Search

Asthma is a heterogeneous disease characterized by multiple phenotypes with varying risk factors and therapeutic responses. This Commentary describes research on biomarkers for T2-"high" and T2-"low" inflammation, a hallmark of the disease. Patients with asthma who exhibit an increase in airway T2 inflammation are classified as having T2-high asthma. In this endotype, Type 2 cytokines interleukins (IL)-4, IL-5, and IL-13, plus other inflammatory mediators, lead to increased eosinophilic inflammation and elevated fractional exhaled nitric oxide (FeNO). In contrast, T2-low asthma has no clear definition. Biomarkers are considered valuable tools as they can help identify various phenotypes and endotypes, as well as treatment response to standard treatment or potential therapeutic targets, particularly for biologics. As our knowledge of phenotypes and endotypes expands, biologics are increasingly integrated into treatment strategies for severe asthma. These treatments block specific inflammatory pathways or single mediators. While single or composite biomarkers may help to identify subsets of patients who might benefit from these treatments, only a few inflammatory biomarkers have been validated for clinical application. One example is sputum eosinophilia, a particularly useful biomarker, as it may suggest corticosteroid responsiveness or reflect non-compliance to inhaled corticosteroids. As knowledge develops, a meaningful goal would be to provide individualized care to patients with asthma. [ABSTRACT FROM AUTHOR]

Simple Summary: The molecular heterogeneity of hepatocellular carcinoma (HCC) and its range of potential etiologies contribute to the complexities in treating this disease. Additionally, inter-sample molecular variability can mean the involvement of different prognostic genes or utilization of distinct molecular pathways in HCC development. This paper examines the genes and pathways most involved in different histological grades of HCC across various pre-cancer risk factors using publicly available bulk transcriptomics data and a systems biology approach. It identifies shared pathways among HCCs of varying grades and risk factors, as well as genes common to these pathways. Furthermore, this study highlights gene clusters preserved across risk factors, which may indicate shared targets for general treatment and gene clusters specific to viral or non-viral etiologies. Overall, this research reveals common and differing molecular pathways across risk factors and similarities in gene expression between histological grades. It provides a framework for understanding HCC development respective of risk factors and underscores the molecular pathways and genes involved. Hepatocellular carcinoma (HCC) has the highest mortality rate and is the most frequent of liver cancers. The heterogeneity of HCC in its etiology and molecular expression increases the difficulty in identifying possible treatments. To elucidate the molecular mechanisms of HCC across grades, data from The Cancer Genome Atlas (TCGA) were used for gene co-expression analysis, categorizing each sample into its pre-existing risk factors. The R library BioNERO was used for preprocessing and gene co-expression network construction. For those modules most correlated with a grade, functional enrichments from different databases were then tested, which appeared to have relatively consistent patterns when grouped by G1/G2 and G3/G4. G1/G2 exhibited the involvement of pathways related to metabolism and the PI3K/Akt pathway, which regulates cell proliferation and related pathways, whereas G3/G4 showed the activation of cell adhesion genes and the p53 signaling pathway, which regulates apoptosis, cell cycle arrest, and similar processes. Module preservation analysis was then used with the no history dataset as the reference network, which found cell adhesion molecules and cell cycle genes to be preserved across all risk factors, suggesting they are imperative in the development of HCC regardless of potential etiology. Through hierarchical clustering, modules related to the cell cycle, cell adhesion, the immune system, and the ribosome were found to be consistently present across all risk factors, with distinct clusters linked to oxidative phosphorylation in viral HCC and pentose and glucuronate interconversions in non-viral HCC, underscoring their potential roles in cancer progression. [ABSTRACT FROM AUTHOR]

Palmitoylation, a lipid-based posttranslational protein modification, plays a crucial role in regulating various aspects of neuronal function through altering protein membrane-targeting, stabilities, and protein–protein interaction profiles. Disruption of palmitoylation has recently garnered attention as disease mechanism in neurodegeneration. Many proteins implicated in neurodegenerative diseases and associated neuronal dysfunction, including but not limited to amyloid precursor protein, β-secretase (BACE1), postsynaptic density protein 95, Fyn, synaptotagmin-11, mutant huntingtin, and mutant superoxide dismutase 1, undergo palmitoylation, and recent evidence suggests that altered palmitoylation contributes to the pathological characteristics of these proteins and associated disruption of cellular processes. In addition, dysfunction of enzymes that catalyze palmitoylation and depalmitoylation has been connected to the development of neurological disorders. This review highlights some of the latest advances in our understanding of palmitoylation regulation in neurodegenerative diseases and explores potential therapeutic implications. [ABSTRACT FROM AUTHOR]

The fruit of Morinda citrifolia, also known as the noni tree, has been extensively used in Polynesian culture as an alternative medicine to various diseases. Recent studies have pointed out its anxiolytic activity in vitro and in mouse models. Despite the effectiveness of developed anxiolytic drugs in the market, the potential side effects of these medications have led people to resort to traditional medicine such as M. citrifolia. However, evidence regarding its anti-anxiety characteristics is still lacking to this day. Hence, this preliminary study implemented combined network pharmacology and molecular docking to validate its anti-anxiety claims. This study highlighted the bioactive compounds of the M. citrifolia fruit part to have excellent absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, particularly their outstanding oral bioavailability and blood–brain barrier penetration, both of which are essential considerations to ensure the effectiveness of anxiolytic drugs to arrive at the site of action. Moreover, noni fruit metabolites target genes involved in glutamatergic synapse pathways, which have been significantly associated with anxiety. Through molecular docking, selected compounds exhibited a strong binding affinity towards GRIA2 and PRKCA, both of which have connections with glutamatergic pathways. With all things considered, the results established that the noni fruit potentially contains therapeutic agents that elicit anti-anxiety potential. Through this, the promotion of a more sustainable, accessible, and affordable treatment of anxiety could be developed. [ABSTRACT FROM AUTHOR]

The Cosmic Evolution Early Release Science program observed the Extended Groth Strip (EGS) with the Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope (JWST) in 2022. In this paper, we discuss the four MIRI pointings that observed with longer-wavelength filters, including F770W, F1000W, F1280W, F1500W, F1800W, and F2100W. We compare the MIRI galaxies with the Spitzer/MIPS 24 μ m population in the EGS field. We find that MIRI can observe an order of magnitude deeper than MIPS in significantly shorter integration times, attributable to JWST's much larger aperture and MIRI’s improved sensitivity. MIRI is exceptionally good at finding faint ( L _IR < 10 ^10 L _⊙ ) galaxies at z ∼ 1–2. We find that a significant portion of MIRI galaxies are “mid-IR weak”—they have strong near-IR emission and relatively weaker mid-IR emission, and most of the star formation is unobscured. We present new IR templates that capture how the mid-to-near-IR emission changes with increasing infrared luminosity. We present two color–color diagrams to separate mid-IR weak galaxies and active galactic nuclei (AGN) from dusty star-forming galaxies and find that these color diagrams are most effective when used in conjunction with each other. We present the first number counts of 10 μ m sources and find that there are ≲10 IR AGN per MIRI pointing, possibly due to the difficulty of distinguishing AGN from intrinsically mid-IR weak galaxies (due to low metallicities or dust content). We conclude that MIRI is most effective at observing moderate-luminosity ( L _IR = 10 ^9 –10 ^10 L _⊙ ) galaxies at z = 1–2, and that photometry alone is not effective at identifying AGN within this faint population.

We present a robust sample of very high redshift galaxy candidates from the first epoch of JWST/NIRCam imaging from the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey. The NGDEEP NIRCam imaging, spanning 9.7 arcmin ^2 in the Hubble Ultra Deep Field Parallel Field 2, reaches m = 30.4 (5 σ , point-source, 2″ diameter apertures corrected to total) in F277W, making it the deepest public JWST GO imaging data set to date. We describe our detailed data reduction process of the six-filter broadband JWST/NIRCam imaging, incorporating custom corrections for systematic effects to produce high-quality calibrated images. Using robust photometric redshift selection criteria, we identify a sample of 38 z ≳ 9 galaxy candidates. These objects span a redshift range of z = 8.5–15.8 and apparent magnitudes of m _F277W = 27–30.5 AB mag, reaching ∼1.5 mag deeper than previous public JWST imaging surveys. We calculate the rest-frame ultraviolet luminosity function at z ∼ 9 and 11 and present a new measurement of the luminosity function faint-end slope at z ∼ 11. We find a faint-end slope of α = −2.5 ± 0.4 and −2.2 ± 0.2 at z ∼ 9 and 11, respectively. This is consistent with no significant evolution in the faint-end slope and number density from z = 9 to 11. Comparing our results with theoretical predictions, we find that some models produce better agreement at the faint end than the bright end. These results will help to constrain how stellar feedback impacts star formation at these early epochs.

We report on the discovery of two low-luminosity, broad-line active galactic nuclei (AGNs) at z > 5 identified using JWST NIRSpec spectroscopy from the Cosmic Evolution Early Release Science (CEERS) survey. We detect broad H α emission in the spectra of both sources, with FWHM of 2060 ± 290 km s ^−1 and 1800 ± 200 km s ^−1 , resulting in virial black hole (BH) masses that are 1–2 dex below those of existing samples of luminous quasars at z > 5. The first source, CEERS 2782 at z = 5.242, is 2–3 dex fainter than known quasars at similar redshifts and was previously identified as a candidate low-luminosity AGN based on its morphology and rest-frame optical spectral energy distribution (SED). We measure a BH mass of M _BH = (1.3 ± 0.4) × 10 ^7 M _⊙ , confirming that this AGN is powered by the least massive BH known in the Universe at the end of cosmic reionization. The second source, CEERS 746 at z = 5.624, is inferred to be a heavily obscured, broad-line AGN caught in a transition phase between a dust-obscured starburst and an unobscured quasar. We estimate its BH mass to be in the range of M _BH ≃ (0.9–4.7) × 10 ^7 M _⊙ , depending on the level of dust obscuration assumed. We perform SED fitting to derive host stellar masses, M _⋆ , allowing us to place constraints on the BH–galaxy mass relationship in the lowest mass range yet probed in the early Universe. The M _BH / M _⋆ ratio for CEERS 2782, in particular, is consistent with or higher than the empirical relationship seen in massive galaxies at z = 0. We examine the narrow emission line ratios of both sources and find that their location on the BPT and OHNO diagrams is consistent with model predictions for moderately low metallicity AGNs with Z / Z _⊙ ≃ 0.2–0.4. The spectroscopic identification of low-luminosity, broad-line AGNs at z > 5 with M _BH ≃ 10 ^7 M _⊙ demonstrates the capability of JWST to push BH masses closer to the range predicted for the BH seed population and provides a unique opportunity to study the early stages of BH–galaxy assembly.

We report the discovery of an accreting supermassive black hole at z = 8.679. This galaxy, denoted here as CEERS_1019, was previously discovered as a Ly α -break galaxy by Hubble with a Ly α redshift from Keck. As part of the Cosmic Evolution Early Release Science (CEERS) survey, we have observed this source with JWST/NIRSpec, MIRI, NIRCam, and NIRCam/WFSS and uncovered a plethora of emission lines. The H β line is best fit by a narrow plus a broad component, where the latter is measured at 2.5 σ with an FWHM ∼1200 km s ^−1 . We conclude this originates in the broadline region of an active galactic nucleus (AGN). This is supported by the presence of weak high-ionization lines (N V, N IV], and C III]), as well as a spatial point-source component. The implied mass of the black hole (BH) is log ( M _BH / M _⊙ ) = 6.95 ± 0.37, and we estimate that it is accreting at 1.2 ± 0.5 times the Eddington limit. The 1–8 μ m photometric spectral energy distribution shows a continuum dominated by starlight and constrains the host galaxy to be massive (log M/M _⊙ ∼9.5) and highly star-forming (star formation rate, or SFR ∼ 30 M _⊙ yr ^−1 ; log sSFR ∼ − 7.9 yr ^−1 ). The line ratios show that the gas is metal-poor ( Z / Z _⊙ ∼ 0.1), dense ( n _e ∼ 10 ^3 cm ^−3 ), and highly ionized (log U ∼ − 2.1). We use this present highest-redshift AGN discovery to place constraints on BH seeding models and find that a combination of either super-Eddington accretion from stellar seeds or Eddington accretion from very massive BH seeds is required to form this object.

We present JWST NIRSpec spectroscopy for 11 galaxy candidates with photometric redshifts of z ≃ 9 − 13 and M _UV ∈ [ −21, −18] newly identified in NIRCam images in the Cosmic Evolution Early Release Science Survey. We confirm emission line redshifts for 7 galaxies at z = 7.762–8.998 using spectra at ∼1–5 μ m either with the NIRSpec prism or its three medium-resolution ( R ∼ 1000) gratings. For z ≃ 9 photometric candidates, we achieve a high confirmation rate of ≃90%, which validates the classical dropout selection from NIRCam photometry. No robust emission lines are identified in three galaxy candidates at z > 10, where the strong [O iii ] and H β lines would be redshifted beyond the wavelength range observed by NIRSpec, and the Ly α continuum break is not detected with the sensitivity of the current data. Compared with Hubble Space Telescope-selected bright galaxies ( M _UV ≃ −22) that are similarly spectroscopically confirmed at z ≃ 8 − 9, these NIRCam-selected galaxies are characterized by lower star formation rates (SFRs; SFR ≃ 4 M _⊙ yr ^−1 ) and lower stellar masses (≃10 ^8 M _⊙ ), but with higher specific SFR (≃40 Gyr ^−1 ), higher [O iii ]+H β equivalent widths (≃1100 Å), and elevated production efficiency of ionizing photons ( $\mathrm{log}({\xi }_{\mathrm{ion}}/\mathrm{Hz}\,{\mathrm{erg}}^{-1})\simeq 25.8$ ) induced by young stellar populations (

We present results from the Cosmic Evolution Early Release Survey on the stellar population parameters for 28 galaxies with redshifts 4 < z < 9 using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 μ m data extend the coverage of the rest-frame spectral energy distribution to nearly 1 μ m for galaxies in this redshift range. By modeling the galaxies’ SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 Å)— I -band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower ratios of stellar mass to light. The MIRI data reduce the stellar masses by $\langle {\rm{\Delta }}\mathrm{log}{M}_{* }\rangle =0.25$ dex at 4 < z < 6 and 0.37 dex at 6 < z < 9. This also reduces the star formation rates (SFRs) by 〈ΔlogSFR〉 = 0.14 dex at 4 < z < 6 and 0.27 dex at 6 < z < 9. The MIRI data also improve constraints on the allowable stellar mass formed in early star formation. We model this using a star formation history that includes both a “burst” at z _f = 100 and a slowly varying (“delayed- τ ”) model. The MIRI data reduce the allowable stellar mass by 0.6 dex at 4 < z < 6 and by ≈1 dex at 6 < z < 9. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early Universe ( z ≈ 9). Therefore, observations of rest-frame ≳1 μ m are paramount for constraining the stellar-mass buildup in galaxies at very high redshifts.

Lyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts ( z ≲ 7) may also mimic the near-infrared (near-IR) colors of z > 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6 σ SCUBA-2 detection at 850 μ m around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4–6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations.

We present an investigation into the first 500 Myr of galaxy evolution from the Cosmic Evolution Early Release Science (CEERS) survey. CEERS, one of 13 JWST ERS programs, targets galaxy formation from z ∼ 0.5 to >10 using several imaging and spectroscopic modes. We make use of the first epoch of CEERS NIRCam imaging, spanning 35.5 arcmin ^2 , to search for candidate galaxies at z > 9. Following a detailed data reduction process implementing several custom steps to produce high-quality reduced images, we perform multiband photometry across seven NIRCam broad- and medium-band (and six Hubble broadband) filters focusing on robust colors and accurate total fluxes. We measure photometric redshifts and devise a robust set of selection criteria to identify a sample of 26 galaxy candidates at z ∼ 9–16. These objects are compact with a median half-light radius of ∼0.5 kpc. We present an early estimate of the z ∼ 11 rest-frame ultraviolet (UV) luminosity function, finding that the number density of galaxies at M _UV ∼ −20 appears to evolve very little from z ∼ 9 to 11. We also find that the abundance (surface density [arcmin ^−2 ]) of our candidates exceeds nearly all theoretical predictions. We explore potential implications, including that at z > 10, star formation may be dominated by top-heavy initial mass functions, which would result in an increased ratio of UV light per unit halo mass, though a complete lack of dust attenuation and/or changing star formation physics may also play a role. While spectroscopic confirmation of these sources is urgently required, our results suggest that the deeper views to come with JWST should yield prolific samples of ultrahigh-redshift galaxies with which to further explore these conclusions.

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of JWST CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at z > 1 based on rest-frame NIR F444W images of high resolution (∼1.3 kpc at z ∼ 1–3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at z > 1 with spectroscopic redshifts, including the two highest-redshift bars at z ∼ 2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at z ∼ 1.1–2.3 presented in our study have projected semimajor axes of ∼2.9–4.3 kpc and projected ellipticities of ∼0.41–0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ∼1 × 10 ^10 to 2 × 10 ^11 M _⊙ and star formation rates of ∼21–295 M _⊙ yr ^−1 , and several have potential nearby companions. Our finding of bars at z ∼ 1.1–2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8–11 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ∼ 0.

We present a comprehensive analysis of the evolution of the morphological and structural properties of a large sample of galaxies at z = 3–9 using early James Webb Space Telescope (JWST) CEERS NIRCam observations. Our sample consists of 850 galaxies at z > 3 detected in both Hubble Space Telescope (HST)/WFC3 and CEERS JWST/NIRCam images, enabling a comparison of HST and JWST morphologies. We conduct a set of visual classifications, with each galaxy in the sample classified three times. We also measure quantitative morphologies across all NIRCam filters. We find that galaxies at z > 3 have a wide diversity of morphologies. Galaxies with disks make up 60% of galaxies at z = 3, and this fraction drops to ∼30% at z = 6–9, while galaxies with spheroids make up ∼30%–40% across the redshift range, and pure spheroids with no evidence for disks or irregular features make up ∼20%. The fraction of galaxies with irregular features is roughly constant at all redshifts (∼40%–50%), while those that are purely irregular increases from ∼12% to ∼20% at z > 4.5. We note that these are apparent fractions, as many observational effects impact the visibility of morphological features at high redshift. On average, Spheroid-only galaxies have a higher Sérsic index, smaller size, and higher axis ratio than disk or irregular galaxies. Across all redshifts, smaller spheroid and disk galaxies tend to be rounder. Overall, these trends suggest that galaxies with established disks and spheroids exist across the full redshift range of this study, and further work with large samples at higher redshift is needed to quantify when these features first formed.

We present the data release and data reduction process for the Epoch 1 NIRCam observations for the Cosmic Evolution Early Release Science Survey (CEERS). These data consist of NIRCam imaging in six broadband filters (F115W, F150W, F200W, F277W, F356W and F444W) and one medium-band filter (F410M) over four pointings, obtained in parallel with primary CEERS MIRI observations. We reduced the NIRCam imaging with the JWST Calibration Pipeline, with custom modifications and reduction steps designed to address additional features and challenges with the data. Here we provide a detailed description of each step in our reduction and a discussion of future expected improvements. Our reduction process includes corrections for known prelaunch issues such as 1/ f noise, as well as in-flight issues including snowballs, wisps, and astrometric alignment. Many of our custom reduction processes were first developed with prelaunch simulated NIRCam imaging over the full 10 CEERS NIRCam pointings. We present a description of the creation and reduction of this simulated data set in the Appendix. We provide mosaics of the real images in a public release, as well as our reduction scripts with detailed explanations to allow users to reproduce our final data products. These represent one of the first official public data sets released from the Directors Discretionary Early Release Science (DD-ERS) program.

We report on the host properties of five X-ray-luminous active galactic nuclei (AGN) identified at 3 < z < 5 in the first epoch of imaging from the Cosmic Evolution Early Release Science Survey. Each galaxy has been imaged with the JWST Near-Infrared Camera, which provides rest-frame optical morphologies at these redshifts. We also derive stellar masses and star formation rates for each host by fitting its spectral energy distribution using a combination of galaxy and AGN templates. We find that three of the AGN hosts have spheroidal morphologies, one is a bulge-dominated disk, and one is dominated by pointlike emission. None are found to show strong morphological disturbances that might indicate a recent interaction or merger event. When compared to a sample of mass-matched inactive galaxies, we find that the AGN hosts have morphologies that are less disturbed and more bulge-dominated. Notably, all four of the resolved hosts have rest-frame optical colors consistent with a quenched or poststarburst stellar population. The presence of AGN in passively evolving galaxies at z > 3 is significant because a rapid feedback mechanism is required in most semianalytic models and cosmological simulations to explain the growing population of massive quiescent galaxies observed at these redshifts. Our findings show that AGN can continue to inject energy into these systems after their star formation is curtailed, potentially heating their halos and preventing renewed star formation. Additional observations will be needed to determine what role this feedback may play in helping to quench these systems and/or maintain their quiescent state.

The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR-faint, mid-IR-bright sources, with HST-dark galaxies among them. We gather JWST data from the CEERS survey in the Extended Groth Strip, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions to estimate photometric redshifts in two dimensions and stellar population properties on a pixel-by-pixel basis for red galaxies detected by NIRCam. We select 138 galaxies with F150W − F356W > 1.5 mag and F356W < 27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies (SFGs) at 2 < z < 6 with $9\lt \mathrm{log}{M}_{\star }/{M}_{\odot }\lt 11$ and a variety of specific SFRs (100 Gyr ^−1 ); (2) 18% are quiescent/dormant (i.e., subject to reignition/rejuvenation) galaxies (QGs) at 3 < z < 5, with $\mathrm{log}{M}_{\star }/{M}_{\odot }\sim 10$ and poststarburst mass-weighted ages (0.5–1.0 Gyr); and (3) 11% are strong young starbursts with indications of high equivalent width emission lines (typically, [O iii ]+H β ) at 6 < z < 7 (XELG- z 6) and $\mathrm{log}{M}_{\star }/{M}_{\odot }\sim 9.5$ . The sample is dominated by disk-like galaxies with remarkable compactness for XELG- z 6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2 < A ( V ) < 5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A ( V ) ∼ 0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and submillimeter galaxies. This study implies high levels of star formation activity between z ∼ 20 and z ∼ 10, where virtually 100% of our galaxies had already formed 10 ^8 M _⊙ , 60% had assembled 10 ^9 M _⊙ , and 10% up to 10 ^10 M _⊙ (in situ or ex situ).

Introduction: Huntington disease is an autosomal dominant neurodegenerative disorder which is caused by a CAG repeat expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. Huntingtin is subjected to multiple post-translational modifications which regulate its cellular functions and degradation. We have previously identified a palmitoylation site at cysteine 214 (C214), catalyzed by the enzymes ZDHHC17 and ZDHHC13. Reduced palmitoylation level of mutant huntingtin is linked to toxicity and loss of function. Moreover, we have described N-terminal myristoylation by the N-myristoyltransferases of a short fragment of huntingtin (HTT553-586) at glycine 553 (G553) following proteolysis at aspartate 552 (D552).Results: Here, we show that huntingtin is palmitoylated at numerous cysteines: C105, C433, C3134 and C3144. In addition, we confirm that full-length huntingtin is cleaved at D552 and post-translationally myristoylated at G553. Importantly, blocking caspase cleavage at the critical and pathogenic aspartate 586 (D586) significantly increases posttranslational myristoylation of huntingtin. In turn, myristoylation of huntingtin promotes the co-interaction between C-terminal and N-terminal huntingtin fragments, which is also protective.Discussion: This suggests that the protective effect of inhibiting caspase-cleavage at D586 may be mediated through post-translational myristoylation of huntingtin at G553.

We investigate the impact of local environment on the galaxy stellar mass function (SMF) spanning a wide range of galaxy densities from the field up to dense cores of massive galaxy clusters. Data are drawn from a sample of eight fields from the Observations of Redshift Evolution in Large-Scale Environments (ORELSE) survey. Deep photometry allow us to select mass-complete samples of galaxies down to 109M⊙. Taking advantage of > 4000 secure spectroscopic redshifts from ORELSE and precise photometric redshifts, we construct threedimensional density maps between 0.55 < z < 1.3 using a Voronoi tessellation approach. We find that the shape of the SMF depends strongly on local environment exhibited by a smooth, continual increase in the relative numbers of high- to low-mass galaxies towards denser environments. A straightforward implication is that local environment proportionally increases the efficiency of (a) destroying lower mass galaxies and/or (b) growth of higher mass galaxies. We also find a presence of this environmental dependence in the SMFs of starforming and quiescent galaxies, although not quite as strongly for the quiescent subsample. To characterize the connection between the SMFof field galaxies and that of denser environments, we devise a simple semi-empirical model. The model begins with a sample of ≈106 galaxies at zstart = 5 with stellar masses distributed according to the field. Simulated galaxies then evolve down to zfinal = 0.8 following empirical prescriptions for star-formation, quenching and galaxy-galaxy merging.We run the simulationmultiple times, testing a variety of scenarios with differing overall amounts of merging. Our model suggests that a large number of mergers are required to reproduce the SMF in dense environments. Additionally, a large majority of these mergers would have to occur in intermediate density environments (e.g. galaxy groups).