Chain Synthesis Research Articles

Neutrophil Gelatinase Associated Lipocalin: A Possible Role in β Thalassemia Syndromes

Abstract Background Beta Thalassemia is a group of inherited blood disorders that caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable outcomes ranging from severe anaemia to clinically asymptomatic individuals. Neutrophil gelatinase-associated lipocalin (NGAL), is a protein which is encoded by the LCN2 gene. NGAL is involved in innate immunity by sequestrating iron that in turn limits bacterial growth. It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and the alimentary tracts. It also plays a key role in the physiology and pathophysiology of red blood cells, particularly in anemia. Aim of the Work The aim of the present work is to assess plasma level of NGAL in Beta thalassemia syndromes and correlate with laboratory hematological data and iron profile. Patients and Methods A Case-Control study conducted on Beta Thalassemia patients of both sexes attending the outpatient clinic of Ain Shams University Hospitals, this Pilot study of 50 previously diagnosed Beta Thalassemia patients and 30 sex and age matched healthy control subjects. Results The results were correlated with clinical and laboratory parameters. Comparative analysis of the results showed that all groups were homogeneous in terms of size and demographic characteristics. This can explain our results that shows that there is a highly statistically significant difference (p-value < 0.001) between the cases subgroups regarding the inter-transfusion interval with longer intervals among the thalassemia intermedia subgroup. While by comparing the Hb electrophoresis parameter between the 2 groups HbA% levels were higher is the group of serum ferritin <1000 ng/ml and HbF% where higher in group of serum ferritin >1000 ng/ml with (p-value < 0.05) for both of them. On conducting a linear regression analysis we found that the intertransfusion interval was the only independent parameter to have an effect on NGAL level on our patient group with regression coefficient -5.78 and this complies with our results of correlation between NGAL and those parameters mentioned and discussed previously. Conclusion The relationship between NGAL and iron level in Egyptian β-TM patients proved in our results has confirmed the proposed regulatory role played by NGAL on erythropoiesis and iron metabolism in β-thalassemia, NGAL at a cutoff value of > 100 proved to be an efficient predictor of increased serum ferritin > 1000 ng/ml. we believe that incorporating NGAL testing in the work up of β-TM patients in the early phases of iron transfusion dependency would provide a promising sensitive and predictive tool for early iron accumulation. We recommend further studies β-TM patients with larger samples size to clarify the co-regulatory role of erythropoiesis and iron metabolism played by NGAL.

The research for various genotypes and phenotypes related to rare -90 (C>T) β-thalassemia mutation in Ganzhou city, Southern China

Thalassemia is a heterogeneous group of genetic disorders affecting the hemoglobin genes leading to decrease synthesis of globin chains of hemoglobin and resulting in ineffective erythropoiesis. It usually contains α- and β-thalassemia, most of common mutation types of which can be detected. However, it’s inclined to miss rare thalassemia mutation types. Here, we analyzed the molecular and hematological characteristics of seven cases with rare β-thalassemia -90 (C>T) (HBB: c.-140 C>T) mutation. Five of them carried β-90 (C>T) heterozygous mutation with a β+ thalassemia trait. One case was αSEA/β-90 genotype with decreasing MCV and MCH obviously, and the other was a β+/β0 intermediate thalassemia patient with β-90/βCD17 genotype, presenting with moderate anemia. A pedigree of one case was analyzed subsequently. It was found that the proband’s maternal grandfather and mother were carriers of α3.7/β-90 double heterozygous thalassemia, who presented that MCV and MCH were decreased normally or slightly, and HbA2 was increased. The proband and his aunt were β-90 (C>T) carriers. It’s necessary to point that the MCV and MCH were much higher in carrier of α3.7/β-90 genotype compared with either αSEA/β-90 genotype or β-90 heterozygous mutation. In this study, we explore the genotypes and phenotypes of four diverse β-90、αSEA/β-90、α3.7/β-90、β-90/βCD17 thalassemia mutations, which enriches the gene profile of β-thalassemia mutation in Chinese population.

Two "Edges" in Our Knowledge on the Functions of Ribosomal Proteins: The Revealed Contributions of Their Regions to Translation Mechanisms and the Issues of Their Extracellular Transport by Exosomes.

Ribosomal proteins (RPs), the constituents of the ribosome, belong to the most abundant proteins in the cell. A highly coordinated network of interactions implicating RPs and ribosomal RNAs (rRNAs) forms the functionally competent structure of the ribosome, enabling it to perform translation, the synthesis of polypeptide chain on the messenger RNA (mRNA) template. Several RPs contact ribosomal ligands, namely, those with transfer RNAs (tRNAs), mRNA or translation factors in the course of translation, and the contribution of a number of these particular contacts to the translation process has recently been established. Many ribosomal proteins also have various extra-ribosomal functions unrelated to translation. The least-understood and -discussed functions of RPs are those related to their participation in the intercellular communication via extracellular vesicles including exosomes, etc., which often carry RPs as passengers. Recently reported data show that such a kind of communication can reprogram a receptor cell and change its phenotype, which is associated with cancer progression and metastasis. Here, we review the state-of-art ideas on the implications of specific amino acid residues of RPs in the particular stages of the translation process in higher eukaryotes and currently available data on the transport of RPs by extracellular vesicles and its biological effects.

Cord Blood Hematological Parameters of Fetuses Detected Different Thalassemia Genotypes in the Second Trimester of Pregnancy

Hemoglobinopathies are the most common inherited diseases in humans resulting from impaired globin chain synthesis of hemoglobin. The progression of thalassemia rates is prevented with prenatal screening methods. To evaluate the hematological parameters of α- and β-thalassemia and normal fetuses aged 17-25 weeks of gestation. A cross-sectional study. Pregnant women who underwent cordocentesis in the second trimester because of the risk of having a baby with thalassemia were included in the study. Hematological indices and molecular DNA methods were analyzed from the cord blood samples of 129 women who were 17-25 weeks into pregnancy. The HPLC method was used for Hb fraction analysis. Amplification refractory mutation system, restriction enzyme analysis, multiplex polymerase chain reaction, and sequencing methods were used for the molecular analysis. Maternal contamination was eliminated by the short tandem repeat method. In total, 112 of the fetuses carry α- and β-thalassemia heterozygous or homozygous (α: 37, β: 58, mixed: 17) and 17 fetuses had a normal genotype for thalassemia. Significant differences in adult hemoglobin (HbA), fetal hemoglobin (HbF), Hb Barts, MCV, MCH, and RDW were detected in three groups compared with the normal group (p < 0.001, except for RBC, Hb, HCT, and MCHC). Differences in HbF, Hb Barts, MCV, MCH, and RDW were observed in the α-thalassemia groups compared with the normal group (p < 0.001). Among the five β-thalassemia subgroups, only HbA and RDW were different from the normal group (p < 0.001). This study could be a good reference for future studies and prenatal diagnostic applications in emphasizing the importance of changes in the blood parameters of fetuses before molecular genotyping. These hematological data give valuable information to clinicians about the fetus to enlighten families in making appropriate decisions during prenatal diagnosis.

A DNA-based hydrogel for exosome separation and biomedical applications

Exosomes (EXOs) have been proven as biomarkers for disease diagnosis and agents for therapeutics. Great challenge remains in the separation of EXOs with high-purity and low-damage from complex biological media, which is critical for the downstream applications. Herein, we report a DNA-based hydrogel to realize the specific and nondestructive separation of EXOs from complex biological media. The separated EXOs were directly utilized in the detection of human breast cancer in clinical samples, as well as applied in the therapeutics of myocardial infarction in rat models. The materials chemistry basis of this strategy involved the synthesis of ultralong DNA chains via an enzymatic amplification, and the formation of DNA hydrogels through complementary base-pairing. These ultralong DNA chains that contained polyvalent aptamers were able to recognize and bind with the receptors on EXOs, and the specific and efficient binding ensured the selective separation of EXOs from media into the further formed networked DNA hydrogel. Based on this DNA hydrogel, rationally designed optical modules were introduced for the detection of exosomal pathogenic microRNA, which achieved the classification of breast cancer patients versus healthy donors with 100% precision. Furthermore, the DNA hydrogel that contained mesenchymal stem cell-derived EXOs was proved with significant therapeutic efficacy in repairing infarcted myocardium of rat models. We envision that this DNA hydrogel-based bioseparation system is promising as a powerful biotechnology, which will promote the development of extracellular vesicles in nanobiomedicine.

Endocrine dysfunction in transfusion dependent thalassemia patients from central India

Background: Thalassemia refers to a group of genetically inherited diseases characterized by decreased or absent synthesis of normal globin chains resulting in defective globin chains. Most of the available studies in the literature have been done in adults and there is a paucity of studies highlighting the prevalence of hormonal dysfunction in transfusion dependent patients in pediatric age group. We conducted the present study with an aim to estimate the prevalence of hormonal dysfunction in transfusion dependent thalassemia (TDT) patients at a tertiary care center of Central India. Aims and Objectives: The aim of the study was to estimate the prevalence of hormonal dysfunction in TDT patients at a tertiary care center of central India. Materials and Methods: It is descriptive cross-sectional study conducted at tertiary care hospital MGM Medical College, Indore, Madhya Pradesh, conducted over a period of 12 months (August 2021–July 2022). Results: Our study recruited a total of 100 children with age ranging from 9 year to 18 years with the mean age of 13.16±2.86 years. Sixty percent (n=60) of our study population were males and 40% (n=40) were females. The prevalence of hypogonadism was 35.18% analyzed in 54 patients, hypothyroidism was 10%, and diabetes was 5%. Although serum ferritin was very elevated in all patients with endocrine dysfunction; statistically significant association was found between serum ferritin and hypothyroidism (P=0.020). Conclusion: Patients with TDT are often associated with endocrinopathies; most commonly hypogonadism, followed by hypothyroidism and diabetes. Early screening and treatment is necessary to improve their outcome.

Estimated Level of Plasma Micro RNA-210 in Beta Thalassemia Patients and Its Relation to Hemoglobin F Level and Disease Severity

BACKGROUND: Beta-thalassemia is an autosomal recessive hereditary blood disorder occurs due to absent or diminished β-globin chains synthesis. The transformation from fetal to adult in globin synthesis is controlled by different mechanisms; one of those is BCL11A which is downregulated by microRNA-210 (miRNA-210). Therefore, this would lead to reactivation of fetal hemoglobin (HbF) production that improves anemia and reduces the needs for transfusion. OBJECTIVE: To study miRNA-210 in the plasma of beta thalassemia patients and its relation to HbF level and disease severity. SUBJECTS AND METHODS: The study was carried out on 50 individuals divided into three groups. Group A included 30 thalassemia major patients, Group B included 10 thalassemia intermedia patients, and Group C is 10 healthy volunteers as control. All individuals underwent to history taking, physical examination, and laboratory investigations, complete blood count, serum ferritin, hemoglobin electrophoresis, and measurement of miRNA-210 expression levels in plasma of peripheral blood samples by quantitative real-time polymerase chain reaction. RESULTS: Examination of miRNA-210 plasma level among different groups revealed no statistically significant association between control and thalassemia group or its subgroups (Major and intermedia) (P = 0.224, P = 0.116, and P = 0.734, respectively). Moreover, miRNA-210 was slightly higher in responders than nonresponders to hydroxyurea but did not reach significant level. CONCLUSION: miRNA-210 levels were not associated with increase in HbF levels in thalassemia patients.

Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis

BackgroundWhile kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA).MethodsWe retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models.ResultsKFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up.ConclusionsOur data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS.

Correlation Between Adherence Therapy of Iron Chelation Levels with Anthropometric Status in Major Beta-Thalassemia Patients

Thalassemia is a condition in which hemoglobin undergoes hemolysis due to impaired synthesis of hemoglobin or globin chains. Growth failure is a common occurrence in patients with thalassemia. Iron overload due to repeated transfusions will cause disturbances in anthropometric status in children with thalassemia. Iron chelation therapy is needed to overcome iron overload in patients with beta-thalassemia major. The level of adherence affects the success of iron chelation therapy. This study aims to determine the relationship between the level of adherence to iron chelation treatment and anthropometric status in patients with thalassemia beta major at Kediri District General Hospital. This type of research is observational analytic with a cross-sectional design. This research was conducted at the SMF Pediatrics (IKA) RSUD Kediri Regency on 16 subjects with B-thalassemia major using a total sampling technique that met the inclusion criteria. The research instruments used in this study were the Morisky Medication Adherence Scale-8 questionnaire and an examination of anthropometric status. The research analysis used the Spearman correlation test. A p-value &lt;0.05 was considered significant. The results showed that there was a significant results between adherence to iron chelation consumption and height for age (p-value = 0.049 &gt; a 0.05), significant results between adherence to iron chelation consumption with weight for age (p-value = 0.036 &lt; a 0.05), and significant results with weight for height (p-value = 0.001 &lt; a 0.05). This study implies that adherence to iron chelation therapy is essential for thalassemia patients. This study shows that patients more adherent to iron chelation treatment have better anthropometric status.

Xylosyltransferase I mediates the synthesis of proteoglycans with long glycosaminoglycan chains and controls chondrocyte hypertrophy and collagen fibers organization of in the growth plate

Genetic mutations in the Xylt1 gene are associated with Desbuquois dysplasia type II syndrome characterized by sever prenatal and postnatal short stature. However, the specific role of XylT-I in the growth plate is not completely understood. Here, we show that XylT-I is expressed and critical for the synthesis of proteoglycans in resting and proliferative but not in hypertrophic chondrocytes in the growth plate. We found that loss of XylT-I induces hypertrophic phenotype-like of chondrocytes associated with reduced interterritorial matrix. Mechanistically, deletion of XylT-I impairs the synthesis of long glycosaminoglycan chains leading to the formation of proteoglycans with shorter glycosaminoglycan chains. Histological and Second Harmonic Generation microscopy analysis revealed that deletion of XylT-I accelerated chondrocyte maturation and prevents chondrocytes columnar organization and arrangement in parallel of collagen fibers in the growth plate, suggesting that XylT-I controls chondrocyte maturation and matrix organization. Intriguingly, loss of XylT-I induced at embryonic stage E18.5 the migration of progenitor cells from the perichondrium next to the groove of Ranvier into the central part of epiphysis of E18.5 embryos. These cells characterized by higher expression of glycosaminoglycans exhibit circular organization then undergo hypertrophy and death creating a circular structure at the secondary ossification center location. Our study revealed an uncovered role of XylT-I in the synthesis of proteoglycans and provides evidence that the structure of glycosaminoglycan chains of proteoglycans controls chondrocyte maturation and matrix organization.

Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate.

Cleft palate is one of the most common birth defects. Previous studies revealed that multiple factors, including impaired intracellular or intercellular signals, and incoordination of oral organs led to cleft palate, but were little concerned about the contribution of the extracellular matrix (ECM) during palatogenesis. Proteoglycans (PGs) are one of the important macromolecules in the ECM. They exert biological functions through one or more glycosaminoglycan (GAG) chains attached to core proteins. The family with sequence similarity 20 member b (Fam20b) are newly identified kinase-phosphorylating xylose residues that promote the correct assembly of the tetrasaccharide linkage region by creating a premise for GAG chain elongation. In this study, we explored the function of GAG chains in palate development through Wnt1-Cre; Fam20bf/f mice, which exhibited complete cleft palate, malformed tongue, and micrognathia. In contrast, Osr2-Cre; Fam20bf/f mice, in which Fam20b was deleted only in palatal mesenchyme, showed no abnormality, suggesting that failed palatal elevation in Wnt1-Cre; Fam20bf/f mice was secondary to micrognathia. In addition, the reduced GAG chains promoted the apoptosis of palatal cells, primarily resulting in reduced cell density and decreased palatal volume. The suppressed BMP signaling and reduced mineralization indicated an impaired osteogenesis of palatine, which could be rescued partially by constitutively active Bmpr1a. Together, our study highlighted the key role of GAG chains in palate morphogenesis.

Edible Biopolymers from Marine Algae used as an Alternate Packaging material: A Review on their characteristics and properties

Food packaging is estimated to account for two-thirds of all plastic waste. As a result, it is crucial to discover alternative packaging materials that are both environmentally friendly and safe for human health. Marine algae are becoming more well-known and in demand as cutting-edge resources for producing biopolymers like proteins and polysaccharides. Because of their biocompatibility, biodegradability, and lack of toxicity, biopolymers have been suggested as potential sources for food packaging materials. Numerous research has thoroughly examined the extraction, separation, and use of marine biopolymers in the creation of sustainable packaging. Marine algae are also rich in protein and mineral content, they also have anticancer, anti-obesity, and hypolipidemic properties due to the presence of polyunsaturated conjugated fatty acids. The edible films enhance the shelf life of food by controlling moisture without changing the elements of food. The marine algae are collected either in the intertidal or subtidal areas and they will be dried for further process. The edible films are environmentally friendly. The edible film made from marine algae is a mixture of protein, polysaccharides, lipids, and resins. The factors which affect the properties of the edible film are the source of raw material, surface charge, hydrophobicity, polymer chain length, plasticizer type, proportion, and synthesis method. There are numerous research has been conducted to develop edible film using various matrix constituents. This review provides an overview of Marine algae, its process, and edible films, its characteristics, and factors affecting the film.

One-Pot, Photocontrolled Enzymatic Assembly of the Structure-Defined Heterotypic Polyubiquitin Chain.

Heterotypic polyubiquitins are an emerging class of polyubiquitins that have attracted interest because of their potential diversity of structures and physiological functions. There is an increasing demand for structure-defined synthesis of heterotypic chains to investigate the topological factors underlying the intracellular signals that are characteristically mediated by the heterotypic chain. However, the applicability of chemical and enzymatic polyubiquitin synthesis developed to date has been limited by laborious rounds of ligation and purification or by a lack of modularity of the chain structure with respect to the length and the branch position. Here, we established a one-pot, photocontrolled synthesis of structurally defined heterotypic polyubiquitin chains. We designed ubiquitin derivatives with a photolabile protecting group at a lysine residue used for polymerization. Repetitive cycles of linkage-specific enzymatic elongation and photoinduced deprotection of the protected ubiquitin units enabled stepwise addition of ubiquitins with appropriate functionalities to control the length and branching positions. The positional control of branching was achieved without isolation of intermediates, allowing one-pot synthesis of K63 triubiqutin chains and a K63/K48 heterotypic tetraubiquitin chain with defined branching positions. The present study provides a chemical platform for the efficient construction of long polyubiquitin chains with defined branch structures that will facilitate the understanding of the essential relationships between functions and structures of the heterotypic chain that have hitherto been overlooked.

Evaluation of conventional renal function tests in β-thalassemia major patients in Nineveh province

β-thalassemia is an inherited anemia, caused by impaired β-globin chain synthesis. The disease leads to serious health problems unless treated by regular blood transfusion and iron chelating therapy. However, complications from continuous therapy may arise due to iron overload and toxicity of iron chelating therapy, it may affects many organs in the body including the renal system. The present study was directed to study the changes in conventional renal function tests that may occur in β-thalassemia patients. The present study consisted of two groups of β-thalassemia patients; group A, 40 transfusion dependent β-thalassemia patients receiving only regular blood transfusion, age ranged 1-4 years; Group B, 40 transfusion dependent β- thalassemia patients receiving regular blood transfusion and deferroxamine chelation therapy, age ranged 4-20 years old. In addition to a control group C, 40 subjects, age ranged 1-20 years. Blood samples were collected and serum was separated for measurement of creatinine, urea, and ferritin. Urine samples were also collected for measurement of microalbuminuria. There was a significant decrease in serum creatinine, and a significant increase in serum urea in group B when compared with their control (P≤0.01). In addition, there was a significant increase in serum ferritin in groups A and B when compared with their controls (P≤0.01). On the other hand, there were no significant changes in microalbuminuria between groups A and B when compared with their controls. The results of the present study showed no deterioration in renal functions in β-thalassemia patients in both groups A and B regarding serum creatinine and urea in addition to microalbuminuria, although, subclinical alteration in renal functions could be expected in those patients, so that measurement of other early markers of renal dysfunction is occasionally recommended.

Cucurbitacin IIb attenuates cancer cachexia induced skeletal muscle atrophy by regulating the IL-6/STAT3/FoxO signaling pathway.

The main features of cancer cachexia include skeletal muscle atrophy, which can significantly reduce the quality of life of patients. Clinical treatment of cancer cachexia is mainly based on nutritional therapy and physical exercise; medication only improves appetite but does not reverse the symptoms of skeletal muscle wasting. In this work, we systematically studied the underlying molecular mechanisms by which cucurbitacin IIb (CuIIb) ameliorates muscle wasting in cancer cachexia both in vitro and in vivo. CuIIb significantly ameliorated the chief features of cancer cachexia in vivo, alleviating weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reductions. In vitro, CuIIb (10 and 20 μM) dose-dependently attenuated conditioned medium (CM)-induced C2C12 myotube atrophy. Collectively, our findings demonstrated that CuIIb prevented the upregulation of the E3 ubiquitin ligase muscle atrophy Fbox protein (MAFbx), myosin heavy chain (MyHC), and myogenin (MyoG) and impacted protein synthesis and degradation. In addition, CuIIb decreased the phosphorylation of Tyr705 in STAT3 by regulating the IL-6/STAT3/FoxO pathway to reduce skeletal muscle atrophy in cancer cachexia.

Two-Step On-Surface Synthesis of One-Dimensional Nanographene Chains

Controllable fabrication of low-dimensional graphene structures is a matter of scientific and technological interest. To date, significant efforts have been devoted to the fabrication of nanographene chains as well as nanographenes and graphene nanoribbons. Here, we present the on-surface synthesis of one-dimensional (1D) nanographene chains composed of hexa-peri-hexabenzocoronene (HBC) which is a common type of nanographene. Using dibromo-substituted hexaphenylbenzene (Br2-HPB) as a precursor, the 1D HBC nanographene chains are achieved through two reaction steps, namely polymerization and cyclodehydrogenation, on a Au(111) surface, which have been investigated by low-temperature scanning tunneling microscopy. The Br2-HPB molecules deposited on Au(111) are formed into a chiral selective self-assembled layer, and the following thermal annealing at 200–300 °C induces debromination and sequential polymerization of Br2-HPB, leading to the formation of long 1D HPB chains. In particular, we find that the same length 1D HPB chains are selectively ordered in a side-by-side arrangement. Finally, by annealing at 400 °C, HBC planar nanographenes are achieved through the cyclodehydrogenation process of HPB within the long 1D chains. The maximum length of the obtained 1D HBC nanographene chains reached is about 30 nm.

Toward the Development of a Manufacturing Process for Milvexian: Scale-Up Synthesis of the Side Chain

Toward the Development of a Manufacturing Process for Milvexian: Scale-Up Synthesis of the Side Chain

5613312 PLASMATIC MICROPARTICLES AS POTENTIAL BIOMARKERS IN THE PREVENTIVE DIAGNOSIS OF BETA THALASSEMIA

Background: Plasmatic microparticles (MPs) are submicron (0.1–1 μm) extracellular vesicles that shed during plasma membrane remodeling in response to cell activation and apoptosis. Over the years, microparticles have evolved from their initial status being a cellular discharge mechanism, by which the cell got rid of unwanted materials, they are now considered as functional units produced in a regulated manner and having an important role in the maintenance of homeostasis. However, MPs also participate in the pathophysiology of several diseases such as beta thalassemia. It is a hemoglobinopathy characterized by reduced or absent synthesis of the beta-globin chain resulting in the excessive accumulation of unpaired alpha-globin chains which causes structural and functional alterations of the cytoplasmic membrane of thalassemic red blood cells. These alterations induce membrane budding and the release of MPs, which increases the risk of thrombotic complications observed in beta thalassemia patients. Aims: Therefore, our study suggests the research for plasmatic microparticles as potential cellular biomarkers and the establishment of a new innovative and predictive diagnosis strategy in order to avoid the thrombotic complications of beta thalassemia. Methods: Blood samples were taken from polytransfused beta thalassemia major patients clinically diagnosed at the National Bone Marrow Transplant Center in Tunis and from healthy donors. A cellular study was carried out by flow cytometry in order to quantify the apoptotic MPs derived from erythrocytes, platelets and endothelial cells using different antibodies and specific fluorescent dyes. Results: Our results showed a statistically significant increase in the number of apoptotic MPs, which suggests a high rate of apoptosis in the cells of the patients compared to those of the healthy controls. We also found that MPs derived from erythrocytes and endothelial cells were clearly elevated in beta thalassemia patients, suggesting their potential contribution to thrombotic risk. Conclusion: This discovery makes it possible to consider MPs as potential cellular biomarkers for preventive diagnosis in beta thalassemia.

Probabilistic Control of Heterogeneous Swarms Subject to Graph Temporal Logic Specifications: A Decentralized and Scalable Approach

We develop a probabilistic control algorithm, GTLProCo, for swarms of agents with heterogeneous dynamics and objectives, subject to high-level task specifications. The resulting algorithm not only achieves decentralized control of the swarm but also significantly improves scalability over state-of-the-art existing algorithms. Specifically, we study a setting in which the agents move along the nodes of a graph, and the high-level task specifications for the swarm are expressed in a recently-proposed language called graph temporal logic (GTL). By constraining the distribution of the swarm over the nodes of the graph, GTL can specify a wide range of properties, including safety, progress, and response. GTLProCo, with a computational complexity agnostic to the number of agents comprising the swarm, controls the density distribution of the swarm in a decentralized and probabilistic manner. To this end, it synthesizes a time-varying Markov chain modeling the time evolution of the density distribution under the GTL constraints. We first identify a subset of GTL, namely reach-avoid specifications, for which we can reduce the synthesis of such a Markov chain to either linear or semi-definite programs. Then, in the general case, we formulate the synthesis of the Markov chain as a mixed-integer nonlinear program (MINLP).We exploit the structure of the problem to provide an efficient sequential mixed-integer linear programming scheme with trust regions to solve the MINLP. We empirically demonstrate that our sequential scheme is at least three orders of magnitude faster than off-the-shelf MINLP solvers and illustrate the effectiveness of GTLProCo in several swarm scenarios.

Achieving Control over the Reduction/Coupling Dichotomy of N2 by Boron Metallomimetics

We report a detailed computational and experimental study of the fixation and reductive coupling of dinitrogen with low-valent boron compounds. Consistent with our mechanistic findings, the selectivity toward nitrogen fixation or coupling can be controlled through either steric bulk or the reaction conditions, allowing for the on-demand synthesis of nitrogen chains. The electronic structure and intriguing magnetic properties of intermediates and products of the reaction of dinitrogen with borylenes are also elucidated using high-level computational approaches.