Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility

Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients.

Interacting effects of change in climate, human population, land use, and water use on biodiversity and ecosystem services

Human population growth and resource use, mediated by changes in climate, land use, and water use, increasingly impact biodiversity and ecosystem services provision. However, impacts of these drivers on biodiversity and ecosystem services are rarely analyzed simultaneously and remain largely unknown. An emerging question is how science can improve the understanding of change in biodiversity and ecosystem service delivery and of potential feedback mechanisms of adaptive governance. We analyzed past and future change in drivers in south-central Sweden. We used the analysis to identify main research challenges and outline important research tasks. Since the 19th century, our study area has experienced substantial and interlinked changes; a 1.6°C temperature increase, rapid population growth, urbanization, and massive changes in land use and water use. Considerable future changes are also projected until the mid-21st century. However, little is known about the impacts on biodiversity and ecosystem services so far, and this in turn hampers future projections of such effects. Therefore, we urge scientists to explore interdisciplinary approaches designed to investigate change in multiple drivers, underlying mechanisms, and interactions over time, including assessment and analysis of matching-scale data from several disciplines. Such a perspective is needed for science to contribute to adaptive governance by constantly improving the understanding of linked change complexities and their impacts.

Transcriptomics and proteomics show that selenium affects inflammation, ctoskeleton, and cancer pathways in human rectal biopsies

Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.

Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells

The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 mu m) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 mu m), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 mu M did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.

Structure, Dynamics, and RNA Interaction Analysis of the Human SBDS Protein

Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS. (C) 2010 Elsevier Ltd. All rights reserved.

Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci

It has been postulated that noncoding RNAs (ncRNAs) are involved in the posttranscriptional control of gene expression, and may have contributed to the emergence of the complex attributes observed in mammalians. We show here that the complement of ncRNAs expressed from intronic regions of the human and mouse genomes comprises at least 78,147 and 39,660 transcriptional units, respectively. To identify conserved intronic sequences expressed in both humans and mice, we used custom-designed human cDNA microarrays to separately interrogate RNA from mouse and human liver, kidney, and prostate tissues. An overlapping tissue expression signature was detected for both species, comprising 198 transcripts; among these, 22 RNAs map to intronic regions with evidence of evolutionary conservation in humans and mice. Transcription of selected human-mouse intronic ncRNAs was confirmed using strand-specific RT-PCR. Altogether, these results support an evolutionarily conserved role of intronic ncRNAs in human and mouse, which are likely to be involved in the fine tuning of gene expression regulation in different mammalian tissues. (C) 2008 Elsevier Inc. All rights reserved.

The functions of Japanese Sound Symbolic Words in Different Types of Texts and Their Translation

Though sound symbolic words (onomatopoeia and mimetic words, or giongo and gitaigo in Japanese) exist in other languages, it would not be so easy to compare them to those in Japanese. This is because unlike in Japanese, in many other languages (here we see English and Spanish) sound symbolic words do not have distinctive forms that separate them immediately from the rest of categories of words. In Japanese, a sound symbolic word has a radical (that is based on the elaborated Japanese sound symbolic system), and often a suffix that shows subtle nuance. Together they give the word a distinctive form that differentiates it from other categories of words, though its grammatical functions could vary, especially in the case of mimetic words (gitaigo). Without such an obvious feature, in other languages, it would not be always easy to separate sound symbolic words from the rest. These expressions are extremely common and used in almost all types of text in Japanese, but their elaborated sound symbolic system and possibly their various grammatical functions are making giongo and gitaigo one of the most difficult challenges for the foreign students and translators. Studying the translation of these expressions into other languages might give some indication related to the comparison of Japanese sound symbolic words and those in other languages. Though sound symbolic words are present in many types of texts in Japanese, their functions in traditional forms of text (letters only) and manga (Japanese comics)are different and they should be treated separately. For example, in traditional types of text such as novels, the vast majority of the sound symbolic words used are mimetic words (gitaigo) and most of them are used as adverbs, whereas in manga, the majority of the sound symbolic words used (excluding those appear within the speech bubbles) are onomatopoeias (giongo) and often used on their own (i.e. not as a part of a sentence). Naturally, the techniques used to translate these expressions in the above two types of documents differ greatly. The presentation will focus on i) grammatical functions of Japanese sound symbolic words in traditional types of texts (novels/poems) and in manga works, and ii) whether their features and functions are maintained (i.e. whether they are translated as sound symbolic words) when translated into other languages (English and Spanish). The latter point should be related to a comparison of sound symbolic words in Japanese and other languages, which will be also discussed.

Expression, localisation and hormone regulation of the human copper transporter hCTR1 in placenta and choriocarcinoma Jeg-3 cells

Copper is an essential trace element necessary for normal growth and development. During pregnancy, copper is transported from the maternal circulation to the fetus by mechanisms which have not been clearly elucidated. The copper uptake protein, hCTR1 is predicted to play a role in copper transport in human placental cells. This study has examined the expression and localisation of hCTR1 in human placental tissue and Jeg-3 cells. In term placental tissue the hCTR1 protein was detected as a 105 kDa protein, consistent with the size of a trimer which may represent the functional protein. A 95 kDa band, possibly representing the glycosylated protein, was also detected. hCTR1 was localised within the syncytiotrophoblast layer and the fetal vascular endothelial cells in the placental villi and interestingly was found to be localised toward the basal plasma membrane. It did not co-localise with either the Menkes or the Wilson copper transporting ATPases. Using the placental cell line Jeg-3, it was shown that the 35 kDa monomer was absent in the extracts of cells exposed to insulin, estrogen or progesterone and in cells treated with estrogen an additional 65 kDa band was detected which may correspond to a dimeric form of the protein. The 95 kDa band was not detected in the cultured cells. These results provide novel insights indicating that hormones have a role in the formation of the active hCTR1 protein. Furthermore, insulin altered the intracellular localisation of hCTR1, suggesting a previously undescribed role of this hormone in regulating copper uptake through the endocytic pathway.

Human health, well-being and global ecological scenarios

This article categorizes four kinds of adverse effects to human health caused by ecosystem change: direct, mediated, modulated, and systems failure. The effects are categorized on their scale, complexity, and lag-time. Some but not all of these can be classified as resulting from reduced ecosystem services. The articles also explores the impacts that different socioeconomic–ecologic scenarios are likely to have on human health and how changes to human health may, in turn, influence the unfolding of four different plausible future scenarios. We provide examples to show that our categorization is a useful taxonomy for understanding the complex relationships between ecosystems and human well-being and for predicting how future ecosystem changes may affect human health.

Linking future ecosystem services and future human well-being

Ecosystem services are necessary, yet not sufficient for human well-being (however defined). Insufficient access to the ecosystem provisioning service of food is a particularly important factor in the loss of human well-being, but all ecosystem services contribute in some way to well-being. Although perhaps long obvious to ecologists, the links between ecosystems and aspects of human well-being, including health, have been less well understood among the social science community. This situation may now be starting to change, thanks in part to the Millennium Ecosystem Assessment (MA). Causality between ecosystem services and well-being is bidirectional; it is increasingly clear that functioning societies can protect or enhance ecosystem services, and accordingly, that societies with impaired well-being (best documented in the case of chronic diseases such as malaria and HIV/AIDS) can also experience a related decline in ecosystem services.

The future state of human well-being and of ecosystem services is more than the co-evolution of these two fundamental elements. Human well-being also depends, critically, upon the human institutions that govern relationships between human individuals and groups, and also between humans and ecosystem services.

The scenarios working group of the MA found that human well-being is highest in the Global Orchestration scenario, which assumes the fastest evolution of beneficial institutions, and is lowest in the Order from Strength scenario. Human well-being was found to be intermediate in the other two scenarios (Adapting Mosaic and Techno-Garden) even though these scenarios share a much greater recognition of the importance of ecosystem services to human well-being.

Understanding what microfinance institutions need to address to aid poverty alleviation, social inclusion and human development

Poverty, in its most basic form can be defined as a deprivation of well-being. It is an issue that has been evident in society for centuries and a concern for government policy makers and more recently for non-government organizations (NGOs). In this paper, we consider how management approaches to resolving the dilemma of poverty can be advanced by drawing on two major areas in the development arena associated with poverty, namely, ‘social exclusion’ and ‘the human development paradigm’. We put forward the argument that for groups of people where social disintegration has already occurred, only structural interventions coupled with a social development mechanism will achieve the desired effect. One method for achieving this is through the use of microfinance programs which provide a broad range of financial services to the poor and low-income households as well as to micro-enterprises. This paper contributes to both management practice and theory by developing a theoretical model that microfinance institutions need to do to aid both ‘human development’ and ‘social inclusion’ processes for the socially excluded and poor.

Developing critical thinking skills through active teaching and learning strategies: a literatre review

Clinical decision-making is an integral part of nursing practice. Critical thinking skills are required by nurses to make effective clinical decisions that have positive outcomes. This paper is a review of literature related to critical thinking and decision making and identifies the teaching and learning strategies that are most likely to encourage these abilities in nurses.

A model to enable organisational cultural change using systemic strategic human resource management

Cultural change in organisations is both difficult to implement and hard to achieve. In this paper, theory from strategic human resource management, organisational cultural change, systemic thinking and practice, and punctuated equilibrium, is integrated in order to build a model for organisational culture change. Evidence is provided showing the capacity of the model to enable researchers and organisational change agents to improve the success of organisational cultural change programs.

Tolling for the luckless, the abandoned and forsaked : therapeutic jurisprudence and international human rights law as applied to prisoners and detainees by forensic psychologists

Objectives. There has been an explosion of interest in therapeutic jurisprudence as both a filter and lens for viewing the extent to which the legal system serves therapeutic or anti-therapeutic consequences. However, little attention has been paid to the impact of therapeutic jurisprudence on questions of international human rights law and the role of forensic psychologists. The paper aims to provide an intersection between human rights, therapeutic jurisprudence, and forensic psychology.

Method. Human rights are based on legal, social, and moral rules. Human rights literature generally considers legal rights but such policy statements do not provide principles to guide forensic psychologists in addressing moral or social rights. Therefore, a framework to guide forensic psychologists is required.

Conclusion. As duty-bearers, forensic psychologists need to address the core values of freedom and well-being in rights holders (in this instance, prisoners and detainees with a mental illness). The paper proposes that human rights principles can add to the normative base of a therapeutic jurisprudence framework, and in-turn, therapeutic jurisprudence can assist forensic psychologists to actively address human rights.

A reservoir of brown adipocyte progenitors in human skeletal muscle

Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-{gamma} (PPAR{gamma}) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR{gamma} agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.