Invariant Sequence Research Articles

A sequence invariable region in TcdB2 is required for toxin escape from Clostridioides difficile.

Clostridioides difficile is a leading cause of antibiotic associated disease in the United States. The primary virulence factors produced by C. difficile are two large glucosylating toxins TcdA and TcdB. To date, several sequence variants of TcdB have been identified that differ in various functional properties. Here, we identified a highly conserved region among TcdB subtypes that is required for release of the toxin from C. difficile. This study reveals a putative role for the longest stretch of invariable sequence among TcdB subtypes and provides new details regarding toxin release into the extracellular environment. Improving our understanding of the functional roles of the conserved regions of TcdB variants aids in the development of new, broadly applicable strategies to treat CDI.

Coping strategies of food insecure households with children and adolescents in Uruguay, a high-income Latin American country: A qualitative study through the lens of Bourdieu's theories of capitals and practice

Food insecurity has been associated with negative short, medium, and long-term health consequences, which are more detrimental for children and adolescents. These effects may depend on the coping strategies developed to deal with food shortages. The present research aimed at exploring coping strategies in food insecure households with children and adolescents in Uruguay, incorporating sociological theoretical insights from Bourdieu. A qualitative approach based on individual semi-structured interviews was used. A total of 40 interviews were conducted with adults who had parental responsibilities of children and adolescents and who received different types of food assistance, between July and December 2022, in four cities. Results showed that adults tend to develop a wide range of coping strategies aimed at: reducing food expenditure, increasing the availability of money for purchasing food, increasing food availability and/or rationing the food available in the household. Some of the strategies were implemented regardless of the severity of food insecurity, whereas others were characteristic of the moderate and severe levels of the construct. Evidence to support the mediation effect of coping strategies on health outcomes was found. Discourses suggested that lower accumulation of economic and cultural capital may be aligned with the adoption of less socially accepted mechanisms to access to food. Expressions of a specific habitus aimed at securing food were identified among participants with more deprivations. Taken together, the findings suggest that coping strategies may not be a universal or invariant sequence according to the severity of food insecurity and stress the importance of considering households’ resources and local context for the development of strategies to improve access to food.

Unraveling the plasticity of translation initiation in prokaryotes: Beyond the invariant Shine-Dalgarno sequence.

Translation initiation in prokaryotes is mainly defined, although not exclusively, by the interaction between the anti-Shine-Dalgarno sequence (antiSD), located at the 3'-terminus of the 16S ribosomal RNA, and a complementary sequence, the ribosome binding site, or Shine-Dalgarno (SD), located upstream of the start codon in prokaryotic mRNAs. The antiSD has a conserved 5'-CCUCC-3' core, but inter-species variations have been found regarding the participation of flanking bases in binding. These variations have been described for certain bacteria and, to a lesser extent, for some archaea. To further analyze these variations, we conducted binding-energy prediction analyses on over 6,400 genomic sequences from both domains. We identified 15 groups of antiSD variants that could be associated with the organisms' phylogenetic origin. Additionally, our findings revealed that certain organisms exhibit variations in the core itself. Importantly, an unaltered core is not necessarily required for the interaction between the 3'-terminus of the rRNA and the region preceding the AUG of the mRNA. In our study, we classified organisms into four distinct categories: i) those possessing a conserved core and demonstrating binding; ii) those with a conserved core but lacking evidence of binding; iii) those exhibiting binding in the absence of a conserved core; and iv) those lacking both a conserved core and evidence of binding. Our results demonstrate the flexibility of organisms in evolving different sequences involved in translation initiation beyond the traditional Shine-Dalgarno sequence. These findings are discussed in terms of the evolution of translation initiation in prokaryotic organisms.

A topological model for the coloured Alexander invariants

Coloured Alexander polynomials form a sequence of non-semisimple quantum invariants coming from the representation theory of the quantum group Uq(sl(2)) at roots of unity. This sequence recovers the original Alexander polynomial as the first term. We give a topological model for these invariants, showing that they can be obtained as graded intersection pairings between homology classes in a covering of the configuration space in the punctured disc.

An elementary alternative to ECH capacities

The embedded contact homology (ECH) capacities are a sequence of numerical invariants of symplectic four-manifolds that give (sometimes sharp) obstructions to symplectic embeddings. These capacities are defined using embedded contact homology, and establishing their basic properties currently requires Seiberg-Witten theory. In this paper we define a sequence of symplectic capacities in four dimensions using only basic notions of holomorphic curves. The capacities satisfy the same basic properties as ECH capacities and agree with the ECH capacities for the main examples for which the latter have been computed, namely convex and concave toric domains. The capacities are also useful for obstructing symplectic embeddings into closed symplectic four-manifolds. This work is inspired by a recent preprint of McDuff and Siegel [D. McDuff, K. Siegel, arXiv [Preprint] (2021)], giving a similar elementary alternative to symplectic capacities from rational symplectic field theory (SFT).

Synthetic refactor of essential genes decodes functionally constrained sequences in yeast genome

SummaryThe relationship between gene sequence and function matters for fundamental and practical reasons. Here, yeast essential genes were systematically refactored to identify invariable sequences in the coding and regulatory regions. The coding sequences were synonymously recoded with all optimal codons to explore the importance of codon choice. The promoters and terminators were swapped with well-characterized CYC1 promoter and terminator to examine whether a specialized expression is required for the function of a specific gene. Among the 10 essential genes from Chr.XIIL, this scheme successfully generated 7 refactored genes that can effectively support wild-type-like fitness under various conditions, thereby revealing amazing sequence plasticity of yeast genes. Moreover, different invariable elements were identified from the remaining 3 genes, exampling the logics for genetic information encoding and regulation. Further refactoring of all essential genes using this strategy will generate comprehensive understanding of gene sequence choice, thereby guiding its design in various applications.

Stages in Theory and Experiment. Fuzzy-Structuralism and Piagetian Stages

The theory of stages in cognitive development is one of Jean Piaget’s enduring legacies, but it has also borne the brunt of much criticism. It maintains that intelligence develops in an invariant sequence of stages, and, in this paper, I situate Piaget’s conceptions of stages historically and functionally in the context of genetic epistemology, his research programme. I highlight some of the objections raised, and I show how the disparity between the conceptions of theoretical and empirical stages in Piaget’s theory is commensurate with the fuzzy-structuralist model of the relationship between theory and empirical research conceived by Rudolf Seising on the basis of Lofti A. Zadeh’s fuzzy set theory. Further, I propose a fuzzy conception of the notion ‘stage’, which not only captures its ordinary use in fuzzy space between theory and empirical research but also does justice to both the construct validity and quantitative variability of stages in empirical research. I therefore open a fuzzy-structuralist perspective on the Crisis of Variability afflicting Piaget’s stage theory during the 1970s and conclude retrospectively that the rift it caused was not necessary since the invariance and variability of stages is not irreconcilable.

Ancient Cults in Ḫattuša (I)


 
 
 The present essay explores the question of continuity and change between Kaneš and Ḫattuša in the cultic sphere, reviewing the cult of Parga, probably a fertility goddess of local Anatolian origin, in the Hittite sources. It reveals that Parga appears in several different cultic contexts but within a relatively invariable sequence of offerings, often appearing with the same, often “exotic” deities, such as Zūluma, Šišumma/i, and Šurra. The probable location for performance of many of these cultic sequences in the lower town of Ḫattuša, one of the most ancient parts of the city, shows a great deal of continuity between the Old Assyrian and the Old Hittite periods, and may further highlight the antiquity of these cults. Since some of the cultic action considered in this essay took place in close proximity to the ašuša-gate, the evidence concerning the location of that gate, probably at the western or northwestern section of the fortification wall and near some of the institutions located in its vicinity, will be examined.
 
 

Spatially and functionally distinct pools of calmodulin mRNA in cardiac myocytes

Calmodulin (CaM) is a multifunctional calcium-binding protein that modulates activity of many different ion channels, enzymes and other proteins. In vertebrates, CaM represents a unique case, where the exact same, invariant amino acid sequence is encoded by multiple genes on different chromosomes (three in case of the mouse and human). These multiple CaM genes have been hypothesized to afford high spatiotemporal resolution in the control of numerous CaM-dependent processes within highly specialized cells, such as neurons and cardiac myocytes.

QTAG-modules isomorphic to their fully invariant submodules

Some algebraic structures are isomorphic to their substructures but it is not always true. Some times they are isomorphic to their substructures with certain properties. Grinshpon et. al. investigated abelian groups which are isomorphic to their subgroups with certain properties.This interesting fact motivates us to investigate QTAG-modules which are isomorphic to their proper submodules with special conditions. Here we study If-modules which are isomorphic to their fully invariant submodules. We define admissible sequence of the Ulm-Kaplansky invariants to define If-module and investigate their properties.

Split objects with respect to a fully invariant short exact sequence in abelian categories

We introduce and investigate (dual) relative split objects with respect to a fully invariant short exact sequence in abelian categories. We compare them with (dual) relative Rickart objects, and we study their behaviour with respect to coproducts and classes all of whose objects are (dual) relative split. We also introduce and study (dual) strongly relative split objects. Applications are given to Grothendieck categories, module categories, and comodule categories.

Average minimum distances of periodic point sets – foundational invariants for mapping periodic crystals

The fundamental model of any solid crystalline material (crystal) at the atomic scale is a periodic point set. The strongest natural equivalence of crystals is rigid motion or isometry that preserves all inter-atomic distances. Past comparisons of periodic structures often used manual thresholds, symmetry groups and reduced cells, which are discontinuous under perturbations or thermal vibrations of atoms. This work defines the infinite sequence of continuous isometry invariants (Average Minimum Distances) to progressively capture distances between neighbors. The asymptotic behaviour of the new invariants is theoretically proved in all dimensions for a wide class of sets including non-periodic. The proposed near linear time algorithm identified all different crystals in the world's largest Cambridge Structural Database within a few hours on a modest desktop. The ultra fast speed and proved continuity provide rigorous foundations to continuously parameterise the space of all periodic crystals as a high-dimensional extension of Mendeleev's table of elements.

Fine spectra and compactness of generalized Cesàro operators in Banach lattices in [formula omitted

The generalized Cesàro operators Ct, for t∈[0,1), introduced in the 1980's by Rhaly, are natural analogues of the classical Cesàro averaging operator C1 and act in various Banach sequence spaces X⊆CN0. In this paper we concentrate on a certain class of Banach lattices for the coordinate-wise order, which includes all separable, rearrangement invariant sequence spaces, various weighted c0 and ℓp spaces and many others. In such Banach lattices X the operators Ct, for t∈[0,1), are always compact (unlike C1) and a full description of their point, continuous and residual spectrum is given. Estimates for the operator norm of Ct are also presented.

Topological Properties of Invariant Convergent Sequences Defined with the Help of a Modulus Function

Bu çalışmada Modülüs fonksiyon yardımı ile tanımlanan invaryant yakınsak dizi uzayları tanımlanarak aralarında bazı kapsam bağıntıları kuruldu. [ω_σ (f)],ω ̅_(σ ) (f) ve ω ̿_(σ ) (f) uzayları [ω_σ (f)(p)],ω ̅_(σ ) (f)(p) ve ω ̿_(σ ) (f)(p) uzaylarına genişletildi. Genelleştirilen bu dizi uzaylarının topolojik özellikleri incelendi.

Pattern formation in a 2-population homogenized neuronal network model

We study pattern formation in a 2-population homogenized neural field model of the Hopfield type in one spatial dimension with periodic microstructure. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. It is shown that the nonlocal synaptic interactions promote a finite band width instability. The stability method relies on a sequence of wave-number dependent invariants of 2times 2-stability matrices representing the sequence of Fourier-transformed linearized evolution equations for the perturbation imposed on the homogeneous background. The generic picture of the instability structure consists of a finite set of well-separated gain bands. In the shallow firing rate regime the nonlinear development of the instability is determined by means of the translational invariant model with connectivity kernels replaced with the corresponding period averaged connectivity functions. In the steep firing rate regime the pattern formation process depends sensitively on the spatial localization of the connectivity kernels: For strongly localized kernels this process is determined by the translational invariant model with period averaged connectivity kernels, whereas in the complementary regime of weak and moderate localization requires the homogenized model as a starting point for the analysis. We follow the development of the instability numerically into the nonlinear regime for both steep and shallow firing rate functions when the connectivity kernels are modeled by means of an exponentially decaying function. We also study the pattern forming process numerically as a function of the heterogeneity parameters in four different regimes ranging from the weakly modulated case to the strongly heterogeneous case. For the weakly modulated regime, we observe that stable spatial oscillations are formed in the steep firing rate regime, whereas we get spatiotemporal oscillations in the shallow regime of the firing rate functions.

Palindromic Sequence-Targeted (PST) PCR, Version 2: An Advanced Method for High-Throughput Targeted Gene Characterization and Transposon Display.

Genome walking (GW), a strategy for capturing previously unsequenced DNA fragments that are in proximity to a known sequence tag, is currently predominantly based on PCR. Recently developed PCR-based methods allow for combining of sequence-specific primers with designed capturing primers capable of annealing to unknown DNA targets, thereby offering the rapidity and effectiveness of PCR. This study presents a methodological improvement to the previously described GW technique known as palindromic sequence-targeted PCR (PST-PCR). Like PST-PCR, this new method (called PST-PCR v.2) relies on targeting of capturing primers to palindromic sequences arbitrarily present in natural DNA templates. PST-PCR v.2 consists of two rounds of PCR. The first round uses a combination of one sequence-specific primer with one capturing (PST) primer. The second round uses a combination of a single (preferred) or two universal primers; one anneals to a 5′ tail attached to the sequence-specific primer and the other anneals to a different 5′ tail attached to the PST primer. The key advantage of PST-PCR v.2 is the convenience of using a single universal primer with invariable sequences in GW processes involving various templates. The entire procedure takes approximately 2–3 h to produce the amplified PCR fragment, which contains a portion of a template flanked by the sequence-specific and capturing primers. PST-PCR v.2 is highly suitable for simultaneous work with multiple samples. For this reason, PST-PCR v.2 can be applied beyond the classical task of GW for studies in population genetics, in which PST-PCR v.2 is a preferred alternative to amplified fragment length polymorphism (AFLP) or next-generation sequencing. Furthermore, the conditions for PST-PCR v.2 are easier to optimize, as only one sequence-specific primer is used. This reduces non-specific random amplified polymorphic DNA (RAPD)-like amplification and formation of non-templated amplification. Importantly, akin to the previous version, PST-PCR v.2 is not sensitive to template DNA sequence complexity or quality. This study illustrates the utility of PST-PCR v.2 for transposon display (TD), which is a method to characterize inter- or intra-specific variability related to transposon integration sites. The Ac transposon sequence in the maize (Zea mays) genome was used as a sequence tag during the TD procedure to characterize the Ac integration sites.

F-Baer objects with respect to a fully invariant short exact sequence in abelian categories

We introduce and study (dual) relative F-Baer objects as specializations of (dual) relative split objects with respect to a fully invariant short exact sequence in (AB3) abelian categories. We analyze their relationship with (dual) relative Baer objects, and we study direct summands and direct sums of (dual) relative F-Baer objects. We give applications to module and comodule categories.

Adaptive multi-model predictive control applied to continuous stirred tank reactor

This paper investigates the design of a Model Predictive Control (MPC) formulation for the case of polytopic multi-model system representation. An adaptive MPC is developed taking into account the scheduling parameters in the multi-model and a terminal invariant set for all the systems that are within the system polytope. This proposed method uses a virtual model-process tuning variable, which is optimized to find the best Linear Time Invariant (LTI) prediction sequence for the horizon, based on the LTI vertices of the polytopic system. Finally, the proposed adaptive MPC is applied to a continuous stirred tank reactor (CSTR) system. Discussions are set upon the a-priori design procedure, the online computational effort and application difficulties.

Correlation of drug resistance with single nucleotide variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate of M. tuberculosis

BackgroundGenome sequencing and genetic polymorphism analysis of clinical isolates of M. tuberculosis is carried out to gain further insight into molecular pathogenesis and host-pathogen interaction. Therefore the functional evaluation of the effect of single nucleotide variation (SNV) is essential. At the same time, the identification of invariant sequences unique to M. tuberculosis contributes to infection detection by sensitive methods. In the present study, genome analysis is accompanied by evaluation of the functional implication of the SNVs in a MDR clinical isolate VPCI591.ResultBy sequencing and comparative analysis of VPCI591 genome with 1553 global clinical isolates of M. tuberculosis (GMTV and tbVar databases), we identified 141 unique strain specific SNVs. A novel intergenic variation in VPCI591 in the putative promoter/regulatory region mapping between embC (Rv3793) and embA (Rv3794) genes was found to enhance the expression of embAB, which correlates with the high resistance of the VPCI591 to ethambutol. Similarly, the unique combination of three genic SNVs in RNA polymerase β gene (rpoB) in VPCI591 was evaluated for its effect on rifampicin resistance through molecular docking analysis.The comparative genomics also showed that along with variations, there are genes that remain invariant. 173 such genes were identified in our analysis.ConclusionThe genetic variation in M. tuberculosis clinical isolate VPCI591 is found in almost all functional classes of genes. We have shown that SNV in rpoB gene mapping outside the drug binding site along with two SNVs in the binding site can contribute to quantitative change in MIC for rifampicin. Our results show the collective effect of SNVs on the structure of the protein, impacting the interaction between the target protein and the drug molecule in rpoB as an example. The study shows that intergenic variations bring about quantitative changes in transcription in embAB and in turn can lead to drug resistance.

Extremely low genetic diversity of Stigonema associated with Stereocaulon in eastern Canada

Stigomena is a genus of cyanobacteria that is often the photobiont associated with the lichen genus Stereocaulon. To elucidate the evolutionary relationships between Stereocaulon and Stigonema and assess whether there is specificity or selectivity at the ecosystem or species levels, we performed phylogenetic analyses on specimens collected throughout Eastern Canada. We generated ITS sequences from the fungal component of the symbiosis and sequences from the operon rbcL-rbcX and the trnL intron from the cyanobacteria of seventy specimens of Stereocaulon. Our ITS results revealed that at least forty Stereocaulon specimens are in 16 distinct species clades (OTUs) and morphologically defined species tend to be paraphyletic. In addition, two genera of cyanobacteria, Stigonema and Nostoc, were detected among the samples and the former is the most common symbiont associated with Stereocaulon. We discovered that nearly invariable Stigonema sequences (rbcL-rbcX) occur across 2,000 km of sampling from temperate to arctic biomes. The lack of geographic structure or species-level specificity for Stigonema suggest a high co-dispersal capability of the cyanobacteria with the ascomycete and selectivity towards a small number of very similar Stigonema haplotypes across eastern Canada.