Biotic response of plankton communities to Middle to Late Miocene monsoon wind and nutrient flux changes in the Oman margin upwelling zone

Understanding past dynamics of upwelling cells is an important aspect of assessing potential upwelling changes in future climate change scenarios. Our present understanding of nutrient fluxes throughout the world's oceans emphasizes the importance of intermediate waters transporting nutrients from the Antarctic divergence into the middle and lower latitudes. These nutrient-rich waters fuel productivity within wind-driven upwelling cells in all major oceans. One such upwelling system is located along the Oman margin in the western Arabian Sea (WAS). Driven by cross-hemispheric winds, the WAS upwelling zone's intense productivity led to the formation of one of the most extensive oxygen minimum zones known today. In this study covering the Middle to Late Miocene at Ocean Drilling Program (ODP) Site 722, we investigate the inception of upwelling-derived primary productivity. This study presents new plankton assemblage data in the context of existing model- and data-based evidence constraining the tectonic and atmospheric boundary conditions for upwelling in the WAS. With this research, we build upon the original planktonic foraminifer-based research by Dick Kroon in 1991 as part of his research based on the ODP LEG 117. We show that monsoonal winds likely sustained upwelling since the emergence of the Arabian Peninsula after the Miocene Climatic Optimum (MCO) ∼ 14.7 Ma, with fully monsoonal conditions occurring since the end of the Middle Miocene Climatic Transition (MMCT) at ∼ 13 Ma. However, changing nutrient fluxes through Antarctic Intermediate and sub-Antarctic Mode Waters (AAIW/SAMW) were only established after ∼ 12 Ma. Rare occurrences of diatom frustules correspond to the maximum abundances of Reticulofenestra haqii and Reticulofenestra antarctica, indicating higher upwelling-derived nutrient levels. By 11 Ma, diatom abundance increases significantly, leading to alternating diatom blooms and high-nutrient-adapted nannoplankton taxa. These changes in primary producers are also well reflected in geochemical proxies with increasing δ15Norg. values (&gt; 6 ‰) and high organic carbon accumulation. These proxies provide further independent evidence for high productivity and the onset of denitrification simultaneously. Our multi-proxy-based evaluation of Site 722 primary producers provides evidence for a stepwise evolution of Middle to Late Miocene productivity in the western Arabian Sea for the first time. The absence of a clear correlation with existing deep marine climate records suggests that both local wind patterns and intermediate water nutrient changes likely modulated productivity in the western Arabian Sea during the Middle to Late Miocene. Finally, we show that using a multi-proxy record provides novel insights into how plankton responded to changing nutrient conditions through time in a monsoon-wind-driven upwelling zone.</p

Sea-level and monsoonal control on the Maldives carbonate platform (Indian Ocean) over the last 1.3 million years

The Maldives Archipelago (Indian Ocean), composed of two rows of atolls that enclose an inner sea, offers an excellent study site to explore the forcings of carbonate production at platforms. Glacial–interglacial sea-level changes have been claimed to be the main factor controlling the carbonate platform factories; however, climatic factors may also have an impact. In this work we used geochemical compositional records, obtained by X-ray fluorescence (XRF) core-scanning from the International Ocean Discovery Program (IODP) Site U1467 in the Maldives Inner Sea, to analyze the orbitally driven fluctuations on the carbonate production and export from the neritic environment into the Maldives Inner Sea over the last 1.3 million years. High Sr aragonite-rich carbonates (HSAC) from neritic settings were deposited in the Maldives Inner Sea during sea-level highstand intervals, increasing the Sr/Ca values. In contrast, low Sr/Ca values are observed coincident with sea-level lowstand periods, suggesting that large areas of the atolls were exposed or unable to grow, and therefore, there was a demise in the carbonate production and sediment export to the Maldives Inner Sea. However, comparison of the Sr/Ca values and the sea-level reconstructions for different interglacial periods before and after the mid-Brunhes event (MBE, ∼ 430 ka) indicates that sea level is not the only factor controlling the production of HSAC during sea-level highstands. The study of monsoon and primary productivity proxies (Fe-normalized, Fe/K, and Br-normalized records) from the same site suggests that the intensity of the summer monsoon and the Indian Ocean dipole probably modulated the carbonate production at the atolls. Moreover, Marine Isotope Stage 11 stands out as a period with high sea level and extraordinary carbonate production in the Maldives platform. This outstanding carbonate production in the Maldives atolls (and in other low-latitude carbonate platforms) probably contributed to the mid-Brunhes dissolution event through a strong shelf-to-basin fractionation of carbonate deposition.</p

New Modularity of DAP-Kinases: Alternative Splicing of the DRP-1 Gene Produces a ZIPk-Like Isoform

DRP-1 and ZIPk are two members of the Death Associated Protein Ser/Thr Kinase (DAP-kinase) family, which function in different settings of cell death including autophagy. DAP kinases are very similar in their catalytic domains but differ substantially in their extra-catalytic domains. This difference is crucial for the significantly different modes of regulation and function among DAP kinases. Here we report the identification of a novel alternatively spliced kinase isoform of the DRP-1 gene, termed DRP-1β. The alternative splicing event replaces the whole extra catalytic domain of DRP-1 with a single coding exon that is closely related to the sequence of the extra catalytic domain of ZIPk. As a consequence, DRP-1β lacks the calmodulin regulatory domain of DRP-1, and instead contains a leucine zipper-like motif similar to the protein binding region of ZIPk. Several functional assays proved that this new isoform retained the biochemical and cellular properties that are common to DRP-1 and ZIPk, including myosin light chain phosphorylation, and activation of membrane blebbing and autophagy. In addition, DRP-1β also acquired binding to the ATF4 transcription factor, a feature characteristic of ZIPk but not DRP-1. Thus, a splicing event of the DRP-1 produces a ZIPk like isoform. DRP-1β is highly conserved in evolution, present in all known vertebrate DRP-1 loci. We detected the corresponding mRNA and protein in embryonic mouse brains and in human embryonic stem cells thus confirming the in vivo utilization of this isoform. The discovery of module conservation within the DAPk family members illustrates a parsimonious way to increase the functional complexity within protein families. It also provides crucial data for modeling the expansion and evolution of DAP kinase proteins within vertebrates, suggesting that DRP-1 and ZIPk most likely evolved from their ancient ancestor gene DAPk by two gene duplication events that occurred close to the emergence of vertebrates

GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1

The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases

Control de cambios / Rastrea los cambios / El camino cambia: Reflexiones sobre un mundo en transformación

“Track changes: Reflecting on a transforming world” was the theme chosen to invite panels, papers, posters and alternative presentations to be part of the 2019 international congress of SIEF that was held in Santiago de Compostela, Galicia (Spain). This introduction includes a description of the content of the congress, the rationale of the choice of plenaries and some reflections about the outcomes of the congress.El lema elegido para presentar paneles, ponencias, posters y presentaciones en formatos alternativos para el congreso internacional 2019 de SIEF -que tuvo lugar en Santiago de Compostela, Galicia (España)- fue&nbsp;“Track changes: Reflecting on a transforming world”.&nbsp;Esta introducción incluye una descripción del contenido del congreso, la idea para la elección de las plenarias y algunas reflexiones sobre los resultados del congreso. &nbsp

BRCA1 is an essential regulator of heart function and survival following myocardial infarction

The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer but its role in protecting other tissues from DNA damage has not been explored. Here we show a new role for BRCA1 as a gatekeeper of cardiac function and survival. In mice, loss of BRCA1 in cardiomyocytes results in adverse cardiac remodelling, poor ventricular function and higher mortality in response to ischaemic or genotoxic stress. Mechanistically, loss of cardiomyocyte BRCA1 results in impaired DNA double-strand break repair and activated p53-mediated pro-apoptotic signalling culminating in increased cardiomyocyte apoptosis, whereas deletion of the p53 gene rescues BRCA1-deficient mice from cardiac failure. In human adult and fetal cardiac tissues, ischaemia induces double-strand breaks and upregulates BRCA1 expression. These data reveal BRCA1 as a novel and essential adaptive response molecule shielding cardiomyocytes from DNA damage, apoptosis and heart dysfunction. BRCA1 mutation carriers, in addition to risk of breast and ovarian cancer, may be at a previously unrecognized risk of cardiac failure

Carbonate delta drift: a new sediment drift type

Based on high-resolution reflection seismic and core data from IODP Expedition 359 we present a new channel-related drift type attached to a carbonate platform slope, which we termed delta drift. Like a river delta, it is comprised of several stacked lobes and connected to a point source. The delta drifts were deposited at the exit of two gateways that connect the Inner Sea of the Maldives carbonate platform with the open ocean. The channels served as conduits focusing and accelerating the water flow; Entrained material was deposited at their mouth where the flows relaxed. The lobe-shaped calcareous sediment drifts must have formed under persistent water through flow. Sediment supply was relatively high and continuous, resulting in an average sedimentation rate of 17 cm ka−1. The two delta drifts occupy 342 and 384 km2, respectively; with a depositional relief of approximately 500 m. They have a sigmoidal clinoform reflection pattern with a particular convex upward bending of the foresets. In the Maldives the drift onset marks the transition from a sea-level controlled to a progressively current dominated depositional regime. This major event occurred in the Serravallian about 13 Ma ago, leading to the partial drowning of the carbonate platform and the creation of shallow seaways. The initial bank-enclosed topography resembles an “empty bucket” geometry which is rapidly filled by the drift sediments that aggrade and prograde into the basin. Thereby the depositional environment of the delta drifts changes from deep water (>500) to shallow-water conditions at their topsets, indicated by the overall coarsening upward trend in grain size and the presence of shallow water large benthic foraminifers at their top

Simultaneous Induction of Non-Canonical Autophagy and Apoptosis in Cancer Cells by ROS-Dependent ERK and JNK Activation

Background: Chemotherapy-induced reduction in tumor load is a function of apoptotic cell death, orchestrated by intracellular caspases. However, the effectiveness of these therapies is compromised by mutations affecting specific genes, controlling and/or regulating apoptotic signaling. Therefore, it is desirable to identify novel pathways of cell death, which could function in tandem with or in the absence of efficient apoptotic machinery. In this regard, recent evidence supports the existence of a novel cell death pathway termed autophagy, which is activated upon growth factor deprivation or exposure to genotoxic compounds. The functional relevance of this pathway in terms of its ability to serve as a stress response or a truly death effector mechanism is still in question; however, reports indicate that autophagy is a specialized form of cell death under certain conditions. Methodology/Principal Findings: We report here the simultaneous induction of non-canonical autophagy and apoptosis in human cancer cells upon exposure to a small molecule compound that triggers intracellular hydrogen peroxide (H2O2) production. Whereas, silencing of beclin1 neither inhibited the hallmarks of autophagy nor the induction of cell death, Atg 7 or Ulk1 knockdown significantly abrogated drug-induced H2O2-mediated autophagy. Furthermore, we provide evidence that activated extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) are upstream effectors controlling both autophagy and apoptosis in response to elevated intracellular H2O2. Interestingly, inhibition of JNK activity reversed the increase in Atg7 expression in this system, thus indicating that JNK may regulate autophagy by activating Atg7. Of note, the small molecule compound triggered autophagy and apoptosis in primary cells derived from patients with lymphoma, but not in non-transformed cells. Conclusions/Significance: Considering that loss of tumor suppressor beclin 1 is associated with neoplasia, the ability of this small molecule compound to engage both autophagic and apoptotic machineries via ROS production and subsequent activation of ERK and JNK could have potential translational implications.Singapore. Biomedical Research CouncilSingapore. Ministry of Educatio

Локальная инъекционная терапия в комплексном лечении болезней костно-мышечной системы: основные принципы использования, доказательная база, безопасность

Local injection therapy (LIT)  is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT.  LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.Локальная инъекционная терапия (ЛИТ)  – важная составляющая комплексного лечения болезней костно-мышечной системы (БКМС), широко используемая в реальной клинической практике. Для ЛИТ применяются глюкокортикоиды, препараты гиалуроновой кислоты (ГлК), аутологичные клеточные препараты, ботулинический токсин типа А, радиоактивные изотопы и др. ЛИТ позволяет добиться выраженного симптоматического эффекта, при этом в ряде случаев, например при проведении повторных курсов лечения ГлК у пациентов с остеоартритом, обсуждается возможность замедления прогрессирования заболевания и снижения потребности в хирургическом лечении.Проведение ЛИТ требует специальной компетенции и навыков врача, тщательного соблюдения правил асептики и антисептики, инструментальной визуализации.  ЛИТ  может быть сопряжена с серьезными осложнениями, поэтому должна выполняться по строгим показаниям.Совет экспертов был посвящен определению основных принципов ЛИТ. Были рассмотрены показания для применения тех или иных видов данной терапии,  доказательная база ее эффективности и безопасности, последовательность использования различных препаратов, а также необходимость комбинации ЛИТ с другими медикаментозными и немедикаментозными методами лечения БКМС