Hydrothermal carbonisation (HTC) of lignocellulose could improve its pyrolytic behaviour, but to date, few studies have evaluated the effect of HTC (150 degrees C and 200 degrees C) on fast pyrolysis. To fill this gap, this paper investigated how HTC affects the chemical composition of fir sawdust and, in turn, how these changes affect biooil yield and composition. HTC significantly alters the chemical properties of the solid material, affecting the content and acetylation degree of hemicellulose while removing inorganics (primarily K2O and CaO). Whereas the relative mass yield of pyrolysis products was not strongly affected by HTC, the pyrolytic behaviour was influenced by the HTC pre-treatment. HTC alters the rheological behaviour of the reacting material during fast pyrolysis, yielding hydrochar that displays an apparently melting and bed agglomeration, similarly to pure lignin, with ultimate fluidisation impairment. Fast pyrolysis products were characterised with an array of analytical techniques, allowing for the identification of changes in pyrolysis pathways and providing the tentative identification of novel holocellulose-derived oligomers in the aqueous phase portion of bio-oil. Beyond the obvious effects related to hemicellulose removal/deacetylation, results showed a meaningful change in biooil composition, with a strong increase in the share of anhydrosugars, which may be due to ash removal. Pyrolytic lignin was the least affected fraction, presenting only a slight reduction in molecular weight and a slight demethoxylation of its components. Results show that HTC at 150 degrees C/200 degrees C extracts or hydrolyses part or all of the hemicellulose and converts biomass into a material with different pyrolytic behaviour. In particular, hydrochar obtained at 200 degrees C behaves similarly to a heterogeneous mixture of pure lignin and cellulose, highlighting the approach's potential (increased selectivity toward anhydrosugars) and pitfalls (in-bed melting of the material).
Early-career researchers (ECRs) play a vital role in advancing macrophyte research, bringing fresh perspectives, collaborative skills, and innovative methods to the field. Across marine and freshwater realms, macrophytes function as ecosystem engineers and key indicators of ecosystem health, yet they are declining due to a plethora of threats. As those who will shape the future of the field, ECRs are well-positioned to identify existing knowledge gaps and future priorities for the field in macrophyte research in a creative, integrative, and sustainable manner (both for the ecosystems and the ECRs themselves). Here, we present a unified perspective informed by the results of an international survey of 147 ECRs, capturing how ECRs see the field of macrophyte research at present and envision its future, including priorities for the field and how to overcome systemic barriers that ECRs face. Across realms and regions, ECRs currently use classical methods (e.g., field work, statistics) to study a wide range of topics including biodiversity, biotic interactions, and anthropogenic impacts. Regardless of research topic, ECRs are aware that technological advances are reshaping how research is conducted but acknowledge that they are not a silver bullet. Such advances should be harnessed to complement classical approaches, particularly taxonomy and field work. However, ECRs face structural barriers, including job insecurity and funding constraints, that disproportionately impact researchers in resource-limited regions within an already underrepresented field. Addressing these barriers and strengthening science-society connections is essential for the field’s future, and requires collaborative, interdisciplinary, and innovative research grounded in a strong ecological foundation.
Leucettinibs are substituted 2-aminoimidazolin-4-ones inspired by the marine sponge natural product Leucettamine B and developed as pharmacological inhibitors of DYRK1A (dual-specificity, tyrosine phosphorylation-regulated kinase 1A), a therapeutic target for indications such as Down syndrome, Alzheimer's disease, Parkinson's disease, diabetes, myocardial infarction, etc. Leucettinib-21 is currently being tested in a phase 1 clinical trial. In this study, four different affinity chromatography-based approaches were developed to identify the rat brain targets of Leucettinib-21: (1) Leucettinib-21 (and its kinase-inactive isomer as control) immobilized on agarose beads, (2) immobilized metal affinity chromatography, (3) KinAffinity bead competition assays, and (4) immunoprecipitation with DYRK1A-specific antibodies. Altogether, these complementary methods (1) confirm known targets of Leucettinib-21, and identify (2) new protein kinases and nonkinases interacting with Leucettinib-21, (3) potential new partners of DYRK1A, and (4) pathways and cellular mechanisms potentially modulated by Leucettinib-21. These methods can be expanded to various cells and tissues from models of pathologies where Leucettinib-21 demonstrates efficacy.
Context. Internal rotation has recently emerged as a fundamental dynamical feature of globular clusters (GCs). Its presence can serve as a direct fossil record of GC formation and of their subsequent evolution within a galactic context, yet its origin and long-term evolution remain poorly understood. Aims. In this paper, we systematically explore the evolution of rotating GCs over a Hubble time under the combined influence of two-body relaxation, external tidal field, and stellar evolution. Our goal is to establish a theoretical framework to interpret the growing wealth of 3D kinematic data and unveil primordial properties of GCs. Methods. We introduce the ROLLIN' simulations, a suite of 25 large N-body simulations of rotating GCs characterized by having a realistic number of stars from 250k to 1.5M and ran with the direct N-body code NBODY6++GPU. The simulations are evolved for 14 Gyr and are initialized with a wide range of rotation strengths, densities, and tidal fields. With present-day masses of 5 & times; 10(4)-5 & times; 10(5) M-circle dot, the models cover the typical parameter space of low-density Milky Way GCs. Results. Our analysis highlights the pivotal role of rotation in shaping the early evolution of GCs. Rapidly rotating GCs experience earlier and more pronounced core collapse, efficiently segregating massive objects-including stellar remnants-in their centers within the first few hundred million years. In the long-term, internal rotation steadily declines, and after 12 Gyr, a correlation emerges between rotation strength and total GC mass, in agreement with recent observations. The primary driver of this evolution is mass loss, capturing both internal (stellar evolution, evaporation) and external processes (tidal stripping). The velocity anisotropy also evolves in response to mass loss: Clusters initially near isotropy develop radial anisotropy, peaking around 40% mass loss, before progressing toward isotropy or tangential anisotropy at higher mass losses. Additionally, the GC orbital history plays a key role, as retrograde rotators retain angular momentum more effectively than prograde rotators, and their rotation profiles differ significantly already well within the Jacobi radius. Finally, our simulations enabled us to quantify the long-term structural changes of GCs after 12 Gyr: (i) The surface density decreases by up to two orders of magnitude. (ii) The half-mass radius increases by a factor of three to five. (iii) The rotation strength decreases by a factor greater than five for clusters that have lost more than 50% of their initial mass. Conclusions. The ROLLIN' simulations demonstrate that angular momentum, along with initial cluster density and mass, is one of the crucial aspects to understand the origin, evolution, and survival of GCs. These simulations therefore provide a valuable benchmark for interpreting GC observations both in the local and high-redshift Universe.
Neuromuscular junction (NMJ) disruption is an early pathogenic event in amyotrophic lateral sclerosis (ALS). Yet, direct links between NMJ pathways and ALS-associated genes such as FUS, whose heterozygous mutations cause aggressive forms of ALS, remain elusive. In a knock-in Fus-ALS mouse model, we identified postsynaptic NMJ defects in newborn homozygous mutants that were attributable to mutant FUS toxicity in skeletal muscle. Adult heterozygous knock-in mice displayed smaller neuromuscular endplates that denervated before motor neuron loss, which is consistent with 'dying-back' neuronopathy. FUS was enriched in subsynaptic myonuclei, and this innervation-dependent enrichment was distorted in FUS-ALS. Mechanistically, FUS collaborates with the ETS transcription factor ERM to stimulate transcription of acetylcholine receptor genes. Co-cultures of induced pluripotent stem cell-derived motor neurons and myotubes from patients with FUS-ALS revealed endplate maturation defects due to intrinsic FUS toxicity in both motor neurons and myotubes. Thus, FUS regulates acetylcholine receptor gene expression in subsynaptic myonuclei, and muscle-intrinsic toxicity of ALS mutant FUS may contribute to dying-back motor neuronopathy.
