Flash forward genetics: new twists in transcription across evolutionary boundaries

“Flash forward genetics” refers to a genetic approach based on the functional interaction of a given factor with unknown partner(s) converging on shared targets across evolutionary boundaries. A study by Li et al (2021), published in this issue of EMBO Reports, illustrates the innovative potential of the approach. The authors applied it to identify interacting factors for FOXN1, a mammalian transcription factor with a highly specialized function in hair follicle morphogenesis and thymus. The authors express FOXN1 in the Drosophila eye to perform an unbiased genetic screen in a totally heterologous system. In a remarkable tour de force, the authors identify and characterize a factor so far known for its ubiquitous function in transcription elongation, AFF4. Li et al show that AFF4 plays also a specific role in hair follicle and thymus development in the mouse overlapping with that of FOXN1

Physical Investigation of the Potentially Hazardous Asteroid (144898) 2004 VD17

In this paper we present the observational campaign carried out at ESO NTT and VLT in April and May 2006 to investigate the nature and the structure of the Near Earth Object (144898) 2004 VD17. In spite of a great quantity of dynamical information, according to which it will have a close approach with the Earth in the next century, the physical properties of this asteroid are largely unknown. We performed visible and near--infrared photometry and spectroscopy, as well as polarimetric observations. Polarimetric and spectroscopic data allowed us to classify 2004 VD17 as an E-type asteroid. A good agreement was also found with the spectrum of the aubrite meteorite Mayo Belwa. On the basis of the polarimetric albedo (p_v=0.45) and of photometric data, we estimated a diameter of about 320 m and a rotational period of about 2 hours. The analysis of the results obtained by our complete survey have shown that (144898) 2004 VD17 is a peculiar NEO, since it is close to the breakup limits for fast rotator asteroids, as defined by Pravec and Harris (2000). These results suggest that a more robust structure must be expected, as a fractured monolith or a rubble pile in a "strength regime" (Holsapple 2002).Comment: 32 pages, 7 figure, paper accepted for publication in Icaru

Visualizing cellular heterogeneity by quantifying the dynamics of MAPK activity in live mammalian cells with synthetic fluorescent biosensors.

Mitogen-Activated Protein Kinases (MAPKs) control a wide array of cellular functions by transducing extracellular information into defined biological responses. In order to understand how these pathways are regulated, dynamic single cell measurements are highly needed. Fluorescence microscopy is well suited to perform these measurements. However, more dynamic and sensitive biosensors that allow the quantification of signaling activity in living mammalian cells are required. We have engineered a synthetic fluorescent substrate for human MAPKs (ERK, JNK and p38) that relocates from the nucleus to the cytoplasm when phosphorylated by the kinases. We demonstrate that this reporter displays an improved response compared to other relocation biosensors. This assay allows to monitor the heterogeneity in the MAPK response in a population of isogenic cells, revealing pulses of ERK activity upon a physiological EGFR stimulation. We show applicability of this approach to the analysis of multiple cancer cell lines and primary cells as well as its application in vivo to developing tumors. Using this ERK biosensor, dynamic single cell measurements with high temporal resolution can be obtained. These MAPK reporters can be widely applied to the analysis of molecular mechanisms of MAPK signaling in healthy and diseased state, in cell culture assays or in vivo

Thermal infrared observations of near-Earth asteroid 2002 NY40

We obtained N-band observations of the Apollo asteroid 2002 NY40 during its close Earth fly-by in August 2002 with TIMMI2 at the ESO 3.6 m telescope. The photometric measurement allowed us to derive a radiometric diameter of 0.28+/-0.03 km and an albedo of 0.34+/-0.06 through the near-Earth asteroid thermal model (NEATM) and a thermophysical model (TPM). The values are in agreement with results from radar data, visual and near-IR observations. In this first comparison between these two model approaches we found that the empirical NEATM beaming parameter $\eta$=1.0 corresponds to a thermal inertia values of about 100 $\mathrm{J m^{-2} s^{-0.5} K^{-1}}$ for a typical range of surface roughness, assuming an equator-on viewing angle. Our TPM analysis indicated that the surface of 2002 NY40 consists of rocky material with a thin or no dust regolith. The asteroid very likely has a prograde sense of rotation with a cold terminator at the time of our observations. Although both model approaches can fit the thermal spectra taken at phase angles of 22$^{\circ}$ and 59$^{\circ}$, we did not find a consistent model solution that describes all pieces of photometric and spectroscopic data. In addition to the 2002 NY40 analysis, we discuss the possibilities to distinguish between different models with only very few photometric and/or spectroscopic measurements spread over a range of phase angles.Comment: 6 pages, 4 figures, A&A accepte

Negative control of CSL gene transcription by stress/DNA damage response and p53.

CSL is a key transcriptional repressor and mediator of Notch signaling. Despite wide interest in CSL, mechanisms responsible for its own regulation are little studied. CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts (CAF), promoting keratinocyte tumors. We show here that CSL transcript levels differ among HDF strains from different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression is negatively regulated by stress/DNA damage caused by UVA, Reactive Oxygen Species (ROS), smoke extract, and doxorubicin treatment. P53, a key effector of the DNA damage response, negatively controls CSL gene transcription, through suppression of CSL promoter activity and, indirectly, by increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in acute DNA damage response of cells

Spitzer Observations of Spacecraft Target 162173 (1999 JU3)

Near-Earth asteroid 162173 (1999 JU3) is the primary target of the Hayabusa-2 sample return mission, and a potential target of the Marco Polo sample return mission. Earth-based studies of this object are fundamental to these missions. We present a mid-infrared spectrum (5-38 microns) of 1999 JU3 obtained with NASA's Spitzer Space Telescope in May 2008. These observations place new constraints on the surface properties of this asteroid. To fit our spectrum we used the near-Earth asteroid thermal model (NEATM) and the more complex thermophysical model (TPM). However, the position of the spin-pole, which is uncertain, is a crucial input parameter for constraining the thermal inertia with the TPM; hence, we consider two pole orientations. In the extreme case of an equatorial retrograde geometry we derive a lower limit to the thermal inertia of 150 J/m^2/K/s^0.5. If we adopt the pole orientation of Abe et al. (2008a) our best-fit thermal model yields a value for the thermal inertia of 700+/-200 J/m^2/K/s^0.5 and even higher values are allowed by the uncertainty in the spectral shape due to the absolute flux calibration. The lower limit to the thermal inertia, which is unlikely but possible, would be consistent with a fine regolith similar to wthat is found for asteroid 433 Eros. However, the thermal inertia is expected to be higher, possibly similar to or greater than that on asteroid 25143 Itokawa. Accurately determining the spin-pole of asteroid 162173 will narrow the range of possible values for its thermal inertia.Comment: 4 pages, 2 figures; to be published as a Letter in Astronomy and Astrophysic

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B.

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment

Marco Polo: near Earth object sample return mission

Marco Polo is a joint European-Japanese mission of sample return from a Near Earth Object. The Marco Polo proposal was submitted to ESA on July 2007 in the framework of the Cosmic Vision 2015-2025 context, and on October 2007 passed the first evaluation process. The primary objectives of this mission is to visit a primitive NEO, belonging to a class that cannot be related to known meteorite types, to characterize it at multiple scales, and to bring samples back to Earth. Marco Polo will give us the first opportunity for detailed laboratory study of the most primitive materials that formed the planets. This will allow us to improve our knowledge on the processes which governed the origin and early evolution of the Solar System, and possibly of the life on Earth

Características e desempenho agronômico da cultivar de trigo BRS 220 no estado de Santa Catarina.

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