Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

Development and characterisation of a Y2Ti2O7-based glass-ceramic as a potential oxidation protective coating for titanium suboxide (TiOx)

A silica-based glass-ceramic, with Y₂Ti₂O₇ as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiO_x) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y₂Ti₂O₇ and CaAl₂Si₂O₈ as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiO_x material.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Long-Term Changes in the Course of Ice Phenomena on the Oder River along the Polish–German Border

Ice phenomena are a major component of the hydrological regime of east-central and northern European rivers. However, their occurrence disturbs inland water transportation, particularly affecting the major rivers of the Central European Plain that are part of Europe’s international waterways. The Oder is one of these rivers, and is located on the boundary between the much warmer and the much colder part of the temperate climatic zone. This makes the course of ice phenomena on the river difficult to predict. The main purpose of this work is to document and analyse the dynamic of changes occurring for over 60 years (1956–2015) in the ice phenomena of a river that demonstrates a transitional ice regime. It was found that the duration of all ice phenomena decreased (by up to 0.58 days·year^?1) and so did the duration of ice cover (by up to 0.46 days·year^?1). The rates and trends of the two parameters were, however, different in different parts of the lower stretch of the river. This fact is especially important in the context of climate changes whose characteristics include an increased incidence of extreme weather situations, both meteorological and hydrological. There was also found to be a strong correlation (R² from 0.69 to 0.81) between the duration of ice phenomena and the mean air temperature in winter (December to February) and a much weaker correlation between the duration of ice phenomena and the NAO index (R² from 0.42 to 0.48). Such a little correlation of ice phenomena with NAO is likely to result from the pollution of the Oder River (in particular in the second half of the twentieth century) and icebreaking operations on the river.

     

Volatile organic compound profiles of yoghurt produced from cow's milk with different somatic cell counts

The present study aimed to investigate the effect of somatic cell count (SCC) of raw cow's milk on the volatile organic compound (VOC) profiles of yoghurt. Test yoghurt samples were produced from three batches of cow's milk with low, medium and high SCC, respectively. The VOCs were determined by gas chromatography–mass spectrometry (GC–MS) analysis. A lower diacetyl and acetoin content and a higher content of 2‐heptanone, and butanoic and hexanoic acids were established in the yoghurt samples from batches with high SCC of above 1 000 000 cells/cm³. The increased SCC of cow's milk had a negative effect on the volatile organic compound profiles of yoghurt.     

The alpha-fetoprotein level analysis in open neural tube defects and chromosomal aberrations in the fetus

The effects of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) and two Chinese traditional (Kampo) medicines, Dai-saiko-to and Saiko-ka-ryukotsu-borei-to on spontaneous soft tissue (heart and tongue) mineralization in DBA/2NCrj mice were studied. These agents were given orally for 4 weeks to DBA/2NCrj mice. After 2 weeks of administration in the heart, 0.006 and 0.03% (w/v) HEBP decreased calcium content by 90 and 30%, respectively, while 0.27 and 2.7 mg/ml Dai-saiko-to reduced calcium content by 30 and 45%, respectively. Saiko-ka-ryukotsu-borei-to (0.27 mg/ml) reduced both calcium and phosphorus content by 50 and 35%, respectively. However, their inhibitory effects on the heart were not observed after 4 weeks of administration. The compounds delayed the onset of increases of bulk calcium and phosphorus content. In the tongue, at 4 weeks, 0.006 and 0.03% (w/v) HEBP reduced calcium content by 30 and 45%, respectively, while two Kampo medicines (at both concentrations used) significantly reduced the content of calcium (by 27-79%) and phosphorus (by 24-32%). These results strongly suggest that two Kampo medicines as well as HEBP may be useful in preventing and curing soft tissue calcification.     

Difficult to Let Housing Association Stock in England: Property,Management and Context

Problems related to unpopular housing are not new in Britain's social rented sector. In the past, however, these have generally been associated with housing provided directly by the state through local authorities. For many, the term 'difficult to let' has become synonymous with large, ageing, poor quality estates managed under a centralised framework and subject to a long period of low investment and indifferent management. There has also been a long-standing assumption that social housing allocations systems tend to channel the most vulnerable tenants into the least desirable housing. In fact, the problem of difficult to let property is now as pervasive in the not-for-profit sector managed by housing associations as it is within council housing. In many cases the developments affected are small in scale and, in a significant proportion of cases, recently constructed. In explaining why property becomes difficult to let, the local and regional context is clearly important. The balance between social, economic and housing demand circumstances and property and estate characteristics varies between regions. There is relatively little evidence that difficult to let housing association properties are occupied by disproportionate numbers of the most severely disadvantaged tenants and this suggests that something has happened to modify the segregating effects of allocations systems observed in earlier studies. Nevertheless, this apparent change must be seen within the context of the general trend towards a residual role for social housing in its entirety. The social class and income range of new social sector tenants now is much diminished by comparison with earlier decades with few distinctions between the occupiers of difficult to let and other housing.     

Effects of temperature, ammonium and glucose concentrations on yeast growth in a model wine system

In enology, alcoholic fermentation is a complex process involving several mechanisms. Slow and incomplete alcoholic fermentation is a chronic problem for the wine industry and factors leading to sluggish and stuck fermentations have been extensively studied and reviewed. The most studied cause of sluggish and stuck fermentation is the nitrogen content limitation. Nevertheless, other factors, such as temperature of fermentation and sugar concentration can affect the growth of yeasts. In this study we modelled the yeast growth‐cycle in wine model system as a function of temperature, sugar and ammonium concentrations; the individual effects and the interaction of these factors were analysed by means of a quadratic response surface methodology. Cell concentrations and weight loss were monitored in the whole wine fermentation process. The results of central composite design show that lower is the availability of nitrogen, higher is the cell growth rate; moreover, initial nitrogen concentration also influences survival time of Saccharomyces cerevisiae.