Bentho-Pelagic Divergence of Cichlid Feeding Architecture Was Prodigious and Consistent during Multiple Adaptive Radiations within African Rift-Lakes

<b>Background</b> How particular changes in functional morphology can repeatedly promote ecological diversification is an active area of evolutionary investigation. The African rift-lake cichlids offer a calibrated time series of the most dramatic adaptive radiations of vertebrate trophic morphology yet described, and the replicate nature of these events provides a unique opportunity to test whether common changes in functional morphology have repeatedly facilitated their ecological success.<p></p> <b>Methodology/Principal Findings</b> Specimens from 87 genera of cichlid fishes endemic to Lakes Tanganyka, Malawi and Victoria were dissected in order to examine the functional morphology of cichlid feeding. We quantified shape using geometric morphometrics and compared patterns of morphological diversity using a series of analytical tests. The primary axes of divergence were conserved among all three radiations, and the most prevalent changes involved the size of the preorbital region of the skull. Even the fishes from the youngest of these lakes (Victoria), which exhibit the lowest amount of skull shape disparity, have undergone extensive preorbital evolution relative to other craniofacial traits. Such changes have large effects on feeding biomechanics, and can promote expansion into a wide array of niches along a bentho-pelagic ecomorphological axis.<p></p> <b>Conclusions/Significance</b> Here we show that specific changes in trophic anatomy have evolved repeatedly in the African rift lakes, and our results suggest that simple morphological alterations that have large ecological consequences are likely to constitute critical components of adaptive radiations in functional morphology. Such shifts may precede more complex shape changes as lineages diversify into unoccupied niches. The data presented here, combined with observations of other fish lineages, suggest that the preorbital region represents an evolutionary module that can respond quickly to natural selection when fishes colonize new lakes. Characterizing the changes in cichlid trophic morphology that have contributed to their extraordinary adaptive radiations has broad evolutionary implications, and such studies are necessary for directing future investigations into the proximate mechanisms that have shaped these spectacular phenomena

Ruthenium-cyclopentadienyl bipyridine-biotin based compounds: Synthesis and biological effect

Prospective anticancer metallodrugs should consider target-specific components in their design in order to overcome the limitations of the current chemotherapeutics. The inclusion of vitamins, which receptors are overexpressed in many cancer cell lines, has proven to be a valid strategy. Therefore, in this paper we report the synthesis and characterization of a set of new compounds [Ru(eta(5)-C5H5)(P(C6H4R)(3))(4,4'-R'-2,2'-bpy)](+) (R = F and R' = H, 3; R = F and R' = biotin, 4; R = OCH3 and R' = H, 5; R = OCH3 and R' = biotin, 6), inspired by the exceptional good results recently obtained for the analogue bearing a triphenylphosphane ligand. The precursors for these syntheses were also described following modified literature procedures, [Ru(eta(5)-C5H3)(P(C6H4R)(3))(2)Cl], where R is -F (1) or -OCH3 (2). The structure of all compounds is fully supported by spectroscopic and analytical techniques and by X-ray diffraction studies for compounds 2, 3, and 5. All cationic compounds are cytotoxic in the two breast cancer cell lines tested, MCF7 and MDA-MB-231, and much better than cisplatin under the same experimental conditions. The cytotoxicity of the biotinylated compounds seems to be related with the Ru uptake by the cells expressing biotin receptors, indicating a potential mediated uptake. Indeed, a biotin-avidin study confirmed that the attachment of biotin to the organometallic fragment still allows biotin recognition by the protein. Therefore, the biotinylated compounds might be potent anticancer drugs as they show cytotoxic effect in breast cancer cells at low dose dependent on the compounds' uptake, induce cell death by apoptosis and inhibit the colony formation of cancer cells causing also less severe side effects in zebrafish.This work was financed by the Portuguese Foundation for Science and Technology (Fundacao para a Crencia e Tecnologia, FCT) within the scope of Projects UID/QUI/00100/2019 and PTDC/QUI-QIN/28662/2017. This work was supported by the strategic program UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 -Programa Operacional Competitividade e Intemacionalizacao (POCI). A.V. acknowledges the Investigator FCT2013 Initiative for the Project IF/01302/2013 and CEEC-IND/01974/2017 (acknowledging FCT, as well as POPH and FSE, the European Social Fund). L.C.-R, A.R.B. and A.P. thank FCT for their Ph.D. Grants (SFRH/BD/100515/2014, SFRH/BD/139271/2018, and SFRH/BD/139412/2018, respectively). L.C.-R also acknowledges Fulbright Research Grant 2017/2018 with the support of FCT. Brittany Karas acknowledges NJAES-RutgersNJ01201 and NIEHS Training Grant T32-ES 007148 and B.T.B. and C.D. acknowledge NIH-NIEHS P30 ES005022. K.R.C. acknowledges NJAES Project 01202 (W2045) and NIH ES005022

Neuronal deletion of the circadian clock gene Bmal1 induces cell-autonomous dopaminergic neurodegeneration

Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP. Here we examined the effect of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, postnatal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase+ (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc). This was not replicated by light-induced disruption of behavioral circadian rhythms and was not induced by astrocyte- or microglia-specific Bmal1 deletion. However, either pan-neuronal or TH neuron-specific Bmal1 deletion caused cell-autonomous loss of TH+ neurons in the SNpc. Bmal1 deletion did not change the percentage of TH neuron loss after α-synuclein fibril injection, though Bmal1-KO mice had fewer TH neurons at baseline. Transcriptomics analysis revealed dysregulation of pathways involved in oxidative phosphorylation and Parkinson disease. These findings demonstrate a cell-autonomous role for BMAL1 in regulating dopaminergic neuronal survival and may have important implications for neuroprotection in PD

The Web Epoch of Reionization Lyman-α\alpha Survey (WERLS) I. MOSFIRE Spectroscopy of z∼7−8\mathbf{z \sim 7-8} Lyman-α\alpha Emitters

We present the first results from the Web Epoch of Reionization Lyman-$\alpha$ Survey (WERLS), a spectroscopic survey of Lyman-$\alpha$ emission using Keck I/MOSFIRE and LRIS. WERLS targets bright ($J<26$) galaxy candidates with photometric redshifts of $5.5\lesssim z \lesssim 8$ selected from pre-JWST imaging embedded in the Epoch of Reionization (EoR) within three JWST deep fields: CEERS, PRIMER, and COSMOS-Web. Here, we report 11 $z\sim7-8$ Lyman-$\alpha$ emitters (LAEs; 3 secure and 8 tentative candidates) detected in the first five nights of WERLS MOSFIRE data. We estimate our observed LAE yield is $\sim13$%, broadly consistent with expectations assuming some loss from redshift uncertainty, contamination from sky OH lines, and that the Universe is approximately half-ionized at this epoch, whereby observable Lyman-$\alpha$ emission is unlikely for galaxies embedded in a neutral intergalactic medium. Our targets are selected to be UV-bright, and span a range of absolute UV magnitudes with $-23.1 < M_{\text{UV}} < -19.8$. With two LAEs detected at $z=7.68$, we also consider the possibility of an ionized bubble at this redshift. Future synergistic Keck+JWST efforts will provide a powerful tool for pinpointing beacons of reionization and mapping the large scale distribution of mass relative to the ionization state of the Universe.Comment: 27 pages, 8 figures; ApJ submitte

Direct measurements of meltwater runoff on the Greenland ice sheet surface

Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.1-km2 moulin-terminating internally drained catchment (IDC) on Greenland?s midelevation (1,207?1,381 m above sea level) ablation zone is compared with melt and runoff simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models. Current models cannot reproduce peak discharges or timing of runoff entering moulins but are improved using synthetic unit hydrograph (SUH) theory. Retroactive SUH applications to two older field studies reproduce their findings, signifying that remotely sensed IDC area, shape, and supraglacial river length are useful for predicting delays in peak runoff delivery to moulins. Applying SUH to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs suggests their terminal moulins receive lower peak discharges, less diurnal variability, and asynchronous runoff timing relative to climate/SMB model output alone. Conversely, large IDCs produce high moulin discharges, even at high elevations where melt rates are low. During this particular field experiment, models overestimated runoff by +21 to +58%, linked to overestimated surface ablation and possible meltwater retention in bare, porous, low-density ice. Direct measurements of ice surface runoff will improve climate/SMB models, and incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and subglacial systemspublishersversionPeer reviewe

Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes of Health, an American Heart Association Predoctoral Fellowship (J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a National Science Foundation Predoctoral Fellowship (B.B.)

Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases

The Physical Conditions of Emission-Line Galaxies at Cosmic Dawn from JWST/NIRSpec Spectroscopy in the SMACS 0723 Early Release Observations

We present rest-frame optical emission-line flux ratio measurements for five $z>5$ galaxies observed by the JWST Near-Infared Spectrograph (NIRSpec) in the SMACS 0723 Early Release Observations. We add several quality-control and post-processing steps to the NIRSpec pipeline reduction products in order to ensure reliable relative flux calibration of emission lines that are closely separated in wavelength, despite the uncertain \textit{absolute} spectrophotometry of the current version of the reductions. Compared to $z\sim3$ galaxies in the literature, the $z>5$ galaxies have similar [OIII]$\lambda$5008/H$\beta$ ratios, similar [OIII]$\lambda$4364/H$\gamma$ ratios, and higher ($\sim$0.5 dex) [NeIII]$\lambda$3870/[OII]$\lambda$3728 ratios. We compare the observations to MAPPINGS V photoionization models and find that the measured [NeIII]$\lambda$3870/[OII]$\lambda$3728, [OIII]$\lambda$4364/H$\gamma$, and [OIII]$\lambda$5008/H$\beta$ emission-line ratios are consistent with an interstellar medium that has very high ionization ($\log(Q) \simeq 8-9$, units of cm~s$^{-1}$), low metallicity ($Z/Z_\odot \lesssim 0.2$), and very high pressure ($\log(P/k) \simeq 8-9$, units of cm$^{-3}$). The combination of [OIII]$\lambda$4364/H$\gamma$ and [OIII]$\lambda$(4960+5008)/H$\beta$ line ratios indicate very high electron temperatures of $4.1<\log(T_e/{\rm K})<4.4$, further implying metallicities of $Z/Z_\odot \lesssim 0.2$ with the application of low-redshift calibrations for ``$T_e$-based'' metallicities. These observations represent a tantalizing new view of the physical conditions of the interstellar medium in galaxies at cosmic dawn.Comment: Accepted for publication in AAS Journals. 14 pages, 6 figures, 3 table

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same dataset to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors, and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration, NIRISS AMI can reach contrast levels of $\sim9-10$ mag. These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower mass exoplanets than ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal