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1.
Clin Case Rep ; 12(4): e8749, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38595962

RESUMO

We present a rare case of primary antiphospholipid syndrome in a 38-year-old male who presented with painful digital ischemia. Early initiation of anticoagulation and addition of glucocorticoid led to a significant improvement in the patient.

2.
IDCases ; 36: e01944, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681077

RESUMO

Nalidixic acid-resistant Salmonella enterica serotype Typhi is a well-known cause of enteric fever, and its prevalence is increasing worldwide. However, the incidence of enteric fever complicated by non-immune hemolytic anemia without co-existing thalassemia or glucose-6-phosphate dehydrogenase deficiency is rare. In this case report, we present a case of acute non-immune hemolytic anemia in enteric fever caused by nalidixic acid-resistant Salmonella enterica serotype Typhi.

3.
Food Sci Nutr ; 12(1): 419-429, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268877

RESUMO

Dietary diversity is an indicator of nutrition that has been found positively associated with diet quality, micronutrient adequacy, and improved maternal health and child growth. Due to the cultural responsibility of women in providing food at the household level, their status is very important to perform this role. Hence, this study has been conducted on the status of dietary diversity of the mother and child to understand how it relates to various factors of women in urban settings. Data were obtained from 1978 mother-child pairs living in different cities in Bangladesh. The foods taken by the women and children were categorized into 10 and 7 groups to measure women's dietary diversity (WDD) and children's dietary diversity (CDD), respectively. The study found that more than three-fourths of the mothers and half of the children had low dietary diversity. The household wealth holdings and access to resources by the women were found inadequate, while two-thirds of them had the lowest to medium level of nutritional knowledge. The binomial logistic regression model was used to measure the factors influencing WDD and CDD. The findings also indicated that children's dietary diversity was influenced by the mother's age, education, supportive attitude and behavior of husband, and access to and control over resources. While the household wealth index can enhance both child and mother's dietary variety, nutrition knowledge, dietary counseling, and access to and control over resources can improve maternal dietary diversity. This study recommends improving women's socioeconomic status by increasing their wealth and access to resources and enhancing their nutrition knowledge by providing food and nutrition counseling.

4.
Heliyon ; 10(1): e24268, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38234878

RESUMO

The escalation of healthcare spending in many nations, particularly in emerging countries such as Bangladesh, may be largely attributed to the growing demand for healthcare services. Evidently, there has been a significant expansion in the public funding allocated to the health sector in Bangladesh, intending to enhance health outcomes. Therefore, the purpose of this study was to examine the impact of healthcare expenditure on health outcomes, specifically focusing on the reduction in different mortality rates and the transmission of various infectious diseases. A total of 30 years of data (1990-2019) on the health sector of Bangladesh were collected from different national and international sources. The Vector Autoregression with Exogenous Variables (VARX) model was employed to determine the effects of healthcare expenditure on health outcomes. Results revealed that the per capita health expenditure and the number of doctors showed a significant positive impact on life expectancy and maternal and child health. Also, the government's annual budget on the health sector and number of doctors had a significant positive impact on lowering deaths by Diphtheria, Cholera, Tuberculosis, and Malaria diseases. In order to develop a sustainable healthcare system within the nation, it is imperative for the government to prioritize the allocation of sufficient and effective healthcare funding to cater to the needs of the populace.

5.
Environ Res ; 242: 117640, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007078

RESUMO

Industries today place a high premium on environmentally friendly supplies that may effectively inhibit metal dissolution at a reasonable cost. Hence, in this paper, we assessed the corrosion inhibition effectiveness of the Thiazole derivative namely, 2, 2-Dithio Bisbenzothiazole (DBBT) against mild steel (MS) corrosion in 1 M HCl. Several experimental approaches, including gravimetric analysis, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and surface exploration using scanning electron/atomic force microscopy (SEM/AFM) and contact angle (CA), were utilized to conduct the measurements. In 1 M HCl corrosive medium at 298 K in the subsistence of 800 ppm of DBBT, this experiment indicated DBBT as an environment-friendly and sustainable corrosion inhibitor (CI) for MS, demonstrating an inhibition efficiency (IE %) of 97.71%. To deliver a deeper knowledge of the mechanism behind inhibitive behavior, the calculated thermodynamic and activation characteristics were applied. The calculated Gibbs free energy values indicated that the CI interacted physically and chemically with the MS surface, validating physio-chemical adsorption. The findings of the EIS research revealed that an upsurge in the doses of the CI is escorted by an upsurge in polarization resistance (Rp) from (88.05 → 504.04) Ωcm2, and a diminution in double layer capacitance (Cdl) from (97.46 → 46.33) µFcm-2 at (50 → 800) ppm respectively, affirming the inhibitive potential of DBBT. Additionally, the greatest displacement in Ecorr value being 76.13 mV < 85 mV, indicating that DBBT act as a mixed-form CI. To study the further impacts of DBBT on the inhibition capabilities of the compound under investigation, density functional theory (DFT) and molecular dynamics (MD) simulation were employed. Chemical and electrochemical approaches are in agreement with the computational analysis indicating DBBT is the most efficient CI.


Assuntos
Elétrons , Aço , Corrosão , Adsorção , Concentração de Íons de Hidrogênio
6.
ACS Appl Mater Interfaces ; 16(1): 1234-1242, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38108279

RESUMO

Charge-transfer (CT) interactions between co-facially aligned π-donor/acceptor (π-D/A) arrays engender unique optical and electronic properties that could benefit (supra)molecular electronics and energy technologies. Herein, we demonstrate that a tetragonal prismatic metal-organic cage (MOC18+) having two parallel π-donor tetrakis(4-carboxyphenyl)-Zn-porphyrin (ZnTCPP) faces selectively intercalate planar π-acceptor guests, such as hexaazatriphenylene hexacarbonitrile (HATHCN), hexacyanotriphenylene (HCTP), and napthanelediimide (NDI) derivatives, forming 1:1 πA@MOC18+ inclusion complexes featuring supramolecular π-D/A/D triads. The π-acidity of intercalated π-acceptors (HATHCN ≫ HCTP ≈ NDIs) dictated the nature and strength of their interactions with the ZnTCPP faces, which in turn influenced the binding affinities (Ka) and optical and electronic properties of corresponding πA@MOC18+ inclusion complexes. Owing to its strongest CT interaction with ZnTCPP faces, the most π-acidic HATHCN guest enjoyed the largest Ka (5 × 106 M-1), competitively displaced weaker π-acceptors from the MOC18+ cavity, and generated the highest electrical conductivity (2.1 × 10-6 S/m) among the πA@MOC18+ inclusion complexes. This work demonstrates a unique through-space charge transport capability of πA@MOC18+ inclusion complexes featuring supramolecular π-D/A/D triads, which generated tunable electrical conductivity, which is a rare but much coveted electronic property of such supramolecular assemblies that could further expand their utility in future technologies.

7.
Biomater Sci ; 12(3): 725-737, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38099834

RESUMO

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surfaces by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.


Assuntos
Melanoma , Nanopartículas , Piperazinas , Piridinas , Camundongos , Humanos , Animais , Melanoma/tratamento farmacológico , Simulação de Acoplamento Molecular , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Tensoativos , Portadores de Fármacos/química , Quinase 4 Dependente de Ciclina
8.
bioRxiv ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38045274

RESUMO

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn , and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

9.
Nat Commun ; 14(1): 7524, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980342

RESUMO

TOP3B is stabilized by TDRD3. Hypothesizing that TDRD3 recruits a deubiquitinase, we find that TOP3B interacts with USP9X via TDRD3. Inactivation of USP9X destabilizes TOP3B, and depletion of both TDRD3 and USP9X does not promote further TOP3B ubiquitylation. Additionally, we observe that MIB1 mediates the ubiquitylation and proteasomal degradation of TOP3B by directly interacting with TOP3B independently of TDRD3. Combined depletion of USP9X, TDRD3 and MIB1 causes no additional increase in TOP3B levels compared to MIB1 knockdown alone indicating that the TDRD3-USP9X complex works downstream of MIB1. To comprehend why cells degrade TOP3B in the absence of TDRD3, we measured TOP3Bccs. Lack of TDRD3 increases TOP3Bccs in DNA and RNA, and induced R-loops, γH2AX and growth defect. Biochemical experiments confirm that TDRD3 increases the turnover of TOP3B. Our work provides molecular insights into the mechanisms by which TDRD3 protect cells from deleterious TOP3Bccs which are otherwise removed by TRIM41.


Assuntos
Ubiquitina Tiolesterase , Linhagem Celular Tumoral , Ubiquitinação , Ubiquitina Tiolesterase/metabolismo
10.
Inorg Chem ; 62(46): 18999-19005, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37934947

RESUMO

Electrically conductive porous metal-organic frameworks (MOFs) show great promise in helping advance electronics and clean energy technologies. However, large porosity usually hinders long-range charge transport, an essential criterion of electrical conductivity, underscoring the need for new strategies to combine these two opposing features and realize their diverse potentials. All previous strategies to boost the conductivity of porous MOFs by introducing redox-complementary guest molecules, conducting polymers, and metal nanoparticles have led to a significant loss of frameworks' porosity and surface areas, which could be otherwise exploited to capture additional guests in electrocatalysis and chemiresistive sensing applications. Herein, we demonstrate for the first time that the in situ oxidative polymerization of preloaded 3,4-ethylenedioxythiophene (EDOT) monomers into the polyethylenedioxythiophene (PEDOT) polymer inside the hexagonal cavities of an intrinsically insulating Ni2(NDISA) MOF-74 analogue (NDISA = naphthalenediimide N,N-disalicylate), which easily collapses and becomes amorphous upon drying, simultaneously enhanced the crystallinity, porosity, and electrical conductivity of the resulting PEDOT@Ni2(NDISA) composites. At lower PEDOT loading (∼22 wt %), not only did the Brunauer-Emmett-Teller surface area of the PEDOT@Ni2(NDISA) composite (926 m2/g) more than double from that of evacuated pristine Ni2(NDISA) (387 m2/g), but also its electrical conductivity (1.1 × 10-5 S/cm) soared 105 times from that of the pristine MOF, demonstrating unprecedented dual benefits of our strategy. At higher PEDOT loading (≥33 wt %), the electrical conductivity of Ni2(NDISA)⊃PEDOT composites further increased modestly (10-4 S/cm), but their porosity dropped precipitously as large amounts of PEDOT filled up the hexagonal MOF channels. Thus, our work presents a simple new strategy to simultaneously boost the structural stability, porosity, and electrical conductivity of intrinsically insulating and collapse-prone MOFs by introducing small amounts of conducting polymers that can not only reinforce the MOF scaffolds and prevent them from collapsing but also help create a much coveted non-native property by providing charge carriers and charge transport pathways.

11.
Data Brief ; 51: 109568, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37822883

RESUMO

In the domain of vision-based applications, the importance of text cannot be underestimated due to its natural capacity to provide accurate and comprehensive information. The application of scene text editing systems enables the modification and enhancement of textual material included in natural images while maintaining the integrity of the overall visual layout. The complexity of keeping the original background context and font styles when altering, however, is an extremely difficult challenge considering the changed image must perfectly blend with the original without being altered. This article contains significant simulated data on the dynamic features of digital image editing, advertising, content development, and related fields. The system comprises key components such as 2D simulated text on the styled image (is), text image (it), masking of text (maskt), real background image (tb), real sample image (tf), text skeleton (tsk), and text styled image (tt). The source dataset contains diverse components such as background images, color variations, fonts, and text content, while the synthetic dataset consists of 49,000 randomly generated images. The dataset provides both researchers and practitioners with a rich resource for identifying and evaluating these dynamic features. The dataset is publicly accessible via the link: https://data.mendeley.com/datasets/h9kry9y46s/3.

12.
NAR Cancer ; 5(1): zcad013, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37600974

RESUMO

R-loops are abundant and dynamic structures ubiquitously present in human cells both in the nuclear and mitochondrial genomes. They form in cis in the wake of transcription complexes and in trans apart from transcription complexes. In this review, we focus on the relationship between R-loops and topoisomerases, and cancer genomics and therapies. We summarize the topological parameters associated with the formation and resolution of R-loops, which absorb and release high levels of genomic negative supercoiling (Sc-). We review the deleterious consequences of excessive R-loops and rationalize how human type IA (TOP3B) and type IB (TOP1) topoisomerases regulate and resolve R-loops in coordination with helicase and RNase H enzymes. We also review the drugs (topoisomerase inhibitors, splicing inhibitors, G4 stabilizing ligands) and cancer predisposing genes (BRCA1/2, transcription, and splicing genes) known to induce R-loops, and whether stabilizing R-loops and thereby inducing genomic damage can be viewed as a strategy for cancer treatment.

13.
Proc Natl Acad Sci U S A ; 120(34): e2218483120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37579177

RESUMO

We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.


Assuntos
DNA Topoisomerases Tipo I , Inibidores da Topoisomerase I , Linhagem Celular , DNA Topoisomerases Tipo I/metabolismo , RNA , Inibidores da Topoisomerase I/química
14.
Arch Microbiol ; 205(8): 274, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37401995

RESUMO

Highly hydrophobic compounds like petroleum and their byproducts, once released into the environment, can persist indefinitely by virtue of their ability to resist microbial degradation, ultimately paving the path to severe environmental pollution. Likewise, the accumulation of toxic heavy metals like lead, cadmium, chromium, etc., in the surroundings poses an alarming threat to various living organisms. To remediate the matter in question, the applicability of a biosurfactant produced from the mangrove bacterium Bacillus pumilus NITDID1 (Accession No. KY678446.1) is reported here. The structural characterization of the produced biosurfactant revealed it to be a lipopeptide and has been identified as pumilacidin through FTIR, NMR, and MALDI-TOF MS. The critical micelle concentration of pumilacidin was 120 mg/L, and it showed a wide range of stability in surface tension reduction experiments under various environmental conditions and exhibited a high emulsification index of as much as 90%. In a simulated setup of engine oil-contaminated sand, considerable oil recovery (39.78%) by this biosurfactant was observed, and upon being added to a microbial consortium, there was an appreciable enhancement in the degradation of the used engine oil. As far as the heavy metal removal potential of biosurfactant is concerned, as much as 100% and 82% removal was observed for lead and cadmium, respectively. Thus, in a nutshell, the pumilacidin produced from Bacillus pumilus NITDID1 holds promise for multifaceted applications in the field of environmental remediation.


Assuntos
Bacillus pumilus , Poluentes Ambientais , Petróleo , Biodegradação Ambiental , Lipopeptídeos/química , Bacillus pumilus/genética , Bacillus pumilus/metabolismo , Cádmio , Tensoativos/química , Petróleo/metabolismo
15.
Cancers (Basel) ; 15(10)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37345165

RESUMO

Cholesterol accumulation is documented in various malignancies including breast cancer. Consequently, depleting cholesterol in cancer cells can serve as a viable treatment strategy. We identified the potency of 2-hydroxypropyl-ß-cyclodextrin (HPßCD), a cholesterol-depletor in vitro against two breast cancer cell lines: MCF-7 (Oestrogen-receptor positive, ER+) and MDA-MB-231 (Triple negative breast cancer (TNBC)). The results were then compared against two non-cancerous cell lines using cytotoxic-, apoptosis-, and cholesterol-based assays. Treatment with HPßCD showed preferential and significant cytotoxic potential in cancer cells, inducing apoptosis in both cancer cell lines (p < 0.001). This was mediated due to significant depletion of cholesterol (p < 0.001). We further tested HPßCD in a MF-1 mice (n = 14) xenograft model and obtained 73.9%, 94% and 100% reduction in tumour size for late-, intermediate-, and early-stage TNBC, respectively. We also detected molecular-level perturbations in the expression patterns of several genes linked to breast cancer and cholesterol signalling pathways using RT2-PCR arrays and have identified SFRP1 as a direct binding partner to HPßCD through SPR drug interaction analysis. This work unravels mechanistic insights into HPßCD-induced cholesterol depletion, which leads to intrinsic apoptosis induction. Results from this study potentiate employing cholesterol depletion as a promising unconventional anticancer therapeutic strategy, which warrants future clinical investigations.

16.
Clin Infect Dis ; 77(5): 752-760, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37157867

RESUMO

BACKGROUND: Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMNs rather than strictly PMN counts. METHODS: In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day 5 post-transplant to categorize patients into a high- or a low-pPMN group (>10% or <10% pPMNs). These groups were then used as a predictor of BSIs. RESULTS: A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSIs compared with patients in the high-pPMN group with an odds ratio of 6.5 (95% confidence interval, 2.110-25.07; P = .002). CONCLUSIONS: In patients who receive an allo-HSCT, having <10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sepse , Humanos , Neutrófilos , Estudos Prospectivos , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
17.
Angew Chem Int Ed Engl ; 62(26): e202303819, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37018428

RESUMO

Two-dimensional graphitic metal-organic frameworks (GMOF) often display impressive electrical conductivity chiefly due to efficient through-bond in-plane charge transport, however, less efficient out-of-plane conduction across the stacked layers creates large disparity between two orthogonal conduction pathways and dampens their bulk conductivity. To address this issue and engineer higher bulk conductivity in 2D GMOFs, we have constructed via an elegant bottom-up method the first π-intercalated GMOF (iGMOF1) featuring built-in alternate π-donor/acceptor (π-D/A) stacks of CuII -coordinated electron-rich hexaaminotriphenylene (HATP) ligands and non-coordinatively intercalated π-acidic hexacyano-triphenylene (HCTP) molecules, which facilitated out-of-plane charge transport while the hexagonal Cu3 (HATP)2 scaffold maintained in-plane conduction. As a result, iGMOF1 attained an order of magnitude higher bulk electrical conductivity and much smaller activation energy than Cu3 (HATP)2 (σ=25 vs. 2 S m-1 , Ea =36 vs. 65 meV), demostrating that simultaneous in-plane (through-bond) and out-of-plane (through πD/A stacks) charge transport can generate higher electrical conductivity in novel iGMOFs.


Assuntos
Grafite , Estruturas Metalorgânicas , Condutividade Elétrica , Eletricidade , Elétrons , Engenharia
18.
Nat Commun ; 14(1): 1925, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024461

RESUMO

Topoisomerase IIIα (TOP3A) belongs to the conserved Type IA family of DNA topoisomerases. Here we report that human TOP3A is associated with DNA replication forks and that a "self-trapping" TOP3A mutant (TOP3A-R364W) generates cellular TOP3A DNA cleavage complexes (TOP3Accs). We show that trapped TOP3Accs that interfere with replication, induce DNA damage and genome instability. To elucidate how TOP3Accs are repaired, we explored the role of Spartan (SPRTN), the metalloprotease associated with DNA replication, which digests proteins forming DNA-protein crosslinks (DPCs). We find that SPRTN-deficient cells show elevated TOP3Accs, whereas overexpression of SPRTN lowers cellular TOP3Accs. SPRTN is deubiquitinated and epistatic with TDP2 in response to TOP3Accs. In addition, we found that MRE11 can excise TOP3Accs, and that cell cycle determines the preference for the SPRTN-TDP2 vs. the ATM-MRE11 pathways, in S vs. G2, respectively. Our study highlights the prevalence of TOP3Accs repair mechanisms to ensure normal DNA replication.


Assuntos
DNA Topoisomerases Tipo I , Proteínas de Ligação a DNA , Humanos , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dano ao DNA , Instabilidade Genômica , Ligação Proteica , Reparo do DNA/genética , Replicação do DNA , Diester Fosfórico Hidrolases/metabolismo
19.
J Bioinform Comput Biol ; 21(1): 2250028, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36775259

RESUMO

This work proposes a machine learning-based phylogenetic tree generation model based on agglomerative clustering (PTGAC) that compares protein sequences considering all known chemical properties of amino acids. The proposed model can serve as a suitable alternative to the Unweighted Pair Group Method with Arithmetic Mean (UPGMA), which is inherently time-consuming in nature. Initially, principal component analysis (PCA) is used in the proposed scheme to reduce the dimensions of 20 amino acids using seven known chemical characteristics, yielding 20 TP (Total Points) values for each amino acid. The approach of cumulative summing is then used to give a non-degenerate numeric representation of the sequences based on these 20 TP values. A special kind of three-component vector is proposed as a descriptor, which consists of a new type of non-central moment of orders one, two, and three. Subsequently, the proposed model uses Euclidean Distance measures among the descriptors to create a distance matrix. Finally, a phylogenetic tree is constructed using hierarchical agglomerative clustering based on the distance matrix. The results are compared with the UPGMA and other existing methods in terms of the quality and time of constructing the phylogenetic tree. Both qualitative and quantitative analysis are performed as key assessment criteria for analyzing the performance of the proposed model. The qualitative analysis of the phylogenetic tree is performed by considering rationalized perception, while the quantitative analysis is performed based on symmetric distance (SD). On both criteria, the results obtained by the proposed model are more satisfactory than those produced earlier on the same species by other methods. Notably, this method is found to be efficient in terms of both time and space requirements and is capable of dealing with protein sequences of varying lengths.


Assuntos
Aminoácidos , Aprendizado de Máquina , Filogenia , Sequência de Aminoácidos , Análise por Conglomerados
20.
Environ Sci Pollut Res Int ; 30(12): 33195-33205, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36478548

RESUMO

Waterlogging due to rain-fed floods is considered a natural calamity worldwide that causes lands in the north region of Bangladesh to remain underwater and uncultivable for most crops during the rainy season. This unused wasteland has immense potential for additional earnings for the marginal farmer by converting it to cultivable land through proper utilization by cultivating water chestnuts. Increasing the productivity and efficiency of water chestnut farming in these wastelands would facilitate higher food production for the growing populations. Therefore, this study estimates the farmers' profitability of water chestnut production along with technical efficiency (TE) and land use efficiency (LUE). Primary data from 150 farmers of Natore, Naogaon, and Jamalpur districts were used and stochastic frontier analysis was employed. Results reveal that no farmers had any training in water chestnut farming. Human labor and land use costs incur more than 80% of the total cost and laborers shortage was found due to skin problems working in the water. However, water chestnut farming was profitable in all districts and the average benefit-cost ratio was 1.37. TE results indicate that there was an opportunity to increase the water chestnut production by 20.2% using the same amount of inputs. LUE by the water chestnut farmers was found to be very low; hence, they were using their land inefficiently and this inefficiency was positively affected by farm size and number of family members and negatively affected by age, year of schooling, and income. The study suggests research focusing on improved management of water chestnut without affecting laborers and training to facilitate higher productivity and LUE.


Assuntos
Eleocharis , Humanos , Bangladesh , Agricultura , Fazendas , Verduras
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