Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene.The patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial features.Familial whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family.The p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in vivo.Additionally,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient.The human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.A mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by E13.5.RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Control of a Cheetah Robot in Passive Bounding Gait

Passive dynamics is always one of research emphases of the legged robots. Studies have proved that cheetah robot could achieve stably passive bounding motion under proper initial conditions in the ideal case. However, the actual robot must have energy dissipation because of friction and collision compared with the theoretical model. This paper aims to propose a control method that can drive the cheetah robot running in passive bounding gait. First, a sagittal-plane model with a rigid torso and two compliant legs is introduced to capture the dynamics of robot bounding. Numerical return map studies of the bounding model reveal that there exists a large variety of passively cyclic bounding motions （fixed points）. Based on the distribution law of fixed points, an open-loop control method including touchdown angle control strategy and leg length control strategy is put forward. At last, prototype of the cheetah robot is designed and manufactured, and locomotion experiment are carried out. The experiment results show that the cheetah robot can achieve a stable bounding motion at different speeds with the proposed control method.

Adenocarcinoma transformed into squamous cell carcinoma in non-small cell lung cancer

Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).