Two distinct red giant branch populations in the globular cluster NGC 2419 as tracers of a merger event in the Milky Way

Recent spectroscopic observations of the outer halo globular cluster (GC) NGC 2419 show that it is unique among GCs, in terms of chemical abundance patterns, and some suggest that it was originated in the nucleus of a dwarf galaxy. Here we show, from the Subaru narrow-band photometry employing a calcium filter, that the red giant-branch (RGB) of this GC is split into two distinct subpopulations. Comparison with spectroscopy has confirmed that the redder RGB stars in the $hk$[=(Ca$-b)-(b-y)$] index are enhanced in [Ca/H] by $\sim$0.2 dex compared to the bluer RGB stars. Our population model further indicates that the calcium-rich second generation stars are also enhanced in helium abundance by a large amount ($\Delta$Y = 0.19). Our photometry, together with the results for other massive GCs (e.g., $\omega$ Cen, M22, and NGC 1851), suggests that the discrete distribution of RGB stars in the $hk$ index might be a universal characteristic of this growing group of peculiar GCs. The planned narrow-band calcium photometry for the Local Group dwarf galaxies would help to establish an empirical connection between these GCs and the primordial building blocks in the hierarchical merging paradigm of galaxy formation.Comment: 4 pages, 4 figures, 1 table, accepted for the publication in ApJ

Lignans, amides, and saponins from Haplophyllum tuberculatum and their antiprotozoal activity

A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract of; Haplophyllum tuberculatum; exhibited appreciable bioactivity against; Leishmania donovani; . The antileishmanial activity was tracked by HPLC-based activity profiling, and eight compounds were isolated from the chloroform fraction. These included lignans tetrahydrofuroguaiacin B (; 1; ), nectandrin B (; 2; ), furoguaiaoxidin (; 7; ), and 3,3'-dimethoxy-4,4'-dihydroxylignan-9-ol (; 10; ), and four cinnamoylphenethyl amides, namely dihydro-feruloyltyramine (; 5; ), (; E; )-; N; -feruloyltyramine (; 6; ),; N; ,; N; '-diferuloylputrescine (; 8; ), and 7'-ethoxy-feruloyltyramine (; 9; ). The water fraction yielded steroid saponins; 11; -; 13; . Compounds; 1; ,; 2; , and; 5; -; 13; are reported for the first time from; Haplophyllum; species and the family Rutaceae. The antiprotozoal activity of the compounds plus two stereoisomeric tetrahydrofuran lignans-fragransin B; 2; (; 3; ) and fragransin B; 1; (; 4; )-was determined against; Leishmania donovani; amastigotes,; Plasmodium falciparum,; and; Trypanosoma brucei rhodesiense; bloodstream forms, along with their cytotoxicity to rat myoblast L6 cells. Nectandrin B (; 2; ) exhibited the highest activity against; L. donovani; (IC; 50; 4.5 µM) and the highest selectivity index (25.5)

A 3D flexible neural interface based on a microfluidic interconnection cable capable of chemical delivery

The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks. Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain, and it expands the utility of drugs by bypassing the blood–brain barrier (BBB). In addition, uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes, pointing to a critical issue still to be overcome. Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications, it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures, which differ from two-dimensionally fabricated shank-type neural probes. Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality. We fabricated a microfluidic interconnection cable (µFIC) and integrated it with a flexible penetrating microelectrode array (FPMA) that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base. We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection. This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities. © 2021, The Author(s).1

PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis

SummaryDeregulation of mitogen-activated protein kinase (MAPK) signaling leads to development of pancreatic cancer. Although Ras-mutation-driven pancreatic tumorigenesis is well understood, the underlying mechanism of Ras-independent MAPK hyperactivation remains elusive. Here, we have identified a distinct function of PCNA-associated factor (PAF) in modulating MAPK signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. In mouse models, PAF expression induced pancreatic intraepithelial neoplasia with expression of pancreatic cancer stem cell markers. PAF-induced ductal epithelial cell hyperproliferation was accompanied by extracellular signal-regulated kinase (ERK) phosphorylation independently of Ras or Raf mutations. Intriguingly, PAF transcriptionally activated the expression of late endosomal/lysosomal adaptor, MAPK and mTOR activator 3 (LAMTOR3), which hyperphosphorylates MEK and ERK and is necessary for pancreatic cancer cell proliferation. Our results reveal an unsuspected mechanism of mitogenic signaling activation via LAMTOR3 and suggest that PAF-induced MAPK hyperactivation contributes to pancreatic tumorigenesis

Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Liquid-liquid phase separation occurs in cells and can be induced in artificial systems, but the mechanism of the effect of molecular crowders is unclear. Here dehydration entropy-driven phase separation of model charged polymers lacking any chemical complexity or hydrophobicity is shown to be enhanced by polyethylene glycol. Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)-a widely used molecular crowder-in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.11Ysciescopu

Interaction and ordering of vacancy defects in NiO

By using a first-principles method employing the local density approximation plus Hubbard parameter approach, we study point defects in NiO and interactions between them. The defect states associated with nickel or oxygen vacancies are identified within the energy gap. It is found that nickel vacancies introduce shallow levels in the density of states for the spin direction opposite to that of the removed Ni atom, while the oxygen vacancy creates more localized in-gap states. The interaction profiles between vacancies indicate that specific defect arrangements are strongly favored for both nickel and oxygen vacancies. In the case of nickel vacancies, defect ordering in a simple-cubic style is found to be most stable, leading to a half-metallic behavior. The ionized oxygen vacancies also show a tendency toward clustering, more strongly than neutral pairs. The microscopic origin of vacancy clustering is understood based on overlap integrals between defect states. © 2008 The American Physical Society.open343

Posterior condylar offset changes and its effect on clinical outcomes after posterior-substituting, fixed-bearing total knee arthroplasty: anterior versus posterior referencing

Background We sought to determine whether there was a difference in the posterior condylar offset (PCO), posterior condylar offset ratio (PCOR) and clinical outcomes following total knee arthroplasty (TKA) with anterior referencing (AR) or posterior referencing (PR) systems. We also assessed whether the PCO and PCOR changes, as well as patient factors were related to range of motion (ROM) in each referencing system. Methods This retrospective study included 130 consecutive patients (184 knees) with osteoarthritis who underwent primary posterior cruciate ligament (PCL)-substituting fixed-bearing TKA. The difference between preoperative and postoperative PCO and PCOR values were calculated. Clinical outcomes including ROM and Western Ontario and McMaster University (WOMAC) scores were evaluated. Furthermore, multiple linear regression analysis was performed to determine the factors related to postoperative ROM in each referencing system. Results The postoperative PCO was greater in the AR group (28.4 mm) than in the PR group (27.4 mm), whereas the PCO was more consistently preserved in the PR group. The mean postoperative ROM after TKA was greater in the AR group (129°) than in the PR group (122°), whereas improvement in WOMAC score did not differ between the two groups. Preoperative ROM was the only factor related to postoperative ROM in both groups. Conclusions There was no difference in postoperative PCO in AR and PR group and the PCO was not associated with postoperative ROM. PCO was more consistently preserved after surgery in the PR group. The postoperative PCO and PCOR changes did not affect the postoperative ROM. Furthermore, similar clinical outcomes were achieved in the AR and PR groups. Trial registration Retrospectively registered (Trial registration number: 06-2010-110).This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9D8063538)