Tidal mixing of estuarine and coastal waters in the western English Channel is a control on spatial and temporal variability in seawater CO<sub>2</sub>

Surface ocean carbon dioxide (CO2) measurements are used to compute the oceanic air–sea CO2 flux. The CO2 flux component from rivers and estuaries is uncertain due to the high spatial and seasonal heterogeneity of CO2 in coastal waters. Existing high-quality CO2 instrumentation predominantly utilises showerhead and percolating style equilibrators optimised for open-ocean observations. The intervals between measurements made with such instrumentation make it difficult to resolve the fine-scale spatial variability of surface water CO2 at timescales relevant to the high frequency variability in estuarine and coastal environments. Here we present a novel dataset with unprecedented frequency and spatial resolution transects made at the Western Channel Observatory in the south-west of the UK from June to September 2016, using a fast-response seawater CO2 system. Novel observations were made along the estuarine– coastal continuum at different stages of the tide and reveal distinct spatial patterns in the surface water CO2 fugacity (fCO2) at different stages of the tidal cycle. Changes in salinity and fCO2 were closely correlated at all stages of the tidal cycle and suggest that the mixing of oceanic and riverine endmembers partially determines the variations in fCO2. The correlation between salinity and fCO2 was different in Cawsand Bay, which could be due to enhanced gas exchange or to enhanced biological activity in the region. The observations demonstrate the complex dynamics determining spatial and temporal patterns of salinity and fCO2 in the region. Spatial variations in observed surface salinity were used to validate the output of a regional high-resolution hydrodynamic model. The model enables a novel estimate of the air–sea CO2 flux in the estuarine–coastal zone. Air–sea CO2 flux variability in the estuarine–coastal boundary region is influenced by the state of the tide because of strong CO2 outgassing from the river plume. The observations and model output demonstrate that undersampling the complex tidal and mixing processes characteristic of estuarine and coastal environment biases quantification of air–sea CO2 fluxes in coastal waters. The results provide a mechanism to support critical national and regional policy implementation by reducing uncertainty in carbon budgets

A highly polymorphic insertion in the Y-chromosome amelogenin gene can be used for evolutionary biology, population genetics and sexing in Cetacea and Artiodactyla

<p>Abstract</p> <p>Background</p> <p>The early radiation of the <it>Cetartiodactyla </it>is complex, and unambiguous molecular characters are needed to clarify the positions of hippotamuses, camels and pigs relative to the remaining taxa (<it>Cetacea </it>and <it>Ruminantia</it>). There is also a need for informative genealogic markers for Y-chromosome population genetics as well as a sexing method applicable to all species from this group. We therefore studied the sequence variation of a partial sequence of the evolutionary conserved amelogenin gene to assess its potential use in each of these fields.</p> <p>Results and discussion</p> <p>We report a large interstitial insertion in the Y amelogenin locus in most of the <it>Cetartiodactyla </it>lineages (cetaceans and ruminants). This sex-linked size polymorphism is the result of a 460–465 bp inserted element in intron 4 of the amelogenin gene of Ruminants and Cetaceans. Therefore, this polymorphism can easily be used in a sexing assay for these species.</p> <p>When taking into account this shared character in addition to nucleotide sequence, gene genealogy follows sex-chromosome divergence in <it>Cetartiodactyla </it>whereas it is more congruent with zoological history when ignoring these characters. This could be related to a loss of homology between chromosomal copies given the old age of the insertion.</p> <p>The 1 kbp <it>Amel-Y </it>amplified fragment is also characterized by high nucleotide diversity (64 polymorphic sites spanning over 1 kbp in seven haplotypes) which is greater than for other Y-chromosome sequence markers studied so far but less than the mitochondrial control region.</p> <p>Conclusion</p> <p>The gender-dependent polymorphism we have identified is relevant not only for phylogenic inference within the <it>Cetartiodactyla </it>but also for Y-chromosome based population genetics and gender determination in cetaceans and ruminants. One single protocol can therefore be used for studies in population and evolutionary genetics, reproductive biotechnologies, and forensic science.</p

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy

Population Structure of Humpback Whales from Their Breeding Grounds in the South Atlantic and Indian Oceans

Although humpback whales are among the best-studied of the large whales, population boundaries in the Southern Hemisphere (SH) have remained largely untested. We assess population structure of SH humpback whales using 1,527 samples collected from whales at fourteen sampling sites within the Southwestern and Southeastern Atlantic, the Southwestern Indian Ocean, and Northern Indian Ocean (Breeding Stocks A, B, C and X, respectively). Evaluation of mtDNA population structure and migration rates was carried out under different statistical frameworks. Using all genetic evidence, the results suggest significant degrees of population structure between all ocean basins, with the Southwestern and Northern Indian Ocean most differentiated from each other. Effective migration rates were highest between the Southeastern Atlantic and the Southwestern Indian Ocean, followed by rates within the Southeastern Atlantic, and the lowest between the Southwestern and Northern Indian Ocean. At finer scales, very low gene flow was detected between the two neighbouring sub-regions in the Southeastern Atlantic, compared to high gene flow for whales within the Southwestern Indian Ocean. Our genetic results support the current management designations proposed by the International Whaling Commission of Breeding Stocks A, B, C, and X as four strongly structured populations. The population structure patterns found in this study are likely to have been influenced by a combination of long-term maternally directed fidelity of migratory destinations, along with other ecological and oceanographic features in the region

The Western Channel Observatory: a century of physical, chemical and biological data compiled from pelagic and benthic habitats in the western English Channel

The Western Channel Observatory (WCO) comprises a series of pelagic, benthic and atmospheric sampling sites within 40 km of Plymouth, UK, that have been sampled by the Plymouth institutes on a regular basis since 1903. This longevity of recording and the high frequency of observations provide a unique combi�nation of data; for example temperature data were first collected in 1903, and the reference station L4, where nearly 400 planktonic taxa have been enumerated, has been sampled on a weekly basis since 1988. While the component datasets have been archived, here we provide the first summary database bringing together a wide suite of the observations. This provides monthly average values of some of the key pelagic and benthic measure�ments for the inshore site L4 (50◦15.000 N, 4◦13.020 W; approx. depth 55 m), the offshore site E1 (50◦02.000 N, 4 ◦22.000 W; approx. depth 75 m) and the intermediate L5 site (50◦10.800 N, 4◦18.000 W; approx. depth 58 m). In brief, these data include the following: water temperature (from 1903); macronutrients (from 1934); dissolved inorganic carbon and total alkalinity (from 2008); methane and nitrous oxide (from 2011); chlorophyll a (from 1992); high-performance liquid chromatography (HPLC)-derived pigments (from 1999); <20 µm plankton by flow cytometry, including bacteria (8 functional groups from 2007); phytoplankton by microscopy (6 functional groups from 1992); microplankton and mesozooplankton from FlowCam (6 groups from 2012); Noctiluca sp. dinoflagellate (from 1997); mesozooplankton by microscopy (8 groups from 1988); Calanus helgolandicus egg production rates (from 1992); fish larvae from the Young Fish Trawl survey (4 groups from 1924); benthic macrofauna (4 groups from 2008); demersal fish (19 families from 2008); blue shark, Prionace glauca (from 1958); and 16S alpha diversity for sediment and water column (from 2012). These data have varying coverage with respect to time and depth resolution. The metadata tables describe each dataset and provide pointers to the source data and other related Western Channel Observatory datasets and outputs not compiled here. We pro�vide summaries of the main trends in seasonality and some major climate-related shifts that have been revealed over the last century. The data are available from the Data Archive for Seabed Species and Habitats (DASSH): https://doi.org/10.17031/645110fb81749 (McEvoy and Atkinson, 2023). Making these data fully accessible and including units of both abundance and biomass will stimulate a variety of uptakes. These may include uses as an educational resource for projects, for models and budgets, for the analysis of seasonality and long-term change in a coupled benthic–pelagic system, or for supporting UK and north-eastern Atlantic policy and management

Biocontrol Potential of Forest Tree Endophytes

Peer reviewe

Metastatic epidural spinal cord compression: current concepts and treatment

Metastatic epidural spinal cord compression (MESCC) is a medical emergency complicating the course of 5–10% of patients with cancer [1]. When diagnosis and treatment is early with the patient ambulatory prognosis for continued ambulation is good [2]. If the patient is nonambulatory or paraplegic, prognosis for meaningful recovery of motor and bladder function is markedly decreased. In the last decade, significant advances in the understanding, management and treatment of metastatic epidural spinal cord compression have occurred.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45378/1/11060_2005_Article_BF01051052.pd

WSX-1 signalling inhibits CD4⁺ T cell migration to the liver during malaria infection by repressing chemokine-independent pathways.

IL-27 is an important and non-redundant regulator of effector T cell accumulation in non-lymphoid tissues during infection. Using malaria as a model systemic pro-inflammatory infection, we demonstrate that the aberrant accumulation of CD4⁺ T cells in the liver of infected IL27R(-/-) (WSX-1(-/-)) mice is a result of differences in cellular recruitment, rather than changes in T cell proliferation or cell death. We show that IL-27 both inhibits the migratory capacity of infection-derived CD4⁺ T cells towards infection-derived liver cells, but also suppresses the production of soluble liver-derived mediator(s) that direct CD4⁺ T cell movement towards the inflamed tissue. Although CCL4 and CCL5 expression was higher in livers of infected WSX-1(-/-) mice than infected WT mice, and hepatic CD4⁺ T cells from WSX-1(-/-) mice expressed higher levels of CCR5 than cells from WT mice, migration of CD4⁺ T cells to the liver of WSX-1(-/-) mice during infection was not controlled by chemokine (R) signalling. However, anti-IL-12p40 treatment reduced migration of CD4⁺ T cells towards infection-derived liver cells, primarily by abrogating the hepatotropic migratory capacity of T cells, rather than diminishing soluble tissue-derived migratory signals. These results indicate that IL-27R signalling restricts CD4⁺ T cell accumulation within the liver during infection primarily by suppressing T cell chemotaxis, which may be linked to its capacity to repress Th1 differentiation, as well as by inhibiting the production of soluble, tissue-derived chemotaxins