Compromised mammillary body connectivity and psychotic symptoms in mice with di- and mesencephalic ablation of ST8SIA2.

Altered long-range connectivity is a common finding across neurodevelopmental psychiatric disorders, but causes and consequences are not well understood. Genetic variation in ST8SIA2 has been associated with schizophrenia, autism, and bipolar disorder, and St8sia2-/- mice show a number of related neurodevelopmental and behavioral phenotypes. In the present study, we use conditional knockout (cKO) to dissect neurodevelopmental defects and behavioral consequences of St8sia2 deficiency in cortical interneurons, their cortical environment, or in the di- and mesencephalon. Neither separate nor combined cortical and diencephalic ablation of St8sia2 caused the disturbed thalamus-cortex connectivity observed in St8sia2-/- mice. However, cortical ablation reproduced hypoplasia of corpus callosum and fornix and mice with di- and mesencephalic ablation displayed smaller mammillary bodies with a prominent loss of parvalbumin-positive projection neurons and size reductions of the mammillothalamic tract. In addition, the mammillotegmental tract and the mammillary peduncle, forming the reciprocal connections between mammillary bodies and Gudden's tegmental nuclei, as well as the size of Gudden's ventral tegmental nucleus were affected. Only mice with these mammillary deficits displayed enhanced MK-801-induced locomotor activity, exacerbated impairment of prepulse inhibition in response to apomorphine, and hypoanxiety in the elevated plus maze. We therefore propose that compromised mammillary body connectivity, independent from hippocampal input, leads to these psychotic-like responses of St8sia2-deficient mice.

Revised estimates of ocean-atmosphere CO2 flux are consistent with ocean carbon inventory.

The ocean is a sink for ~25% of the atmospheric CO2 emitted by human activities, an amount in excess of 2 petagrams of carbon per year (PgC yr-1). Time-resolved estimates of global ocean-atmosphere CO2 flux provide an important constraint on the global carbon budget. However, previous estimates of this flux, derived from surface ocean CO2 concentrations, have not corrected the data for temperature gradients between the surface and sampling at a few meters depth, or for the effect of the cool ocean surface skin. Here we calculate a time history of ocean-atmosphere CO2 fluxes from 1992 to 2018, corrected for these effects. These increase the calculated net flux into the oceans by 0.8-0.9 PgC yr-1, at times doubling uncorrected values. We estimate uncertainties using multiple interpolation methods, finding convergent results for fluxes globally after 2000, or over the Northern Hemisphere throughout the period. Our corrections reconcile surface uptake with independent estimates of the increase in ocean CO2 inventory, and suggest most ocean models underestimate uptake.

Cell-autonomous impact of polysialic acid-producing enzyme ST8SIA2 on developmental migration and distribution of cortical interneurons.

In humans, variations in the polysialic acid-producing enzyme ST8SIA2 and disturbances in the cortical inhibitory system are associated with neurodevelopmental psychiatric disorders such as schizophrenia and autism. In mice, the ST8SIA2-dependent formation of polysialic acid during embryonic development is crucial for the establishment of interneuron populations of the medial prefrontal cortex. However, the spatial pattern and the neurodevelopmental mechanisms of interneuron changes caused by loss of ST8SIA2 function have not been fully characterized. Here, we use immunohistochemical analysis to demonstrate that densities of parvalbumin-positive interneurons are not only reduced in the medial prefrontal cortex, but also in the adjacent motor and somatosensory cortices of St8sia2-deficient male mice. These reductions, however, were confined to the rostral parts of the analyzed region. Mice with conditional knockout of St8sia2 under the interneuron-specific Lhx6 promoter, but not mice with a deletion under the Emx1 promoter that targets cortical excitatory neurons and glia, largely recapitulated the area-specific changes of parvalbumin-positive interneurons in the anterior cortex of St8sia2-/- mice. Live imaging of interneuron migration in slice cultures of the developing cortex revealed a comparable reduction of directional persistence accompanied by increased branching of leading processes in slice cultures obtained from St8sia2-/- embryos or from embryos with interneuron-specific ablation of St8sia2. Together, the data demonstrate a cell-autonomous impact of ST8SIA2 on cortical interneuron migration and the distribution of parvalbumin-positive interneurons in the anterior cortex. This provides a neurodevelopmental mechanism for how dysregulation of ST8SIA2 may lead to disturbed inhibitory balance as observed in schizophrenia and autism.

Winter weather controls net influx of atmospheric CO2 on the north-west European shelf.

Shelf seas play an important role in the global carbon cycle, absorbing atmospheric carbon dioxide (CO2) and exporting carbon (C) to the open ocean and sediments. The magnitude of these processes is poorly constrained, because observations are typically interpolated over multiple years. Here, we used 298500 observations of CO2 fugacity (fCO2) from a single year (2015), to estimate the net influx of atmospheric CO2 as 26.2 ± 4.7 Tg C yr-1 over the open NW European shelf. CO2 influx from the atmosphere was dominated by influx during winter as a consequence of high winds, despite a smaller, thermally-driven, air-sea fCO2 gradient compared to the larger, biologically-driven summer gradient. In order to understand this climate regulation service, we constructed a carbon-budget supplemented by data from the literature, where the NW European shelf is treated as a box with carbon entering and leaving the box. This budget showed that net C-burial was a small sink of 1.3 ± 3.1 Tg C yr-1, while CO2 efflux from estuaries to the atmosphere, removed the majority of river C-inputs. In contrast, the input from the Baltic Sea likely contributes to net export via the continental shelf pump and advection (34.4 ± 6.0 Tg C yr-1).

Monitoring and interpreting the ocean uptake of atmospheric CO2.

The oceans are an important sink for anthropogenically produced CO(2), and on time scales longer than a century they will be the main repository for the CO(2) that humans are emitting. Our knowledge of how ocean uptake varies (regionally and temporally) and the processes that control it is currently observation-limited. Traditionally, and based on sparse observations and models at coarse resolution, ocean uptake has been thought to be relatively invariant. However, in the few places where we have enough observations to define the uptake over periods of many years or decades, it has been found to change substantially at basin scales, responding to indices of climate variability. We illustrate this for three well-studied regions: the equatorial Pacific, the Indian Ocean sector of the Southern Ocean, and the North Atlantic. A lesson to take from this is that ocean uptake is sensitive to climate (regionally, but presumably also globally). This reinforces the expectation that, as global climate changes in the future owing to human influences, ocean uptake of CO(2) will respond. To evaluate and give early warning of such carbon-climate feedbacks, it is important to track trends in both ocean and land sinks for CO(2). Recent coordinated observational programmes have shown that, by organization of an observing network, the atmosphere-ocean flux of CO(2) can, in principle, be accurately tracked at seasonal or better resolution, over at least the Northern Hemisphere oceans. This would provide a valuable constraint on both the ocean and (by difference) land vegetation sinks for atmospheric CO(2).

Tracking the variable North Atlantic sink for atmospheric CO2.

The oceans are a major sink for atmospheric carbon dioxide (CO2). Historically, observations have been too sparse to allow accurate tracking of changes in rates of CO2 uptake over ocean basins, so little is known about how these vary. Here, we show observations indicating substantial variability in the CO2 uptake by the North Atlantic on time scales of a few years. Further, we use measurements from a coordinated network of instrumented commercial ships to define the annual flux into the North Atlantic, for the year 2005, to a precision of about 10%. This approach offers the prospect of accurately monitoring the changing ocean CO2 sink for those ocean basins that are well covered by shipping routes.