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ABC transporters as cancer drivers : Potential functions in cancer development

BACKGROUND: ABC transporters have attracted considerable attention for their function as drug transporters in a broad range of tumours and are therefore considered as major players in cancer chemoresistance. However, less attention has been focused on their potential role as active players in cancer development and progression.SCOPE OF REVIEW: This review presents the evidence suggesting that ABC

Pancreatic Ductal Adenocarcinoma : Current and Evolving Therapies

Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms an

Class II Phosphoinositide 3-Kinases as Novel Drug Targets

The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes. Despite the vast knowledge around class I PI3Ks, the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery. Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ, in d

ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer : What is the way forward?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATP-binding cassette (ABC) transporters in this resistance, the therapeutic potential of their pharmaco

ABCC3 is a novel target for the treatment of pancreatic cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is a very aggressive disease, lacking effective therapeutic approaches and leaving PDAC patients with a poor prognosis. The life expectancy of PDAC patients has not experienced a significant change in the last few decades with a five-year survival rate of only 8%. To address this unmet need, novel pharmacological targets must be identified for clinical inter

Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

Acute respiratory distress syndrome (ARDS), an inflammatory condition with high mortality rates, is common in severe COVID-19, whose risk is reduced by metformin rather than other anti-diabetic medications. Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. We show that m

Temperature and Tree Size Explain the Mean Time to Fall of Dead Standing Trees across Large Scales

AbstractDead standing trees (DSTs) generally decompose slower than wood in contact with the forest floor. In many regions, DSTs are being created at an increasing rate due to accelerating tree mortality caused by climate change. Therefore, factors determining DST fall are crucial for predicting dead wood turnover time but remain poorly constrained. Here, we conduct a re-analysis of published DST f

Capturing the spatiotemporal variations in the gross primary productivity in coastal wetlands by integrating eddy covariance, Landsat, and MODIS satellite data : A case study in the Yangtze Estuary, China

Accurate monitoring of the spatiotemporal variations in the gross primary productivity (GPP) in coastal wetlands is essential for blue carbon quantification. However, the currently available moderate-spatial-resolution GPP algorithms and products may contain large uncertainties and may rarely meet the demands of tidal wetland research. In this paper, we examine two statistical methods, namely, sim

Exposure to phthalates and DiNCH among preschool children in Sweden : Urinary metabolite concentrations and predictors of exposure

Several plasticizing chemicals induce endocrine disrupting effects in humans, and the indoor environment is suggested to be a source of exposure. As children are particularly vulnerable to the effects from exposure to endocrine disrupting chemicals (EDCs), it is essential to monitor exposure to EDCs such as phthalates and non-phthalate plasticizers in indoor environments intended for use by childr

Differentiated knowledge bases and catch-up in creative industries – A case of the online game industry in China

Catch-up phenomena have been studied intensively in many manufacturing industries, but they have not been well explored in creative industries. Moreover, the internal heterogeneity of different segments within a specific industry has also largely been overlooked in the catch-up literature. This paper fills these gaps by analyzing the catch-up of a creative industry—the online game industry in Chin

Realisations of elliptic operators on compact manifolds with boundary

This paper investigates realisations of elliptic differential operators of general order on manifolds with boundary following the approach of Bär-Ballmann to first order elliptic operators. The space of possible boundary values of elements in the maximal domain is described as a Hilbert space densely sandwiched between two mixed order Sobolev spaces. The description uses Calderón projectors which,

IRF1 regulates self-renewal and stress-responsiveness to support hematopoietic stem cell maintenance

Inflammatory mediators induce emergency myelopoiesis and cycling of adult hematopoietic stem cells (HSCs) through incompletely understood mechanisms. To suppress the unwanted effects of inflammation and preserve its beneficial outcomes, the mechanisms by which inflammation affects hematopoiesis need to be fully elucidated. Rather than focusing on specific inflammatory stimuli, we here investigated

An automated buffer management system for small-scale continuous downstream bioprocessing

Buffer management for biopharmaceutical purification processes include buffer preparation, storage of buffers and restocking the buffers when needed. This is usually performed manually by the operators for small scale operations. However, buffer management can become a bottleneck when running integrated continuous purification processes for prolonged times, even at small scale. To address this iss

Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques

Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0. The techniques were Dynamic Light Scattering (DLS), Asymmetric Flow-Field Flow-Fractionation (AF4), and the TEM-based analysis system MiniTEM™. In addition, Differential Scanning Calorimetry (DSC) was used to study the thermal unfolding and stabi

Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age

Aging negatively affects hematopoiesis, with consequences for immunity and acquired blood cell disorders. Although impairments in hematopoietic stem cell (HSC) function contribute to this, the in vivo dynamics of such changes remain obscure. Here, we integrate extensive longitudinal functional assessments of HSC-specific lineage tracing with single-cell transcriptome and epitope profiling. In cont

Beyond Massive MIMO : Trade-offs and Opportunities with Large Multi-Antenna Systems

After the commercial emergence of 5G, the research community is already putting its focus on proposing innovative solutions to enable the upcoming 6G. One important lesson put forth by 5G research was that scaling up the conventional multiple-input-multiple-output (MIMO) technology by increasing the number of antennas could be extremely beneficial for effectively multiplexing data streams in the s