Modern Sedimentation and Authigenic Mineral Formation in the Chew Bahir Basin, Southern Ethiopia:Implications for Interpretation of Late Quaternary Paleoclimate Records

We present new mineralogical and geochemical data from modern sediments in the Chew Bahir basin and catchment, Ethiopia. Our goal is to better understand the role of modern sedimentary processes in chemical proxy formation in the Chew Bahir paleolake, a newly investigated paleoclimatic archive, to provide environmental context for human evolution and dispersal. Modern sediment outside the currently dry playa lake floor have higher SiO2 and Al2O3 (50-70 wt.%) content compared to mudflat samples. On average, mudflat sediment samples are enriched in elements such as Mg, Ca, Ce, Nd, and Na, indicating possible enrichment during chemical weathering (e.g., clay formation). Thermodynamic modeling of evaporating water in upstream Lake Chamo is shown to produce an authigenic mineral assemblage of calcite, analcime, and Mg-enriched authigenic illitic clay minerals, consistent with the prevalence of environments of enhanced evaporative concentration in the Chew Bahir basin. A comparison with samples from the sediment cores of Chew Bahir based on whole-rock MgO/Al2O3, Ba/Sr and authigenic clay mineral delta O-18 values shows the following: modern sediments deposited in the saline mudflats of the Chew Bahir dried out lake bed resemble paleosediments deposited during dry periods, such as during times of the Last Glacial Maximum and Younger Dryas stadial. Sediments from modern detrital upstream sources are more similar to sediments deposited during wetter periods, such as the early Holocene African Humid Period

Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used recreational substance inducing acute release of serotonin. Previous studies in chronic MDMA users demonstrated selective adaptations in the serotonin system, which were assumed to be associated with cognitive deficits. However, serotonin functions are strongly entangled with glutamate as well as γ-aminobutyric acid (GABA) neurotransmission, and studies in MDMA-exposed rats show long-term adaptations in glutamatergic and GABAergic signaling. Methods: We used proton magnetic resonance spectroscopy (MRS) to measure the glutamate-glutamine complex (GLX) and GABA concentrations in the left striatum and medial anterior cingulate cortex (ACC) of 44 chronic but recently abstinent MDMA users and 42 MDMA-naïve healthy controls. While the Mescher-Garwood point-resolved-spectroscopy sequence (MEGA-PRESS) is best suited to quantify GABA, recent studies reported poor agreement between conventional short–echo-time PRESS and MEGA-PRESS for GLX measures. Here, we applied both sequences to assess their agreement and potential confounders underlying the diverging results. Results: Chronic MDMA users showed elevated GLX levels in the striatum but not the ACC. Regarding GABA, we found no group difference in either region, although a negative association with MDMA use frequency was observed in the striatum. Overall, GLX measures from MEGA-PRESS, with its longer echo time, appeared to be less confounded by macromolecule signal than the short–echo-time PRESS and thus provided more robust results. Conclusion: Our findings suggest that MDMA use affects not only serotonin but also striatal GLX and GABA concentrations. These insights may offer new mechanistic explanations for cognitive deficits (e.g., impaired impulse control) observed in MDMA users

Hydroclimate changes in eastern Africa over the past 200,000 years may have influenced early human dispersal

Abstract: Reconstructions of climatic and environmental conditions can contribute to current debates about the factors that influenced early human dispersal within and beyond Africa. Here we analyse a 200,000-year multi-proxy paleoclimate record from Chew Bahir, a tectonic lake basin in the southern Ethiopian rift. Our record reveals two modes of climate change, both associated temporally and regionally with a specific type of human behavior. The first is a long-term trend towards greater aridity between 200,000 and 60,000 years ago, modulated by precession-driven wet-dry cycles. Here, more favorable wetter environmental conditions may have facilitated long-range human expansion into new territory, while less favorable dry periods may have led to spatial constriction and isolation of local human populations. The second mode of climate change observed since 60,000 years ago mimics millennial to centennial-scale Dansgaard-Oeschger cycles and Heinrich events. We hypothesize that human populations may have responded to these shorter climate fluctuations with local dispersal between montane and lowland habitats

Pleistocene climate variability in eastern Africa influenced hominin evolution

AbstractDespite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from ~620,000 to 275,000 years bp (episodes 1–6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7–9 (~275,000–60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiens in eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10–12 (~60,000–10,000 years bp) could have facilitated the global dispersal of H. sapiens.</jats:p

Impairment of Immunoproteasome Function by β5i/LMP7 Subunit Deficiency Results in Severe Enterovirus Myocarditis

Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu

Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation

Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1 alpha, beta, and gamma in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of beta-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms alpha and gamma but unaltered PP1 beta levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1 alpha abundance and activity, as indicated by higher phosphorylation of the PP1 alpha-specific substrate eIF2 alpha. Greater eIF2 alpha phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1 alpha activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions

Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex

Background 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used recreational substance inducing acute release of serotonin. Previous studies in chronic MDMA users demonstrated selective adaptations in the serotonin system, which were assumed to be associated with cognitive deficits. However, serotonin functions are strongly entangled with glutamate as well as gamma-aminobutyric acid (GABA) neurotransmission, and studies in MDMA-exposed rats show long-term adaptations in glutamatergic and GABAergic signaling. Methods We used proton magnetic resonance spectroscopy (MRS) to measure the glutamate-glutamine complex (GLX) and GABA concentrations in the left striatum and medial anterior cingulate cortex (ACC) of 44 chronic but recently abstinent MDMA users and 42 MDMA-naive healthy controls. While the Mescher-Garwood point-resolved-spectroscopy sequence (MEGA-PRESS) is best suited to quantify GABA, recent studies reported poor agreement between conventional short-echo-time PRESS and MEGA-PRESS for GLX measures. Here, we applied both sequences to assess their agreement and potential confounders underlying the diverging results. Results Chronic MDMA users showed elevated GLX levels in the striatum but not the ACC. Regarding GABA, we found no group difference in either region, although a negative association with MDMA use frequency was observed in the striatum. Overall, GLX measures from MEGA-PRESS, with its longer echo time, appeared to be less confounded by macromolecule signal than the short-echo-time PRESS and thus provided more robust results. Conclusion Our findings suggest that MDMA use affects not only serotonin but also striatal GLX and GABA concentrations. These insights may offer new mechanistic explanations for cognitive deficits (e.g., impaired impulse control) observed in MDMA users.ISSN:1461-1457ISSN:1469-511