Measuring gravitational lens time delays using low-resolution radio monitoring observations

Obtaining lensing time delay measurements requires long-term monitoring campaigns with a high enough resolution (< 1 arcsec) to separate the multiple images. In the radio, a limited number of high-resolution interferometer arrays make these observations difficult to schedule. To overcome this problem, we propose a technique for measuring gravitational time delays which relies on monitoring the total flux density with low-resolution but high-sensitivity radio telescopes to follow the variation of the brighter image. This is then used to trigger high-resolution observations in optimal numbers which then reveal the variation in the fainter image. We present simulations to assess the efficiency of this method together with a pilot project observing radio lens systems with the Westerbork Synthesis Radio Telescope (WSRT) to trigger Very Large Array (VLA) observations. This new method is promising for measuring time delays because it uses relatively small amounts of time on high-resolution telescopes. This will be important because instruments that have high sensitivity but limited resolution, together with an optimum usage of followup high-resolution observations from appropriate radio telescopes may in the future be useful for gravitational lensing time delay measurements by means of this new method.Comment: 10 pages, 7 figures, accepted by MNRA

Oxidative-Stress-Associated Proteostasis Disturbances and Increased DNA Damage in the Hippocampal Granule Cells of the Ts65Dn Model of Down Syndrome

Oxidative stress (OS) is one of the neuropathological mechanisms responsible for the deficits in cognition and neuronal function in Down syndrome (DS). The Ts65Dn (TS) mouse replicates multiple DS phenotypes including hippocampal-dependent learning and memory deficits and similar brain oxidative status. To better understand the hippocampal oxidative profile in the adult TS mouse, we analyzed cellular OS-associated alterations in hippocampal granule cells (GCs), a neuronal population that plays an important role in memory formation and that is particularly affected in DS. For this purpose, we used biochemical, molecular, immunohistochemical, and electron microscopy techniques. Our results indicate that TS GCs show important OS-associated alterations in the systems essential for neuronal homeostasis: DNA damage response and proteostasis, particu larly of the proteasome and lysosomal system. Specifically, TS GCs showed: (i) increased DNA damage, (ii) reorganization of nuclear proteolytic factories accompanied by a decline in proteasome activity and cytoplasmic aggregation of ubiquitinated proteins, (iii) formation of lysosomal-related structures containing lipid droplets of cytotoxic peroxidation products, and (iv) mitochondrial ultrastructural defects. These alterations could be implicated in enhanced cellular senescence, accelerated aging and neurodegeneration, and the early development of Alzheimer?s disease neuropathology present in TS mice and the DS population.Funding: This work was supported by the following grants: “Instituto de Investigación Valdecilla” (IDIVAL; NVAL 19/23), Santander, Spain; “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CIBERNED; CB06/05/0037) Spain; and “Agencia Estatal de Investicación, MICIN” (grant number: PID2020-117601RB-I00). Acknowledgments: The authors would like to thank Raquel García-Ceballos and Eva García Iglesias for their technical assistance

A new perspective on the submillimetre galaxy MM 18423+5938 at redshift 3.9296 from radio continuum imaging

The bright submillimetre (sub-mm) galaxy MM 18423+5938 at redshift 3.9296 has been predicted from mid-infrared and millimetre photometry to have an exceptionally large total infrared (IR) luminosity. We present new radio imaging at 1.4 GHz with the Westerbork Synthesis Radio Telescope that is used to determine a radio-derived total IR luminosity for MM 18423+5938 via the well established radio-far-infrared correlation. The flux density is found to be S_1.4 GHz = 217 +/- 37 \mu Jy, which corresponds to a rest-frame luminosity density of L_1.4 GHz = 2.32 +/- 0.40 x 10^25 / u W / Hz, where u is the magnification from a probable gravitational lens. The radio-derived total IR luminosity and star-formation rate are L_8-1000 \mu m = 5.6^+4.1_-2.4 x 10^13 / u L_sol and SFR = 9.4^+7.4_-4.9 x 10^3 / u M_sol / yr, respectively, which are ~9 times smaller than those previously reported. These differences are attributed to the IR spectral energy distribution of MM 18423+5938 being poorly constrained by the limited number of reliable photometric data that are currently available, and from a previous misidentification of the object at 70 \mu m. Using the radio derived total IR luminosity as a constraint, the temperature of the cold dust component is found to be T ~ 24^+7_-5 K for a dust emissivity of \beta = 1.5 +/- 0.5. The radio-derived properties of this galaxy are still large given the low excitation temperature implied by the CO emission lines and the temperature of the cold dust. Therefore, we conclude that MM 18423+5938 is probably gravitationally lensed.Comment: 5 pages, 2 figures, 1 table, accepted for publication in MNRAS Letter

Genes involved in immune reinduction may constitute biomarkers of response for metastatic melanoma patients treated with targeted therapy

Targeted therapy in metastatic melanoma often achieves a major tumour regression response and significant long-term survival via the release of antigens that reinduce immunocompetence. The biomarkers thus activated may guide the prediction of response, but this association and its mechanism have yet to be established. Blood samples were collected from nineteen consecutive patients with metastatic melanoma before, during, and after treatment with targeted therapy. Differential gene expression analysis was performed, which identified the genes involved in the treatment, both in the first evaluation of response and during progression. Although clinical characteristics of the patients were poorer than those obtained in pivotal studies, radiological responses were similar to those reported previously (objective response rate: 73.7%). In the first tumour assessment, the expression of some genes increased (CXCL-10, SERPING1, PDL1, and PDL2), while that of others decreased (ARG1, IL18R1, IL18RAP, IL1R1, ILR2, FLT3, SLC11A1, CD163, and S100A12). The analysis of gene expression in blood shows that some are activated and others inhibited by targeted therapy. This response pattern may provide biomarkers of the immune reinduction response, which could be used to study potential combination treatments. Nevertheless, further studies are needed to validate these results.Fundación Progreso y Salud, Junta de Andalucí

Nuclear Reorganization in Hippocampal Granule Cell Neurons from a Mouse Model of Down Syndrome: Changes in Chromatin Configuration, Nucleoli and Cajal Bodies

Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice

Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G&#x3e;T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10

Comparison of an X-ray selected sample of massive lensing clusters with the MareNostrum Universe LCDM simulation

A long-standing problem of strong lensing by galaxy clusters regards the observed high rate of giant gravitational arcs as compared to the predictions in the framework of the "standard" cosmological model. Recently, few other inconsistencies between theoretical expectations and observations have been claimed which regard the large size of the Einstein rings and the high concentrations of few clusters with strong lensing features. All of these problems consistently indicate that observed galaxy clusters may be gravitational lenses stronger than expected. We use clusters extracted from the MareNostrum Universe to build up mock catalogs of galaxy clusters selected through their X-ray flux. We use these objects to estimate the probability distributions of lensing cross sections, Einstein rings, and concentrations for the sample of 12 MACS clusters at $z>0.5$ presented in Ebeling et al. (2007) and discussed in Zitrin et al. (2010). We find that simulated clusters produce $\sim 50$ less arcs than observed clusters do. The medians of the distributions of the Einstein ring sizes differ by $\sim 25$ between simulations and observations. We estimate that, due to cluster triaxiality and orientation biases affecting the lenses with the largest cross sections, the concentrations of the individual MACS clusters inferred from the lensing analysis should be up to a factor of $\sim 2$ larger than expected from the $\Lambda$CDM model. The arc statistics, the Einstein ring, and the concentration problems in strong lensing clusters are mitigated but not solved on the basis of our analysis. Nevertheless, due to the lack of redshifts for most of the multiple image systems used for modeling the MACS clusters, the results of this work will need to be verified with additional data. The upcoming CLASH program will provide an ideal sample for extending our comparison (abridged).Comment: 11 pages, 9 figures, accepted for publication on A&

DEMON: a Proposal for a Satellite-Borne Experiment to study Dark Matter and Dark Energy

We outline a novel satellite mission concept, DEMON, aimed at advancing our comprehension of both dark matter and dark energy, taking full advantage of two complementary methods: weak lensing and the statistics of galaxy clusters. We intend to carry out a 5000 sqdeg combined IR, optical and X-ray survey with galaxies up to a redshift of z~2 in order to determine the shear correlation function. We will also find ~100000 galaxy clusters, making it the largest survey of this type to date. The DEMON spacecraft will comprise one IR/optical and eight X-ray telescopes, coupled to multiple cameras operating at different frequency bands. To a great extent, the technology employed has already been partially tested on ongoing missions, therefore ensuring improved reliability.Comment: 12 pages, 3 figures, accepted for publication in the SPIE conference proceeding