Special Sequence Research Articles

Exploring new molecules that regulate hematopoietic stem cells and early stages of lymphoid hematopoiesis: the functional significance of ESAM and SATB1

Hematopoietic stem cells (HSCs) possess multilineage differentiation capability, which sustains the production of blood and immune cells throughout life. However, the precise mechanisms by which HSCs initiate differentiation toward a particular lineage and the factors that attenuate their lymphopoietic potential with aging are yet to be elucidated. Our group has investigated this issue for over two decades. We initially developed a method for segregating early lymphoid progenitors from HSCs and identified two molecules: endothelial cell-selective adhesion molecule (ESAM), highly expressed in HSCs, and special AT-rich sequence binding protein 1 (SATB1), expressed in early lymphoid progenitors. ESAM marks HSCs across species, including humans. In addition to its significance in stress-induced hematopoiesis, ESAM is also useful in identifying features of human acute myeloid leukemia stem cells. Further, we determined the role of SATB1 in the early HSC differentiation processes toward the lymphoid lineage. Remarkably, SATB1 expression in HSCs significantly decreased with aging, whereas its exogenous induction in aged HSCs rejuvenated their lymphopoietic potential. Furthermore, SATB1-expressing HSCs demonstrated robust lymphopoietic and long-term reconstituting capability, whereas HSCs without SATB1 skewed toward the myeloid lineage. Thus, our continuing research has revealed the significance of ESAM and SATB1 in the fundamental biology of HSCs.

Единственность восстановления оператора Штурма-Лиувилля со спектральным параметром, квадратично входящим в граничное условие

The work is devoted to the study of the inverse problem for the Sturm-Liouville operator with a real square-integrable potential. The boundary conditions are non-separated. One of these boundary conditions includes a quadratic function of the spectral parameter. A uniqueness theorem is proved and an algorithm for solving the inverse problem is constructed. As spectral data, we use the spectrum of the considered boundary value problem, the constant term of the quadratic function of the spectral parameter included in the boundary condition, and some special sequence of signs. From these spectral data, the characteristic function of the boundary value problem is first reconstructed in the form of an infinite product and the parameters of the boundary conditions, and then the problem is reduced to the inverse problem of reconstructing the potential of the Sturm-Liouville operator from the spectra of two boundary value problems with separated boundary conditions. The results of the article can be used for solving various versions of inverse problems of spectral analysis for differential operators, as well as for integrating some nonlinear equations of mathematical physics.

A corpus-based study of successive patterns of Chinese modals

Abstract Being different from previous researches which explore the possible multiple modal patterns in Mandarin Chinese basically with invented examples, this study examines the attested patterns of successive use of modals facilitated by two large Chinese corpora (Corpus of Center for Chinese Linguistics Peking University or CCL, and Beijing Language and Culture University Corpus Center or BCC) and the reasons underlying these patterns. The data reveal that combinations of Chinese modals of different types comply with the proximity to the predicate verb of the proposition. The exact sequential order is demonstrated as follows: dynamic modality precedes the predicate verb; deontic modality precedes dynamic modality; and epistemic modality precedes deontic and dynamic modalities. In addition, different modal auxiliaries of the same type also co-occur in a special sequence. From the perspective of subjectivity and objectivity, we argue that the underlying principle of this ordering is that the more subjective a modal auxiliary is, the more distant it will be from the predicate verb of the proposition and vice versa. For successive patterns of different modal auxiliaries within the same type, the concept of gradability is employed. Although modal auxiliaries of the same type might occur at the same distance to the predicate verb of the proposition, they could characterize different degrees of gradabilities. Modals with higher degree of gradability could precede those with lower degrees, whereas those with the same degree of gradability are capable of the successive co-occurrence in either way.

SATB1 enhances gastric cancer progression and metastasis via upregulation of CLIP4/DZIP1/ PRICKLE2 axis in gastric cancer patients

SATB1 (Special AT-rich sequence binding protein 1) plays key role in chromatin remodeling and geneexpression. SATB1 has been shown to promote invasion, migration and metastasis. However, the underlying molecular mechanisms, function and clinicopathological features of SATB1 in gastric cancer (GC) remains poorly understood. Here, we show that SATB1 plays critical role in GC progression. SATB1 upregulates in GC patients’ samples and shows co-apmlification with a subset of oncogenic proteins (PRICKLE2, ZEB1, CBWX7, WWTR1, ENAH, DZIP1, IGSF11, ZSCAN18, GFRA2, GFRA1, FGFR1, HDAC4, GHR, TIMP3, CLIP4, TAGLN and ILK) in different subtypes of GC. SATB1 shows positive correlation with GC promoting oncogenes and enhances the expression of metastasis associated genes in GC samples to potentiate GC progression. SATB1 enhances WNT/NOTCH signaling axis in GC samples. In contrast, STAB1 suppresses a network of tumor suppressor genes in GC samples. Moreover, SATB1 expression negatively correlates with GC patient’s survival. Importantly, we found that SATB1 co-amplified genes CLIP4, DZIP1 and PRICKLE2 independently involve in GC progression. Overexpression of CLIP4, DZIP1 and PRICKLE2 show poor survival rates in GC patients. DZIP1 empowers AKT3/FGF2/FGFR1 and CXCR3/CXCR6 in GC patients. PRICKLE2 enhances GC progression by targeting FGFR1/NOTCH3/WNT4 signaling. Taken together, these results identified novel roles of SATB1, CLIP4, DZIP1 and PRICKLE2 in the GC invasion, migration and metastasis using cancer bioinformatics approach. These results highlights clinical significance of SATB1, CLIP4, DZIP1 and PRICKLE2 in GC patients and furthermore, these proteins may serve as prognostic markers in GC. These results also provide SATB1, CLIP4, DZIP1 and PRICKLE2 as potential chemotherapeutic targets in treatment of gastric cancer patients.

О сюжетосложении «Песни о том, как богдо Джангар мангаса Уту Цагана покорил» и «Песни о том, как богдо Джангар хана мангасов Кюрюл Эрдени покорил» Малодербетовского цикла эпоса «Джангар»

Introduction. The article studies plot formation patterns in The Song of How Bogdo Jangar Defeated Mangas Utu Tsagan and The Song of How Bogdo Jangar Defeated the Mangas Khan Kürül Erdeni included in the Baga Dorbet cycle of the Jangar (early narratives recorded in 1862). Materials. The work explores original Clear Script texts of the songs kept at the Manuscript Department of St. Petersburg University Library under the title ‘(Handwritten Records of) the Jangar (Made in B[aga] Dorbet District)’. Goals. The paper aims at examining the plot formation patterns in early songs of the Jangar through the use of descriptive and comparative research methods. Results. The analysis of plots shows the epic poems are interrelated and arranged in special sequence. The set of intertwined motifs serves to shape a plot based on some conflict (song one — an ultimatum of the enemy, song two — a horse raid) determining and determined by exposition, climax, and denouement. Plots of combats involving Bumba’s heroes are successive chains of separate episodes aimed at revealing the key idea of the epic — glorification of heroic exploits undertaken by Bogdo Jangar and his warriors for the sake of Motherland’s liberation from hostile invaders.

Understanding the usability issues in contact management of illiterate and semi-literate users.

The effective utilization of a communication channel like calling a person involves two steps. The first step is storing the contact information of another user, and the second step is finding contact information to initiate a voice or text communication. However, the current smartphone interfaces for contact management are mainly textual; which leaves many emergent users at a severe disadvantage in using this most basic functionality to the fullest. Previous studies indicated that less-educated users adopt various coping strategies to store and identify contacts. However, all of these studies investigated the contact management issues of these users from a qualitative angle. Although qualitative or subjective investigations are very useful, they generally need to be augmented by a quantitative investigation for a comprehensive problem understanding. This work presents an exploratory study to identify the usability issues and coping strategies in contact management by emergent users; by using a mixture of qualitative and quantitative approaches. We identified coping strategies of the Pakistani population and the effectiveness of these strategies through a semi-structured qualitative study of 15 participants and a usability study of 9 participants, respectively. We then obtained logged data of 30 emergent and 30 traditional users, including contact-books and dual-channel (call and text messages) logs to infer a more detailed understanding; and to analyse the differences in the composition of contact-books of both user groups. The analysis of the log data confirmed problems that affect the emergent users’ communication behaviour due to the various difficulties they face in storing and searching contacts. Our findings revealed serious usability issues in current communication interfaces over smartphones. The emergent users were found to have smaller contact-books and preferred voice communication due to reading/writing difficulties. They also reported taking help from others for contact saving and text reading. The alternative contact management strategies adopted by our participants include: memorizing whole number or last few digits to recall important contacts; adding special character sequence with contact numbers for better recall; writing a contact from scratch rather than searching it in the phone-book; voice search; and use of recent call logs to redial a contact. The identified coping strategies of emergent users could aid the developers and designers to come up with solutions according to emergent users’ mental models and needs.

Doubly Selective Channel Estimation Algorithms for Millimeter Wave Hybrid MIMO Systems

In this paper, we propose three new compressive sensing-based algorithms for channel estimation in millimeter wave hybrid MIMO systems over doubly (time and frequency) selective channels. Utilizing the basis expansion model (BEM) for effectively representing doubly selective channels, we first propose a BEM-based block orthogonal matching pursuit (BBOMP) algorithm, which can work with any training sequence structure. Next, we present the second algorithm to reduce the complexity of the BBOMP method by employing a special training sequence which results in a computationally efficient block sparse sensing matrix. Finally, in order to further decrease the computational complexity, we propose the third algorithm, where the channel estimation is split into two separate steps of tap detection and gain estimation. The proposed algorithms exploit the entire available training sequence to estimate all channel parameters, and can capture channel variations across the entire training frames without requiring a feedback channel. The Cramer-Rao lower bound and the computational complexity of the proposed algorithms are also addressed. Intensive computer simulations are conducted to evaluate the accuracy of the proposed approaches, showing that they can significantly improve the mean squared error performance compared with the state-of-the-art approaches.

The Fundamental Theorem of Algebra Via Newton’s Identities

To any complex polynomial f with constant term 1 we associate a special sequence by Newton’s identities in terms of the coefficients of f. This sequence constitutes the coefficients of the power series representation of . We prove the fundamental theorem of algebra by showing that this sequence does not converge to zero, or equivalently, is not an entire function.

Dual CHA-mediated high-efficient formation of a tripedal DNA walker for constructing a novel proteinase-free dual-mode biosensing strategy

DNA walkers have been recognized as a type of powerful signal amplification tool for biosensors, but how to adopt a proper strategy to increase their amplification efficiency is still highly desirable. Herein we design a dual-catalytic hairpin assembly (CHA)-mediated strategy for the high-efficient formation of a tripedal Mg2+-dependent DNAzyme (MNAzyme)-DNA walker, and thus develop a novel proteinase-free dual-mode biosensing method for the kanamycin (Kana) antibiotic assay. The first CHA is initiated by a target-biorecognition reaction, which can produce the DNA walker and also induce the target recycling. The second CHA is initiated by a special base sequence designed as a one-half substrate of the MNAzyme. Upon the first CHA-triggered DNA walking at a magnetic bead (MB) track, this “pseudo-target” sequence can be released to induce another CHA-cycle for the formation of the same DNA walker. Meanwhile, the other one-half substrate strand exposed on the MB surface will trigger the quantitative hybridization chain reaction (HCR)-assembly of a G-quadruplex DNAzyme (G-DNAzyme)-enriched double-stranded DNA polymer. So the enzymatic reaction of G-DNAzymes enabled the convenient colorimetric and photoelectrochemical dual-mode signal transduction of the method. Due to the dual-CHA facilitation to the tripedal and three-dimensional DNA walking and synergetic signal amplification of HCR, this method exhibits very low detection limits of 9.4 and 0.55 fg mL−1, respectively. In combination with its wide linear range, automated manipulation, and excellent selectivity, repeatability and reliability, the proposed method is expected to be used for the convenient semiquantitative screening and accurate determination of possible antibiotic residues in complicated matrices.

De Novo Design of Antimicrobial Peptides With a Special Charge Pattern and Their Application in Combating Plant Pathogens.

Plant diseases are important issues in agriculture, and the development of effective and environment-friendly means of disease control is crucial and highly desired. Antimicrobial peptides (AMPs) are known as potential alternatives to chemical pesticides because of their potent broad-spectrum antimicrobial activity and because they have no risk, or have only a low risk, of developing chemical-resistant pathogens. In this study, we designed a series of amphipathic helical peptides with different spatial distributions of positive charges and found that the peptides that had a special sequence pattern “BBHBBHHBBH” (“B” for basic residue and “H” for hydrophobic residue) displayed excellent bactericidal and fungicidal activities in a wide range of economically important plant pathogens. The peptides with higher helical propensity had lower antimicrobial activity. When we modified the peptides with a long acyl chain at their N-terminus, their plant protection effect improved. Our application of the fatty acyl-modified peptides on the leaves of tomato and Arabidopsis plants lessened the infection caused by Pectobacterium carotovorum subsp. carotovorum and Botrytis cinerea. Our study provides important insights on the development of more potent novel AMPs for plant protection.

SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells.

Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells. SATB1-deficient CD4 T cells cannot respond to TCR stimulation; however, the cause of this unresponsiveness is to be clarified. Here, we demonstrate that SATB1 is indispensable to proper mitochondrial functioning and necessary for the activation of signal cascades via the TCR in CD4 T cells. Naïve SATB1-deficient CD4 T cells contain fewer mitochondria than WT T cells, as the former do not express mitochondrial transcription factor A (TFAM). Impaired mitochondrial function in SATB1-deficient T cells subverts mitochondrial ROS production and SHP-1 inactivation by constitutive oxidization. Ectopic TFAM expression increases mitochondrial mass and mitochondrial ROS production and rescues defects in the antigen-specific response in the SATB1-deficient T cells. Thus, SATB1 is vital for maintaining mitochondrial mass and function by regulating TFAM expression, which is necessary for TCR signaling.

Limiting profile for stationary solutions maximizing the total population of a diffusive logistic equation

This paper focuses on the stationary problem of the diffusive logistic equation on a bounded interval. We consider the ratio of a population size of a species to a carrying capacity which denotes a spatial heterogeneity of an environment. In one-dimensional case, Wei-Ming Ni proposed a variational conjecture that the supremum of this ratio varying a diffusion coefficient and a carrying function is 3. Recently, Xueli Bai, Xiaoqing He, and Fang Li [Proc. Amer. Math. Soc. 144 (2016), pp. 2161–2170] settled the conjecture by finding a special sequence of diffusion coefficients and carrying functions. Our interest is to derive a profile of the solutions corresponding to this maximizing sequence. Among other things, we obtain the exact order of the maximum and the minimum of solutions of the sequence. The proof is based on separating the stationary problem into two ordinary differential equations and smoothly adjoining each solution.

Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription.

Inhibitors of histone deacetylases (HDACi) have shown promising effects in preclinical applications for the treatment of many diseases. Confusedly though, the effects of the HDACi trichostatin A (TSA) on angiogenesis are variable among different diseases. This study investigated the direct effects of TSA on endothelial cells, which plays essential roles in angiogenesis and the underlying molecular events. TSA reduced the viability of human umbilical vein endothelial cells (HUVECs), in which proliferation-related genes including BIRC5, CKS1B, and NDC80 were found to be involved. Furthermore, signal transducer and activator of transcription 5 A (STAT5A) was demonstrated to be reduced by TSA and to mediate TSA-induced downregulation of BIRC5, CKS1B, and NDC80 and HUVEC proliferation. Mechanistically, data showed that STAT5A directly bound to the promoters of BIRC5, CKS1B, and NDC80 and activated their transcription through special DNA sequence sites. Finally, the TSA–STAT5A–BIRC5, CKS1B, and NDC80 axis also worked in a cancerous endothelial cell angiogenesis model. The results of this study revealed novel mechanisms underlying the effects of TSA on endothelial cells and provided insights for angiogenesis-associated diseases.

Butterfly spirals

In this article special sequences involving the Butterfly theorem are defined. The Butterfly theorem states that if M is the midpoint of a chord PQ of a circle, then following some definite instructions, it is possible to get two other points X and Y on PQ, such that M is also the midpoint of the segment XY. The convergence investigation of those sequences reveals bounded piecewise spirals, and is done by using the free dynamic mathematics software GeoGebra. It is also supported with rigorous reasoning concerning the convergence of a special sequence. Moreover, it raises related problems that encourage further investigation. This article suggests a content that can be useful for students at secondary as well as undergraduate levels since it incorporates principles taught to students during their first courses in Algebra, Calculus and Geometry especially those related to convergent sequences, the algebra of complex numbers, plane isometries and basic Euclidean geometry.

Positivity for SATB2 distinguishes Islet1 positive rectal neuroendocrine tumours from pancreaticoduodenal neuroendocrine tumours

AimsDetermining the site of origin of a metastatic neuroendocrine tumour (NET) can be challenging and has important prognostic and therapeutic implications. An immunohistochemical (IHC) panel consisting of TTF1, CDX2, PAX8/PAX6...

A Sturm‐Liouville equation on the crossroads of continuous and discrete hypercomplex analysis

The paper studies discrete structural properties of polynomials that play an important role in the theory of spherical harmonics in any dimensions. These polynomials have their origin in the research on problems of harmonic analysis by means of generalized holomorphic (monogenic) functions of hypercomplex analysis. The Sturm‐Liouville equation that occurs in this context supplements the knowledge about generalized Vietoris number sequences , first encountered as a special sequence (corresponding to ) by Vietoris in connection with positivity of trigonometric sums. Using methods of the calculus of holonomic differential equations, we obtain a general recurrence relation for , and we derive an exponential generating function of expressed by Kummer's confluent hypergeometric function.

Development of chemiluminescence method based on serum type I collagen hydroxyl terminal peptide β special sequence (β-CTX)

The objective of this work is to develop and verify the analytical performance of a chemiluminescence immunoassay for the specific sequence β-carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX) in human serum. Two specific monoclonal antibodies (mAb-8A03 and mAb-3D12) with high affinity for β-CTX were selected, and, under optimized conditions, a chemiluminescence immunoassay method (CLIA) for β-CTX was established. The CLIA of β-CTX detected β-CTX in a wide range of 2.0–6000 ng/L. The recovery rate in serum is 95–105%, the specificity is high, and the cross-reaction rate with common easily interfering substances is low (not more than 0.01%). The CLIA correlates well with Roche electrochemiluminescence immunoassay (ECLIA), with a correlation coefficient of 0.9551, which fully meets the requirements of clinical analysis. The developed β-CTX CLIA kit has high sensitivity and good stability. It has the same performance as the commercial Roche ECLIA kit and can be applied clinically.

Expansion of GARP-Expressing CD4+CD25-FoxP3+ T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa.

Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as persistent chronic inflammation, immune activation or exhaustion that can promote the onset of co-morbidities. As the exact function of regulatory T (Treg) cells in HIV remains unclear, this cross-sectional study investigated three expression markers (Forkhead box protein P3 [FOXP3], glycoprotein A repetitions predominant [GARP], special AT-rich sequence binding protein 1 [SATB1]) and compared their expansion between CD4+CD25- and CD4+CD25++ T cells. Age-matched study subjects were recruited (Western Cape, South Africa) and sub-divided: HIV-negative subjects (n = 12), HIV-positive naïve treated (n = 22), HIV-positive treated based on CD4 count cells/µL (CD4 > 500 and CD4 < 500) (n = 34) and HIV-treated based on viral load (VL) copies/mL (VL < 1000 and VL > 1000) (n = 34). Markers of immune activation (CD38) and coagulation (CD142) on T cells (CD8) were assessed by flow cytometry together with FOXP3, GARP and SATB1 expression on CD4+CD25- and CD4+CD25++ T cells. Plasma levels of interleukin-10 (IL-10; anti-inflammatory marker), IL-6 (inflammatory marker) and D-dimer (coagulation marker) were assessed. This study revealed three major findings in immuno-compromised patients with virological failure (CD4 < 500; VL > 1000): (1) the expansion of the unconventional Treg cell subset (CD4+CD25-FOXP3+) is linked with disease progression markers; (2) increased GARP expression in the CD4+CD25- and CD4+CD25++ subsets; and (3) the identification of a strong link between CD4+CD25-SATB1+ cells and markers of immune activation (CD8+CD38+) and coagulation (CD8+CD142+ and D-dimer).

НАЛАШТУВАННЯ НЕЧІТКОГО АДАПТИВНОГО РЕГУЛЯТОРА КОМПРЕСОРНОЇ УСТАНОВКИ ДЛЯ ЗРІДЖЕННЯ ПРИРОДНОГО ГАЗУ

The main properties of the object are studied, as well as the methods by which new parameters can be found for the regulator of the compressor unit for liquefaction of natural gas. The main properties of the adaptive regulator itself are studied, as well as the method by which the work was performed is developed. A comparison was also made with other types of automatic control systems that can be used in this facility. The sequence of construction of the adaptive controller and its interaction with the object is studied. The initial results of the adaptive controller and their comparison with other automatic control systems are investigated. The general properties and rules of construction of the adaptive regulator, the basic subtleties at work with it are studied. New possibilities for regulation of the compressor installation for liquefaction of natural gas are fully considered and the basic rules concerning application of this adaptive regulator are deduced. A study of the effectiveness of the adaptive regulator for this object was conducted and conclusions were made on the work of the regulator and the effectiveness of its results. A special sequence of work was also developed for the construction of an adaptive controller and its application on site. In general, the basic rules for working with such a regulator and its application in a natural gas liquefaction plant are derived. The behavior of the plant is investigated and new settings for the regulation of the natural gas liquefaction plant are derived. The main types of regulation of this object are applied and new rules for finding settings for the main regulator of the compressor unit are derived. The work on comparison of already traditional types of regulation with the adaptive regulator is made and conclusions on application of this or that type of regulation of compressor installation comparing results of regulation are made. The possibility of real use of this regulator on a constant basis in production is investigated, conclusions on the main work of the regulator and also shortcomings which can arise at a choice of regulation with the adaptive regulator are made.

SATB2-AS1 acts as miR-299-3p sponge to facilitate tumorigenesis in human non-small cell lung cancer

IntroductionNon-small cell lung cancer (NSCLC), the most common pathological type of lung cancer, is partly responsible for an increasing number of tumor-related deaths worldwide. This study aimed to explore the biological role of the anti-sense transcript of special AT-rich sequence binding protein 2 (SATB2-AS1), a novel cancer-related long non-coding RNA (lncRNA), and illustrate the potential molecular mechanisms.Material and methodsThe expression patterns of SATB2-AS1 were determined via qPCR analysis in clinical samples and tumor cell lines. Kaplan-Meier survival analysis was conducted to assess the relationship between SATB2-AS1 expression and survival time of NSCLC patients. NSCLC tumors were transfected with SATB2-AS1 expression vectors or specific short hairpin RNAs (sh-SATB2-AS1). Tumor cell proliferation, cell cycle progression and apoptosis was detected by MTT assays and flow cytometric method, respectively. Nude mouse transplantation models were applied to investigate the effects of SATB2-AS1 on tumor cell growth in vivo. Bio-informatics analysis, luciferase reporter assays and rescue assays were performed to elucidate possible molecular mechanisms.ResultsSATB2-AS1 up-regulation was observed in tumorous tissues and cell lines. Up-regulated SATB2-AS1 expression was associated with shorter overall survival time of patients. SATB2-AS1 over-expression facilitated tumor cell proliferation, cell cycle progression and survival, while its knockdown inhibited tumor cell proliferation, cell cycle progression and survival. SATB2-AS1 depletion suppressed tumor growth in vivo. SATB2-AS1 was revealed to act as a miR-299-3p sponge to exert carcinogenic role.ConclusionsOur data indicate that SATB2-AS1 acts as a miR-299-3p sponge to facilitate NSCLC development, providing a novel candidate therapeutic target for NSCLC.