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Speleothem-based reconstruction of Holocene changes in monsoonal patterns and environmental conditions in Central Brazil
No full textThe east-west precipitation dipole that occurs in South America has been vastly investigated in previous studies using paleoclimate records from east and west of the continent, but the climate dynamics of central-eastern Brazil remains less understood. While δ18O values have been widely used to study past rainfall variability over South America, their ability to resolve local hydrological changes in central Brazil during the Holocene has been proven to be difficult. Recent studies in the region have used δ13C values and 87Sr/86Sr ratios from speleothems to assess local paleo-hydrology and environmental conditions. Here, we revisit this topic for the last 11,000 years based on a novel multi-proxy record (δ18O, δ13C, and 87Sr/86Sr) from a stalagmite collected in central Brazil at the northern side of the present day South Atlantic Convergence Zone (SACZ). The overall climate shifted from drier to wetter conditions throughout the Holocene, reflecting the increasing southern insolation and the monsoon-driven wetting trend based on the local and regional δ13C and pollen records. Changes in atmospheric circulation patterns during the Holocene might have been responsible for the increase in δ18O values through time. A north-eastern climate influence during the weaker monsoon phase from early-to-mid Holocene contrasts the late Holocene and present-day influence of SACZ over the area. Hence, a negative correlation between δ18O and δ13C indicates a decoupling of monsoon activity from local climate conditions. The Sr isotope signals in our site may be influenced by mixed lithology or increased dust input from nearby sandstone during drier periods, revealing the complexity of this proxy. The São Mateus record highlights the complex, non-stationary interplay between monsoon strength
Mitochondrial dysfunction and impaired oxidative stress defense as potential trigger of cerebral X-linked adrenoleukodystrophy
No full textX-linked adrenoleukodystrophy (X-ALD) is caused by pathogenic ABCD1 variants, leading to a dysfunctional peroxisomal ABCD1 transporter, crucial for β-oxidation of very long chain fatty acids (VLCFA). The clinical manifestation ranges from asymptomatic carriers to severe childhood cerebral ALD (CALD). The underlying pathophysiology remains unclear, and while elevated oxidative stress and signs of mitochondrial dysfunction have been observed in X-ALD cells and tissues, their precise roles are still uncertain. This study aims to elucidate the interplay among excess VLCFA, mitochondrial function and oxidative stress in fibroblasts derived from CALD and non-CALD patients.Therefore, we measured reactive oxygen species (ROS) using the 2′,7′-dichlorofluorescein diacetate assay, mitochondrial function with the Seahorse XFe24 flux analyzer and assessed the regulation of stress homeostasis on the genetic level by qPCR of NRF2-dependent genes NQO1, AR1B10 and AKR1C1. Additional stress was induced by exposure to tert-butyl hydroperoxide (TBHP) and hexacosanoic acid (C26:0). Scanning confocal microscopy and STED super-resolution microscopy was implemented for evaluation of mitochondrial structure and peroxisomal-mitochondrial crosstalk.Our findings indicate that non-CALD cell lines exhibit an overall compromised oxidative status under basal conditions, characterized by significantly reduced oxygen consumption rates (OCR) relative to both CALD and healthy controls, along with diminished expression of NRF2-regulated genes. Notably, ROS levels in non-CALD cells are comparable to those observed in CALD cells. However, when exposed to additional stress, these non-CALD cells show greater potential of defense mechanisms and compensation compared to CALD cells. These findings significantly improve our understanding of metabolic changes in X-ALD, focusing on the ability of different X-ALD phenotypes to cope with oxidative stress. They pave the way for further investigations to understand the different phenotypes and their disease progression, to find reliant biomarkers, and to develop therapeutic approaches and preventive measures for individual patients
Blood mitochondrial metabolism predicts flight performance without lasting effects of early-life thyroid hormones
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Altered Cohesin Dynamics During Cellular Differentiation
No full textThe cohesin complex plays essential roles in chromosome organization and gene regulation, yet how cohesin dynamics are controlled during cell-state transitions remains poorly understood. Here, we examined how cohesin regulation is remodeled during the differentiation of mouse embryonic stem cells (mESCs) into the cardiomyocyte lineage using an in vitro differentiation system. We found that core cohesin subunits remain broadly stable at the protein level. In contrast, the levels of cohesin regulators, including the cohesin removal protein WAPL and the cohesin stabilizing protein ESCO1, decline sharply despite modest transcript-level changes. The cohesion maintenance factor Sororin was also reduced. To better understand the net effect of these changes on cohesin dynamics, we use live-cell FRAP of RAD21, which revealed increased cohesin mobility in differentiated cells without a change in recovery kinetics, consistent with reduced stable chromatin engagement or redistribution into a chromatin-unbound nuclear pool. To test functional consequences, we generated homozygous degron alleles for Wapl and Esco1 and induced acute degradation using a dTAG-based system. Loss of WAPL altered cell-cycle dynamics in stem cells and produced a characteristic "vermicelli" chromosome phenotype, consistent with abnormally high and lethal cohesin retention on chromatin. Surprisingly, depletion of ESCO1 had no clear impact on viability and cell cycle progression. Notably, despite loss of detectable WAPL protein in the differentiated cell population, we find that WAPL remains functionally required to maintain a viable interphase chromosome organization. Together, these findings identify cohesin regulators, rather than cohesin abundance, as central drivers of changes in cohesin dynamics during differentiation. They further show that even very low levels of WAPL continue to provide critical structural plasticity of chromosomes following cell cycle exit and lineage commitment
Do it yourself: Creating 3D brain-surface models and custom-made brain matrices for guided sectioning using photogrammetry and three-dimensional printing technology
No full textBroadband single-shot THz sampling using reflection gratings
No full textSingle-shot electro-optic sampling (EOS) is a powerful method enabling the measurement of weak terahertz signals that would otherwise require prohibitively long acquisition times. This is generally achieved by encoding the EOS time delay into a spatial, angular, or frequency coordinate. In general, angular-encoding techniques operate well up to 3 THz but become more challenging for larger bandwidths, due to dispersion and imaging imperfections. Here, we demonstrate a reliable angular-encoding single-shot EOS implementation that reaches frequencies beyond 6 THz. Diffraction simulations are used to design the experimental setup and adapt this technique to commercial reflection gratings, removing the need for custom-built echelon mirrors. Furthermore, we show that, contrary to earlier reports, group delay dispersion from angular dispersion does not reduce the bandwidth of single-shot EOS