Weak Sequence Research Articles

The GDAP1 p.Glu222Lys Variant-Weak Pathogenic Effect, Cumulative Effect of Weak Sequence Variants, or Synergy of Both Factors?

Charcot–Marie–Tooth disorders (CMT) represent a highly heterogeneous group of diseases of the peripheral nervous system in which more than 100 genes are involved. In some CMT patients, a few weak sequence variants toward other CMT genes are detected instead of one leading CMT mutation. Thus, the presence of a few variants in different CMT-associated genes raises the question concerning the pathogenic status of one of them. In this study, we aimed to analyze the pathogenic effect of c.664G>A, p.Glu222Lys variant in the GDAP1 gene, whose mutations are known to be causative for CMT type 4A (CMT4A). Due to low penetrance and a rare occurrence limited to five patients from two Polish families affected by the CMT phenotype, there is doubt as to whether we are dealing with real pathogenic mutation. Thus, we aimed to study the pathogenic effect of the c.664G>A, p.Glu222Lys variant in its natural environment, i.e., the neuronal SH-SY5Y cell line. Additionally, we have checked the pathogenic status of p.Glu222Lys in the broader context of the whole exome. We also have analyzed the impact of GDAP1 gene mutations on the morphology of the transfected cells. Despite the use of several tests to determine the pathogenicity of the p.Glu222Lys variant, we cannot point to one that would definitively solve the problem of pathogenicity.

Existence of solutions for critical Fractional FitzHugh–Nagumo type systems

AbstractIn this paper we study the existence of radially symmetric solutions for a Fractional FitzHugh–Nagumo type systems where , , denotes the fractional Laplacian operator and is a continuous function which is allowed to have critical growth: polynomial in case and exponential if and . We transform the system into an equation with a nonlocal term. We find a critical point of the corresponding energy functional defined in the space of functions with norm endowed by a scalar product that takes into account such nonlocal term. For that matter, and due to the lack of compactness, we deal with weak convergent minimizing sequences and sequences of Lagrange multipliers of an action minima problem.

Relation of Morrey Sequence Spaces, Weak Type Morrey Sequence Spaces, and Sequence Spaces

Relation of Morrey Sequence Spaces, Weak Type Morrey Sequence Spaces, and Sequence Spaces

The UPRmt preserves mitochondrial import to extend lifespan.

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial proteins, we surprisingly find that mitochondrial import increases when the UPRmt is activated in an ATFS-1-dependent manner, despite reduced mitochondrial membrane potential. The import machinery is upregulated, and an intact import machinery is essential for UPRmt-mediated lifespan extension. ATFS-1 has a weak mitochondrial targeting sequence (MTS), allowing for dynamic subcellular localization during the initial stages of UPRmt activation.

KAJIAN KEKONVERGENAN LEMAH DI RUANG HILBERT

We have the sequence , where a norm space. We have a dual space too is the collection of linier and continous functional from norm space into riil number system . If for all the sequence convergent to and then convergent to . The converse of this implication is not applicable . This study aims to explain the properties that apply to the ranks of the weak convergent and explain the relationship between the strong convergent sequence and the weak convergent sequence. From several reference sources then through the review process obtained weak nature of singularity limit sequence and relationship between the strong convergent sequence and the weak convergent sequence that if the sequence is strong convergent therefore the sequence it weak convergent.

α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain

The alpha subunit of the cytoplasmic Phenylalanyl tRNA synthetase (α-PheRS, FARSA in humans) displays cell growth and proliferation activities and its elevated levels can induce cell fate changes and tumor-like phenotypes that are neither dependent on the canonical function of charging tRNAPhe with phenylalanine nor on stimulating general translation. In intestinal stem cells of Drosophila midguts, α-PheRS levels are naturally slightly elevated and human FARSA mRNA levels are elevated in multiple cancers. In the Drosophila midgut model, elevated α-PheRS levels caused the accumulation of many additional proliferating cells resembling intestinal stem cells (ISCs) and enteroblasts (EBs). This phenotype partially resembles the tumor-like phenotype described as Notch RNAi phenotype for the same cells. Genetic interactions between α-PheRS and Notch suggest that their activities neutralize each other and that elevated α-PheRS levels attenuate Notch signaling when Notch induces differentiation into enterocytes, type II neuroblast stem cell proliferation, or transcription of a Notch reporter. These non-canonical functions all map to the N-terminal part of α-PheRS which accumulates naturally in the intestine. This truncated version of α-PheRS (α-S) also localizes to nuclei and displays weak sequence similarity to the Notch intracellular domain (NICD), suggesting that α-S might compete with the NICD for binding to a common target. Supporting this hypothesis, the tryptophan (W) residue reported to be key for the interaction between the NICD and the Su(H) BTD domain is not only conserved in α-PheRS and α-S, but also essential for attenuating Notch signaling.

Existence of solution for a class of activator–inhibitor systems

AbstractWe prove the existence of a solution for a class of activator–inhibitor system of type $- \Delta u +u = f(u) -v$ , $-\Delta v+ v=u$ in $\mathbb{R}^{N}$ . The function f is a general nonlinearity which can grow polynomially in dimension $N\geq 3$ or exponentiallly if $N=2$ . We are able to treat f when it has critical growth corresponding to the Sobolev space we work with. We transform the system into an equation with a nonlocal term. We find a critical point of the corresponding energy functional defined in the space of functions with norm endowed by a scalar product that takes into account such nonlocal term. For that matter, and due to the lack of compactness, we deal with weak convergent minimizing sequences and sequences of Lagrange multipliers of an action minima problem.

Linking Signal Relevancy and Intensity in Predictive Tactile Suppression.

Predictable somatosensory feedback leads to a reduction in tactile sensitivity. This phenomenon, called tactile suppression, relies on a mechanism that uses an efference copy of motor commands to help select relevant aspects of incoming sensory signals. We investigated whether tactile suppression is modulated by (a) the task-relevancy of the predicted consequences of movement and (b) the intensity of related somatosensory feedback signals. Participants reached to a target region in the air in front of a screen; visual or tactile feedback indicated the reach was successful. Furthermore, tactile feedback intensity (strong vs. weak) varied across two groups of participants. We measured tactile suppression by comparing detection thresholds for a probing vibration applied to the finger either early or late during reach and at rest. As expected, we found an overall decrease in late-reach suppression, as no touch was involved at the end of the reach. We observed an increase in the degree of tactile suppression when strong tactile feedback was given at the end of the reach, compared to when weak tactile feedback or visual feedback was given. Our results suggest that the extent of tactile suppression can be adapted to different demands of somatosensory processing. Downregulation of this mechanism is invoked only when the consequences of missing a weak movement sequence are severe for the task. The decisive factor for the presence of tactile suppression seems not to be the predicted action effect as such, but the need to detect and process anticipated feedback signals occurring during movement.

An iterative method for solving a PDE with free boundary arising from pricing corporate bond with credit rating migration

<abstract><p>In this paper an iterative method is proposed to solve a partial differential equation (PDE) with free boundary arising from pricing corporate bond with credit grade migration risk. A iterative algorithm is designed to construct two sequences of fixed internal boundary problems, which produce two weak solution sequences. It is proved that both weak solution sequences are convergent. In each iteration step, an implicit-upwind difference scheme is used to solve the fixed internal boundary problem. It is shown that the scheme is stable and first-order convergent. Numerical experiments verify that the limit of the weak solution sequence is the solution of the free boundary problem. This method simplifies the free boundary problem solving, ensures the stability of the discrete scheme and reduces the amount of calculation.</p></abstract>

Asymptotic Extremal Distribution for Non-Stationary, Strongly-Dependent Data

Fisher-Tippet-Gnedenko classical theory shows that the normalized maximum of n iid random variables with distribution F belonging to a very wide class of functions, converges in law to an extremal distribution H, that is determined by the tail of F. Extensions of this theory from the iid case to stationary and weak dependent sequences are well known from the work of Leadbetter, Lindgreen and Rootzén. In this paper, we present a very simple class of random processes that runs from iid sequences to non-stationary and strongly dependent processes, and we study the asymptotic behavior of its normalized maximum. More interesting, we show that when the process is strongly dependent, the asymptotic distribution is no longer an extremal one, but a mixture of extremal distributions. We present very simple theoretical and simulated examples of this result. This provides a simple framework to asymptotic approximations of extremes values not covered by classical extremal theory and its well-known extensions.

Fuzzy Convergence Sequence and Fuzzy Compact Operators on Standard Fuzzy Normed Spaces

The main purpose of this work is to introduce some types of fuzzy convergence sequences of operators defined on a standard fuzzy normed space (SFN-spaces) and investigate some properties and relationships between these concepts. Firstly, the definition of weak fuzzy convergence sequence in terms of fuzzy bounded linear functional is given. Then the notions of weakly and strongly fuzzy convergence sequences of operators are introduced and essential theorems related to these concepts are proved. In particular, if ( ) is a strongly fuzzy convergent sequence with a limit where linear operator from complete standard fuzzy normed space into a standard fuzzy normed space then belongs to the set of all fuzzy bounded linear operators . Furthermore, the concept of a fuzzy compact linear operator in a standard fuzzy normed space is introduced. Also, several fundamental theorems of fuzzy compact linear operators are studied in the same space. More accurately, every fuzzy compact linear operator is proved to be fuzzy bounded where and are two standard fuzzy normed spaces

Expansion of weak reconstruction sequences to approximate Schauder frames for Banach spaces

It is known in Hilbert space frame theory that a Bessel sequence can be expanded to a frame. Contrary to Hilbert space situation, using a result of Casazza and Christensen, we show that there are Banach spaces and weak reconstruction sequences which cannot be expanded to approximate Schauder frames. We characterize Banach spaces in which one can expand weak reconstruction sequences to approximate Schauder frames.

An Alternative and Conserved Cell Wall Enzyme That Can Substitute for the Lipid II Synthase MurG.

The cell wall is a stress-bearing structure and a unifying trait in bacteria. Without exception, synthesis of the cell wall involves formation of the precursor molecule lipid II by the activity of the essential biosynthetic enzyme MurG, which is encoded in the division and cell wall synthesis (dcw) gene cluster. Here, we present the discovery of a cell wall enzyme that can substitute for MurG. A mutant of Kitasatospora viridifaciens lacking a significant part of the dcw cluster, including murG, surprisingly produced lipid II and wild-type peptidoglycan. Genomic analysis identified a distant murG homologue, which encodes a putative enzyme that shares only around 31% amino acid sequence identity with MurG. We show that this enzyme can replace the canonical MurG, and we therefore designated it MglA. Orthologues of mglA are present in 38% of all genomes of Kitasatospora and members of the sister genus Streptomyces CRISPR interference experiments showed that K. viridifaciens mglA can also functionally replace murG in Streptomyces coelicolor, thus validating its bioactivity and demonstrating that it is active in multiple genera. All together, these results identify MglA as a bona fide lipid II synthase, thus demonstrating plasticity in cell wall synthesis.IMPORTANCE Almost all bacteria are surrounded by a cell wall, which protects cells from environmental harm. Formation of the cell wall requires the precursor molecule lipid II, which in bacteria is universally synthesized by the conserved and essential lipid II synthase MurG. We here exploit the unique ability of an actinobacterial strain capable of growing with or without its cell wall to discover an alternative lipid II synthase, MglA. Although this enzyme bears only weak sequence similarity to MurG, it can functionally replace MurG and can even do so in organisms that naturally have only a canonical MurG. The observation that MglA proteins are found in many actinobacteria highlights the plasticity in cell wall synthesis in these bacteria and demonstrates that important new cell wall biosynthetic enzymes remain to be discovered.

Light-Dependent Translation Change of Arabidopsis psbA Correlates with RNA Structure Alterations at the Translation Initiation Region.

mRNA secondary structure influences translation. Proteins that modulate the mRNA secondary structure around the translation initiation region may regulate translation in plastids. To test this hypothesis, we exposed Arabidopsis thaliana to high light, which induces translation of psbA mRNA encoding the D1 subunit of photosystem II. We assayed translation by ribosome profiling and applied two complementary methods to analyze in vivo RNA secondary structure: DMS-MaPseq and SHAPE-seq. We detected increased accessibility of the translation initiation region of psbA after high light treatment, likely contributing to the observed increase in translation by facilitating translation initiation. Furthermore, we identified the footprint of a putative regulatory protein in the 5′ UTR of psbA at a position where occlusion of the nucleotide sequence would cause the structure of the translation initiation region to open up, thereby facilitating ribosome access. Moreover, we show that other plastid genes with weak Shine-Dalgarno sequences (SD) are likely to exhibit psbA-like regulation, while those with strong SDs do not. This supports the idea that changes in mRNA secondary structure might represent a general mechanism for translational regulation of psbA and other plastid genes.

High-spin states and possible chirality in odd-odd Ag110

High-spin states of $^{110}\mathrm{Ag}$ have been studied by in-beam $\ensuremath{\gamma}$-ray spectroscopic techniques using the fusion-evaporation reaction $^{110}\mathrm{Pd}$($^{7}\mathrm{Li}, \ensuremath{\alpha}3\mathrm{n}$)$^{110}\mathrm{Ag}$ at a beam energy of 46 MeV. The previously known level scheme of $^{110}\mathrm{Ag}$ is significantly extended and modified with the addition of 50 new $\ensuremath{\gamma}$ transitions and 21 new levels. In total, four new rotational bands are observed, among which two negative-parity coupled bands are assigned to the four-quasiparticle $\ensuremath{\pi}{g}_{9/2}^{\ensuremath{-}1}\ensuremath{\bigotimes}\ensuremath{\nu}{h}_{11/2}{({g}_{7/2}/{d}_{5/2})}^{2}$ configuration based on the quasiparticle alignment analysis and cranked shell model calculations. The properties of both bands show general agreement with the fingerprints of chiral rotation, and thus such two negative-parity bands are suggested to be candidates for near degenerate chiral doublet bands. A new decoupled $\mathrm{\ensuremath{\Delta}}I=2$ band decaying directly to the yrast band is established, and probably results from one-particle-one-hole (1p-1h) proton excitation from the ${g}_{9/2}$ orbital to the ${g}_{7/2}$ orbital across the large $Z=50$ shell gap, i.e., the 2p2h $\ensuremath{\pi}{g}_{9/2}^{\ensuremath{-}2}{g}_{7/2}\ensuremath{\bigotimes}\ensuremath{\nu}{h}_{11/2}$ configuration. In addition to, a weak positive-parity sequence consisting of magnetic dipole $(M1)$ and no $E2$ crossover transitions is also identified in the present work.

The structure of SeviL, a GM1b/asialo-GM1 binding R-type lectin from the mussel Mytilisepta virgata

SeviL is a recently isolated lectin found to bind to the linear saccharides of the ganglioside GM1b (Neu5Acalpha(2-3)Galbeta(1-3)GalNAcbeta(1-4)Galbeta(1-4)Glc) and its precursor, asialo-GM1 (Galbeta(1-3)GalNAcbeta(1-4)Galbeta(1-4)Glc). The crystal structures of recombinant SeviL have been determined in the presence and absence of ligand. The protein belongs to the beta-trefoil family, but shows only weak sequence similarity to known structures. SeviL forms a dimer in solution, with one binding site per subunit, close to the subunit interface. Molecular details of glycan recognition by SeviL in solution were analysed by ligand- and protein-based NMR techniques as well as ligand binding assays. SeviL shows no interaction with GM1 due to steric hindrance with the sialic acid branch that is absent from GM1b. This unusual specificity makes SeviL of great interest for the detection and control of certain cancer cells, and cells of the immune system, that display asialo-GM1.

Prediction of rifampicin resistance beyond the RRDR using structure-based machine learning approaches

Rifampicin resistance is a major therapeutic challenge, particularly in tuberculosis, leprosy, P. aeruginosa and S. aureus infections, where it develops via missense mutations in gene rpoB. Previously we have highlighted that these mutations reduce protein affinities within the RNA polymerase complex, subsequently reducing nucleic acid affinity. Here, we have used these insights to develop a computational rifampicin resistance predictor capable of identifying resistant mutations even outside the well-defined rifampicin resistance determining region (RRDR), using clinical M. tuberculosis sequencing information. Our tool successfully identified up to 90.9% of M. tuberculosis rpoB variants correctly, with sensitivity of 92.2%, specificity of 83.6% and MCC of 0.69, outperforming the current gold-standard GeneXpert-MTB/RIF. We show our model can be translated to other clinically relevant organisms: M. leprae, P. aeruginosa and S. aureus, despite weak sequence identity. Our method was implemented as an interactive tool, SUSPECT-RIF (StrUctural Susceptibility PrEdiCTion for RIFampicin), freely available at https://biosig.unimelb.edu.au/suspect_rif/.

Taxonomic treatment and phylogenetic analysis of the family Potamogetonaceae in Turkey

AbstractThe family Potamogetonaceae has been taxonomically re‐evaluated in Turkey, employing traditional morphological as well as molecular approaches (rbcL, ITS). Our fieldwork, herbarium studies and molecular analyses proved the existence of 22 taxa, of which 18 belong to Potamogeton (including 4 interspecific hybrids), 3 to Stuckenia and 1 to monotypic Groenlandia. Morphological re‐descriptions of the recognized taxa were prepared, and the information concerning their distribution in Turkey was refined, based on plant material from extensive fieldwork and on specimens stored in herbaria that were previously not examined. Additionally, new identification keys to genera and species, and distribution maps of the species were prepared. Phylogenetic relationships and intraspecific variations were assessed by including samples from other regions. The status of the Zannichelliaceae was investigated using nuclear and chloroplast DNA markers. Our results from ITS sequence divergence corroborate the separation of the two families noted by some authors, and are in accordance with the substantial morphological differences between them. Relatively large genetic distance and non‐monophyly indicate that two genotypes of P. gramineus constitute cryptic species, for which the Turkish localities expand upon the previously known distribution areas. We identified P. schweinfurthii as a new species for Turkey and report P. ×angustifolius for the first time for this country. Weak morphological differentiation and high sequence similarity did not permit reliable differentiation between the closely related Stuckenia amblyphylla and S. filiformis.

A Mechanosensitive Channel, Mouse Transmembrane Channel-Like Protein 1 (Mtmc1) Is Translated from a Splice Variant mTmc1ex1 but Not from the Other Variant mTmc1ex2.

Mechanical stimuli caused by sound waves are detected by hair cells in the cochlea through the opening of mechanoelectrical transduction (MET) channels. Transmembrane channel-like protein 1 (TMC1) has been revealed to be the pore-forming component of the MET channel. The two splice variants for mouse Tmc1 (mTmc1ex1 and mTmc1ex2) were reported to be expressed in the cochlea of infant mice, though only the sequence of mTmc1ex2 had been deposited in GenBank. However, due to the presence of an upstream open reading frame (uORF) and the absence of a typical Kozak sequence in mTmc1ex2, we questioned whether mTMC1 was translated from mTmc1ex2. Therefore, in this study, we evaluated which splice variant was protein-coding mRNA. Firstly, the results of RT-PCR and cDNA cloning of mTmc1 using mRNA isolated from the cochlea of five-week-old mice suggested that more Tmc1ex1 were expressed than mTmc1ex2. Secondly, mTMC1 was translated from mTmc1ex1 but not from mTmc1ex2 in a heterologous expression system. Finally, analyses using site-directed mutagenesis revealed that the uORF and the weak Kozak sequence in mTmc1ex2 prevented the translation of mTMC1 from mTmc1ex2. These results suggest that mTmc1ex1 plays a main role in the expression of mTMC1 in the mouse cochlea, and therefore, mTmc1ex1 should be the mRNA for mTMC1 hereafter.

ON CATEGORICITY IN SUCCESSIVE CARDINALS

AbstractWe investigate, in ZFC, the behavior of abstract elementary classes (AECs) categorical in many successive small cardinals. We prove for example that a universal $\mathbb {L}_{\omega _1, \omega }$ sentence categorical on an end segment of cardinals below $\beth _\omega $ must be categorical also everywhere above $\beth _\omega $ . This is done without any additional model-theoretic hypotheses (such as amalgamation or arbitrarily large models) and generalizes to the much broader framework of tame AECs with weak amalgamation and coherent sequences.