Effect of membrane tension on antimicrobial peptide PGLa-induced pore formation in lipid bilayers.

The osmotic pressure (Π) method has recently been developed to quantitatively examine the effect of membrane tension (σ) on pore formation in giant unilamellar vesicles (GUVs) induced by antimicrobial peptides (AMPs). Here, we used the Π method to reveal the effect of σ on the interaction of an AMP, PGLa, with lipid bilayers comprising dioleoylphosphatidylglycerol (DOPG) and dioleoylphosphatidylcholine (DOPC) (4/6). PGLa induced leakage of fluorescent probes from single GUVs under Π, indicating nanopore formation. Membrane tension did not transform a PGLa-induced nanopore into a micropore nor cause GUV burst up to 3.4 mN/m, which is in contrast with the effect of σ on another AMP, magainin 2-induced pore formation, where lower σ resulted in GUV burst. The fraction of leaking GUVs at a specific time increased with increasing σ, indicating that the rate of PGLa-induced pore formation increases with increasing σ. The rate of transfer of fluorescent probe-labeled PGLa across the lipid bilayer without pore formation also increased with increasing σ. PGLa-induced pore formation requires a symmetric distribution of peptides in both leaflets of the GUV bilayer, and thus we infer that the increase in the rate of PGLa transfer from the outer leaflet to the inner leaflet underlies the increase in the rate of pore formation with increasing σ. On the basis of these results, we discuss the difference between the effect of σ on nanopore formation in GUV membranes induced by PGLa and that by magainin 2.

Relationship between antimicrobial peptides-induced cell membrane damage and bactericidal activity.

Most antimicrobial peptides (AMPs) act by killing bacterial cells. However, there is little information regarding the required interaction time between AMPs and bacterial cells to exert the bactericidal activity. One of the causes of the bactericidal activity is considered to be cell membrane damage, although little direct evidence is available. Here, we investigated the relationship between AMP-induced cell membrane damage in Escherichia coli and AMP-induced cell death at the single-cell level. Magainin 2, lactoferricin B, and PGLa were selected as the AMPs. First, we examined the interaction time (t) of AMPs with cells required to induce cell death using the single-cell analysis. The fraction of microcolonies containing only a single cell, Psingle (t), which indicates the fraction of dead cells, increased with time to reach ∼1 in a short time (≤5 min). Then, we examined the interaction between AMPs and single cells using confocal laser scanning microscopy in the presence of membrane-impermeable SYTOX green. Within a short time interaction, the fluorescence intensity of the cells due to SYTOX green increased, indicating that AMPs induced cell membrane damage through which the dye entered the cytoplasm. The fraction of cells in which SYTOX green entered the cytoplasm among all examined cells after the interaction time (t), Pentry (t), increased with time, reaching ∼1 in a short time (≤5 min). The values of Psingle (t) and Pentry (t) were similar at t ≥ 3 min for all AMPs. The bindings of AMPs to cells were largely reversible, whereas the AMP-induced cell membrane damages were largely irreversible because SYTOX green entered the cells after dilution of AMP concentration. Based on these results, we conclude that the rapid, substantial membrane permeabilization of cytoplasmic contents after a short interaction time with AMPs and the residual damage after dilution induce cell death.

Statistical Bioinformatics to Uncover the Underlying Biological Mechanisms That Linked Smoking with Type 2 Diabetes Patients Using Transcritpomic and GWAS Analysis.

Type 2 diabetes (T2D) is a chronic metabolic disease defined by insulin insensitivity corresponding to impaired insulin sensitivity, decreased insulin production, and eventually failure of beta cells in the pancreas. There is a 30-40 percent higher risk of developing T2D in active smokers. Moreover, T2D patients with active smoking may gradually develop many complications. However, there is still no significant research conducted to solve the issue. Hence, we have proposed a highthroughput network-based quantitative pipeline employing statistical methods. Transcriptomic and GWAS data were analysed and obtained from type 2 diabetes patients and active smokers. Differentially Expressed Genes (DEGs) resulted by comparing T2D patients' and smokers' tissue samples to those of healthy controls of gene expression transcriptomic datasets. We have found 55 dysregulated genes shared in people with type 2 diabetes and those who smoked, 27 of which were upregulated and 28 of which were downregulated. These identified DEGs were functionally annotated to reveal the involvement of cell-associated molecular pathways and GO terms. Moreover, protein-protein interaction analysis was conducted to discover hub proteins in the pathways. We have also identified transcriptional and post-transcriptional regulators associated with T2D and smoking. Moreover, we have analysed GWAS data and found 57 common biomarker genes between T2D and smokers. Then, Transcriptomic and GWAS analyses are compared for more robust outcomes and identified 1 significant common gene, 19 shared significant pathways and 12 shared significant GOs. Finally, we have discovered protein-drug interactions for our identified biomarkers.

Implementing a digital human resources management tool in the government health sector in Bangladesh: a policy content analysis.

INTRODUCTION: In Bangladesh, to address the challenges of ensuring adequate human resources for health (HRH), the government began implementing a digital tool for HRH management in 2017. However, evidence suggests institutionalizing such tools in low-and-middle-income countries is impeded by policy aspects like implementation strategy and poor regulatory framework. Therefore, we aimed to explore factors in the current policy landscape that might facilitate and challenge the implementation of the tool in Bangladesh. METHODS: We conducted a review of policies related to ICT implementation and human resources management in the health sector in Bangladesh using qualitative content analysis method. Ten policies have been identified, and extensive reading was done to ascertain common themes and patterns. A document analysis matrix was developed to synthesize and help interpret the findings. RESULTS: Regarding facilitators, strong upstream level commitments were reflected in the content of policies in terms of setting out specific objectives, targets, timelines, and budget allocation. However, the lack of explicit monitoring strategy and extent of stakeholders' engagement was not well-defined, ultimately creating chances for impeding downstream implementation. In addition, effective coordination among stakeholders and different HRH and ICT policies could be strengthened. DISCUSSION: Findings support the current discourse that national commitment plays a vital role in the integration of ICTs in health services. However, well-defined monitoring strategy and inter-ministry and intra-ministry policy coordination are crucial.

Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review.

Antimicrobial resistance has emerged as a global health crisis and, therefore, new drug discovery is a paramount need. Cannabis sativa contains hundreds of chemical constituents produced by secondary metabolism, exerting outstanding antimicrobial, antiviral, and therapeutic properties. This paper comprehensively reviews the antimicrobial and antiviral (particularly against SARS-CoV-2) properties of C. sativa with the potential for new antibiotic drug and/or natural antimicrobial agents for industrial or agricultural use, and their therapeutic potential against the newly emerged coronavirus disease (COVID-19). Cannabis compounds have good potential as drug candidates for new antibiotics, even for some of the WHO's current priority list of resistant pathogens. Recent studies revealed that cannabinoids seem to have stable conformations with the binding pocket of the Mpro enzyme of SARS-CoV-2, which has a pivotal role in viral replication and transcription. They are found to be suppressive of viral entry and viral activation by downregulating the ACE2 receptor and TMPRSS2 enzymes in the host cellular system. The therapeutic potential of cannabinoids as anti-inflammatory compounds is hypothesized for the treatment of COVID-19. However, more systemic investigations are warranted to establish the best efficacy and their toxic effects, followed by preclinical trials on a large number of participants.

Role of Membrane Potential on Entry of Cell-Penetrating Peptide Transportan 10 into Single Vesicles.

Cell-penetrating peptides (CPPs) can translocate across plasma membranes to enter the cytosol of eukaryotic cells without decreasing cell viability. We revealed the mechanism underlying this translocation by examining the effect of membrane potential, φm, on the entry of a CPP, transportan 10 (TP10), into the lumen of single giant unilamellar vesicles (GUVs). For this purpose, we used the single GUV method to detect the entry of carboxyfluorescein (CF)-labeled TP10 (CF-TP10) into the lumen of single GUVs. First, we used various K+ concentration differences to apply different negative membrane potentials on single GUVs containing gramicidin A in their membrane and confirmed these potentials using the φm-sensitive fluorescent probe 3,3'-dihexyloxacarbocyanine iodine. The fluorescence intensity of the GUV membranes (i.e., the rim intensity) due to 3,3'-dihexyloxacarbocyanine iodine increased with |φm| up to 118 mV, and its dependence on |φm| less than 28 mV agreed with a theoretical estimation (i.e., the dye concentration in the inner leaflet of a GUV is larger than that in the outer leaflet according to the Boltzmann distribution). We then examined the effect of φm on the entry of CF-TP10 into GUVs using single GUVs containing small GUVs or large unilamellar vesicles inside the mother GUV lumen. We found that CF-TP10 entered the GUV lumen without pore formation and the rate of entry of CF-TP10 into the GUV lumen, Ventry, increased with an increase in |φm|. The rim intensity due to CF-TP10 increased with an increase in |φm|, indicating that the CF-TP10 concentration in the inner leaflet of the GUV increased with |φm|. These results indicate that the φm-induced elevation in Ventry can be explained by the increase in CF-TP10 concentration in the inner leaflet with |φm|. We discuss the mechanism underlying this effect of membrane potential based on the pre-pore model of the translocation of CF-TP10 across a GUV membrane.

Membrane potential is vital for rapid permeabilization of plasma membranes and lipid bilayers by the antimicrobial peptide lactoferricin B.

Lactoferricin B (LfcinB) is a cationic antimicrobial peptide, and its capacity to damage the bacterial plasma membrane is suggested to be a main factor in LfcinB's antimicrobial activity. However, the specific processes and mechanisms in LfcinB-induced membrane damage are unclear. In this report, using confocal laser-scanning microscopy, we examined the interaction of LfcinB with single Escherichia coli cells and spheroplasts containing the water-soluble fluorescent probe calcein in the cytoplasm. LfcinB induced rapid calcein leakage from single E. coli cells and from single spheroplasts, indicating that LfcinB interacts directly with the plasma membrane and induces its rapid permeabilization. The proton ionophore carbonyl cyanide m-chlorophenylhydrazone suppressed this leakage. Next, we used the single giant unilamellar vesicle (GUV) method to examine LfcinB's interaction with GUVs comprising polar lipid extracts of E. coli containing a water-soluble fluorescent probe, Alexa Fluor 647 hydrazide (AF647). We observed that LfcinB stochastically induces local rupture in single GUVs, causing rapid AF647 leakage; however, higher LfcinB concentrations were required for AF647 leakage from GUVs than from E. coli cells and spheroplasts. To identify the reason for this difference, we examined the effect of membrane potential on LfcinB-induced pore formation, finding that the rate of LfcinB-induced local rupture in GUVs increases greatly with increasing negative membrane potential. These results indicate that membrane potential plays an important role in LfcinB-induced local rupture of lipid bilayers and rapid permeabilization of E. coli plasma membranes. On the basis of these results, we discuss the mode of action of LfcinB's antimicrobial activity.

Elementary processes for the entry of cell-penetrating peptides into lipid bilayer vesicles and bacterial cells.

Cell-penetrating peptides (CPPs) can translocate across the plasma membrane of living eukaryotic cells and enter the cytosol without significantly affecting cell viability. Consequently, CPPs have been used for the intracellular delivery of biological cargo such as proteins and oligonucleotides. However, the mechanisms underlying the translocation of CPPs across the plasma membrane remain unclear. In this mini-review, we summarize the experimental results regarding the entry of CPPs into lipid bilayer vesicles obtained using three methods: the large unilamellar vesicle (LUV) suspension method, the giant unilamellar vesicle (GUV) suspension method, and the single GUV method. The advantages and disadvantages of these methods are also discussed. Experimental results to date clearly indicate that CPPs can translocate across lipid bilayers and enter the vesicle lumen. Three models for the mechanisms and pathways by which CPPs translocate across lipid bilayers are described: (A) through pores induced by CPPs, (B) through transient prepores, and (C) via formation of inverted micelles. Both the pathway of translocation and the efficiency of entry of CPPs depend on the lipid composition of the bilayer and the type of CPP. We also describe the interaction of CPPs with bacterial cells. Some CPPs have strong antimicrobial activities. There are two modes of action of CPPs on bacterial cells: CPPs can induce damage to the plasma membrane and thus increase permeability, or CPPs enter the cytosol of bacterial cells without damaging the plasma membrane. The information currently available on the elementary processes by which CPPs enter lipid bilayer vesicles and bacterial cells is valuable for elucidating the mechanisms of entry of CPPs into the cytosol of various eukaryotic cells.

Entry of a Six-Residue Antimicrobial Peptide Derived from Lactoferricin B into Single Vesicles and Escherichia coli Cells without Damaging their Membranes.

Lactoferricin B (LfcinB) and shorter versions of this peptide have antimicrobial activity. However, the elementary processes of interactions of these peptides with lipid membranes and bacteria are still not well understood. To elucidate the mechanism of their antimicrobial activity, we investigated the interactions of LfcinB (4-9) (its sequence of RRWQWR) with Escherichia coli cells and giant unilamellar vesicles (GUVs). LfcinB (4-9) and lissamine rhodamine B red-labeled LfcinB (4-9) (Rh-LfcinB (4-9)) did not induce an influx of a membrane-impermeant fluorescent probe, SYTOX green, from the outside of E. coli cells into their cytoplasm, indicating that no damage occurred in their plasma membrane. To examine the activity of LfcinB (4-9) to enter E. coli cytoplasm, we investigated the interaction of Rh-LfcinB (4-9) with single cells of E. coli containing calcein using confocal microscopy. We found that Rh-LfcinB (4-9) entered the cytoplasm without leakage of calcein. Next, we investigated the interactions of Rh-LfcinB (4-9) with single GUVs of dioleoylphosphatidylglycerol (DOPG) and dioleoylphosphatidylcholine (DOPC) mixtures containing a fluorescent probe, Alexa Fluor 647 hydrazide (AF647), using the single GUV method. The results indicate that Rh-LfcinB (4-9) outside the GUV translocated through the GUV membrane and entered its lumen without leakage of AF647. Interaction of Rh-LfcinB (4-9) with DNA increased its fluorescence intensity greatly. Therefore, we can conclude that Rh-LfcinB (4-9) can translocate across lipid membrane regions of the plasma membrane of E. coli cells to enter their cytoplasm without leakage of calcein and its antimicrobial activity is not due to damage of their plasma membranes.

Low-pH-Induced Lamellar to Bicontinuous Primitive Cubic Phase Transition in Dioleoylphosphatidylserine/Monoolein Membranes.

Electrostatic interactions (EIs) play important roles in the structure and stability of inverse bicontinuous cubic (QII) phases of lipid membranes. We examined the effect of pH on the phase of dioleoylphosphatidylserine (DOPS)/monoolein (MO) membranes at low ionic strengths using small-angle X-ray scattering (SAXS). We found that the phase transitions from lamellar liquid-crystalline (Lα) to primitive cubic (QIIP) phases in DOPS/MO (2/8 molar ratio) membranes occurred in buffers containing 50 mM NaCl at and below the final pH of 2.75 as the pH of the membrane suspension was decreased from a neutral value. The kinetic pathway of this transition was revealed using time-resolved SAXS with a stopped-flow apparatus. The first step is a rapid transition from the Lα phase to the hexagonal II (HII) phase, and the second step is a slow transition from the HII phase to the QIIP phase. We determined the rate constants of the first step, k1, and of the second step, k2, by analyzing the time course of SAXS intensities quantitatively. The k1 value increased with temperature. The analysis of this result provided the values of its apparent activation energy, which were constant over temperature but increased with pH. This can be explained by an EI effect on the free energy of the transition state. In contrast, the k2 value decreased with temperature, indicating that the true activation energy increased with temperature. These experimental results were analyzed using the theory of the activation energy of phase transitions of lipid membranes when the free energy of the transition state depends on temperature. On the basis of these results, we discussed the mechanism of this phase transition.

Effects of Mechanical Properties of Lipid Bilayers on the Entry of Cell-Penetrating Peptides into Single Vesicles.

The translocation of cell-penetrating peptides (CPPs) through plasma membranes of living cells is an important physiological phenomenon in biomembranes. To reveal the mechanism underlying the translocation of a CPP, transportan 10 (TP10), through lipid bilayers, we examined the effects of the mechanical properties of lipid bilayers on the entry of carboxyfluorescein (CF)-labeled TP10 (CF-TP10) into a giant unilamellar vesicle (GUV) using the single GUV method. First, we examined the effect of lateral tension in membranes on the entry of CF-TP10 into single GUVs comprising a mixture of dioleoylphosphatidylglycerol (DOPG) and dioleoylphosphatidylcholine (DOPC) (2/8). CF-TP10 entered the GUV lumen before the membrane permeation of Alexa Fluor 647 hydrazide (AF647) from the GUV and thus before pore formation in the membrane. The fraction of entry of CF-TP10 before pore formation and the rate of membrane rupture increased with tension. The CF-TP10-induced fractional change in the membrane area increased continuously with time until membrane rupture, but it increased more slowly than did the CF-TP10 concentration in the GUV membrane. A high mole fraction of cholesterol inhibited the entry of CF-TP10 into single GUVs by suppressing the translocation of CF-TP10 from the external to the internal monolayer, although higher concentrations of CF-TP10 induced the formation of pores through which CF-TP10 rapidly translocated. Suppression of the translocation of CF-TP10 by cholesterol can be reasonably explained by the large line tension of a prepore. We discussed the role of mechanical properties in membranes on the entry of CF-TP10 into single GUVs and proposed a hypothesis of the mechanism that CF-TP10 translocates across a bilayer through transient hydrophilic prepores in the membrane.

Effects of Lipid Composition on the Entry of Cell-Penetrating Peptide Oligoarginine into Single Vesicles.

The cell-penetrating peptide R9, an oligoarginine comprising nine arginines, has been used to transport biological cargos into cells. However, the mechanisms underlying its translocation across membranes remain unclear. In this report, we investigated the entry of carboxyfluorescein (CF)-labeled R9 (CF-R9) into single giant unilamellar vesicles (GUVs) of various lipid compositions and the CF-R9-induced leakage of a fluorescent probe, Alexa Fluor 647 hydrazide (AF647), using a method developed recently by us. First, we investigated the interaction of CF-R9 with dioleoylphosphatidylglycerol (DOPG)/dioleoylphosphatidylcholine (DOPC) GUVs containing AF647 and small DOPG/DOPC vesicles. The fluorescence intensity of the GUV membrane due to CF-R9 (i.e., the rim intensity) increased with time to a steady-state value, and then the fluorescence intensity of the membranes of the small vesicles in the GUV lumen increased without leakage of AF647. This result indicates that CF-R9 entered the GUV lumen from the outside by translocating across the lipid membrane without forming pores through which AF647 could leak. The fraction of entry of CF-R9 at 6 min in the absence of pore formation, Pentry (6 min), increased with an increase in CF-R9 concentration, but the CF-R9 concentration in the lumen was low. We obtained similar results for dilauroyl-PG (DLPG)/ditridecanoyl-PC (DTPC) (2/8) GUVs. The values of Pentry (6 min) of CF-R9 for DLPG/DTPC (2/8) GUVs were larger than those obtained with DOPG/DOPC (2/8) GUVs at the same CF-R9 concentrations. In contrast, a high concentration of CF-R9 induced pores in DLPG/DTPC (4/6) GUVs through which CF-R9 entered the GUV lumen, so the CF-R9 concentration in the lumen was higher. However, CF-R9 could not enter DOPG/DOPC/cholesterol (2/6/4) GUVs. Analysis of the rim intensity showed that CF-R9 was located only in the outer monolayer of the DOPG/DOPC/cholesterol (2/6/4) GUVs. On the basis of analyses of these results, we discuss the elementary processes by which CF-R9 enters GUVs of various lipid compositions.

The Impact of a Participatory Care Model on Work Satisfaction of Care Workers and the Functionality, Connectedness, and Mental Health of Community-Dwelling Older People.

This study describes and evaluates an innovative program designed to reduce functional decline among seniors, using a participatory care approach and integrated health teams. The evaluation provides older people and community support workers (CSWs) with the opportunity to share their experiences of being involved with an innovative program to reduce functional decline (mobility, skin integrity, nutrition, mental health, continence) of older, community dwelling adults implemented by a Nursing Service in a major capital city in Australia. As part of the program, CSWs were trained to provide care that aimed to reduce functional decline, and improve the quality of life for the care recipients. Data were collected through in-depth interviews with older people receiving care and a focus group (FG) was conducted with CSWs. Seven themes emerged during data analysis: 1) functionality/independence; 2) prevention; 3) confidence; 4) connection; 5) the approach; 6) care plans; and 7) the role of the CSWs. The relationship built between care giver and receiver and the mutual respect facilitated through adopting a participatory care approach was crucial. This relationship-focused care contributed to improved functionality and consequently quality of life for the older person, and for the CSW professional it contributed to their development, improved satisfaction with their role, and increased pride in the difference they make in the lives of their clients. Opportunities for improvement of the program included ensuring that participants understood the rationale for all aspects of the program, including regular reminders, as well as the use of regular reviews of individual outcomes.

Data Mining and Privacy of Social Network Sites' Users: Implications of the Data Mining Problem.

This paper explores the potential of data mining as a technique that could be used by malicious data miners to threaten the privacy of social network sites (SNS) users. It applies a data mining algorithm to a real dataset to provide empirically-based evidence of the ease with which characteristics about the SNS users can be discovered and used in a way that could invade their privacy. One major contribution of this article is the use of the decision forest data mining algorithm (SysFor) to the context of SNS, which does not only build a decision tree but rather a forest allowing the exploration of more logic rules from a dataset. One logic rule that SysFor built in this study, for example, revealed that anyone having a profile picture showing just the face or a picture showing a family is less likely to be lonely. Another contribution of this article is the discussion of the implications of the data mining problem for governments, businesses, developers and the SNS users themselves.

Entry of cell-penetrating peptide transportan 10 into a single vesicle by translocating across lipid membrane and its induced pores.

The cell-penetrating peptide, transportan 10 (TP10), can translocate across the plasma membrane of living cells and thus can be used for the intracellular delivery of biological cargo such as proteins. However, the mechanisms underlying its translocation and the delivery of large cargo remain unclear. In this report we investigated the entry of TP10 into a single giant unilamellar vesicle (GUV) and the TP10-induced leakage of fluorescent probes using the single GUV method. GUVs of 20% dioleoylphosphatidylglycerol (DOPG)/80% dioleoylphosphatidylcholine (DOPC) were prepared, and they contained a water-soluble fluorescent dye, Alexa Fluor 647 hydrazide (AF647), and smaller vesicles composed of 20% DOPG/80% DOPC. The interaction of carboxyfluorescein (CF)-labeled TP10 (CF-TP10) with these loaded GUVs was investigated using confocal microscopy. The fluorescence intensity of the GUV membrane increased with time to a saturated value, then the fluorescence intensity due to the membranes of the smaller vesicles inside the GUV increased prior to leakage of AF647. This result indicates that CF-TP10 entered the GUV from the outside by translocating across the lipid membrane before CF-TP10-induced pore formation. The rate constant of TP10-induced pore formation in lipid membranes increased with an increase in TP10 concentration. Large molecules such as Texas Red Dextran 40,000, and vesicles with a diameter of 1-2 µm, permeated through the TP10-induced pores or local rupture in the lipid membrane. These results provide the first direct experimental evidence that TP10 can deliver large cargo through lipid membranes, without the need for special transport mechanisms such as those found in cells.

The single GUV method for revealing the functions of antimicrobial, pore-forming toxin, and cell-penetrating peptides or proteins.

We recently developed the single giant unilamellar vesicle (GUV) method for investigating the functions and dynamics of biomembranes. The single GUV method can provide detailed information on the elementary processes of physiological phenomena in biomembranes, such as their rate constants. Here we describe the process of pore formation induced by the antimicrobial peptide (AMP), magainin 2, and the pore-forming toxin (PFT), lysenin, as revealed by the single GUV method. We obtained the rate constants of several elementary steps, such as peptide/protein-induced pore formation in lipid membranes and the membrane permeation of fluorescent probes through the pores. Information on the entry of the cell-penetrating peptide (CPP), transportan 10 (TP10), into a single GUV and its induced pore formation in lipid membranes was also obtained. We compare the single GUV method with other methods for investigating the interaction of peptides/proteins with lipid membranes (i.e., the large unilamellar vesicle (LUV) suspension method, the GUV suspension method, and single channel recording), and discuss the pros and cons of the single GUV method. On the basis of these data, we discuss the advantages of the single GUV method.

How do R&D and remittances affect economic growth? Evidence from middle-income countries.

Sustainable development through technical progress for middle-income countries (MICs) is overlooked in growth allied studies. Despite their crucial role in alleviating poverty and resource shortages, MICs encounter challenges in global economic competition, driving persistent efforts to find practical solutions. Therefore, this study explores the integrated impact of R&D expenditure and remittances on economic growth in MICs. Using data from 25 MICs between 1996 and 2021, this study employs the "2nd generation unit root" and "panel autoregressive distributed lag (ARDL)" methods. The "feasible generalized least square (FGLS)" techniques and the "Dumitrescu-Hurlin (D-H)" causality test are employed to verify the robustness of the panel ARDL estimation. The Westerlund cointegration tests confirm a long-term cointegration between variables. The findings of the panel ARDL approach show that R&D expenditure and remittances positively and significantly influence economic growth. The robustness of the panel ARDL results is confirmed by the FGLS estimation, which produces similar outcomes. The outcomes from the FGLS and the ARDL methods are additionally validated by the D-H causality check. Therefore, encouraging R&D and remittances is crucial to accelerate middle-income nations' economic growth. The study reveals a novel mechanism of R&D expenditures, remittances, and economic growth in MICs, shaping their mutual influence on this economic landscape. The study supports middle-income countries' policymakers in creating effective policies for their financial institutions regarding R&D expenditure and remittances.

Effect of Phosphatidylethanolamine on Pore Formation Induced by the Antimicrobial Peptide PGLa.

Most antimicrobial peptides (AMPs) induce pore formation and a burst of lipid bilayers and plasma membranes. This causes severe leakage of the internal contents and cell death. The AMP PGLa forms nanopores in giant unilamellar vesicles (GUVs) comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylglycerol (DOPG). We here elucidated the effect of the line tension of a prepore rim on PGLa-induced nanopore formation by investigating the interaction of PGLa with single GUVs comprising dioleoylphosphatidylethanolamine (DOPE)/DOPG (6:4) in buffer using the single GUV method. We found that PGLa forms nanopores in the GUV membrane, which evolved into a local burst and burst of GUVs. The rate of pore formation in DOPE/DOPG-GUVs was smaller than that in DOPC/DOPG-GUVs. PGLa is located only in the outer leaflet of a GUV bilayer just before a fluorescent probe AF647 leakage from the inside, indicating that this asymmetric distribution induces nanopore formation. PGLa-induced local burst and burst of GUVs were observed at 10 ms-time resolution. After nanopore formation started, dense particles and small vesicles appeared in the GUVs, followed by a decrease in the GUV diameter. The GUV was finally converted into smaller GUV or lipid membrane aggregates. We discuss the mechanisms of PGLa-induced nanopore formation and its direct evolution to a GUV burst.

Processes and mechanisms underlying burst of giant unilamellar vesicles induced by antimicrobial peptides and compounds.

To clarify the damage of lipid bilayer region in bacterial cell membrane caused by antimicrobial peptides (AMPs) and antimicrobial compounds (AMCs), their interactions with giant unilamellar vesicles (GUVs) of various lipid compositions have been examined. The findings revealed two main causes for the leakage: nanopore formation in the membrane and burst of GUVs. Although GUV burst has been explained previously based on the carpet model, the supporting evidence is limited. In this review, to better clarify the mechanism of GUV burst by AMPs, AMCs, and other membrane-active peptides, we described current knowledge of the conditions, characteristics, and detailed processes of GUV burst and the changes in the shape of the GUVs during burst. We identified several physical factors that affect GUV burst, such as membrane tension, electrostatic interaction, structural changes of GUV membrane such as membrane folding, and oil in the membrane. We also clarified one of the physical mechanisms underlying the instability of lipid bilayers that are associated with leakage in the carpet model. Based on these results, we propose a mechanism underlying some types of GUV burst induced by these substances: the growth of a nanopore to a micropore, resulting in GUV burst.

Determinants of low birth weight and its effect on childhood health and nutritional outcomes in Bangladesh.

BACKGROUND: The high incidence of low birth weight (LBW) is associated with an increased risk of infant mortality, adverse pregnancy outcomes for mothers, and a decline in overall health and well-being. The current study aimed to identify the various determinants of LBW and its effect on adverse health and nutritional outcomes of children aged 0-23 months in Bangladesh. METHODS: Bangladesh Demography and Health Survey (BDHS) 2017-18 data was used. A chi-square test and multivariable logistic regression analysis were used to find out the associations between independent variables and outcomes (e.g., LBW, child illness and undernutrition). RESULTS: The overall prevalence of LBW among was 16.3%. Mother with no formal education (AOR = 2.64, 95% CI = 0.55-3.30, p = 0.01), female child (AOR = 1.31, 95% CI = 1.04-1.65, p = 0.023); and poorest economic status (AOR = 1.69, 95% CI = 1.13-2.51, p = 0.010), were identified significant determinants of LBW. Of home environment and hygiene factors, unimproved toilet facilities (AOR = 1.38, 95% CI = 1.03-1.84, p = 0.030) had a significant effect on LBW. In addition, children born with LBW were more likely to suffer fever (AOR = 1.26, 95% CI = 1.05-1.60, p = 0.050), stunting (AOR = 2.42, 95% CI = 1.86-3.15, p = < 0.001), wasting (AOR = 1.47, 95% CI = 1.02-2.25 p = 0.049), and underweight (AOR = 3.19, 95% CI = 2.40-4.23, p = < 0.001). CONCLUSION: One out of five children was LBW in Bangladesh. Maternal education, sex of child, wealth index, and toilet facilities had significant effects on LBW. In addition, LWB contributed to children's poor health and nutritional outcomes. Enhancing maternal pregnancy, and child health outcomes necessitates policies addressing poverty, gender inequality, and social disparities. Key strategies include promoting regular prenatal care, early medical intervention, reproductive health education, and safe hygiene practices. To combat the negative impacts of LBW, a comprehensive strategy is vital, encompassing exclusive breastfeeding, nutritional support, growth monitoring, accessible healthcare, and caregiver education.