Tbr1 instructs laminar patterning of retinal ganglion cell dendrites.

Visual information is delivered to the brain by >40 types of retinal ganglion cells (RGCs). Diversity in this representation arises within the inner plexiform layer (IPL), where dendrites of each RGC type are restricted to specific sublaminae, limiting the interneuronal types that can innervate them. How such dendritic restriction arises is unclear. We show that the transcription factor Tbr1 is expressed by four mouse RGC types with dendrites in the outer IPL and is required for their laminar specification. Loss of Tbr1 results in elaboration of dendrites within the inner IPL, while misexpression in other cells retargets their neurites to the outer IPL. Two transmembrane molecules, Sorcs3 and Cdh8, act as effectors of the Tbr1-controlled lamination program. However, they are expressed in just one Tbr1+ RGC type, supporting a model in which a single transcription factor implements similar laminar choices in distinct cell types by recruiting partially non-overlapping effectors

Overexpression Of Chd1l Is Positively Associated With Metastasis Of Lung Adenocarcinoma And Predicts Patients Poor Survival

CHD1L (chromodomain helicase/ATPase DNA binding protein 1-like gene) has been demonstrated as an oncogene in hepatocellular carcinoma (HCC), however, the role of CHD1L in non-small-cell lung cancer (NSCLC) tumorigenesis hasn't been elucidated. In this study, the expression and amplification status of CHD1L were examined by immunohistochemistry and fluorescence in situ hybridization respectively in 248 surgically resected NSCLCs. The associations between CHD1L expression and clinicopathologic features and the prognostic value of CHD1L were analyzed. Overexpression and amplification of CHD1L was found in 42.1% and 17.7% of NSCLCs, respectively. The frequency of CHD1L overexpression (53.2% vs. 28.1%, P = 0.002) and amplification (25.2% vs. 8.2%, P = 0.020) in adenocarcinoma (ADC), was much higher than that in squamous cell carcinoma (SCC). CHD1L overexpression was associated closely with ascending pN status (P < 0.001), advanced clinical stage (P = 0.001) and tumor distant metastasis (P = 0.001) in ADCs, but not in SCCs. For the whole cohort and ADC patients, univariate survival analysis demonstrated a significant association of CHD1L overexpression with shortened survival; and in multivariate analysis, CHD1L overexpression was evaluated as a independent predictor for overall survival and distant metastasis free survival. These results suggested that overexpression of CHD1L is positively associated with tumor metastasis of lung ADC, and might serve as a novel prognostic biomarker and potential therapeutic target for lung ADC patients.published_or_final_versio

Cryptanalysis of SKINNY in the Framework of the SKINNY 2018--2019 Cryptanalysis Competition

In April 2018, Beierle et al. launched the 3rd SKINNY cryptanalysis competition, a contest that aimed at motivating the analysis of their recent tweakable block cipher SKINNY . In contrary to the previous editions, the focus was made on practical attacks: contestants were asked to recover a 128-bit secret key from a given set of 2^20 plaintext blocks. The suggested SKINNY instances are 4- to 20-round reduced variants of SKINNY-64-128 and SKINNY-128-128. In this paper, we explain how to solve the challenges for 10-round SKINNY-128-128 and for 12-round SKINNY-64-128 in time equivalent to roughly 2^52 simple operations. Both techniques benefit from the highly biased sets of messages that are provided and that actually correspond to the encryption of various books in ECB mode

Sampling strategies and integrated reconstruction for reducing distortion and boundary slice aliasing in high-resolution 3D diffusion MRI

Purpose: To develop a new method for high-fidelity, high-resolution 3D multi-slab diffusion MRI with minimal distortion and boundary slice aliasing. Methods: Our method modifies 3D multi-slab imaging to integrate blip-reversed acquisitions for distortion correction and oversampling in the slice direction (kz) for reducing boundary slice aliasing. Our aim is to achieve robust acceleration to keep the scan time the same as conventional 3D multi-slab acquisitions, in which data are acquired with a single direction of blip traversal and without kz-oversampling. We employ a two-stage reconstruction. In the first stage, the blip-up/down images are respectively reconstructed and analyzed to produce a field map for each diffusion direction. In the second stage, the blip-reversed data and the field map are incorporated into a joint reconstruction to produce images that are corrected for distortion and boundary slice aliasing. Results: We conducted experiments at 7T in six healthy subjects. Stage 1 reconstruction produces images from highly under-sampled data (R = 7.2) with sufficient quality to provide accurate field map estimation. Stage 2 joint reconstruction substantially reduces distortion artifacts with comparable quality to fully-sampled blip-reversed results (2.4× scan time). Whole-brain in-vivo results acquired at 1.22 mm and 1.05 mm isotropic resolutions demonstrate improved anatomical fidelity compared to conventional 3D multi-slab imaging. Data demonstrate good reliability and reproducibility of the proposed method over multiple subjects. Conclusion: The proposed acquisition and reconstruction framework provide major reductions in distortion and boundary slice aliasing for 3D multi-slab diffusion MRI without increasing the scan time, which can potentially produce high-quality, high-resolution diffusion MRI

Rehebbilitating Memory

Amnesia is a deficit of memory function that can result from trauma, stress, disease, drug use, or ageing. Though efforts are made to prevent and treat the various causes of amnesia, there remains no treatment for the symptom of memory loss itself. Because the defining feature of amnesia is an inability recall memory, any given case may be due to the possibility that the memory is damaged, or the alternative that it is present but irretrievable (Squire, 1982). Discriminating between these two scenarios would be of scientific value, because the neurobiology of memory formation is anchored in experimental amnesia. Pathological cases of amnesia that are due to retrieval deficits may in principal be treatable rather than merely preventable. Amnesia could be attributed to a retrieval deficit if the ostensible ‘lost’ memory could be evoked through brain stimulation. The challenge here is to identify exactly where in the brain a particular memory is stored.JPB FoundationRIKEN Brain Science Institut

Surveying adjustment datum and relative deformation accuracy analysis

In the surveying adjustment, unknown parameters are usually not direct observations, but the elements related to these direct observations. In order to determine the unknown parameters adequate known data should be provided, and these necessarily required known data are used to form the adjustment datum. Under different datums, different results will be obtained even with the same direct observations. However, in the practical adjustment calculation, the datum and its effect on the results are always ignored. In this paper, the adjustment datum is firstly discussed and defined as datum equations. Then an adjustment method based on the datum equations and least squares is presented. This method is a generic one, not only suited for the case in an ordinary datum but also in the gravity centre datum or a quasi-datum, and can be easily used to analyse different deformations. Based on this method, the transformation between different reference frames is derived. It shows that the calculation results, deformation and positioning accuracy under one kind of datum are relative and generic. A case study is further introduced and used to test this new method. Based on the case study, the conclusions are reached. It is found that the relative positional root mean square error of each point becomes bigger as the distance between the point and the datum increases, and the relative deformation offsets under different kinds of datum are helpful for reliable deformation analysis

Down-regulation of hippocampal genes regulating dopaminergic, GABAergic and glutamatergic function following combined neonatal phencyclidine and post-weaning social isolation of rats as a neurodevelopmental model for schizophrenia

Background: Dysfunction of dopaminergic, GABAergic and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP) and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterise alterations in hippocampal neurotransmitter-related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model. Methods: Fifty-four male Lister-hooded rat pups either received phencyclidine (PCP, 10 mg/kg, s.c.), on post-natal day (PND) 7, 9 and 11 before being weaned on PND 23 into separate cages (isolation, PCP-SI, n=31), or vehicle injection and group-housing (2-4 per cage, V-GH, n=23) from weaning. The effect of lamotrigine on locomotor activity, novel object recognition, and prepulse inhibition of acoustic startle was examined (PND60-75) and drug-free hippocampal gene expression on PND70. Results: Acute lamotrigine (10-15mg/kg i.p.) reversed the hyperactivity and novel object recognition impairment induced by PCP-SI but had no effect on the prepulse inhibition deficit. Microarray revealed small but significant down-regulation of hippocampal genes involved in glutamate metabolism, dopamine neurotransmission and GABA receptor signalling, and in specific schizophrenia-linked genes, including PVALB and GAD67, in PCP-SI rats which resemble changes reported in schizophrenia. Conclusions: Findings indicate that alterations in dopamine neurotransmission, glutamate metabolism and GABA signalling may contribute to some of the behavioral deficits observed following PCP-SI, and that lamotrigine may have some utility as an adjunctive therapy to improve certain cognitive deficits symptoms in schizophrenia

Discovery of lead compounds targeting the bacterial sliding clamp using a fragment-based approach

The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity. © 2014 American Chemical Society

Near-Infrared Super Resolution Imaging with Metallic Nanoshell Particle Chain Array

We propose a near-infrared super resolution imaging system without a lens or a mirror but with an array of metallic nanoshell particle chain. The imaging array can plasmonically transfer the near-field components of dipole sources in the incoherent and coherent manners and the super resolution images can be reconstructed in the output plane. By tunning the parameters of the metallic nanoshell particle, the plasmon resonance band of the isolate nanoshell particle red-shifts to the near-infrared region. The near-infrared super resolution images are obtained subsequently. We calculate the field intensity distribution at the different planes of imaging process using the finite element method and find that the array has super resolution imaging capability at near-infrared wavelengths. We also show that the image formation highly depends on the coherence of the dipole sources and the image-array distance.Comment: 15 pages, 6 figure