CNNM2-Related Disorders: Phenotype and Its Severity Were Associated With the Mode of Inheritance

CNNM2 (Cystathionine-β-synthase-pair Domain Divalent Metal Cation Transport Mediator 2) pathogenic variants have been reported to cause hypomagnesemia, epilepsy, and intellectual disability/developmental delay (ID/DD). We identified two new cases with CNNM2 novel de novo pathogenic variants, c.814T>C and c.976G>C. They both presented with infantile-onset epilepsy with DD and hypomagnesemia refractory to magnesium supplementation. To date, 21 cases with CNNM2-related disorders have been reported. We combined all 23 cases to analyze the features of CNNM2-related disorders. The phenotypes can be classified into three types: type 1, autosomal dominant (AD) inherited simple hypomagnesemia; type 2, AD inherited hypomagnesemia with epilepsy and ID/DD; and type 3, autosomal recessive (AR) inherited hypomagnesemia with epilepsy and ID/DD. All five type 1 cases had no epilepsy or ID/DD; they all had hypomagnesemia, and three of them presented with symptoms secondary to hypomagnesemia. Fifteen type 2 patients could have ID/DD and seizures, which can be controlled with antiseizure medications (ASMs); their variations clustered in the DUF21 domain of CNNM2. All three type 3 patients had seizures from 1 to 6 days after birth; the seizures were refractory, and 1/3 had status epilepticus; ID/DD in these AR-inherited cases was more severe than that of AD-inherited cases; they all had abnormalities of brain magnetic resonance imaging (MRI). Except for one patient whose serum magnesium was the lower limit of normal, others had definite hypomagnesemia. Hypomagnesemia could be improved after magnesium supplement but could not return to the normal level. Variations in the CBS2 domain may be related to lower serum magnesium. However, there was no significant difference in the level of serum magnesium among the patients with three different types of CNNM2-related disorders. The severity of different phenotypes was therefore not explained by decreased serum magnesium. We expanded the spectrum of CNNM2 variants and classified the phenotypes of CNNM2-related disorders into three types. We found that DUF21 domain variations were most associated with CNNM2-related central nervous system phenotypes, whereas hypomagnesemia was more pronounced in patients with CBS2 domain variations, and AR-inherited CNNM2-related disorders had the most severe phenotype. These results provide important clues for further functional studies of CNNM2 and provide basic foundations for more accurate genetic counseling.

Hierarchical Instance Feature Alignment for 2D Image-Based 3D Shape Retrieval

2D image-based 3D shape retrieval has become a hot research topic since its wide industrial applications and academic significance. However, existing view-based 3D shape retrieval methods are restricted by two settings, 1) learn the common-class features while neglecting the instance visual characteristics, 2) narrow the global domain variations while ignoring the local semantic variations in each category. To overcome these problems, we propose a novel hierarchical instance feature alignment (HIFA) method for this task. HIFA consists of two modules, cross-modal instance feature learning and hierarchical instance feature alignment. Specifically, we first use CNN to extract both 2D image and multi-view features. Then, we maximize the mutual information between the input data and the high-level feature to preserve as much as visual characteristics of an individual instance. To mix up the features in two domains, we enforce feature alignment considering both global domain and local semantic levels. By narrowing the global domain variations we impose the identical large norm restriction on both 2D and 3D feature-norm expectations to facilitate more transferable possibility. By narrowing the local variations we propose to minimize the distance between two centroids of the same class from different domains to obtain semantic consistency. Extensive experiments on two popular and novel datasets, MI3DOR and MI3DOR-2, validate the superiority of HIFA for 2D image-based 3D shape retrieval task.

Shape optimization for an elliptic operator with infinitely many positive and negative eigenvalues

This paper deals with an eigenvalue problem possessing infinitely many positive and negative eigenvalues. Inequalities for the smallest positive and the largest negative eigenvalues, which have the same properties as the fundamental frequency, are derived. The main question is whether or not the classical isoperimetric inequalities for the fundamental frequency of membranes hold in this case. The arguments are based on the harmonic transplantation for the global results and the shape derivatives (domain variations) for nearly circular domains.

Mechanistic and functional diversity in the mechanosensory kinases of the titin-like family

The giant cytoskeletal kinases of the titin-like family are emerging as key mediators of stretch-sensing in muscle. It is thought that their elastic conformational deformation during muscle function regulates both their catalysis and the recruitment of regulatory proteins to signalosomes that assemble in their vicinity. In the present article, we discuss the speciation of mechanosensory mechanisms in titin-like kinases, their scaffolding properties and the kinase/pseudokinase domain variations that define a rich functional diversity across the family.

Temporal electrical response of chiral smectic liquid crystal displays with V/W-shaped electrooptical characteristic

Chiral smectic liquid crystal cells showing V-shaped electrooptical switching have been reported as one of the most promising technologies for high-end display applications. In this work, time-resolved electrical behaviour of these devices has been obtained through a set of systematic measurements. The electrical equivalent circuit has been derived, a number of simulations at different frequencies have been performed using commercial software for analogue circuits. Performance of this electrical model to account for time domain variations of switching currents in chiral smectic LC displays with V/W-shaped electrooptical response has been analyzed as well.