Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic ...nanoarchitecture, peptide-appended hybrid4arene (PAH4), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH4s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH4s can transport >10
water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~10
, as illustrated by the water/NaCl permeability-selectivity trade-off curve. PAH4's unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production and barrier applications.
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The promise of using reprogrammed human neurons for disease modeling and regenerative medicine relies on the ability to induce patient-derived neurons with high efficiency and subtype specificity. We ...have previously shown that ectopic expression of brain-enriched microRNAs (miRNAs), miR-9/9∗ and miR-124 (miR-9/9∗-124), promoted direct conversion of human fibroblasts into neurons. Here we show that coexpression of miR-9/9∗-124 with transcription factors enriched in the developing striatum, BCL11B (also known as CTIP2), DLX1, DLX2, and MYT1L, can guide the conversion of human postnatal and adult fibroblasts into an enriched population of neurons analogous to striatal medium spiny neurons (MSNs). When transplanted in the mouse brain, the reprogrammed human cells persisted in situ for over 6 months, exhibited membrane properties equivalent to native MSNs, and extended projections to the anatomical targets of MSNs. These findings highlight the potential of exploiting the synergism between miR-9/9∗-124 and transcription factors to generate specific neuronal subtypes.
•Striatal transcription factors with miRNAs robustly converts human fibroblasts to MSNs•Converted cells show a gene expression profile analogous to primary human MSNs•Transplanted MSNs converted from human fibroblasts can function in vivo•Engrafted cells wire into the circuit properly and are capable of long-term survival
Victor et al. demonstrate that microRNAs (miR-9/9∗ and miR-124) and striatal transcription factors directly convert human fibroblasts into striatal medium spiny neurons. When transplanted in the mouse brain, converted human cells functionally integrate into the striatum.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RATIONALE:Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium play a critical role in the pathophysiology of sepsis and organ failure. The ...intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood.
OBJECTIVE:To determine the central role of YAP (Yes-associated protein), the major transcriptional coactivator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation.
METHODS AND RESULTS:Endothelial-specific YAP knockout mice showed increased basal expression of E-selectin and ICAM (intercellular adhesion molecule)-1 in endothelial cells, a greater number of adherent neutrophils in postcapillary venules and increased neutrophil counts in bronchoalveolar lavage fluid. Lipopolysaccharide challenge of these mice augmented NF-κB (nuclear factor-κB) activation, expression of endothelial adhesion proteins, neutrophil and monocyte adhesion to cremaster muscle venules, transendothelial neutrophil migration, and lung inflammatory injury. Deletion of YAP in endothelial cells also markedly augmented the inflammatory response and cardiovascular dysfunction in a polymicrobial sepsis model induced by cecal ligation and puncture. YAP functioned by interacting with the E3 ubiquitin-protein ligase TLR (Toll-like receptor) signaling adaptor TRAF6 (tumor necrosis factor receptor-associated factor 6) to ubiquitinate TRAF6, and thus promoted TRAF6 degradation and modification resulting in inhibition of NF-κB activation. TRAF6 depletion in endothelial cells rescued the augmented inflammatory phenotype in mice with endothelial cell–specific deletion of YAP.
CONCLUSIONS:YAP modulates the activation of endothelial cells and suppresses vascular inflammation through preventing TRAF6-mediated NF-κB activation and is hence essential for limiting the severity of sepsis-induced inflammation and organ failure.
Voltage-gated Na and Ca(2+) channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and ...chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca(2+) and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.
A
bstract
We consider the bound state problem for a field theory that contains a Dirac fermion
χ
that Yukawa couples to a (light) scalar field
ϕ
. We are interested in bound states with a large ...number
N
of
χ
particles. A Fermi gas model is used to numerically determine the dependence of the radius
R
of these bound states on
N
and also the dependence of the binding energy on
N
. Since scalar interactions with relativistic
χ
’s are suppressed two regimes emerge. For modest values of
N
the state is composed of non-relativistic
χ
particles. In this regime as
N
increases
R
decreases. Eventually the core region becomes relativistic and the size of the state starts to increase as
N
increases. As a result, for fixed Yukawa coupling and
χ
mass, there is a minimum sized state that occurs roughly at the value of
N
where the core region first becomes relativistic. We also compute an elastic scattering form factor that can be relevant for direct detection if the dark matter is composed of such
χ
particles.
Abstract
Studies of rest-frame optical emission in quasars at
z
> 6 have historically been limited by the wavelengths accessible by ground-based telescopes. The James Webb Space Telescope (JWST) now ...offers the opportunity to probe this emission deep into the reionization epoch. We report the observations of eight quasars at
z
> 6.5 using the JWST/NIRCam Wide Field Slitless Spectroscopy as a part of the “A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE)” program. Our JWST spectra cover the quasars’ emission between rest frame ∼4100 and 5100 Å. The profiles of these quasars’ broad H
β
emission lines span a full width at half maximum from 3000 to 6000 km s
−1
. The H
β
-based virial black hole (BH) masses, ranging from 0.6 to 2.1 billion solar masses, are generally consistent with their Mg
ii
-based BH masses. The new measurements based on the more reliable H
β
tracer thus confirm the existence of a billion solar-mass BHs in the reionization epoch. In the observed O
iii
λ
λ
4960,5008 doublets of these luminous quasars, broad components are more common than narrow core components (≤ 1200 km s
−1
), and only one quasar shows stronger narrow components than broad. Two quasars exhibit significantly broad and blueshifted O
iii
emission, thought to trace galactic-scale outflows, with median velocities of −610 and −1430 km s
−1
relative to the C
ii
158
μ
m line. All eight quasars show strong optical Fe
ii
emission and follow the eigenvector 1 relations defined by low-redshift quasars. The entire ASPIRE program will eventually cover 25 quasars and provide a statistical sample for the studies of the BHs and quasar spectral properties.
ABSTRACT After two Atacama Large Millimeter/submillimeter Array (ALMA) observing cycles, only a handful of C ii 158 m emission line searches in z > 6 galaxies have reported a positive detection, ...questioning the applicability of the local C ii-star formation rate (SFR) relation to high-z systems. To investigate this issue we use the Vallini et al. (V13) model,based on high-resolution, radiative transfer cosmological simulations to predict the C ii emission from the interstellar medium of a z 7 (halo mass Mh = 1.17 × 1011 M ) galaxy. We improve the V13 model by including (a) a physically motivated metallicity (Z) distribution of the gas, (b) the contribution of photodissociation regions (PDRs), and (c) the effects of cosmic microwave background (CMB) on the C ii line luminosity. We study the relative contribution of diffuse neutral gas to the total C ii emission (Fdiff/Ftot) for different SFR and Z values. We find that the C ii emission arises predominantly from PDRs: regardless of the galaxy properties, Fdiff/Ftot ≤ 10%, since at these early epochs the CMB temperature approaches the spin temperature of the C ii transition in the cold neutral medium (TCMB ∼ ∼ 20 K). Our model predicts a high-z C ii-SFR relation, consistent with observations of local dwarf galaxies (0.02 < Z/Z < 0.5). The C ii deficit suggested by actual data (LCii < 2.0 × 107 L in BDF3299 at z 7.1) if confirmed by deeper ALMA observations, can be ascribed to negative stellar feedback disrupting molecular clouds around star formation sites. The deviation from the local C ii-SFR would then imply a modified Kennicutt-Schmidt relation in z > 6 galaxies. Alternatively/in addition, the deficit might be explained by low gas metallicities (Z < 0.1 Z ).
We measured the density of vibrational states (DOS) and the specific heat of various glassy and crystalline polymorphs of SiO2. The typical (ambient) glass shows a well-known excess of specific heat ...relative to the typical crystal (α-quartz). This, however, holds when comparing a lower-density glass to a higher-density crystal. For glassy and crystalline polymorphs with matched densities, the DOS of the glass appears as the smoothed counterpart of the DOS of the corresponding crystal; it reveals the same number of the excess states relative to the Debye model, the same number of all states in the low-energy region, and it provides the same specific heat. This shows that glasses have higher specific heat than crystals not due to disorder, but because the typical glass has lower density than the typical crystal.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Despite the high charge-carrier mobility in covalent organic frameworks (COFs), the low intrinsic conductivity and poor solution processability still impose a great challenge for their applications ...in flexible electronics. We report the growth of oriented thin films of a tetrathiafulvalene-based COF (TTF-COF) and its tunable doping. The porous structure of the crystalline TTF-COF thin film allows the diffusion of dopants such as I 2 and tetracyanoquinodimethane (TCNQ) for redox reactions, while the closely packed 2D grid sheets facilitate the cross-layer delocalization of thus-formed TTF radical cations to generate more conductive mixed-valence TTF species, as is verified by UV-vis-NIR and electron paramagnetic resonance spectra. Conductivity as high as 0.28 S m −1 is observed for the doped COF thin films, which is three orders of magnitude higher than that of the pristine film and is among the highest for COF materials.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
![ON THE [C ii]-SFR RELATION ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0004-637X_1538-4357/small "ON THE [C ii]-SFR RELATION IN HIGH REDSHIFT GALAXIES")
