Autoantibodies as Diagnostic and Predictive Markers of Vitiligo

Genetic and environmental factors are believed to influence development of systemic lupus erythematosus (SLE). Endogenous retroviruses (ERV) correspond to the integrated proviral form of infectious retroviruses, which are trapped within the genome due to mutations. ERV represent a key molecular link between the host genome and infectious viral particles. ERV-encoded proteins are recognized by antiviral immune responses and become targets of autoreactivity. Alternatively, ERV protein may influence cellular processes and the life cycle of infectious viruses. As examples, the HRES-1 human ERV encodes a 28-kDa nuclear autoantigen and a 24-kDa small GTP-ase, termed HRES-1/Rab4. HRES-1/p28 is a nuclear autoantigen recognized by cross-reactive antiviral antibodies, while HRES-1/Rab4 regulates surface expression of CD4 and the transferrin receptor (TFR) through endosome recycling. Expression of HRES-1/Rab4 is induced by the tat gene of HIV-1, which in turn down-regulates expression of CD4 and susceptibility to re-infection by HIV-1. CD4 and the TFR play essential roles in formation of the immunological synapse (IS) during normal T-cell activation by a cognate MHC class II peptide complex. The key intracellular transducer of T-cell activation, Lck, is brought to the IS via binding to CD4. T-cell receptorζ (TCRζ) chain binds to the TFR. Abnormal T-cell responses in SLE have been associated with reduced lck and TCRζ chain levels. HRES-1 is centrally located on chromosome 1 at q42 relative to lupus-linked microsatellite markers and polymorphic HRES-1 alleles have been linked to the development of SLE. 1q42 is one of the three most common fragile sites in the human genome, and is inducible by DNA demethylation, a known mechanism of retroviral gene activation. Molecular mimicry and immunomodulation by a ERV, such as HRES-1, may contribute to self-reactivity and abnormal T and B-cell functions in SLE.     

Abnormalities of intrinsic brain activity in essential tremor: A meta‐analysis of resting‐state functional imaging

Neuroimaging studies using a variety of techniques have demonstrated abnormal patterns of spontaneous brain activity in patients with essential tremor (ET). However, the findings are variable and inconsistent, hindering understanding of underlying neuropathology. We conducted a meta‐analysis of whole‐brain resting‐state functional neuroimaging studies in ET compared to healthy controls (HC), using anisotropic effect‐size seed‐based d mapping, to identify the most consistent brain activity alterations and their relation to clinical features. After systematic literature search, we included 13 studies reporting 14 comparisons, describing 286 ET patients and 254 HC. Subgroup analyses were conducted considering medication status, head tremor status, and methodological factors. Brain activity in ET is altered not only in the cerebellum and cerebral motor cortex, but also in nonmotor cortical regions including prefrontal cortex and insula. Most of the results remained unchanged in subgroup analyses of patients with head tremor, medication‐naive patients, studies with statistical threshold correction, and the large subgroup of studies using functional magnetic resonance imaging. These findings not only show consistent and robust abnormalities in specific brain regions but also provide new information on the biology of patient heterogeneity, and thus help to elucidate the pathophysiology of ET.     

New evidence for,and challenges in,linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ‐carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.     

Correction to: Irreversible Electroporation For Hepatocellular Carcinoma: Longer-Term Outcomes At A Single Centre

CardioVascular and Interventional Radiology - An author was inadvertently omitted from the author list. Helen Kavnoudias should be listed as third author. The added author’s name and...     

Platelet—Rich—Plasma Injections in Treating Lateral Epicondylosis: a Review of the Recent Evidence

Lateral epicondylosis is common, with various treatment modalities. Platelet—rich—plasma injections from autologous blood have recently been used in centres worldwide for the treatment of tennis elbow. We review and present the recent published evidence on the effectiveness of PRP injections for lateral epicondylosis. Nine studies met our inclusion criteria including 6 RCT’s for the purpose of analysis. PRP injections have an important and effective role in the treatment of this debilitating pathology, in cases where physiotherapy has been unsuccessful.     

Synthetic hexapeptide substrates and inhibitors of 3'':5''-cyclic AMP-dependent protein kinase.

The substrate specificity of the catalytic subunit of rabbit skeletal muscle 3': 5'-cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP: protein phosphotransferase) has been studied using the synthetic peptide Arg-Gly-Tyr-Ser-Leu-Gly corresponding to the sequence around serine 24, a phosphorylation site in reduced, carboxymethylated, maleylated (RCMM) chicken egg white lysozyme. This peptide served as a substrate for the enzyme and exhibited a 6-fold higher Vmax and a 100-fold higher Km than RCMM-lysozyme. Replacement of the arginine with glycine, histidine, or lysine resulted in a dramatic reduction in the Vmax. These results support the concept that arginine is an important residue in determining the substrate specificity of the protein kinase, predominantly influencing the Vmax of the phosphorylation reaction. Two synthetic peptides in which serine was replaced by an alanine acted as competitive inhibitors of phosphorylation of the synthetic peptide substrate and RCMM-lysozyme.     

From the Cover: Conflict translates environmental and social risk into business costs

Sustainability science has grown as a field of inquiry, but has said little about the role of large-scale private sector actors in socio-ecological systems change. However, the shaping of global trends and transitions depends greatly on the private sector and its development impact. Market-based and command-and-control policy instruments have, along with corporate citizenship, been the predominant means for bringing sustainable development priorities into private sector decision-making. This research identifies conflict as a further means through which environmental and social risks are translated into business costs and decision making. Through in-depth interviews with finance, legal, and sustainability professionals in the extractive industries, and empirical case analysis of 50 projects worldwide, this research reports on the financial value at stake when conflict erupts with local communities. Over the past decade, high commodity prices have fueled the expansion of mining and hydrocarbon extraction. These developments profoundly transform environments, communities, and economies, and frequently generate social conflict. Our analysis shows that mining and hydrocarbon companies fail to factor in the full scale of the costs of conflict. For example, as a result of conflict, a major, world-class mining project with capital expenditure of between US$3 and US$5 billion was reported to suffer roughly US$20 million per week of delayed production in net present value terms. Clear analysis of the costs of conflict provides sustainability professionals with a strengthened basis to influence corporate decision making, particularly when linked to corporate values. Perverse outcomes of overemphasizing a cost analysis are also discussed.Large-scale natural resource extraction projects (including exploration and processing activities) profoundly transform environments, communities, and economies, and often generate social conflict (2, 3). Previous studies of resource extraction and conflict have highlighted the relationship between mining and hydrocarbon resources and broader civil conflict (4, 5) and individual cases of project level conflict (6, 7). In this study, we investigate the importance of company–community conflict in the context of regulation of the sustainability performance of mining and hydrocarbon companies. We estimate the cost of social conflict to companies, determine how companies interpret this conflict, and explain how they respond to conflict. Costs were understood broadly as the negative impacts of company–community conflict on a company’s tangible and intangible assets, including value erosion. Conflict is defined as the coexistence of aspirations, interests, and world views that cannot be met simultaneously, or that actors do not perceive as being subject to simultaneous satisfaction, and is viewed in this assessment as ranging from low-level tension to escalated situations involving a complete relationship breakdown or violence (8).There is growing appreciation that unmitigated environmental and social risks have the potential to negatively influence the financial success of large-scale developments in the extractive industries. A 2008 study of 190 projects operated by the major international oil companies showed that the time taken for projects to come on-line nearly doubled in the preceding decade, causing significant increases in costs (9), although this increase reflects project remoteness, scale, technical difficulty, and input price, as well as social conflict. A follow-up of a subset of those projects found that nontechnical risks accounted for nearly one-half of the total risks faced by these companies, and that risks related to company relationships with other social actors constituted the single largest category (10). A separate empirical study of 19 publicly traded junior gold-mining companies found two-thirds of the market capitalization of these firms was a function of the firm’s stakeholder engagement practices, whereas only one-third was a function of the value of gold in the ground (11).In its analysis of socio-ecological systems (SESs), the sustainability science literature has said little about the large-scale private sector as an important actor within, and regulator of, SES behavior. A review of the 450 sustainability science articles published in PNAS, for example, finds just 23 referring to “corporate,” “industry,” “private sector,” or “company” in their texts. An extensive word cloud produced by a historical review of 20,000 papers related to sustainability science (12) notes just five terms implying a focus on the private sector (“corporate social,” “corporate sustainability,” “social responsibility,” “industrial ecology,” and “supply chain”), with none of these terms invoking core company decision making, culture, or calculations. However, large-scale corporate actors are obviously of central importance to the “major questions” for research in sustainability science (13), and perhaps especially the questions: “What shapes the long-term trends and transitions that provide the major directions for this century?” and “What determines the adaptability, vulnerability, and resilience of human–environment systems?” (13).The relevance of private sector actors is particularly clear in the extractive industries where, given the evolution of technology and industrial structure in these sectors, large enterprises have become highly influential actors in SES dynamics. Dramatic events and disasters, such as the Deepwater Horizon in the Gulf of Mexico, make this clear. Such enterprises can also be critical actors in slower processes of SES change, such as those mediating the relationships among water, agriculture, livelihoods, mining, and climate change (14, 15). Companies in the extractive industries have, to greater or lesser extent, developed policies for sustainable development and used sustainability professionals to respond to the changes induced by their activities on SESs. It is therefore important to understand the drivers of company behavior to build adequate models of socio-ecological change.This study addresses one potential driver of company behavior: conflicts motivated by the social and environmental risks created by, and the impacts of, corporate activities. More specifically, the study understands social conflict as a means through which populations communicate perceptions of risk and which generate costs for companies. The study refers to risk from the perspective of the entity experiencing the risk (i.e., environmental risks are risks to the environment; social risks are risks to society, social groups, or individuals; and business risks are the risks to the business). We ask about the significance of the costs associated with community conflict to companies, how far companies are prepared to respond to these costs by seeking strategies to reduce the environmental and social risk that they generate within SESs, and the conditions that can induce regulatory and strategic change within the corporate sector itself such that it reduces any negative environmental and social impacts.Although the report addresses just one dimension of large-scale private sector activity, the purpose is to suggest the importance of paying far more attention to corporate behavior in studies of socio-ecological dynamics. Emerging research on large-scale land acquisitions, or “land grabs” (16), and the implications for land-change science (17) suggests the same need to attend to corporate actors in sustainability science. In addressing this theme, our primary purpose is to map out, explore, and identify (rather than test) particular relationships between large-scale business and SES dynamics. The intent of the research is to build SES theory in ways that treat corporate behavior as endogenous to these systems.Through in-depth confidential interviews with corporate finance, legal, and sustainability professionals, and empirical case analysis, we investigate the extent to which recognition of the costs of conflict has the potential to change the ways in which companies address the environmental and social risks of mining and hydrocarbon development. Case studies combined desk-based analysis of secondary materials with key informant interviews to confirm or supplement the analysis. Case studies were used to characterize the types of company–community conflicts affecting mining projects, the point at which conflict took effect within the project cycle, and the types of effects that conflict appeared to have on projects. Key informant interviews were used to address how large-scale mining and hydrocarbon companies interpret these conflicts, how they respond to them, the factors determining different types of company response, and the extent to which calculations of the financial costs of conflict change the ways in which companies respond.