Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregation

The HIF prolyl hydroxylases (PHDs/EGLNs) are central regulators of the molecular responses to oxygen availability. One isoform, PHD3, is expressed in response to hypoxia and causes apoptosis in oxygenated conditions in neural cells. Here we show that PHD3 forms subcellular aggregates in an oxygen-dependent manner. The aggregation of PHD3 was seen under normoxia and was strongly reduced under hypoxia or by the inactivation of the PHD3 hydroxylase activity. The PHD3 aggregates were dependent on microtubular integrity and contained components of the 26S proteasome, chaperones, and ubiquitin, thus demonstrating features that are characteristic for aggresome-like structures. Forced expression of the active PHD3 induced the aggregation of proteasomal components and activated apoptosis under normoxia in HeLa cells. The apoptosis was seen in cells prone to PHD3 aggregation and the PHD3 aggregation preceded apoptosis. The data demonstrates the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response to varying oxygen availability

Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort

We studied prospectively the midlife handgrip strength, living habits, and parents’ longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu–Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965–1968, when they were 56–68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90–99 years, n = 545), octogenarian (80–89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23–5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06–10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02–1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06–5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity

Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma

BACKGROUND Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. AIM To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC. METHODS Immunohislochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival. RESULTS Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression (P = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo (P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, P = 0.001) and 2.2 (CI: 1.2-3.9, P = 0.02), respectively. CONCLUSION HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.Peer reviewe

Promocijas darbs

Elektroniskā versija nesatur pielikumu

Atmospheric and ecosystem big data providing key contributions in reaching United Nations' sustainable development goals

Big open data comprising comprehensive, long-term atmospheric and ecosystem in-situ observations will give us tools to meet global grand challenges and to contribute towards sustainable development. United Nations' Sustainable Development Goals (UN SDGs) provide framework for the process. We present synthesis on how Station for Measuring Earth Surface-Atmosphere Relations (SMEAR) observation network can contribute to UN SDGs. We describe SMEAR II flagship station in Hyytiala, Finland. With more than 1200 variables measured in an integrated manner, we can understand interactions and feedbacks between biosphere and atmosphere. This contributes towards understanding impacts of climate change to natural ecosystems and feedbacks from ecosystems to climate. The benefits of SMEAR concept are highlighted through outreach project in Eastern Lapland utilizing SMEAR I observations from Varrio research station. In contrast to boreal environment, SMEAR concept was also deployed in Beijing. We underline the benefits of comprehensive observations to gain novel insights into complex interactions between densely populated urban environment and atmosphere. Such observations enable work towards solving air quality problems and improve the quality of life inside megacities. The network of comprehensive stations with various measurements will enable science-based decision making and support sustainable development by providing long-term view on spatio-temporal trends on atmospheric composition and ecosystem parameters.Peer reviewe

Bioclimatic atlas of the terrestrial Arctic

The Arctic is the region on Earth that is warming at the fastest rate. In addition to rising means of temperature-related variables, Arctic ecosystems are affected by increasingly frequent extreme weather events causing disturbance to Arctic ecosystems. Here, we introduce a new dataset of bioclimatic indices relevant for investigating the changes of Arctic terrestrial ecosystems. The dataset, called ARCLIM, consists of several climate and event-type indices for the northern high-latitude land areas > 45 degrees N. The indices are calculated from the hourly ERA5-Land reanalysis data for 1950-2021 in a spatial grid of 0.1 degree (similar to 9 km) resolution. The indices are provided in three subsets: (1) the annual values during 1950-2021; (2) the average conditions for the 1991-2020 climatology; and (3) temporal trends over 1951-2021. The 72-year time series of various climate and event-type indices draws a comprehensive picture of the occurrence and recurrence of extreme weather events and climate variability of the changing Arctic bioclimate.Peer reviewe

Adaptation of the Troponin T ELISA Test to a Microplate Immunoassay Reader

Peer Reviewe

Some Findings Concerning Requirements in Agile Methodologies

gile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies