities of the theory, but do not call for a revision in its fundamental structure. Gould acknowledges that the theory has withstood all presumptive challenges that would destroy it, and has accommodated those that simply extend and add to it. His principal concern is with those challenges that would revise the theory substantially: for example, if processes other than natural selection were of great importance in evolution; if selection acted in important ways at the level of species and clades, and (or) at the level of the genes, alleles, and chromosomes; and if the extrapolation of what is known from living populations could not by itself explain many patterns of large-scale evolution seen in the fossil record. He thinks that, both through the history of evolution since Darwin and in the present day, challenges that substantially revise these basic propositions are valid, and that the theory needs to integrate them in order to retain the explanatory power that it has had for many decades. To cite this article: K. Padian, C. R. Palevol 2 (2003).     

Reconfiguring the Empty Center: Drinking,Sobriety, and Identity in Native American Women’s Narratives

Although anthropologists have paid little attention to popular American psychological discourse about addiction and recovery, the cultural politics of its engagement by Native North American communities warrant closer examination. By ethnographically contextualizing personal narratives, this paper describes how addiction/recovery discourse has been selectively engaged by younger generations of women in a northern Plains reservation community. Sobriety is not only a therapeutic transformation but also a socially negotiated identity change in this community and, therefore, engages ongoing local identity politics. Many community members evaluate the legitimacy of claims to Native identity by essentializing boundaries between Native and non-Native, as well as between past and present-a discursive convention that O'Nell has called "the rhetoric of the empty center" (Disciplined Hearts: History, Identity and Depression in an American Indian Community. Berkeley: University of California Press, 1996, p. 55). Yet by selectively appropriating elements of addiction/recovery discourse, younger women in the 1990s increasingly positioned emotional experience and expression as central arbiters of the legitimacy of Native identity. In so doing, they reconfigured the rhetoric of the empty center, eliciting both controversy and support from the larger community. This analysis highlights new dimensions of the social life of addiction/recovery discourse in contemporary Native North America, and calls for increased ethnographic attention to how localized cultural politics can orient the ways in which communities engage therapeutic discourses.     

From Haeckel’s phylogenetics and Hennig’s cladistics to the method of maximum likelihood: Advantages and limitations of modern and traditional approaches to phylogeny reconstruction

The maximum likelihood and Bayesian methods are based on parametric models of character evolution. They assume that if we know these models as well as distribution of character states in studied organisms, we can infer the probability of different phylogenetic trajectories leading from ancestors to modern forms. In fact, these methods are mathematized variants of the traditional Haeckel’s approach to phylogeny reconstruction. In contrast to classical and parsimonious cladistics, they infer phylogenies without such limitations as necessity of strictly dichotomous evolution, exclusion of plesiomorphic characters, and acceptance of only holophyletic taxa. They assume that evolution may be reticulated, any homologous characters—both apomorphic and plesiomorphic—can be used for inferring phylogenies, and interpretation of evolutionary lineages as taxa is optional. Thus, the main difference between the new and more traditional approaches to phylogeny reconstruction lies not in the characters used (molecular or morphological) but in the methodology of analysis. It must be admitted that a revolution began in phylogenetics 10–20 years ago. However, the fundamental changes in phylogenetics have been carried out so calmly and neatly by the people who started this revolution, that many systematists still do not realize their importance.     

Strasburger’s legacy to mitosis and cytokinesis and its relevance for the Cell Theory

Eduard Strasburger was one of the most prominent biologists contributing to the development of the Cell Theory during the nineteenth century. His major contribution related to the characterization of mitosis and cytokinesis and especially to the discovery of the discrete stages of mitosis, which he termed prophase, metaphase and anaphase. Besides his observations on uninucleate plant and animal cells, he also investigated division processes in multinucleate cells. Here, he emphasised the independent nature of mitosis and cytokinesis. We discuss these issues from the perspective of new discoveries in the field of cell division and conclude that Strasburger's legacy will in the future lead to a reformulation of the Cell Theory and that this will accommodate the independent and primary nature of the nucleus, together with its complement of perinuclear microtubules, for the organisation of the eukaryotic cell.     

Biomechanics of the Peacock’s Display: How Feather Structure and Resonance Influence Multimodal Signaling

Courtship displays may serve as signals of the quality of motor performance, but little is known about the underlying biomechanics that determines both their signal content and costs. Peacocks (Pavo cristatus) perform a complex, multimodal “train-rattling” display in which they court females by vibrating the iridescent feathers in their elaborate train ornament. Here we study how feather biomechanics influences the performance of this display using a combination of field recordings and laboratory experiments. Using high-speed video, we find that train-rattling peacocks stridulate their tail feathers against the train at 25.6 Hz, on average, generating a broadband, pulsating mechanical sound at that frequency. Laboratory measurements demonstrate that arrays of peacock tail and train feathers have a broad resonant peak in their vibrational spectra at the range of frequencies used for train-rattling during the display, and the motion of feathers is just as expected for feathers shaking near resonance. This indicates that peacocks are able to drive feather vibrations energetically efficiently over a relatively broad range of frequencies, enabling them to modulate the feather vibration frequency of their displays. Using our field data, we show that peacocks with longer trains use slightly higher vibration frequencies on average, even though longer train feathers are heavier and have lower resonant frequencies. Based on these results, we propose hypotheses for future studies of the function and energetics of this display that ask why its dynamic elements might attract and maintain female attention. Finally, we demonstrate how the mechanical structure of the train feathers affects the peacock’s visual display by allowing the colorful iridescent eyespots–which strongly influence female mate choice–to remain nearly stationary against a dynamic iridescent background.