Double-edged Role of KNa Channels in Brain Tuning: Identifying Epileptogenic Network Micro-Macro Disconnection

: Epilepsy is commonly recognized as a disease driven by generalized hyperexcited and hypersynchronous neural activity. Sodium-activated potassium channels (KNa channels), which are encoded by the Slo 2.2 and Slo 2.1 genes, are widely expressed in the central nervous system and considered as “brakes” to adjust neuronal adaptation through regulating action potential threshold or after-hyperpolarization under physiological condition. However, the variants in KNa channels, especially gain-of-function variants, have been found in several childhood epileptic conditions. Most previous studies focused on mapping the epileptic network on the macroscopic scale while ignoring the value of microscopic changes. Notably, paradoxical role of KNa channels working on individual neuron/microcircuit and the macroscopic epileptic expression highlights the importance of understanding epileptogenic network through combining microscopic and macroscopic methods. Here, we first illustrated the molecular and physiological function of KNa channels on preclinical seizure models and patients with epilepsy. Next, we summarized current hypothesis on the potential role of KNa channels during seizures to provide essential insight into what emerged as a micro-macro disconnection at different levels. Additionally, we highlighted the potential utility of KNa channels as therapeutic targets for developing innovative anti-seizure medications.

Environmental protection in the Constitution of the Czech Republic

This article aims to analyse the constitutional order of Czechia and the decision-making practice of the courts to define the legal means of environmental protection at the constitutional level. The aim is also to provide the reader with an essential insight into environmental protection in Czechia at the constitutional level so that the legal regulation and decision-making practice can be compared with other countries.

Pemberdayaan Masyarakat Melalui Program Rumah Literasi Kreatif di Kabupaten Kutai Kartanegara

Sampai hari ini, sebagian besar penduduk dari daerah tertinggal di Indonesia masih menghadapi persoalan kualitas pendidikan yang kurang memadai. Mengeksplorasi program kolaborasi edukasi antara Rulika Bunga Kertas dan perusahaan Pertamina Hulu Sanga Sanga, makalah ini berupaya mengembangkan pemahaman tentang bagaimana inisiatif pemberdayaan diimplementasikan dengan menempatkan masyarakat lokal sebagai subjek pembangunan. Terkait dengan hal ini, sembilan pemangku kepentingan di Desa Beringin Agung, Kabupaten Samboja di wawancarai dan ditemukan bahwa pemberdayaan lembaga lokal telah berkontribusi efektif terhadap peningkatan literasi dasar bagi penerima manfaat. Selain itu, pemberdayaan agensi lokal juga terbukti telah memberikan efek keberlanjutan, mengindikasikan keberhasilan program. Secara keseluruhan, Rulika Bunga Kertas telah memainkan peranannya sebagai solusi efektif bagi warga dari daerah transmigrasi. Makalah ini dengan demikian, memberikan wawasan penting dalam studi tentang relasi komunitas-sektor swasta dalam inisiatif pemberdayaan. Kata Kunci: Rumah Literasi Kreatif; Rulika Bunga Kertas; Taman Baca Masyarakat It is widely acknowledged that a key proportion of residents from backward areas in Indonesia are remained to suffer from inadequate quality of education. Exploring the case of a fruitful collaboration of Rulika Bunga Kertas and Pertamina Hulu Sunga company, this paper aims at developing an understanding of how empowerment initiatives are implemented by situating local communities as development subjects for improving education in Beringin Agung Village, Samboja District. Based on interviews with 9-stakeholders, the findings demonstrate that empowering local agencies have provided them with the necessary capacity to help their residents in improving basic literacy skills. Furthermore, the empowered local agency has contributed to sustainability, indicating a successful empowerment strategy. Overall, Rulika Bunga Kertas has expanded and played as an effective solution for residents from transmigration areas. This paper, therefore, offers essential insight into discussing the community-private sector relationship against empowerment initiatives.. Keywords: Rumah Literasi Kreatif; Rulika Bunga Kertas; Community Reading Gardens

A network model of glymphatic flow under different experimentally-motivated parametric scenarios

Rapidly growing evidence demonstrates that flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) – annular tunnels surrounding vasculature in the brain – is a critically-important component of neurophysiology. CSF inflow contributes during physiological conditions to clearance of metabolic waste and in pathological situations to edema formation. However, brain-wide imaging methods cannot resolve PVSs, and high-resolution methods cannot access deep tissue or be applied to human subjects, so theoretical models provide essential insight. We model this CSF pathway as a network of hydraulic resistances, built from published parameters. A few parameters have very wide uncertainties, so we focus on the limits of their feasible ranges by analyzing different parametric scenarios. We identify low-resistance PVSs and high-resistance parenchyma (brain tissue) as the scenario that best explains experimental observations. Our results point to the most important parameters that should be measured in future experiments. Extensions of our modeling may help predict stroke severity or lead to neurological disease treatments and drug delivery methods.

Merohedral disorder and impurity impacts on superconductivity of fullerenes

Local quasiparticle states around impurities provide essential insight into the mechanism of unconventional superconductivity, especially when the candidate materials are proximate to an antiferromagnetic Mott-insulating phase. While such states have been reported in atom-based cuprates and iron-based compounds, they are unexplored in organic superconductors which feature tunable molecular orientation. Here we employ scanning tunneling microscopy and spectroscopy to reveal multiple forms of robustness of an exotic s-wave superconductivity in epitaxial Rb3C60 films against merohedral disorder, non-magnetic single impurities and step edges at the atomic scale. Yu-Shiba-Rusinov (YSR) states, induced by deliberately incurred Fe adatoms that act as magnetic scatterers, have also been observed. The YSR bound states show abrupt spatial decay and vary in energy with the Fe adatom registry. These results and a doping-dependent study of superconductivity point towards local electron pairing in which the multiorbital electronic correlations and intramolecular phonons together drive the high-temperature superconductivity of doped fullerenes.

Statistical Mechanics: Entropy, Order Parameters, and Complexity

This text distills the core ideas of statistical mechanics to make room for new advances important to information theory, complexity, active matter, and dynamical systems. Chapters address random walks, equilibrium systems, entropy, free energies, quantum systems, calculation and computation, order parameters and topological defects, correlations and linear response theory, and abrupt and continuous phase transitions. Exercises explore the enormous range of phenomena where statistical mechanics provides essential insight — from card shuffling to how cells avoid errors when copying DNA, from the arrow of time to animal flocking behavior, from the onset of chaos to fingerprints. The text is aimed at graduates, undergraduates, and researchers in mathematics, computer science, engineering, biology, and the social sciences as well as to physicists, chemists, and astrophysicists. As such, it focuses on those issues common to all of these fields, background in quantum mechanics, thermodynamics, and advanced physics should not be needed, although scientific sophistication and interest will be important.

Proteotoxicity and Neurodegenerative Diseases

Neurodegenerative diseases are a major burden for our society, affecting millions of people worldwide. A main goal of past and current research is to enhance our understanding of the mechanisms underlying proteotoxicity, a common theme among these incurable and debilitating conditions. Cell proteome alteration is considered to be one of the main driving forces that triggers neurodegeneration, and unraveling the biological complexity behind the affected molecular pathways constitutes a daunting challenge. This review summarizes the current state on key processes that lead to cellular proteotoxicity in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, providing a comprehensive landscape of recent literature. A foundational understanding of how proteotoxicity affects disease etiology and progression may provide essential insight towards potential targets amenable of therapeutic intervention.

Deep Functional Profiling Facilitates the Evaluation of the Antibacterial Potential of the Antibiotic Amicoumacin

The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies to counteract it. Deep functional profiling of microbiomes provides an alternative source for the discovery of novel antibiotic producers and probiotics. Recently, we implemented this ultrahigh-throughput screening approach for the isolation of Bacillus pumilus strains efficiently producing the ribosome-targeting antibiotic amicoumacin A (Ami). Proteomics and metabolomics revealed essential insight into the activation of Ami biosynthesis. Here, we applied omics to boost Ami biosynthesis, providing the optimized cultivation conditions for high-scale production of Ami. Ami displayed a pronounced activity against Lactobacillales and Staphylococcaceae, including methicillin-resistant Staphylococcus aureus (MRSA) strains, which was determined using both classical and massive single-cell microfluidic assays. However, the practical application of Ami is limited by its high cytotoxicity and particularly low stability. The former is associated with its self-lactonization, serving as an improvised intermediate state of Ami hydrolysis. This intramolecular reaction decreases Ami half-life at physiological conditions to less than 2 h, which is unprecedented for a terminal amide. While we speculate that the instability of Ami is essential for Bacillus ecology, we believe that its stable analogs represent attractive lead compounds both for antibiotic discovery and for anticancer drug development.

Searching for multiple populations in the integrated light of the young and extremely massive clusters in the merger remnant NGC 7252

ABSTRACT Recent work has shown that the properties of multiple populations (MPs) within massive stellar clusters (i.e. in the extent of their abundance variations as well as the fraction of stars that show the anomalous chemistry) depend on the mass as well as the age of the host cluster. Such correlations are largely unexpected in current models for the formation of MPs and hence provide essential insight into their origin. Here, we extend our previous study into the presence or absence of MPs using integrated light spectroscopy of the ∼600 Myr, massive (∼107–108 M⊙) clusters, W3 and W30, in the galactic merger remnant, NGC 7252. Due to the extreme mass of both clusters, the expectation is that they should host rather extreme abundance spreads, manifested through high mean [Na/Fe] abundances. However, we do not find evidence for a strong [Na/Fe] enhancement, with the observations being consistent with the solar value. This suggests that age is playing a key role, or alternatively that MPs only manifest below a certain stellar mass, as the integrated light at all ages above ∼100 Myr is dominated by stars near or above the main-sequence turn-off.

Skin-interfaced microfluidic devices with one-opening chambers and hydrophobic valves for sweat collection and analysis

Soft, skin-interfaced microfluidic platforms are capable of capturing, storing, and assessing sweat chemistry and total sweat loss, which provides essential insight into human physiological health.