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1.
Mar Policy ; 126: 104422, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33568881

RESUMO

COVID-19 is now a major global health crisis, can lead to severe food crisis unless proper measures are taken. Though a number of scientific studies have addressed the possible impacts of COVID-19 in Bangladesh on variety of issues, problems and food crises associated with aquatic resources and communities are missing. Therefore, this study aimed at bridging the gap in the existing situation and challenges of COVID-19 by linking its impact on aquatic food sector and small-scale fisheries with dependent population. The study was conducted based on secondary data analysis and primary fieldwork. Secondary data focused on COVID-19 overview and number of confirmed, recovered and death cases in Bangladesh; at the same time its connection with small-scale fisheries, aquatic food production, demand and supply was analyzed. Community perceptions were elicited to present how the changes felt and how they affected aquatic food system and small-scale fisheries and found devastating impact. Sudden illness, reduced income, complication to start production and input collection, labor crisis, transportation abstraction, complexity in food supply, weak value chain, low consumer demand, rising commodity prices, creditor's pressure were identified as the primary affecting drivers. Dependent people felt the measures taken by the Government should be based on protecting both the health and food security. Scope of alternative income generating opportunities, rationing system, training and motivational program could improve the situation. The study provides insight into policies adopted by the policy makers to mitigate the effects of the pandemic on aquatic food sector and small-scale fisheries.

2.
Plant Cell Environ ; 43(11): 2650-2665, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32744331

RESUMO

Rising tropospheric ozone affects the performance of important cereal crops thus threatening global food security. In this study, genetic variation of wheat regarding its physiological and yield responses to ozone was explored by exposing a diversity panel of 150 wheat genotypes to elevated ozone and control conditions throughout the growing season. Differential responses to ozone were observed for foliar symptom formation quantified as leaf bronzing score (LBS), vegetation indices and yield components. Vegetation indices representing the carotenoid to chlorophyll pigment ratio (such as Lic2) were particularly ozone-responsive and were thus considered suitable for the non-invasive diagnosing of ozone stress. Genetic variation in ozone-responsive traits was dissected by a genome-wide association study (GWAS). Significant marker-trait associations were identified for LBS on chromosome 5A and for vegetation indices (NDVI and Lic2) on chromosomes 6B and 6D. Analysis of linkage disequilibrium (LD) in these chromosomal regions revealed distinct LD blocks containing genes with a putative function in plant redox biology such as cytochrome P450 proteins and peroxidases. This study gives novel insight into the natural genetic variation in wheat ozone response, and lays the foundation for the molecular breeding of tolerant wheat varieties.


Assuntos
Variação Genética/genética , Ozônio/metabolismo , Triticum/genética , Adaptação Fisiológica/genética , Genes de Plantas/genética , Estudos de Associação Genética , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética
3.
Sensors (Basel) ; 20(3)2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991907

RESUMO

It remains elusive why there was only weak and limited ground shaking in Kathmandu valley during the 25 April 2015 Mw 7.8 Gorkha, Nepal, earthquake. Our spectral element numerical simulations show that, during this earthquake, surface topography restricted the propagation of seismic energy into the valley. The mountains diverted the incoming seismic wave mostly to the eastern and western margins of the valley. As a result, we find de-amplification of peak ground displacement in most of the valley interior. Modeling of alternative earthquake scenarios of the same magnitude occurring at different locations shows that these will affect the Kathmandu valley much more strongly, up to 2-3 times more, than the 2015 Gorkha earthquake did. This indicates that surface topography contributed to the reduced seismic shaking for this specific earthquake and lessened the earthquake impact within the valley.

4.
Plant Cell Environ ; 41(12): 2882-2898, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30107647

RESUMO

Monitoring of ozone damage to crops plays an increasingly important role for the food security of many developing countries. Ethylenediurea (EDU) could be a tool to assess ozone damage to vegetation on field scale, but its physiological mode of action remains unclear. This study investigated mechanisms underlying the ozone-protection effect of EDU in controlled chamber experiments. Ozone sensitive and tolerant rice genotypes were exposed to ozone (108 ppb, 7 hr day-1 ) and control conditions. EDU alleviated ozone effects on plant morphology, foliar symptoms, lipid peroxidation, and photosynthetic parameters in sensitive genotypes. Transcriptome profiling by RNA sequencing revealed that thousands of genes responded to ozone in a sensitive variety, but almost none responded to EDU. Significant interactions between ozone and EDU application occurred mostly in ozone responsive genes, in which up-regulation was mitigated by EDU application. Further experiments documented ozone degrading properties of EDU, as well as EDU deposits on leaf surfaces possibly related to surface protection. EDU application did not mitigate the reaction of plants to other abiotic stresses, including iron toxicity, zinc deficiency, and salinity. This study provided evidence that EDU is a surface protectant that specifically mitigates ozone stress without interfering directly with the plants' stress response systems.


Assuntos
Oryza/metabolismo , Ozônio/antagonistas & inibidores , Compostos de Fenilureia/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ferro/metabolismo , Microscopia Eletrônica de Varredura , Oryza/efeitos dos fármacos , Ozônio/metabolismo , Fotossíntese , Estresse Salino , Estresse Fisiológico/efeitos dos fármacos , Zinco/deficiência
5.
Biochem Biophys Res Commun ; 445(2): 463-8, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24530910

RESUMO

Regulation of membrane protein functions due to hydrophobic coupling with a lipid bilayer has been investigated. An energy formula describing interactions between lipid bilayer and integral ion channels with different structures, which is based on the screened Coulomb interaction approximation, has been developed. Here the interaction energy is represented as being due to charge-based interactions between channel and lipid bilayer. The hydrophobic bilayer thickness channel length mismatch is found to induce channel destabilization exponentially while negative lipid curvature linearly. Experimental parameters related to channel dynamics are consistent with theoretical predictions. To measure comparable energy parameters directly in the system and to elucidate the mechanism at an atomistic level we performed molecular dynamics (MD) simulations of the ion channel forming peptide-lipid complexes. MD simulations indicate that peptides and lipids experience electrostatic and van der Waals interactions for short period of time when found within each other's proximity. The energies from these two interactions are found to be similar to the energies derived theoretically using the screened Coulomb and the van der Waals interactions between peptides (in ion channel) and lipids (in lipid bilayer) due to mainly their charge properties. The results of in silico MD studies taken together with experimental observable parameters and theoretical energetic predictions suggest that the peptides induce ion channels inside lipid membranes due to peptide-lipid physical interactions. This study provides a new insight helping better understand of the underlying mechanisms of membrane protein functions in cell membrane leading to important biological implications.


Assuntos
Canais Iônicos/metabolismo , Bicamadas Lipídicas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Canais Iônicos/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Eletricidade Estática
6.
Proc Natl Acad Sci U S A ; 108(31): 12717-22, 2011 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-21768343

RESUMO

Linear rate-equilibrium (RE) relations, also known as linear free energy relations, are widely observed in chemical reactions, including protein folding, enzymatic catalysis, and channel gating. Despite the widespread occurrence of linear RE relations, the principles underlying the linear relation between changes in activation and equilibrium energy in macromolecular reactions remain enigmatic. When examining amphiphile regulation of gramicidin channel gating in lipid bilayers, we noted that the gating process could be described by a linear RE relation with a simple geometric interpretation. This description is possible because the gating process provides a well-understood reaction, in which structural changes in a bilayer-embedded model protein can be studied at the single-molecule level. It is thus possible to obtain quantitative information about the energetics of the reaction transition state and its position on a spatial coordinate. It turns out that the linear RE relation for the gramicidin monomer-dimer reaction can be understood, and the quantitative relation between changes in activation energy and equilibrium energy can be interpreted, by considering the effects of amphiphiles on the changes in bilayer elastic energy associated with channel gating. We are not aware that a similar simple mechanistic explanation of a linear RE relation has been provided for a chemical reaction in a macromolecule. RE relations generally should be useful for examining how amphiphile-induced changes in bilayer properties modulate membrane protein folding and function, and for distinguishing between direct (e.g., due to binding) and indirect (bilayer-mediated) effects.


Assuntos
Gramicidina/química , Canais Iônicos/química , Bicamadas Lipídicas/química , Lipídeos de Membrana/química , Algoritmos , Capsaicina/farmacologia , Cromanos/farmacologia , Transferência de Energia/efeitos dos fármacos , Genisteína/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Ativação do Canal Iônico/efeitos dos fármacos , Cinética , Modelos Químicos , Octoxinol/farmacologia , Fosfatidilcolinas/química , Dobramento de Proteína , Rosiglitazona , Tiazolidinedionas/farmacologia , Troglitazona
7.
Contin Educ ; 4(1): 50-66, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38774901

RESUMO

This article is based on a critical review of the Learning Competency Framework and Approach (LCFA) developed for providing education to the Rohingya refugee children living in refugee camps in Bangladesh. A sectoral approach was adopted to develop the LCFA under the leadership of United Nations Children's Fund (UNICEF). To review the LCFA, a Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis was used as an analytical tool. The SWOT analysis showed that the major strengths of the LCFA include its emphasis on pedagogical aspects, the inclusion of content on life skills, and the scope of engaging communities in the implementation phase. However, the major limitations of the LCFA comprised of lack of contents on post-traumatic mental wellbeing, child abuse, trafficking, and technology. In addition, the volume of content seemed too heavy concerning the duration of the levels. It was not clear if the LCFA was a research-based output, other than consultations. Several challenges were identified by this critical review in implementing the LCFA in the Rohingya refugee camps in Bangladesh. These include a lack of understanding of the Rohingya children's needs, including historical, physical (both geographical and infrastructural), and livelihood, the barrier to comprehending their language and culture, and existing resource constraints for implementing this framework. Considering the Rohingya people's perspectives, this review makes suggestions to ensure the whole education process becomes more operational, effective, successful and sustainable.

8.
Materials (Basel) ; 16(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37687423

RESUMO

Dye-sensitized solar cells (DSSCs) have emerged as a potential candidate for third-generation thin film solar energy conversion systems because of their outstanding optoelectronic properties, cost-effectiveness, environmental friendliness, and easy manufacturing process. The electron transport layer is one of the most essential components in DSSCs since it plays a crucial role in the device's greatest performance. Silver ions as a dopant have drawn attention in DSSC device applications because of their stability under ambient conditions, decreased charge recombination, increased efficient charge transfer, and optical, structural, and electrochemical properties. Because of these concepts, herein, we report the synthesis of pristine TiO2 using a novel green modified solvothermal simplistic method. Additionally, the prepared semiconductor nanomaterials, Ag-doped TiO2 with percentages of 1, 2, 3, and 4%, were used as photoanodes to enhance the device's performance. The obtained nanomaterials were characterized using XRD, FTIR, FE-SEM, EDS, and UV-vis techniques. The average crystallite size for pristine TiO2 and Ag-doped TiO2 with percentages of 1, 2, 3, and 4% was found to be 13 nm by using the highest intensity peaks in the XRD spectra. The Ag-doped TiO2 nanomaterials exhibited excellent photovoltaic activity as compared to pristine TiO2. The incorporation of Ag could assist in successful charge transport and minimize the charge recombination process. The DSSCs showed a Jsc of 8.336 mA/cm2, a Voc of 698 mV, and an FF of 0.422 with a power conversion efficiency (PCE) of 2.45% at a Ag concentration of 4% under illumination of 100 mW/cm2 power with N719 dye, indicating an important improvement when compared to 2% Ag-doped (PCE of 0.97%) and pristine TiO2 (PCE of 0.62%).

9.
PLoS One ; 18(5): e0273592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37163561

RESUMO

Apyrase (APY) is a nucleoside triphosphate (NTP) diphosphohydrolase (NTPDase) which is a member of the superfamily of guanosine diphosphatase 1 (GDA1)-cluster of differentiation 39 (CD39) nucleoside phosphatase. Under various circumstances like stress, cell growth, the extracellular adenosine triphosphate (eATP) level increases, causing a detrimental influence on cells such as cell growth retardation, ROS production, NO burst, and apoptosis. Apyrase hydrolyses eATP accumulated in the extracellular membrane during stress, wounds, into adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and regulates the stress-responsive pathway in plants. This study was designed for the identification, characterization, and for analysis of APY gene expression in Oryza sativa. This investigation discovered nine APYs in rice, including both endo- and ecto-apyrase. According to duplication event analysis, in the evolution of OsAPYs, a significant role is performed by segmental duplication. Their role in stress control, hormonal responsiveness, and the development of cells is supported by the corresponding cis-elements present in their promoter regions. According to expression profiling by RNA-seq data, the genes were expressed in various tissues. Upon exposure to a variety of biotic as well as abiotic stimuli, including anoxia, drought, submergence, alkali, heat, dehydration, salt, and cold, they showed a differential expression pattern. The expression analysis from the RT-qPCR data also showed expression under various abiotic stress conditions, comprising cold, salinity, cadmium, drought, submergence, and especially heat stress. This finding will pave the way for future in-vivo analysis, unveil the molecular mechanisms of APY genes in stress response, and contribute to the development of stress-tolerant rice varieties.


Assuntos
Oryza , Oryza/metabolismo , Apirase/genética , Apirase/metabolismo , Nucleosídeos , Monofosfato de Adenosina , Trifosfato de Adenosina/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica
10.
Curr Aging Sci ; 15(2): 97-109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35043775

RESUMO

Transport of materials and information across cellular boundaries, such as plasma, mitochondrial and nuclear membranes, happens mainly through varieties of ion channels and pumps. Various biophysical and biochemical processes play vital roles. The underlying mechanisms and associated phenomenological lipid membrane transports are linked directly or indirectly to the cell health condition. Mitochondrial membranes (mitochondrial outer membrane (MOM) and mitochondrial inner membrane (MIM)) host crucial cellular processes. Their malfunction is often found responsible for the rise of cell-originated diseases, including cancer, Alzheimer's, neurodegenerative disease, etc. A large number of ion channels active across MOM and MIM are known to belong to vital cell-based structures found to be linked directly to cellular signaling. Hence, their malfunctions are often found to contribute to abnormalities in intracellular communication, which may even be associated with the rise of various diseases. This article aims to pinpoint ion channels that are directly or indirectly linked to especially aging and related abnormalities in health conditions. An attempt has been made to address the natural structures of these channels, their mutated conditions, and the ways we may cause interventions in their malfunctioning. The malfunction of ion channel subunits, especially various proteins, involved directly in channel formation and/or indirectly in channel stabilization leads to the rise of various channel-specific diseases, which are known as channelopathies. Channelopathies in aging will be discussed briefly. This mini-review may be found as an important reference for drug discovery scientists dealing with aging-related diseases.


Assuntos
Canalopatias , Doenças Neurodegenerativas , Envelhecimento , Canalopatias/metabolismo , Humanos , Canais Iônicos/metabolismo , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo
11.
Biotechnol Rep (Amst) ; 35: e00740, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35646621

RESUMO

It is essential to develop high salt-tolerant rice varieties in order to cultivate the salt-affected lands. In this study, Na+/H+ exchanger 1 (NHX1) gene isolated from Vigna radiata L. Wilczek was transferred in Bangladesh Rice Research Institute (BRRI) developed two indica rice genotypes BRRI Dhan28 and BRRI Dhan29 using in-planta approach for improvement of salinity tolerance. Embryonic axes of matured dehusked rice seeds were injured and co-cultivated with Agrobacterium strain harboring VrNHX1 gene and finally regenerated. GUS histochemical assay and PCR amplification of GUS-a and VrNHX1 were performed to confirm the transformation. Expression confirmation was done by semi-quantitative RT-PCR. Under salinity stress, transgenic lines showed higher chlorophyll, relative water content and decreased electrolyte leakage, proline content, lipid peroxidation level, and catalase enzyme activity which represent the better physiology than control plants. Moreover, under salinity stress (150 mM), transgenic lines exhibited superior growth and salt tolerant than non-transgenic plants.

12.
ACS Appl Bio Mater ; 5(6): 2431-2460, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35583460

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2, a ribonucleic acid (RNA) virus that emerged less than two years ago but has caused nearly 6.1 million deaths to date. Recently developed variants of the SARS-CoV-2 virus have been shown to be more potent and expanded at a faster rate. Until now, there is no specific and effective treatment for SARS-CoV-2 in terms of reliable and sustainable recovery. Precaution, prevention, and vaccinations are the only ways to keep the pandemic situation under control. Medical and scientific professionals are now focusing on the repurposing of previous technology and trying to develop more fruitful methodologies to detect the presence of viruses, treat the patients, precautionary items, and vaccine developments. Nanomedicine or nanobased platforms can play a crucial role in these fronts. Researchers are working on many effective approaches by nanosized particles to combat SARS-CoV-2. The role of a nanobased platform to combat SARS-CoV-2 is extremely diverse (i.e., mark to personal protective suit, rapid diagnostic tool to targeted treatment, and vaccine developments). Although there are many theoretical possibilities of a nanobased platform to combat SARS-CoV-2, until now there is an inadequate number of research targeting SARS-CoV-2 to explore such scenarios. This unique mini-review aims to compile and elaborate on the recent advances of nanobased approaches from prevention, diagnostics, treatment to vaccine developments against SARS-CoV-2, and associated challenges.


Assuntos
COVID-19 , Nanoestruturas , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Humanos , Nanoestruturas/uso terapêutico , Pandemias/prevenção & controle , SARS-CoV-2/genética , Desenvolvimento de Vacinas
13.
Membranes (Basel) ; 11(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808204

RESUMO

We recently published two novel findings where we found the chemotherapy drugs (CDs) thiocolchicoside (TCC) and taxol to induce toroidal type ion pores and the antimicrobial peptide gramicidin S (GS) to induce transient defects in model membranes. Both CD pores and GS defects were induced under the influence of an applied transmembrane potential (≈100 mV), which was inspected using the electrophysiology record of membrane currents (ERMCs). In this article, I address the regulation of the membrane adsorption and pore formation of CDs due to GS-induced possible alterations of lipid bilayer physical properties. In ERMCs, low micromolar (≥1 µM) GS concentrations in the aqueous phase were found to cause an induction of defects in lipid bilayers, but nanomolar (nM) concentration GS did nothing. For the binary presence of CDs and GS in the membrane-bathing aqueous phase, the TCC pore formation potency is found to increase considerably due to nM concentration GS in buffer. This novel result resembles our recently reported finding that due to the binary aqueous presence of two AMPs (gramicidin A or alamethicin and GS), the pore or defect-forming potency of either AMP increases considerably. To reveal the underlying molecular mechanisms, the influence of GS (0-400 nM) on the quantitative liposome (membrane) adsorption of CD molecules, colchicine and TCC, was tested. I used the recently patented direct detection method, which helps detect the membrane active agents directly at the membrane in the mole fraction relative to its concentrations in aqueous phase. We find that GS, at concentrations known to do nothing to the lipid bilayer electrical barrier properties in ERMCs, increases the membrane adsorption (membrane uptake) of CDs considerably. This phenomenological finding along with the GS effects on CD-induced membrane conductance increase helps predict an important conclusion. The binary presence of AMPs alongside CDs in the lipid membrane vicinity may work toward enhancing the physical adsorption and pore formation potency of CDs in lipid bilayers. This may help understand why CDs cause considerable cytotoxicity.

14.
Saudi J Biol Sci ; 28(5): 3100-3109, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34025185

RESUMO

Chemotherapy drugs (CDs), e.g. colchicine derivative thiocolchicoside (TCC) and taxol, have been found to physically bind with lipid bilayer membrane and induce ion pores. Amphiphiles capsaicin (Cpsn) and triton X-100 (TX100) are known to regulate lipid bilayer physical properties by altering bilayer elasticity and lipid monolayer curvature. Both CDs and amphiphiles are predicted to physically accommodate alongside lipids in membrane to exert their membrane effects. The effects of their binary accommodation in the lipid membrane are yet to be known. Firstly, we have performed experimental studies to inspect whether membrane adsorption of CDs (colchicine or TCC) gets regulated due to any membrane effects of Cpsn or TX100. We find that the aqueous phase presence of these amphiphiles, known to reduce the membrane stiffness, works towards enhancing the membrane adsorption of CDs. Our recently patented technology 'direct detection method' helps address the membrane adsorption mechanisms. Secondly, in electrophysiology records, we measured the amphiphile effects on the potency of ion channel induction due to CDs. We find that amphiphiles increase the CD induced channel induction potency. Specifically, the membrane conductance, apparently due to the ion channel induction by the TCC, increases substantially due to the Cpsn or TX100 induced alterations of the bilayer physical properties. Thus we may conclude that the binary presence of CDs and amphiphiles in lipid membrane may influence considerably in CD's membrane adsorption, as well as the membrane effects, such as ion pore formation.

15.
Membranes (Basel) ; 11(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34564489

RESUMO

Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the necessary expertise and interests in computer science techniques including versatile algorithms have started covering a multitude of physiological aspects including especially evolution, mutations, and genomics of functional channels and channel subunits. In these focused research areas, the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) algorithms and associated models have been found very popular. With the help of available articles and information, this review provide an introduction to this novel research trend. Ion channel understanding is usually made considering the structural and functional perspectives, gating mechanisms, transport properties, channel protein mutations, etc. Focused research on ion channels and related findings over many decades accumulated huge data which may be utilized in a specialized scientific manner to fast conclude pinpointed aspects of channels. AI, ML, and DL techniques and models may appear as helping tools. This review aims at explaining the ways we may use the bioinformatics techniques and thus draw a few lines across the avenue to let the ion channel features appear clearer.

16.
Membranes (Basel) ; 11(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209282

RESUMO

Chemotherapy drugs (CDs) disrupt the lipid membrane's insulation properties by inducing stable ion pores across bilayer membranes. The underlying molecular mechanisms behind pore formation have been revealed in this study using several methods that confirm molecular interactions and detect associated energetics of drugs on the cell surface in general and in lipid bilayers in particular. Liposome adsorption and cell surface binding of CD colchicine has been demonstrated experimentally. Buffer dissolved CDs were considerably adsorbed in the incubated phospholipid liposomes, measured using the patented 'direct detection method'. The drug adsorption process is regulated by the membrane environment, demonstrated in cholesterol-containing liposomes. We then detailed the phenomenology and energetics of the low nanoscale dimension cell surface (membrane) drug distribution, using atomic force microscopy (AFM) imaging what addresses the surface morphology and measures adhesion force (reducible to adhesive energy). Liposome adsorption and cell surface binding data helped model the cell surface drug distribution. The underlying molecular interactions behind surface binding energetics of drugs have been addressed in silico numerical computations (NCs) utilizing the screened Coulomb interactions among charges in a drug-drug/lipid cluster. Molecular dynamics (MD) simulations of the CD-lipid complexes detected primarily important CD-lipid electrostatic and van der Waals (vdW) interaction energies. From the energetics point of view, both liposome and cell surface membrane adsorption of drugs are therefore obvious findings. Colchicine treated cell surface AFM images provide a few important phenomenological conclusions, such as drugs bind generally with the cell surface, bind independently as well as in clusters of various sizes in random cell surface locations. The related adhesion energy decreases with increasing drug cluster size before saturating for larger clusters. MD simulation detected electrostatic and vdW and NC-derived charge-based interactions explain molecularly of the cause of cell surface binding of drugs. The membrane binding/association of drugs may help create drug-lipid complexes with specific energetics and statistically lead to the creation of ion channels. We reveal here crucial molecular understanding and features of the pore formation inside lipid membranes that may be applied universally for most of the pore-forming existing agents and novel candidate drugs.

17.
Membranes (Basel) ; 12(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35054563

RESUMO

We aim to discover diagnostic tools to detect phosphatidylserine (PS) externalization on apoptotic cell surface using PS binding aptamers, AAAGAC and TAAAGA, and hence to understand chemotherapy drug efficacy when inducing apoptosis into cancer cells. The entropic fragment-based approach designed aptamers have been investigated to inspect three aspects: lipid specificity in aptamers' membrane binding and bilayer physical properties-induced regulation of binding mechanisms, the apoptosis-induced cancer cell surface binding of aptamers, and the aptamer-induced cytotoxicity. The liposome binding assays show preferred membrane binding of aptamers due to presence of PS in predominantly phosphatidylcholine-contained liposomes. Two membrane stiffness reducing amphiphiles triton X-100 and capsaicin were found to enhance membrane's aptamer adsorption suggesting that bilayer physical properties influence membrane's adsorption of drugs. Microscopic images of fluorescence-tagged aptamer treated LoVo cells show strong fluorescence intensity only if apoptosis is induced. Aptamers find enhanced PS molecules to bind with on the surface of apoptotic over nonapoptotic cells. In cytotoxicity experiments, TAAAGA (over poor PS binding aptamer CAGAAAAAAAC) was found cytotoxic towards RBL cells due to perhaps binding with nonapoptotic externalized PS randomly and thus slowly breaching plasma membrane integrity. In these three experimental investigations, we found aptamers to act on membranes at comparable concentrations and specifically with PS binding manner. Earlier, we reported the origins of actions through molecular mechanism studies-aptamers interact with lipids using mainly charge-based interactions. Lipids and aptamers hold distinguishable charge properties, and hence, lipid-aptamer association follows distinguishable energetics due to electrostatic and van der Waals interactions. We discover that our PS binding aptamers, due to lipid-specific interactions, appear as diagnostic tools capable of detecting drug-induced apoptosis in cancer cells.

18.
Acta Histochem Cytochem ; 43(1): 9-17, 2010 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-20300219

RESUMO

Alopecia areata (AAR) and androgenetic alopecia (AGA) are two major forms of alopecia based on altered hair growth condition. In general, the cell cycle is regulated by several mechanisms including the stem cell factor/c-kit signaling. To assess a role for stem cell activity in alopecia, we performed histopathological, immunohistochemical, and semiquantitative analyses of c-kit as well as Ki-67 in scalp biopsy specimens obtained from 14 patients with AAR, 18 patients with AGA, and 6 age-matched control subjects, using the specific antibodies. Formalin-fixed, paraffin-embedded skin sections were examined. Immunoreactivities for Ki-67 and c-kit were localized in keratinocytes and melanocytes in the outermost layer of hair follicles. The mean length of hair follicles was significantly shorter in the AAR and AGA groups than in the control group. The mean number of Ki-67-immunoreactive cells per follicle was significantly reduced in the AAR and AGA groups as compared with the control group. The mean number of c-kit-immunoreactive cells per follicle was significantly increased in the AAR and AGA groups as compared with the control group. Our results indicate that c-kit is upregulated in the hair follicle cells in these forms of alopecia, and suggest that the upregulation reflects a negative feedback mechanism in response to possible downregulation of the ligand stem cell factor.

19.
J Mol Graph Model ; 95: 107502, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31805474

RESUMO

Membrane-active agents (MAAs), such as antimicrobial peptides (AMPs) and chemotherapy drugs (CDs), induce ion pores/channels inside lipid bilayer membrane, as confirmed by standard electrophysiology experiments. A novel experimental method is described which detects agents directly at the membrane as confirmed for MAAs, CDs and aptamers. MAAs exhibit characteristic 'charge based' interactions with lipids. Electrostatic (ES) and van der Waals (vdW) contributions to the interaction energies have been estimated using molecular dynamics (MD) simulations. These results are consistent with the screened Coulomb interaction predictions recently developed for lipid bilayer binding of integral AMP channels. Energy- and distance-dependence of MAA-lipid interactions from MD simulations are represented by universal probability functions. A generalized model of MAA-lipid interactions is developed based on the charge and geometrical profiles of the participating lipids and AMPs. The corresponding driving force correlates directly with the stability of MAA-lipid structures as observed in electrophysiology experiments. We conclude that MAAs and similar agents that target lipid membranes exhibit physiological effects mainly due to ES and vdW interactions determined by their charge profiles.


Assuntos
Bicamadas Lipídicas , Preparações Farmacêuticas , Simulação de Dinâmica Molecular , Proteínas Citotóxicas Formadoras de Poros , Eletricidade Estática
20.
Data Brief ; 29: 105138, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32016146

RESUMO

We address drug interactions with lipids using in silico simulations and in vitro experiments. The data article provides extended explanations on molecular mechanisms behind membrane action of membrane-active agents (MAAs): antimicrobial peptides and chemotherapy drugs. Complete interpretation of the data is found in the associated original article 'charge-based interactions of antimicrobial peptides and general drugs with lipid bilayers' [1]. Data on molecular dynamic simulations of the drug lipid complexes are provided. Additional data and information are provided here to explain the connectivity among various information and techniques used for understanding of the membrane action and/or binding of MAAs including aptamers. Brief explanation has been provided on the possibility of achieving a converted triangle from newly discovered quadrangle, sides of which explain four different phenomena: 'membrane effects', 'detection and quantification', 'origin of energetics' and 'structure stability' while drug effects occur. Triangle or quadrangle corners represent various techniques that were applied.

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