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Recollection is thought to be the hallmark of episodic memory. Here we provide evidence that the hippocampus binds together the diverse elements forming an event, allowing holistic recollection via pattern completion of all elements. Participants learn complex ‘events’ from multiple overlapping pairs of elements, and are tested on all pairwise associations. At encoding, element ‘types’ (locations, people and objects/animals) produce activation in distinct neocortical regions, while hippocampal activity predicts memory performance for all within-event pairs. When retrieving a pairwise association, neocortical activity corresponding to all event elements is reinstated, including those incidental to the task. Participant’s degree of incidental reinstatement correlates with their hippocampal activity. Our results suggest that event elements, represented in distinct neocortical regions, are bound into coherent ‘event engrams’ in the hippocampus that enable episodic recollection—the re-experiencing or holistic retrieval of all aspects of an event—via a process of hippocampal pattern completion and neocortical reinstatement. The holistic retrieval of complex event memories is thought to be the hallmark of episodic memory. Here, the authors provide behavioural and neuroimaging evidence that the hippocampus binds together the elements forming an event to allow holistic episodic recollection via pattern completion of all elements.

It has been hypothesized that the overall size of—or efficiency of carbon export from—the biosphere decreased at the end of the Great Oxidation Event (GOE) (ca. 2,400 to 2,050 Ma). However, the timing, tempo, and trigger for this decrease remain poorly constrained. Here we test this hypothesis by studying the isotope geochemistry of sulfate minerals from the Belcher Group, in subarctic Canada. Using insights from sulfur and barium isotope measurements, combined with radiometric ages from bracketing strata, we infer that the sulfate minerals studied here record ambient sulfate in the immediate aftermath of the GOE (ca. 2,018 Ma). These sulfate minerals captured negative triple-oxygen isotope anomalies as low as ∼ −0.8‰. Such negative values occurring shortly after the GOE require a rapid reduction in primary productivity of >80%, although even larger reductions are plausible. Given that these data imply a collapse in primary productivity rather than export efficiency, the trigger for this shift in the Earth system must reflect a change in the availability of nutrients, such as phosphorus. Cumulatively, these data highlight that Earth’s GOE is a tale of feast and famine: A geologically unprecedented reduction in the size of the biosphere occurred across the end-GOE transition.

Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in turn play a major role in post-mitotic structure and function of adult neurons. Our understanding of the interactions between neuronal behavior, patterns of neural activity, and the surrounding environment is evolving at a rapid pace. Brain derived neurotrophic factor is a critical mediator of activity-associated plasticity, while multiple immediate early genes mediate plasticity of neurons following bouts of neural activity. New research has uncovered genetic mechanisms that govern the expression of DNA following changes in neural activity patterns, including RNAPII pause-release and activity-associated double stranded breaks. Discovery of novel mechanisms governing activity-associated plasticity of neurons hints at a layered and complex molecular control of neuronal response to depolarization. Importantly, patterns of depolarization in neurons are shown to be important mediators of genetic expression patterns and molecular responses. More research is needed to fully uncover the molecular response of different types of neurons-to-activity patterns; however, known responses might be leveraged to facilitate recovery after neural damage. Physical rehabilitation through passive or active exercise modulates neurotrophic factor expression in the brain and spinal cord and can initiate cortical plasticity commensurate with functional recovery. Rehabilitation likely relies on activity-associated mechanisms; however, it may be limited in its application. Electrical and magnetic stimulation direct specific activity patterns not accessible through passive or active exercise and work synergistically to improve standing, walking, and forelimb use after injury. Here, we review emerging concepts in the molecular mechanisms of activity-derived plasticity in order to highlight opportunities that could add value to therapeutic protocols for promoting recovery of function after trauma, disease, or age-related functional decline.

Groundwater-derived solute fluxes to the ocean have long been assumed static and subordinate to riverine fluxes, if not neglected entirely, in marine isotope budgets. Here we present concentration and isotope data for Li, Mg, Ca, Sr, and Ba in coastal groundwaters to constrain the importance of groundwater discharge in mediating the magnitude and isotopic composition of terrestrially derived solute fluxes to the ocean. Data were extrapolated globally using three independent volumetric estimates of groundwater discharge to coastal waters, from which we estimate that groundwater-derived solute fluxes represent, at a minimum, 5% of riverine fluxes for Li, Mg, Ca, Sr, and Ba. The isotopic compositions of the groundwater-derived Mg, Ca, and Sr fluxes are distinct from global riverine averages, while Li and Ba fluxes are isotopically indistinguishable from rivers. These differences reflect a strong dependence on coastal lithology that should be considered a priority for parameterization in Earth-system models. Groundwater discharge is a mechanism that transports chemicals from inland systems to the ocean, but it has been considered of secondary influence compared to rivers. Here the authors assess the global significance of groundwater discharge, finding that it has a unique and important contribution to ocean chemistry and Earth-system models.

Geochemical analyses of sedimentary barites (barium sulfates) in the geological record have yielded fundamental insights into the chemistry of the Archean environment and evolutionary origin of microbial metabolisms. However, the question of how barites were able to precipitate from a contemporary ocean that contained only trace amounts of sulfate remains controversial. Here we report dissolved and particulate multi-element and barium-isotopic data from Lake Superior that evidence pelagic barite precipitation at micromolar ambient sulfate. These pelagic barites likely precipitate within particle-associated microenvironments supplied with additional barium and sulfate ions derived from heterotrophic remineralization of organic matter. If active during the Archean, pelagic precipitation and subsequent sedimentation may account for the genesis of enigmatic barite deposits. Indeed, barium-isotopic analyses of barites from the Paleoarchean Dresser Formation are consistent with a pelagic mechanism of precipitation, which altogether offers a new paradigm for interpreting the temporal occurrence of barites in the geological record. The question of how significant barite deposits were able to form from early Earth’s low-sulfate seas remains controversial. Here, the authors show pelagic barite precipitation within a strongly barite-undersaturated ecosystem, highlighting the importance of particle-associated microenvironments.

Mechanisms regulating material transfer from subducted slabs to arc magmas remain debated, centered on metasomatized mantle wedge interactions versus mélange mobilization at the slab-mantle interface. The South Sandiwch Islands arc offers a unique setting to distinguish between these models due to the significant barium isotope contrast between altered oceanic crust and sediments, the latter displaying unusually light barium isotope compositions compared to the global sediment range. Here we show substantial barium isotope variations coupled with invariant strontium isotope ratios in arc lavas, consistent with mélange mobilization beneath the arc. Northern arc lavas display a broader range of barium isotope values than expected from slab inputs, suggesting barium isotope fractionation during slab material transport, potentially driven by phengite-related barium retention within the mélange. Notably, sediments, rather than altered oceanic crust, emerge as the dominant source of barium in arc lavas. While a comparison of barium isotope data from four additional arcs indicates mantle wedge metasomatism remains visible in several cases, mélange mobilization is consistent with available data across all of these subduction zones. Sediments, not oceanic crust, dominate barium transfer to arc magmas according to barium isotope variations in volcanic rocks from the South Sandwich Islands arc that arise from material mixing in subduction zones.

Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense of long-term testing, few studies have modeled antioxidant therapy for prevention of neurodegeneration. We investigated the contribution of oxidative stress to the pathogenesis of glaucoma in the DBA/2J mouse model of glaucoma. Similar to other neurodegenerative diseases, we observed lipid peroxidation and upregulation of oxidative stress-related mRNA and protein in DBA/2J retina. To test the role of oxidative stress in disease progression, we chose to deliver the naturally occurring, antioxidant α-lipoic acid (ALA) to DBA/2J mice in their diet. We used two paradigms for ALA delivery: an intervention paradigm in which DBA/2J mice at 6 months of age received ALA in order to intervene in glaucoma development, and a prevention paradigm in which DBA/2J mice were raised on a diet supplemented with ALA, with the goal of preventing glaucoma development. At 10 and 12 months of age (after 4 and 11 months of dietary ALA respectively), we measured changes in genes and proteins related to oxidative stress, retinal ganglion cell (RGC) number, axon transport, and axon number and integrity. Both ALA treatment paradigms showed increased antioxidant gene and protein expression, increased protection of RGCs and improved retrograde transport compared to control. Measures of lipid peroxidation, protein nitrosylation, and DNA oxidation in retina verified decreased oxidative stress in the prevention and intervention paradigms. These data demonstrate the utility of dietary therapy for reducing oxidative stress and improving RGC survival in glaucoma.

The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants’ memories when they were recalling and evaluating these items. An unrelated modulation by the participant’s familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories.

The global marine distributions of Cd and phosphate are closely correlated, which has led to Cd being considered as a marine micronutrient, despite its toxicity to life. The explanation for this nutrient-like behavior is unknown because there is only one identified biochemical function for Cd, an unusual Cd/Zn carbonic anhydrase. Recent developments in Cd isotope mass spectrometry have revealed that Cd uptake by phytoplankton causes isotopic fractionation in the open ocean and in culture. Here we investigate the physiochemical pathways that fractionate Cd isotopes by performing subcellular Cd isotope analysis on genetically modified microorganisms. We find that expression of the Cd/Zn carbonic anhydrase makes no difference to the Cd isotope composition of whole cells. Instead, a large proportion of the Cd is partitioned into cell membranes with a similar direction and magnitude of Cd isotopic fractionation to that seen in surface seawater. This observation is well explained if Cd is mistakenly imported with other divalent metals and subsequently managed by binding within the cell to avoid toxicity. This process may apply to other divalent metals, whereby nonspecific uptake and subsequent homeostasis may contribute to elemental and isotopic distributions in seawater, even for elements commonly considered as micronutrients.

An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.