Deepening our understanding of HDL proteome

ABSTRACT

Introduction: High-density lipoprotein (HDL) particles are heterogeneous and their proteome is complex and distinct from HDL cholesterol. However, it is largely unknown whether HDL proteins are associated with cardiovascular protection.

Areas covered: HDL isolation techniques and proteomic analyses are reviewed. A list of HDL proteins reported in 37 different studies was compiled and the effects of different isolation techniques on proteins attributed to HDL are discussed. Mass spectrometric techniques used for HDL analysis and the need for precise and robust methods for quantification of HDL proteins are discussed.

Expert opinion: Proteins associated with HDL have the potential to be used as biomarkers and/or help to understand HDL functionality. To achieve this, large cohorts must be studied using precise quantification methods. Key factors in HDL proteome quantification are the isolation methodology and the mass spectrometry technique employed. Isolation methodology affects what proteins are identified in HDL and the specificity of association with HDL particles needs to be addressed. Shotgun proteomics yields imprecise quantification, but the majority of HDL studies relied on this approach. Few recent studies used targeted tandem mass spectrometry to quantify HDL proteins, and it is imperative that future studies focus on the application of these precise techniques.     

Alaskan marine mammal tissue archival project

A project to establish an archive of Alaskan marine mammal tissues was conceived in 1987 to be a part of the National Biomonitoring Specimen Bank (NBSB). Protocols and field collection of marine mammals, long-term storage, and analysis are summarized in this paper. Instrumental neutron activation analysis has been used for an initial evaluation of trace element content in samples of northern fur seal (Callorhinus ursinus) from the Pribilof Islands. The findings agree with previously observed trace element levels in northern fur seals. The archived specimens can be used in future studies when comparisons of past and present pollution levels are needed.

     

Use of wireless phones and serum β-trace protein in randomly recruited persons aged 18–65 years: a cross-sectional study

Background: There are studies suggesting effects on sleep from pulse-modulated radiofrequency fields used in mobile and cordless phones. So far, reports of adverse effects in observational studies are of limited value for risk assessment while effects from experimental studies seem to be more consistent but unclear as to their importance for health. The aim of this study was to investigate whether use of wireless phones is associated with lower concentrations of β-trace protein (lipocalin-type prostaglandin D synthase), a key enzyme in the synthesis of prostaglandin D₂, an endogenous sleep-promoting neurohormone.

Methods: Three hundred and fourteen people, aged 18–65 years and living in the municipality of Örebro, Sweden, were recruited randomly using the population registry. Total and age-specific linear regression analyses adjusted for known covariates were used to calculate associations between levels of β-trace protein and short- and long-term use of wireless phones.

Results: Overall, no statistically significant association between use of wireless phones and the serum concentration of β-trace protein was found, neither with respect to short-term nor long-term use. Age-specific analyses, however, yielded negative associations for long-term use (cumulative hours of use) and β-trace protein in the youngest age group (18–30 years). Conclusion: This study provided no overall evidence of an association between wireless phone use and serum concentrations of β-trace protein. While the findings in the 18–30 year age group indicating lower concentrations with more cumulative hours of use should be further investigated, no causal inferences can be made from the results of the present study.     

Life cycle assessment of electricity generation: a review of the characteristics of existing literature

Purpose

The environmental impacts of electricity generation are a critical issue towards sustainability and thus an important research topic in several countries. The life cycle assessment methodology has been widely employed to assess electricity generation. However, there are still gaps in research to be explored within this theme. Therefore, this paper aims to conduct a systematic theoretical analysis of the state of the art of the scientific research on LCA of electricity generation systems in the world.

Methods

A critical review of 47 studies was conducted. The study is comprehensive in the analysis of the main aspects of the identified high impact studies as follows: authors, countries, universities, keywords, journals, number of citations, life cycle impact assessment methods, impact categories, software tools, and databases. The Methodi Ordinatio was applied to rank the studies in terms of impact factor and number of citations, pointing out high impact research.

Results and discussion

Wind and solar powers have two of the smallest impact indices in their generation in terms of global warming, compared to other sources. The ecoinvent database was the most used among the studies analyzed, providing data for potential environmental impacts. The most frequently used impact category in the assessments was climate change. The studies are not equally distributed but most of them are concentrated in European countries. In some countries, clean sources seem promising due to their capacity to generate electricity in places with high wind incidence and high capacity for sunlight capture.

Conclusions

The conclusions of this article summarize the characteristics of existing literature and provide suggestions for future work. The results of the study can also be used to promote development actions and foment changes in energy matrices in a global context. The main studies in this area point that in the future, the main sources for electricity generation will be renewable ones, since life cycle assessment of electricity generation systems has been seeking to generate knowledge to support informed decision-making.

     

Environmental impacts of wooden,plastic, and wood-polymer composite pallet: a life cycle assessment approach

Purpose

Waste recycling is one of the essential tools for the European Union’s transition towards a circular economy. One of the possibilities for recycling wood and plastic waste is to utilise it to produce composite product. This study analyses the environmental impacts of producing composite pallets made of wood and plastic waste from construction and demolition activities in Finland. It also compares these impacts with conventional wooden and plastic pallets made of virgin materials.

Methods

Two different life cycle assessment methods were used: attributional life cycle assessment and consequential life cycle assessment. In both of the life cycle assessment studies, 1000 trips were considered as the functional unit. Furthermore, end-of-life allocation formula such as 0:100 with a credit system had been used in this study. This study also used sensitivity analysis and normalisation calculation to determine the best performing pallet.

Result and discussion

In the attributional cradle-to-grave life cycle assessment, wood-polymer composite pallets had the lowest environmental impact in abiotic depletion potential (fossil), acidification potential, eutrophication potential, global warming potential (including biogenic carbon), global warming potential (including biogenic carbon) with indirect land-use change, and ozone depletion potential. In contrast, wooden pallets showed the lowest impact on global warming potential (excluding biogenic carbon). In the consequential life cycle assessment, wood-polymer composite pallets showed the best environmental impact in all impact categories. In both attributional and consequential life cycle assessments, plastic pallet had the maximum impact. The sensitivity analysis and normalisation calculation showed that wood-polymer composite pallets can be a better choice over plastic and wooden pallet.

Conclusions

The overall results of the pallets depends on the methodological approach of the LCA. However, it can be concluded that the wood-polymer composite pallet can be a better choice over the plastic pallet and, in most cases, over the wooden pallet. This study will be of use to the pallet industry and relevant stakeholders.

     

Differences in the diurnal and nocturnal use of intertidal feeding grounds by Redshank Tringa totanus

Capsule Redshank used more sites and had larger ranges at night than during the day.

Aims To determine whether there were differences in how wintering Redshank used intertidal feeding grounds during the day and night.

Methods The movements of 38 Redshank caught and radiotagged at two neighbouring sites on the Severn Estuary were monitored during four different study periods between January 1997 and October 1999.

Results Individuals used a greater number of sites at night than in the day (on average, two as opposed to one). Kernel home range analyses also indicated that individuals used larger core areas and home ranges at night. In addition, there was a significant difference between the sizes of ranges of birds caught at two neighbouring sites. One foraging site was almost entirely avoided during the day, probably due to disturbance from an adjacent heliport, but was used by the majority of individuals at night when the heliport was unused. This site was rich in invertebrates as a result of the high organic and nutrient input from a sewage outfall pipe. Redshank also used riverine mudflats less during the night, preferring more open mudflats – perhaps to avoid nocturnal predators.

Conclusions Comparison with previous studies suggests that the importance of sites predominantly used at night and the total extent of the areas used by waders may be underestimated by studies that rely on daytime surveys alone. It is important, therefore, that information on nocturnal distributions should be available to inform decisions on site management and protection.     

SIRT2 Plays Significant Roles in Lipopolysaccharides-Induced Neuroinflammation and Brain Injury in Mice

Several recent studies have suggested seemingly contrasting roles of SIRT2 in inflammation: Our previous cell culture study has indicated that SIRT2 siRNA-produced decrease in SIRT2 levels can lead to significant inhibition of lipopolysaccharides (LPS)-induced activation of BV2 microglia, suggesting that SIRT2 is required for LPS-induced microglial activation. In contrast, some studies have suggested that SIRT2 deficiency can lead to increased inflammation. In our current study, we used a mouse model of neuroinflammation to determine the roles of SIRT2 in LPS-induced inflammation. We found that administration of SIRT2 inhibitor AGK2 can significantly decrease LPS-induced increases in CD11b signals and the mRNA of TNF-α and IL-6. We further found that AGK2 can block LPS-induced nuclear translocation of NFκB. In addition, our study has shown that AGK2 can decrease not only LPS-induced increase in TUNEL signals—a marker of apoptosis-like damage, but also LPS-induced increases in the levels of active Caspase-3 and Bax. Collectively, our current in vivo study, together with our previous cell culture study, has suggested that SIRT2 is required for LPS-induced neuroinflammation and brain injury.

     

Insulin concentrations used in in vitro embryo production systems: a pilot study on insulin stability with an emphasis on concentrations measured in vivo

Background

Insulin has been used as a stimulatory factor for in vitro cell culture since many years. Even for routine in vitro embryo production (IVP), insulin is added to the media during different steps. There is a strong difference in concentrations used in vitro compared to what is measured in vivo in follicular fluid or serum. We performed a pilot study on insulin stability to explain possible reasons for that variation.

Results

We measured insulin concentrations before and after bovine oocyte maturation in an experiment by using a quantitative ELISA (Mercodia bovine insulin ELISA immunoassay) and found that concentrations were stable up to 22 h of incubation. We compared our results with eleven in vivo studies measuring insulin in either serum or follicular fluid and nine IVP-protocols using insulin. In all studies, in vitro concentrations were much higher compared with those found physiologically in vivo. Limited knowledge is available concerning the different activity and stability of insulin in vitro versus in vivo.

Conclusions

The concentrations of insulin used in vitro are quite high in comparison to physiological concentrations found in serum or follicular fluid. One explanation may be a different stability or activity of insulin in vitro even if we could measure stable concentrations of insulin in our pilot study. More precise dose–effect studies have to be performed to draw clear conclusions about the consequences of the use of such high doses as they might have negative consequences for the developing embryo. Insulin has direct effects on the regulation of the metabolism and could even influence the epigenetic programming of the metabolism with unknown consequences for the offspring later in life.

     

Life cycle environmental and economic assessment of industrial symbiosis networks: a review of the past decade of models and computational methods through a multi-level analysis lens

Purpose

Industrial symbiosis network (ISN) facilitation tools seek to holistically evaluate the environmental and economic performance of ISNs through life cycle assessment (LCA) and life cycle costing (LCC). ISNs have many stakeholders with diverse interests in the LCA and LCC results thus requiring multi-level analysis. The objective of this review was to examine the state-of-the-art methodologies used in LCAs and LCCs of ISNs and understand how multi-level analysis can be conducted.

Methods

The systematic literature review methodology was applied to develop a corpus of peer-reviewed LCA and LCC studies of ISNs published between 2010 and 2019 without any geographic boundary. Abstracts were reviewed to shortlist studies that conducted an LCA or LCC of an ISN with numerical results. LCA and LCC methodologies used in the shortlisted studies were collected and categorized. Each methodology was examined to understand how the foreground and background systems are represented, how waste-to-resource exchanges are analyzed, and how the results can be computed at the network, entity, and flow levels.

Results and discussion

The review yielded 42 LCA studies and 11 LCC studies of ISNs that used eight different methodologies. Process-based LCA was used in 71% of the LCA studies, whereas tiered hybrid LCA was used in 14% of the studies. Waste-to-resource exchanges in ISN scenarios were represented either through process analysis or as a black box. Fewer LCC studies that evaluate the economic performance of ISNs exist compared with LCA studies. Economic studies often evaluated financial feasibility, net present value, profitability, or payback period of specific waste-to-resource exchanges or the network overall.

Conclusions

The insights derived from this review chart future areas of research in multi-level modeling and analysis of the life cycle environmental and economic performance of ISNs. To improve the model construction and analysis process, research should be explored in developing a methodology for constructing a single model that represents multiple entities linked together by waste-to-resource exchanges and can provide LCA and LCC results for different stakeholder perspectives. The lack of LCC studies of ISNs merits the need for more research in this area at both the network and entity levels to quantify potential economic trade-offs between stakeholders. Developing a methodology for unified LCA and LCC modeling and analysis of ISNs can help ISN facilitation tool developers conduct simultaneous life cycle environmental and economic analysis of the potential symbiosis connections identified and how they contribute to the overall network.

     

Serum metabolomics identifies metabolite panels that differentiate lame dairy cows from healthy ones

Background

Metabolomics provides measurement of numerous metabolites in human samples, which can be a useful tool in clinical research. Blood and urine are regarded as preferred subjects of study because of their minimally invasive collection and simple preprocessing methods. Adhering to standard operating procedures is an essential factor in ensuring excellent sample quality and reliable results.

Aim of review

In this review, we summarize the studies about the impacts of various preprocessing factors on metabolomics studies involving clinical blood and urine samples in order to provide guidance for sample collection and preprocessing.

Key scientific concepts of review

Clinical information is important for sample grouping and data analysis which deserves attention before sample collection. Plasma and serum as well as urine samples are appropriate for metabolomics analysis. Collection tubes, hemolysis, delay at room temperature, and freeze–thaw cycles may affect metabolic profiles of blood samples. Collection time, time between sampling and examination, contamination, normalization strategies, and storage conditions may alter analysis results of urine samples. Taking these collection and preprocessing factors into account, this review provides suggestions of standard sample preprocessing.

     

Comparison of oxidative stress markers in vaginal deliveries with or without epidural analgesia

Abstract

Background

It has been demonstrated that oxidative stress can induce red blood cell rigidity and haemolysis, which in turn can cause hyperviscosity and hyperbilirubinaemia, respectively. However, haemolysis may be associated with a low level of haemoglobin, which reduces whole blood viscosity (WBV). Bilirubin can behave as antioxidant or oxidant, and one uncharted course for diagnostic pathology is how or whether bilirubinaemia and viscosity are associated. Further, oxidative stress is now being assessed using lipoprotein-a (Lp(a)), among other things but whether it is associated with blood viscosity has not been established.

Aim

This study investigates the association and correlation of haemoglobin level and WBV with serum Lp(a) and bilirubin levels in a general population of patients.

Materials and methods

Sixty-eight cases that were tested for Lp(a), concomitantly with full blood count and liver function, in our archived clinical pathology database were used in this study. WBV levels were determined using a validated formula. Multivariate and univariate analyses as well as correlation were performed.

Results

WBV was found to be significantly associated with bilirubin (P < 0.02), but not with Lp(a). Haemoglobin concentration was inversely correlated with Lp(a) (P < 0.04), but not with bilirubinaemia.

Conclusion

This pilot study suggests that hyperbilirubinaemia and hyperviscosity are associated and positively correlated. Consideration of whether serum bilirubin (as an indirect index of oxidative stress) can be used in combination with WBV (as index of macrovascular effect of oxidative stress) to assess oxidative damage is recommended.     

The prognostic impact of tumour NSD2 expression in advanced prostate cancer

Abstract

Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).

Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.

Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p?=?0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.

Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.     

Acetic acid triggers cytochrome c release in yeast heterologously expressing human Bax

Proteins of the Bcl-2 protein family, including pro-apoptotic Bax and anti-apoptotic Bcl-xL, are critical for mitochondrial-mediated apoptosis regulation. Since yeast lacks obvious orthologs of Bcl-2 family members, heterologous expression of these proteins has been used to investigate their molecular and functional aspects. Active Bax is involved in the formation of mitochondrial outer membrane pores, through which cytochrome c (cyt c) is released, triggering a cascade of downstream apoptotic events. However, when in its inactive form, Bax is largely cytosolic or weakly bound to mitochondria. Given the central role of Bax in apoptosis, studies aiming to understand its regulation are of paramount importance towards its exploitation as a therapeutic target. So far, studies taking advantage of heterologous expression of human Bax in yeast to unveil regulation of Bax activation have relied on the use of artificial mutated or mitochondrial tagged Bax for its activation, rather than the wild type Bax (Bax α). Here, we found that cell death could be triggered in yeast cells heterologoulsy expressing Bax α with concentrations of acetic acid that are not lethal to wild type cells. This was associated with Bax mitochondrial translocation and cyt c release, closely resembling the natural Bax function in the cellular context. This regulated cell death process was reverted by co-expression with Bcl-xL, but not with Bcl-xLΔC, and in the absence of Rim11p, the yeast ortholog of mammalian GSK3β. This novel system mimics human Bax α regulation by GSK3β and can therefore be used as a platform to uncover novel Bax regulators and explore its therapeutic modulation.

     

Towards social life cycle assessment of mobility services: systematic literature review and the way forward

Purpose

The main purpose of this review is to describe the state of the art of social impact assessment with a focus on mobility services. Whereas the use phase plays an important role for the assessment of services in general, the evaluation of the use phase has been underrepresented in previous social life cycle assessment studies. For that reason, particular attention has been paid to indicators, which allow the assessment of social impacts during the use phase of mobility services.

Methods

Continuous efforts to mitigate climate change and to improve quality of life in cities result in new mobility solutions based on collective use. This will have a huge impact on our society transforming the use of vehicles. In order to better understand the implications for cities, society and the automotive industry, it is essential to evaluate the social impact generated along a product life cycle with particular attention to the use phase. To reach the goal, a systematic literature review was carried out with a focus on social indicators that allow assessing use phase impacts of mobility services. The indicators were analysed and allocated to stakeholder groups. Based on the analysis, a core set of indicators is proposed under consideration of data availability.

Results and discussion

Based on the selected search strings, 51 publications were selected for the literature review, including 579 social indicators. The analysis revealed a wide variety and diversity of indicators that are trying to measure the same aspect. The allocation to the respective stakeholder groups showed that most of the indicators (36%) evaluate impacts regarding the stakeholder group local community. The majority of analysed indicators are of quantitative nature (63%). Nevertheless, a clear assessment method was often missing in the respective publications. Therefore, for the core set of indicators, an assessment method is proposed for every indicator.

Conclusions

The results from this study can help practitioners as well as researchers in the field of urban mobility assessment as it systematically analyses social sustainability aspects. The presented data gives an overview of various indicators that are suggested in other publications, and the proposed core set of indicators can be used to evaluate different mobility services in further research.

     

Quantifying life cycle inventories of agricultural field operations by considering different operational parameters

Purpose

The ability to estimate fuel and lubricant consumption as well as depreciated weight of agricultural machinery used for field operations is very useful for energy and environmental analyses. In this study, life cycle inventory data of agricultural field operations were established by considering different parameters of such operations.

Methods

Agricultural operations considered in this study include tillage, cultivation, planting, harvesting and post-harvest operations. For these operations, the fuel and lubricant consumption as well as depreciated weight of tractors, combine harvesters and agricultural implements was estimated by considering different operational parameters such as tractor power, field condition, depth of operation, soil condition, tractor type, operational capacity of machine, width of operation and speed. Technical standards were used to estimate different types of power required for most agricultural operations (drawbar power, rotary power and motion power). The standards were then used to evaluate the variability of the fuel and lubricant consumption as well as depreciated weight of the implements by varying the aforementioned parameters.

Results and discussion

The results were compared to those that can be calculated with other approaches for life cycle inventory analysis of agricultural operations. Such comparison indicates that by using different parameters, representing the diverse local conditions of different field operations, a great variability of the results is obtained. For instance, diesel fuel consumption of tillage operations ranges from 12.6 to 76.0 L ha^?1, with an average of 34.15 L ha^?1 and standard deviation of 11.7 L ha^?1. Such representativeness of the different conditions of each field operation cannot be modelled with other tools or via the use of standard LCI datasheets.

Conclusions

The final result of this study is a novel approach for the life cycle inventory analysis of agricultural operations, in terms of fuel and lubricant consumption and of depreciated weight of the machines, which are estimated by simply selecting the operational parameters which best represent the effect of local conditions.

     

Molecular role of catalase on oxidative stress-induced Ca2+ signaling and TRP cation channel activation in nervous system

Background: Catalase catalyzes the reduction of H₂O₂ to water and it can also remove organic hydroperoxides. Nervous system in body is especially sensitive to free radical damage due to rich content of easily oxidizible fatty acids and relatively low content of antioxidants including catalase. Recent studies indicate that reactive oxygen species actually target active channel function, in particular TRP channels. I review the effects of catalase on Ca²⁺ signaling and on TRP channel activation in neuroglial cells such as microglia and substantia nigra.

Materials: Review of the relevant literature and results from recent our basic studies, as well as critical analyses of published systematic reviews were obtained from the pubmed and the Science Citation Index.

Results: It was observed that oxidative stress-induced activations of TRPM2, TRPC3, TRPC5 and TRPV1 cation channels in neuronal cells are modulated by catalase, suggesting antioxidant-dependent activation/inhibition of the channels. I provide also, a general overview of the most important oxidative stress-associated changes in neuronal mitochondrial Ca²⁺ homeostasis due to oxidative stress-induced channel neuropathies. Catalase incubation induces protective effects on rat brain mitochondrial function and neuronal survival. A decrease in catalase activity through oxidative stress may have an important role in etiology of Parkinson’s disease and sensory pain.

Conclusion: The TRP channels can be activated by oxidative stress products, opening of nonspecific cation channels would result in Ca²⁺ influx, and then elevation of cytoplasmic free Ca²⁺ could stimulate mitochondrial Ca²⁺ uptake. Catalase modulates oxidative stress-induced Ca²⁺ influx and some TRP channels activity in neuronal cells.     

Key Features for Designing Phosphodiesterase-5 Inhibitors

Abstract

Phosphodiesterase superfamily is the key regulator of 3′,5′-cyclic guanosine monophosphate (cGMP) decomposition in human body. Phosphodiesterase-5 (PDE-5) inhibitors, sildenafil, vardenafil and tadalafil, are well known oral treatment for males with erectile dysfunction. To investigate the inhibitory effects of traditional Chinese medicine (TCM) compounds to PDE-5, we performed both ligand-based and structure-based studies on this topic. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted to construct three dimensional quantitative structure-activity relationship (3D-QSAR) models of series of known PDE-5 inhibitors. The predictive models had cross-validated, q², and non cross-validated coefficient, r², values of 0.791 and 0.948 for CoMFA and 0.724 and 0.908 for CoMSIA. These two 3D-QSAR models were used to predict activity of TCM compounds. Docking simulations were performed to further analyze the binding mode of training set and TCM compounds. A putative binding model was proposed based on CoMFA and CoMSIA contour maps and docking simulations; formation of pi-stacking, water bridge and specific hydrogen bonding were deemed important interactions between ligands and PDE-5. Of our TCM compounds, engeletin, satisfied our binding model, and hence, emerged as PDE-5 inhibitor candidate.

Using this study as an example, we demonstrated that docking should be conducted for qualitative purposes, such as identifying protein characteristics, rather than for quantitative analyses that rank compound efficacy based on results of scoring functions. Prediction of compound activity should be reserved for QSAR analyses, and scoring functions and docking scores should be used for preliminary screening of TCM database (http://tcm.cmu.edu.tw/index.php).