How Can Scientific Literature Support Decision-Making in the Renovation of Historic Buildings? An Evidence-Based Approach for Improving the Performance of Walls

Buildings of heritage significance due to their historical, architectural, or cultural value, here called historic buildings, constitute a large proportion of the building stock in many countries around the world. Improving the performance of such buildings is necessary to lower the carbon emissions of the stock, which generates around 40% of the overall emissions worldwide. In historic buildings, it is estimated that heat loss through external walls contributes significantly to the overall energy consumption, and is associated with poor thermal comfort and indoor air quality. Measures to improve the performance of walls of historic buildings require a balance between energy performance, indoor environmental quality, heritage significance, and technical compatibility. Appropriate wall measures are available, but the correct selection and implementation require an integrated process throughout assessment (planning), design, construction, and use. Despite the available knowledge, decision-makers often have limited access to robust information on tested retrofit measures, hindering the implementation of deep renovation. This paper provides an evidence-based approach on the steps required during assessment, design, and construction, and after retrofitting through a literature review. Moreover, it provides a review of possible measures for wall retrofit within the deep renovation of historic buildings, including their advantages and disadvantages and the required considerations based on context

Algal Toxins Alter Copepod Feeding Behavior

Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod’s feeding appendages–a “sampling beating” that has short durations (<100 ms) and involves little fluid entrainment and a longer duration “grazing beating” that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod’s grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod’s feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods

The functional significance of microRNA-145 in prostate cancer

BackgroundMicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer.Methods and resultsWe investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3-transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis.ConclusionOne of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer

Using hippocampal microRNA expression differences between mouse inbred strains to characterise miRNA function

Micro-RNAs (miRNAs) are short, single-stranded, noncoding RNAs that are involved in the regulation of protein-coding genes at the level of messenger RNA (mRNA). They are involved in the regulation of numerous traits, including developmental timing, apoptosis, immune function, and neuronal development. To better understand how the expression of the miRNAs themselves is regulated, we looked for miRNA expression differences among four mouse inbred strains, A/J, BALB/cJ, C57BL/6J, and DBA/2J, in one tissue, the hippocampus. A total of 166 miRNA RT-PCR assays were used to screen RNA pools for each strain. Twenty miRNA species that were markedly different between strains were further investigated using eight individual samples per strain, and 11 miRNAs showed significant differences across strains (p < 0.05). This is the first observation of miRNA expression differences across inbred mice strains. We conducted an in silico correlation analysis of the expression of these differentially expressed miRNAs with phenotype data and mRNA expression to better characterise the effects of these miRNAs on both phenotype and the regulation of mRNA expression. This approach has allowed us to nominate miRNAs that have potential roles in anxiety, exploration, and learning and memory

Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach

MicroRNAs (miRNAs) are short (∼22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ∼11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs in vivo is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs in vivo. Our findings underscore the complexities of miRNA-mediated regulation in vivo and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized

Pathogenesis, diagnosis and management of pneumorrhachis

Pneumorrhachis (PR), the presence of intraspinal air, is an exceptional but eminent radiographic finding, accompanied by different aetiologies and possible pathways of air entry into the spinal canal. By reviewing the literature and analysing a personal case of traumatic cervical PR after head injury, we present current data regarding the pathoanatomy, clinical and radiological presentation, diagnosis and differential diagnosis and treatment modalities of patients with PR and associated pathologies to highlight this uncommon phenomenon and outline aetiology-based guidelines for the practical management of PR. Air within the spinal canal can be divided into primary and secondary PR, descriptively classified into extra- or intradural PR and aetiologically subsumed into iatrogenic, traumatic and nontraumatic PR. Intraspinal air is usually found isolated not only in the cervical, thoracic and, less frequently, the lumbosacral regions but can also be located in the entire spinal canal. PR is almost exceptional associated with further air distributions in the body. The pathogenesis and aetiologies of PR are multifold and can be a diagnostic challenge. The diagnostic procedure should include spinal CT, the imaging tool of choice. PR has to be differentiated from free intraspinal gas collections and the coexistence of air and gas within the spinal canal has to be considered differential diagnostically. PR usually represents an asymptomatic epiphenomenon but can also be symptomatic by itself as well as by its underlying pathology. The latter, although often severe, might be concealed and has to be examined carefully to enable adequate patient treatment. The management of PR has to be individualized and frequently requires a multidisciplinary regime

miR-210: fine-tuning the hypoxic response

Hypoxia is a central component of the tumor microenvironment and represents a major source of therapeutic failure in cancer therapy. Recent work has provided a wealth of evidence that noncoding RNAs and, in particular, microRNAs, are significant members of the adaptive response to low oxygen in tumors. All published studies agree that miR-210 specifically is a robust target of hypoxia-inducible factors, and the induction of miR-210 is a consistent characteristic of the hypoxic response in normal and transformed cells. Overexpression of miR-210 is detected in most solid tumors and has been linked to adverse prognosis in patients with soft-tissue sarcoma, breast, head and neck, and pancreatic cancer. A wide variety of miR-210 targets have been identified, pointing to roles in the cell cycle, mitochondrial oxidative metabolism, angiogenesis, DNA damage response, and cell survival. Additional microRNAs seem to be modulated by low oxygen in a more tissue-specific fashion, adding another layer of complexity to the vast array of protein-coding genes regulated by hypoxia