A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.

Dysregulated expression of factors that control protein synthesis is associated with poor prognosis of many cancers, but the underlying mechanisms are not well defined. Analysis of the diffuse large B-cell lymphoma (DLBCL) translatome revealed selective upregulation of mRNAs encoding anti-apoptotic and DNA repair proteins. We show that enhanced synthesis of these proteins in DLBCL is mediated by the relief of repression that is normally imposed by structure in the 5'-untranslated regions of their corresponding mRNAs. This process is driven by signaling through mammalian target of rapamycin, resulting in increased synthesis of eukaryotic initiation factor (eIF) 4B complex (eIF4B), a known activator of the RNA helicase eIF4A. Reducing eIF4B expression alone is sufficient to decrease synthesis of proteins associated with enhanced tumor cell survival, namely DAXX, BCL2 and ERCC5. Importantly, eIF4B-driven expression of these key survival proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in DLBCL. Our work provides new insights into the mechanisms by which the cancer-promoting translational machinery drives lymphomagenesis

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.

We have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a 'ribosome-related' signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis

Spatial and temporal dimensions of landscape fragmentation across the Brazilian Amazon

The Brazilian Amazon in the past decades has been suffering severe landscape alteration, mainly due to anthropogenic activities, such as road building and land clearing for agriculture. Using a high-resolution time series of land cover maps (classified as mature forest, non-forest, secondary forest) spanning from 1984 through 2011, and four uncorrelated fragmentation metrics (edge density, clumpiness index, area-weighted mean patch size and shape index), we examined the temporal and spatial dynamics of forest fragmentation in three study areas across the Brazilian Amazon (Manaus, Santarém and Machadinho d’Oeste), inside and outside conservation units. Moreover, we compared the impacts on the landscape of: (1) different land uses (e.g. cattle ranching, crop production), (2) occupation processes (spontaneous vs. planned settlements) and (3) implementation of conservation units. By 2010/2011, municipalities located along the Arc of Deforestation had more than 55% of the remaining mature forest strictly confined to conservation units. Further, the planned settlement showed a higher rate of forest loss, a more persistent increase in deforested areas and a higher relative incidence of deforestation inside conservation units. Distinct agricultural activities did not lead to significantly different landscape structures; the accessibility of the municipality showed greater influence in the degree of degradation of the landscapes. Even with a high proportion of the landscapes covered by conservation units, which showed a strong inhibitory effect on forest fragmentation, we show that dynamic agriculturally driven economic activities, in municipalities with extensive road development, led to more regularly shaped, heavily fragmented landscapes, with higher densities of forest edge

Managerial Views of Corporate Impacts and Dependencies on Ecosystem Services : A Case of International and Domestic Forestry Companies in China

A line of research is emerging investigating the private sector impacts and dependencies on critical biodiversity and ecosystem services, and related business risks and opportunities. While the ecosystem services narrative is being forwarded globally as a key paradigm for promoting business sustainability, there is scarce knowledge of how these issues are considered at managerial level. This study thus investigates managerial views of corporate sustainability after the ecosystem services concept. We analyse interviews conducted with 20 managers from domestic and international forestry companies operating with a plantation-based business model in China. Content analysis was employed to analyse the data, with a focus on four key areas: (1) interviewee familiarity with the ecosystem services concept; (2) their views of corporate dependencies and impacts on ecosystem services; (3) related business risks and opportunities; and (4) viability of existing instruments and practices that can be employed in detecting and addressing business impacts and dependencies on ecosystem services. Through an inductive approach to the empirical findings, we refined a framework that holds operational value for developing company response strategies to ecosystem services impact/dependence assessment, ensuring that all issues are addressed comprehensively, and that related risks and opportunities are properly acknowledged.Peer reviewe

Social anxiety symptoms in young children:Investigating the interplay of theory of mind and expressions of shyness

Children’s early onset of social anxiety may be associated with their social understanding, and their ability to express emotions adaptively. We examined whether social anxiety in 48-month-old children (N = 110; 54 boys) was related to: a) a lower level of theory of mind (ToM); b) a lower proclivity to express shyness in a positive way (adaptive); and c) a higher tendency to express shyness in a negative way (non-adaptive). In addition, we investigated to what extent children’s level of social anxiety was predicted by the interaction between ToM and expressions of shyness. Children’s positive and negative expressions of shyness were observed during a performance task. ToM was measured with a validated battery, and social anxiety was assessed using both parents’ reports on questionnaires. Socially anxious children had a lower level of ToM, and displayed more negative and less positive shy expressions. However, children with a lower level of ToM who expressed more positive shyness were less socially anxious. Additional results show that children who displayed shyness only in a negative manner were more socially anxious than children who expressed shyness only in a positive way and children who did not display any shyness. Moreover, children who displayed both positive and negative expressions of shyness were more socially anxious than children who displayed shyness only in a positive way. These findings highlight the importance of ToM development and socio-emotional strategies, and their interaction, on the early development of social anxiety

Safeguarding pollinators and their values to human well-being

Wild and managed pollinators provide a wide range of benefits to society in terms of contributions to food security, farmer and beekeeper livelihoods, social and cultural values, as well as the maintenance of wider biodiversity and ecosystem stability. Pollinators face numerous threats, including changes in land-use and management intensity, climate change, pesticides and genetically modified crops, pollinator management and pathogens, and invasive alien species. There are well-documented declines in some wild and managed pollinators in several regions of the world. However, many effective policy and management responses can be implemented to safeguard pollinators and sustain pollination services

Genomic view of the evolution of the complement system

The recent accumulation of genomic information of many representative animals has made it possible to trace the evolution of the complement system based on the presence or absence of each complement gene in the analyzed genomes. Genome information from a few mammals, chicken, clawed frog, a few bony fish, sea squirt, fruit fly, nematoda and sea anemone indicate that bony fish and higher vertebrates share practically the same set of complement genes. This suggests that most of the gene duplications that played an essential role in establishing the mammalian complement system had occurred by the time of the teleost/mammalian divergence around 500 million years ago (MYA). Members of most complement gene families are also present in ascidians, although they do not show a one-to-one correspondence to their counterparts in higher vertebrates, indicating that the gene duplications of each gene family occurred independently in vertebrates and ascidians. The C3 and factor B genes, but probably not the other complement genes, are present in the genome of the cnidaria and some protostomes, indicating that the origin of the central part of the complement system was established more than 1,000 MYA

The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories

The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses

Abstract Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids and specialized proteins that determine their structure and functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca2+ homeostasis and apoptosis. Since these functions are essential for cell biology, it is therefore not surprising that MERCs also play a critical role in organ physiology among which the immune system stands by its critical host defense function. This defense system must discriminate and tolerate host cells and beneficial commensal microorganisms while eliminating pathogenic ones in order to preserve normal homeostasis. To meet this goal, the immune system has two lines of defense. First, the fast acting but unspecific innate immune system relies on anatomical physical barriers and subsets of hematopoietically derived cells expressing germline-encoded receptors called pattern recognition receptors (PRR) recognizing conserved motifs on the pathogens. Second, the slower but very specific adaptive immune response is added to complement innate immunity. Adaptive immunity relies on another set of specialized cells, the lymphocytes, harboring receptors requiring somatic recombination to be expressed. Both innate and adaptive immune cells must be activated to phagocytose and process pathogens, migrate, proliferate, release soluble factors and destroy infected cells. Some of these functions are strongly dependent on lipid transfer, autophagosome formation, mitochondrial fission, and Ca2+ flux; this indicates that MERCs could regulate immunity