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Abstract Multisystem proteinopathy (MSP) is a rare, dominantly inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Paget’s disease of bone. MSP is caused by mutations in the gene encoding valosin-containing protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP co-factors that direct VCP’s many roles in the cell. Small VCP-interacting protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to lysosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at Glycine 2 and palmitoylated at Cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.

Abstract During infection, virus-specific CD8+ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8+ T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the Cullin RING Ligase 4 (CRL4) complex. Despite expressing c-Myc at high levels, Cul4b-deficient CD8+ T cells do not expand and clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) in vivo. Cul4b-deficient CD8+ T cells accrue DNA damage and succumb to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b knockout induces an accumulation of p21 and Cyclin E2, resulting in replication stress. Our data show that c-Myc supports cell proliferation by maintaining genome stability via Cul4b, thereby directly coupling these two interdependent pathways. These data clarify how CD8+ T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses.

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.

Purpose: This study examined differences in measures of health-related physical fitness in adolescents before and after extended school closures due to COVID-19. Method: The sample consisted of 298 students (135 males and 163 females) from a laboratory high school. Data were collected through FITNESSGRAM assessments. A repeated-measures multivariate analysis of covariance was calculated to analyze differences in fitness before and after COVID-19 closures, including McNemar-Bowker and McNemar tests. Results: Statistically significant differences were identified for Progressive Aerobic Capacity Endurance Run (-4.2%; 1.8 ml·kg[superscript -1]·min[superscript -1]) and curl-up (-12.5%; 7.9 repetitions). In addition, 18.8% fewer students were classified within the Healthy Fitness Zone for Progressive Aerobic Capacity Endurance Run, 4% for curl-up, 10.8% for push-up, and 6.4% for sit and reach. Conclusion: Results of this study demonstrate that there was a significant decline in physical fitness for secondary students during extended school closures and social isolation as a result of COVID-19.

Abstract Background The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are involved in smooth muscle contraction. Regulation of complex cytoskeletal signaling is not entirely elucidated. The aim of this study was to evaluate the role of nestin (a type VI intermediate filament protein) in cytoskeletal signaling in airway smooth muscle. Methods Nestin expression in human airway smooth muscle (HASM) was knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain (MLC) phosphorylation, and contraction were evaluated by cellular and physiological approaches. Moreover, we assessed the effects of non-phosphorylatable nestin mutant on these biological processes. Results Nestin KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Moreover, contractile stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD diminished nestin phosphorylation at this residue. Conclusions Nestin is an essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in smooth muscle. Plk1 and nestin form an activation loop during contractile stimulation.

We present a sample of 88 candidate z ∼ 8.5–14.5 galaxies selected from the completed NIRCam imaging from the Cosmic Evolution Early Release Science survey. These data cover ∼90 arcmin ^2 (10 NIRCam pointings) in six broadband imaging filters and one medium-band imaging filter. With this sample we confirm at higher confidence early JWST conclusions that bright galaxies in this epoch are more abundant than predicted by most theoretical models. We construct the rest-frame ultraviolet luminosity functions at z ∼ 9, 11, and 14 and show that the space density of bright ( M _UV = −20) galaxies changes only modestly from z ∼ 14 to z ∼ 9, compared to a steeper increase from z ∼ 8 to z ∼ 4. While our candidates are photometrically selected, spectroscopic follow-up has now confirmed 13 of them, with only one significant interloper, implying that the fidelity of this sample is high. Successfully explaining the evidence for a flatter evolution in the number densities of UV-bright z > 10 galaxies may thus require changes to the dominant physical processes regulating star formation. While our results indicate that significant variations of dust attenuation with redshift are unlikely to be the dominant factor at these high redshifts, they are consistent with predictions from models that naturally have enhanced star formation efficiency and/or stochasticity. An evolving stellar initial mass function could also bring model predictions into better agreement with our results. Deep spectroscopic follow-up of a large sample of early galaxies can distinguish between these competing scenarios.

We present the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) Survey, a deep slitless spectroscopic and imaging Cycle 1 JWST treasury survey designed to constrain feedback mechanisms in low-mass galaxies across cosmic time. NGDEEP targets the Hubble Ultra Deep Field (HUDF) with NIRISS slitless spectroscopy ( ${f}_{\mathrm{lim},\mathrm{line},5\sigma }\approx 1.2\,\times \,$ 10 ^−18 erg s ^−1 cm ^−2 ) to measure metallicities and star formation rates (SFRs) for low-mass galaxies through the peak of the cosmic SFR density (0.5 < z < 4). In parallel, NGDEEP targets the HUDF-Par2 parallel field with NIRCam ( ${m}_{\mathrm{lim},5\sigma }=30.6-30.9$ ) to discover galaxies to z > 12, constraining the slope of the faint end of the rest-ultraviolet luminosity function. NGDEEP overlaps with the deepest HST Advanced Camera for Surveys optical imaging in the sky, F435W in the HUDF ( ${m}_{\mathrm{lim},{\rm{F}}435{\rm{W}}}=29.6$ ) and F814W in HUDF-Par2 ( ${m}_{\mathrm{lim},{\rm{F}}814{\rm{W}}}=30$ ), making this a premier HST+JWST deep field. As a treasury survey, NGDEEP data are public immediately, and we will rapidly release data products and catalogs in the spirit of previous deep-field initiatives. In this paper we present the NGDEEP survey design, summarize the science goals, and detail plans for the public release of NGDEEP reduced data products.

One of the first molecular events in neurodegenerative diseases, regardless of etiology, is protein mislocalization. Protein mislocalization in neurons is often linked to proteostasis deficiencies leading to the build-up of misfolded proteins and/or organelles that contributes to cellular toxicity and cell death. By understanding how proteins mislocalize in neurons, we can develop novel therapeutics that target the earliest stages of neurodegeneration. A critical mechanism regulating protein localization and proteostasis in neurons is the protein-lipid modification S-acylation, the reversible addition of fatty acids to cysteine residues. S-acylation is more commonly referred to as S-palmitoylation or simply palmitoylation, which is the addition of the 16-carbon fatty acid palmitate to proteins. Like phosphorylation, palmitoylation is highly dynamic and tightly regulated by writers (i.e., palmitoyl acyltransferases) and erasers (i.e., depalmitoylating enzymes). The hydrophobic fatty acid anchors proteins to membranes; thus, the reversibility allows proteins to be re-directed to and from membranes based on local signaling factors. This is particularly important in the nervous system, where axons (output projections) can be meters long. Any disturbance in protein trafficking can have dire consequences. Indeed, many proteins involved in neurodegenerative diseases are palmitoylated, and many more have been identified in palmitoyl-proteomic studies. It follows that palmitoyl acyl transferase enzymes have also been implicated in numerous diseases. In addition, palmitoylation can work in concert with cellular mechanisms, like autophagy, to affect cell health and protein modifications, such as acetylation, nitrosylation, and ubiquitination, to affect protein function and turnover. Limited studies have further revealed a sexually dimorphic pattern of protein palmitoylation. Therefore, palmitoylation can have wide-reaching consequences in neurodegenerative diseases.

Substantial populations of massive quiescent galaxies at z ≥ 3 challenge our understanding of rapid galaxy growth and quenching over short timescales. In order to piece together this evolutionary puzzle, more statistical samples of these objects are required. Established techniques for identifying massive quiescent galaxies are increasingly inefficient and unconstrained at z > 3. As a result, studies report that as much as 70% of quiescent galaxies at z > 3 may be missed from existing surveys. In this work, we propose a new empirical color selection technique designed to select massive quiescent galaxies at 3 ≲ z ≲ 6 using JWST NIRCam imaging data. We use empirically constrained galaxy spectral energy distribution (SED) templates to define a region in the F277W − F444W versus F150W − F277W color plane that captures quiescent galaxies at z > 3. We apply these color selection criteria to the Cosmic Evolution Early Release Science (CEERS) Survey and use SED fitting on sources in the region to identify 44 candidate z ≳ 3 quiescent galaxies. Over half of these sources are newly discovered and, on average, exhibit specific star formation rates of poststarburst galaxies. Most of these sources would not be discovered using canonical UVJ diagrams. We derive volume density estimates of n ∼ 1–4 × 10 ^−5 Mpc ^−3 at 3 < z < 5, finding excellent agreement with existing reports on similar populations in the CEERS field. Thanks to NIRCam’s wavelength coverage and sensitivity, this technique provides an efficient tool to search for large samples of these rare galaxies.

The Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey program was designed specifically to include Near Infrared Slitless Spectroscopic observations (NGDEEP-NISS) to detect multiple emission lines in as many galaxies as possible and across a wide redshift range using the Near Infrared Imager and Slitless Spectrograph. We present early results obtained from the first set of observations (Epoch 1, 50% of the allocated orbits) of this program (NGDEEP-NISS1). Using a set of independently developed calibration files designed to deal with a complex combination of overlapping spectra, multiple position angles, and multiple cross filters and grisms, in conjunction with a robust and proven algorithm for quantifying contamination from overlapping dispersed spectra, NGDEEP-NISS1 has achieved a 3 σ sensitivity limit of 2 × 10 ^−18 erg s ^−1 cm ^−2 . We demonstrate the power of deep wide field slitless spectroscopy (WFSS) to characterize the star formation rates, and metallicity ([O iii ]/H β ), and dust content, of galaxies at 1 < z < 3.5. The latter showing intriguing initial results on the applicability and assumptions made regarding the use of Case B recombination. Further, we identify the presence of active galactic nuclei and infer the mass of their supermassive black holes using broadened restframe Mg ii and H β emission lines. The spectroscopic results are then compared with the physical properties of galaxies extrapolated from fitting spectral energy distribution models to photometry alone. The results clearly demonstrate the unique power and efficiency of WFSS at near-infrared wavelengths over other methods to determine the properties of galaxies across a broad range of redshifts.

We study a new population of extremely red objects (EROs) recently discovered by the James Webb Space Telescope (JWST) based on their NIRCam colors F277W − F444W > 1.5 mag. We find 37 EROs in the Cosmic Evolution Early Release Science Survey (CEERS) field with F444W < 28 mag and photometric redshifts between 5 < z < 7, with median $z={6.9}_{-1.6}^{+1.0}$ . Surprisingly, despite their red long-wavelength colors, these EROs have blue short-wavelength colors (F150W − F200W ∼ 0 mag) indicative of bimodal spectral energy distributions (SEDs) with a red, steep slope in the rest-frame optical, and a blue, flat slope in the rest-frame UV. Moreover, all these EROs are unresolved, point-like sources in all NIRCam bands. We analyze the SEDs of eight of them with MIRI and NIRSpec observations using stellar population models and active galactic nucleus (AGN) templates. We find that dusty galaxies or obscured AGNs provide similarly good SED fits but different stellar properties: massive and dusty, $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ∼ 10 and A _V ≳ 3 mag, or low mass and obscured, $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ∼ 7.5 and A _V ∼ 0 mag, hosting an obscured quasi-stellar object (QSO). SED modeling does not favor either scenario, but their unresolved sizes are more suggestive of AGNs. If any EROs are confirmed to have $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ≳ 10.5, it would increase the pre-JWST number density at z > 7 by up to a factor ∼60. Similarly, if they are QSOs with luminosities in the L _bol > 10 ^45–46 erg s ^−1 range, their number would exceed that of bright blue QSOs by more than three orders of magnitude. Additional photometry at mid-infrared wavelengths will reveal the true nature of the red continuum emission in these EROs and will place this puzzling population in the right context of galaxy evolution.

The 3D geometries of high-redshift galaxies remain poorly understood. We build a differentiable Bayesian model and use Hamiltonian Monte Carlo to efficiently and robustly infer the 3D shapes of star-forming galaxies in James Webb Space Telescope Cosmic Evolution Early Release Science observations with $\mathrm{log}{M}_{* }/{M}_{\odot }=9.0\mbox{--}10.5$ at z = 0.5–8.0. We reproduce previous results from the Hubble Space Telescope Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey in a fraction of the computing time and constrain the mean ellipticity, triaxiality, size, and covariances with samples as small as ∼50 galaxies. We find high 3D ellipticities for all mass–redshift bins, suggesting oblate (disky) or prolate (elongated) geometries. We break that degeneracy by constraining the mean triaxiality to be ∼1 for $\mathrm{log}{M}_{* }/{M}_{\odot }=9.0\mbox{--}9.5$ dwarfs at z > 1 (favoring the prolate scenario), with significantly lower triaxialities for higher masses and lower redshifts indicating the emergence of disks. The prolate population traces out a “banana” in the projected $b/a\mbox{--}\mathrm{log}a$ diagram with an excess of low- b / a , large- $\mathrm{log}a$ galaxies. The dwarf prolate fraction rises from ∼25% at z = 0.5–1.0 to ∼50%–80% at z = 3–8. Our results imply a second kind of disk settling from oval (triaxial) to more circular (axisymmetric) shapes with time. We simultaneously constrain the 3D size–mass relation and its dependence on 3D geometry. High-probability prolate and oblate candidates show remarkably similar Sérsic indices ( n ∼ 1), nonparametric morphological properties, and specific star formation rates. Both tend to be visually classified as disks or irregular, but edge-on oblate candidates show more dust attenuation. We discuss selection effects, follow-up prospects, and theoretical implications.

We use James Webb Space Telescope Near-Infrared Camera Wide Field Slitless Spectroscopy (NIRCam WFSS) and the Near-Infrared spectrograph (NIRSpec) in the Cosmic Evolution Early Release survey to measure rest-frame optical emission-line ratios of 155 galaxies at z > 2. The blind NIRCam grism observations include a sample of galaxies with bright emission lines that were not observed on the NIRSpec masks. We study the changes of the H α , [O III ]/H β , and [Ne III ]/[O II ] emission lines in terms of redshift by comparing to lower-redshift SDSS, CLEAR, and MOSDEF samples. We find a significant (>3 σ ) correlation between [O III ]/H β with redshift, while [Ne III ]/[O II ] has a marginal (2 σ ) correlation with redshift. We compare [O III ]/H β and [Ne III ]/[O II ] to stellar mass and H β SFR. We find that both emission-line ratios have a correlation with H β SFR and an anticorrelation with stellar mass across the redshifts 0 < z < 9. Comparison with MAPPINGS V models indicates that these trends are consistent with lower metallicity and higher ionization in low-mass and high-SFR galaxies. We additionally compare to IllustrisTNG predictions and find that they effectively describe the highest [O III ]/H β ratios observed in our sample, without the need to invoke MAPPINGS models with significant shock ionization components.

Visual inspections of the first optical rest-frame images from JWST have indicated a surprisingly high fraction of disk galaxies at high redshifts. Here, we alternatively apply self-supervised machine learning to explore the morphological diversity at z ≥ 3. Our proposed data-driven representation scheme of galaxy morphologies, calibrated on mock images from the TNG50 simulation, is shown to be robust to noise and to correlate well with the physical properties of the simulated galaxies, including their 3D structure. We apply the method simultaneously to F200W and F356W galaxy images of a mass-complete sample ( M _* / M _⊙ > 10 ^9 ) at 3 ≤ z ≤ 6 from the first JWST/NIRCam CEERS data release. We find that the simulated and observed galaxies do not exactly populate the same manifold in the representation space from contrastive learning. We also find that half the galaxies classified as disks—either convolutional neural network-based or visually—populate a similar region of the representation space as TNG50 galaxies with low stellar specific angular momentum and nonoblate structure. Although our data-driven study does not allow us to firmly conclude on the true nature of these galaxies, it suggests that the disk fraction at z ≥ 3 remains uncertain and possibly overestimated by traditional supervised classifications. Deeper imaging and spectroscopic follow-ups as well as comparisons with other simulations will help to unambiguously determine the true nature of these galaxies, and establish more robust constraints on the emergence of disks at very high redshift.

Cytokine signaling influences the differentiation of CD4+ T cells into varying functional subsets. Here the authors show that an E3 ubiquitin ligase Cul5 alters TH2 and TH9 development and absence of Cul5 in T cells results in higher levels of allergy-associated IL-4 and IL-9 secreting T cells.

Purpose: This study examined differences in measures of health-related physical fitness in adolescents before and after extended school closures due to COVID-19. Method: The sample consisted of 298 students (135 males and 163 females) from a laboratory high school. Data were collected through FITNESSGRAM assessments. A repeated-measures multivariate analysis of covariance was calculated to analyze differences in fitness before and after COVID-19 closures, including McNemar–Bowker and McNemar tests. Results: Statistically significant differences were identified for Progressive Aerobic Capacity Endurance Run (−4.2%; 1.8 ml·kg−1·min−1) and curl-up (−12.5%; 7.9 repetitions). In addition, 18.8% fewer students were classified within the Healthy Fitness Zone for Progressive Aerobic Capacity Endurance Run, 4% for curl-up, 10.8% for push-up, and 6.4% for sit and reach. Conclusion: Results of this study demonstrate that there was a significant decline in physical fitness for secondary students during extended school closures and social isolation as a result of COVID-19. [ABSTRACT FROM AUTHOR]

Aortoenteric fistula is a rare complication after endovascular stent grafting. In the present report, we have described the case of a 69-year-old man 3 years after endovascular repair of an abdominal aortic aneurysm who had presented with worsening back pain and fever. Computed tomography had demonstrated dilated bowel and a thickened aortic wall, with air foci within the native aneurysm sac. He underwent emergent right axillary–bifemoral bypass with explantation of the aortic endograft and primary repair of the duodenal fistula. Tissue cultures grew Streptococcus anginosus, Prevotella denticola, and Parvimonas micra, and he was discharged home with 6 weeks of intravenous ceftriaxone and oral metronidazole after an 18-day hospital admission.

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]

Asthma is characterized by aberrant airway smooth muscle (ASM) proliferation, which increases the thickness of the ASM layer within the airway wall and exacerbates airway obstruction during asthma attacks. The mechanisms that drive ASM proliferation in asthma are not entirely elucidated. Ten-eleven translocation methylcytosine dioxygenase (TET) is an enzyme that participates in the regulation of DNA methylation by catalyzing the hydroxylation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). The generation of 5-hmC disinhibits the gene silencing effect of 5-mC. In this study, TET1 activity and protein were enhanced in asthmatic human ASM cell cultures. Moreover, the concentration of 5-hmC was higher in asthmatic ASM cells than in nonasthmatic ASM cells. Knockdown (KD) of TET1, but not TET2, reduced the concentration of 5-hmC in asthmatic cells. Because the cytoskeletal protein nestin controls cell proliferation by modulating mTOR, we evaluated the effects of TET1 KD on this pathway. TET1 KD reduced nestin expression in ASM cells. In addition, TET1 inhibition alleviated the platelet-derived growth factor–induced phosphorylation of p70S6K, 4E-BP, S6, and Akt. TET1 inhibition also attenuated the proliferation of ASM cells. Taken together, these results suggest that TET1 drives ASM proliferation via the nestin–mTOR axis. [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).

Large-scale photoautotrophic production of microalgae has the potential to provide a sustainable supply of omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) for human and animal nutrition. This study presents a kinetic model for the EPA-producing microalga Phaeodactylum tricornutum in photoautotrophic conditions, with light and nitrogen being the growth limiting factors. The model was developed using a dataset obtained from bench-scale (5 L) cultures and was successfully validated against pilot-scale (50 L) cultures. This model is the first to predict the biomass and total fatty acid accumulation along with the EPA concentrations in the biomass and total fatty acid fraction for microalgae. The model was used to develop an optimized repeated-batch strategy; implementation of this led to increases in the biomass and EPA productivities of 50 and 20% respectively. This clearly indicates the potential of the model to be used as a tool in the design, optimization and scale-up of microalgal systems for EPA production.