All morphologically complex life on Earth, beyond the level of cyanobacteria, is eukaryotic. All eukaryotes share a common ancestor that was already a complex cell. Despite their biochemical ...virtuosity, prokaryotes show little tendency to evolve eukaryotic traits or large genomes. Here I argue that prokaryotes are constrained by their membrane bioenergetics, for fundamental reasons relating to the origin of life. Eukaryotes arose in a rare endosymbiosis between two prokaryotes, which broke the energetic constraints on prokaryotes and gave rise to mitochondria. Loss of almost all mitochondrial genes produced an extreme genomic asymmetry, in which tiny mitochondrial genomes support, energetically, a massive nuclear genome, giving eukaryotes three to five orders of magnitude more energy per gene than prokaryotes. The requirement for endosymbiosis radically altered selection on eukaryotes, potentially explaining the evolution of unique traits, including the nucleus, sex, two sexes, speciation, and aging.
Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA ...replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by a set of master transcription factors but also at the enzyme level by allosteric regulation and feedback inhibition. Here we review the cellular demands of nucleotide biosynthesis, their metabolic pathways and mechanisms of regulation during the cell cycle. The use of stable isotope tracers for delineating the biosynthetic routes of the multiple intersecting pathways and how these are quantitatively controlled under different conditions is also highlighted. Moreover, the importance of nucleotide synthesis for cell viability is discussed and how this may lead to potential new approaches to drug development in diseases such as cancer.
River restoration is one of the most prominent areas of applied water‐resources science. From an initial focus on enhancing fish habitat or river appearance, primarily through structural modification ...of channel form, restoration has expanded to incorporate a wide variety of management activities designed to enhance river process and form. Restoration is conducted on headwater streams, large lowland rivers, and entire river networks in urban, agricultural, and less intensively human‐altered environments. We critically examine how contemporary practitioners approach river restoration and challenges for implementing restoration, which include clearly identified objectives, holistic understanding of rivers as ecosystems, and the role of restoration as a social process. We also examine challenges for scientific understanding in river restoration. These include: how physical complexity supports biogeochemical function, stream metabolism, and stream ecosystem productivity; characterizing response curves of different river components; understanding sediment dynamics; and increasing appreciation of the importance of incorporating climate change considerations and resiliency into restoration planning. Finally, we examine changes in river restoration within the past decade, such as increasing use of stream mitigation banking; development of new tools and technologies; different types of process‐based restoration; growing recognition of the importance of biological‐physical feedbacks in rivers; increasing expectations of water quality improvements from restoration; and more effective communication between practitioners and river scientists.
Key Points
River restoration is a prominent area of applied water‐resources science
restoration includes connectivity, physical‐biotic interactions, and history
effective restoration requires collaboration among scientists and practitioners
This paper asks a simple question: if humans and their actions co-evolve with hydrological systems (Sivapalan et al., 2012), what is the role of hydrological scientists, who are also humans, within ...this system? To put it more directly, as traditionally there is a supposed separation of scientists and society, can we maintain this separation as socio-hydrologists studying a socio-hydrological world? This paper argues that we cannot, using four linked sections. The first section draws directly upon the concern of science-technology studies to make a case to the (socio-hydrological) community that we need to be sensitive to constructivist accounts of science in general and socio-hydrology in particular. I review three positions taken by such accounts and apply them to hydrological science, supported with specific examples: (a) the ways in which scientific activities frame socio-hydrological research, such that at least some of the knowledge that we obtain is constructed by precisely what we do; (b) the need to attend to how socio-hydrological knowledge is used in decision-making, as evidence suggests that hydrological knowledge does not flow simply from science into policy; and (c) the observation that those who do not normally label themselves as socio-hydrologists may actually have a profound knowledge of socio-hydrology. The second section provides an empirical basis for considering these three issues by detailing the history of the practice of roughness parameterisation, using parameters like Manning's n, in hydrological and hydraulic models for flood inundation mapping. This history sustains the third section that is a more general consideration of one type of socio-hydrological practice: predictive modelling. I show that as part of a socio-hydrological analysis, hydrological prediction needs to be thought through much more carefully: not only because hydrological prediction exists to help inform decisions that are made about water management; but also because those predictions contain assumptions, the predictions are only correct in so far as those assumptions hold, and for those assumptions to hold, the socio-hydrological system (i.e. the world) has to be shaped so as to include them. Here, I add to the "normal" view that ideally our models should represent the world around us, to argue that for our models (and hence our predictions) to be valid, we have to make the world look like our models. Decisions over how the world is modelled may transform the world as much as they represent the world. Thus, socio-hydrological modelling has to become a socially accountable process such that the world is transformed, through the implications of modelling, in a fair and just manner. This leads into the final section of the paper where I consider how socio-hydrological research may be made more socially accountable, in a way that is both sensitive to the constructivist critique (Sect. 1), but which retains the contribution that hydrologists might make to socio-hydrological studies. This includes (1) working with conflict and controversy in hydrological science, rather than trying to eliminate them; (2) using hydrological events to avoid becoming locked into our own frames of explanation and prediction; (3) being empirical and experimental but in a socio-hydrological sense; and (4) co-producing socio-hydrological predictions. I will show how this might be done through a project that specifically developed predictive models for making interventions in river catchments to increase high river flow attenuation. Therein, I found myself becoming detached from my normal disciplinary networks and attached to the co-production of a predictive hydrological model with communities normally excluded from the practice of hydrological science.
Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein ...expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. We also show that increased P4HA1 expression correlates with short relapse-free survival in TNBC patients who received chemotherapy. These results suggest that P4HA1 promotes chemoresistance by modulating HIF-1-dependent cancer cell stemness. Targeting collagen P4H is a promising strategy to inhibit tumor progression and sensitize TNBC to chemotherapeutic agents.
Quantification of climate forcing of glacial hydrological systems at the decadal scale is rare because most measurement stations are too far downstream for glacier impacts to be clearly detected. ...Here we apply a measure of daily hydrograph entropy to a unique set of reliable, high‐altitude gauging stations, dating from the late 1960s. We find a progressive shift to a greater number of days with diurnal discharge variation as well as more pronounced diurnal discharge amplitude. These changes were associated with the onset of rapid warming in the 1980s as well as declining end of winter snow depths as inferred from climate data. In glaciated catchments, lower winter snow depths reduce the magnitude and duration of snowpack buffering and encourage the earlier onset of glacier ice exposure, with associated lower surface albedo and more rapid melt. Together, these processes explain the increase in the observed intensity of diurnal discharge fluctuations.
Plain Language Summary
River basins that have a high proportion of ice cover are particularly sensitive to climate warming. Daily variations in insolation and temperature typically lead to fluctuations in snow and/or ice melt and thus a daily rise and fall in river flow. Snow, and the glaciers themselves, can buffer this rise and fall. For six high mountain Alpine basins, we show that daily discharge fluctuations are changing due to climate warming at the decadal scale, with both increasing daily discharge maxima and reducing daily discharge minima. These changes reflect decreased snow accumulation at the end of winter, reducing the buffering and increasing the onset of rapid glacier melt.
Key Points
A Shannon Entropy Index is used to quantify changing daily hydrograph shape for six high‐altitude Alpine basins, with a range of degrees of glacier cover, between 1969 and 2014
For the five most glaciated basins, there has been an increase in the frequency and amplitude of diurnal discharge fluctuations since the onset of more rapid warming in the 1980s
These changes in diurnal discharge are driven by reduced snow buffering of ice melt and runoff resulting from declining end of winter snow depths and greater mean annual temperatures
Proglacial margins form when glaciers retreat and create zones with distinctive ecological, geomorphological and hydrological properties in Alpine environments. There is extensive literature on the ...geomorphology and sediment transport in such areas as well as on glacial hydrology, but there is much less research into the specific hydrological behavior of the landforms that develop after glacier retreat in and close to proglacial margins. Recent reviews have highlighted the presence of groundwater stores even in such rapidly draining environments. Here, we describe the hydrological functioning of different superficial landforms within and around the proglacial margin of the Otemma glacier, a temperate Alpine glacier in the Swiss Alps; we characterize the timing and amount of the transmission of different water sources (rain, snowmelt, ice melt) to the landforms and between them, and we compare the relationship between these processes and the catchment-scale discharge. The latter is based upon a recession-analysis-based framework. In quantifying the relative groundwater storage volumes of different superficial landforms, we show that steep zones only store water on the timescale of days, while flatter areas maintain baseflow on the order of several weeks. These landforms themselves fail to explain the catchment-scale recession patterns; our results point towards the presence of an unidentified storage compartment on the order of 40 mm, which releases water during the cold months. We suggest attributing this missing storage to deeper bedrock flowpaths. Finally, the key insights gained here into the interplay of different landforms as well as the proposed analysis framework are readily transferable to other similar proglacial margins and should contribute to a better understanding of the future hydrogeological behavior of such catchments.
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