Controlled release mechanisms of spontaneously forming unilamellar vesicles

Spontaneously forming small unilamellar vesicles (SULVs) are easy to prepare and show great promise for use in delivering therapeutic payloads. We report of SULVs made up of the ternary phospholipid mixture, dimyristoyl-phosphatidylcholine (DMPC), dihexanoyl-phosphatidylcholine (DHPC) and dimyristoyl-phosphatidylglycerol (DMPG), which have been characterized by small angle neutron scattering (SANS). These low-polydispersity (0.14-0.19) SULVs range in size (i.e., radius) from 110 to 215 A and are capable of entrapping, and subsequently releasing, hydrophilic molecules (e.g., fluorescent dyes and quenchers) in a controlled fashion over two different temperature ranges. The low-temperature release mechanism involves the SULVs transforming into discoidal micelles, with an onset temperature (T(o)) of ~32 degrees C, while the high-temperature release mechanism is more gradual, presumably the result of defects formed through the continuous dissolution of DHPC into solution. Both of these mechanisms differ from other, previously reported thermosensitive liposomes.     

Ether- versus Ester-Linked Phospholipid Bilayers Containing either Linear or Branched Apolar Chains

We studied the properties of bilayers formed by ether-and ester-containing phospholipids, whose hydrocarbon chains can be either linear or branched, using sn-1,2 dipalmitoyl, dihexadecyl, diphytanoyl, and diphytanyl phosphatidylcholines (DPPC, DHPC, DPhoPC, and DPhPC, respectively) either pure or in binary mixtures. Differential scanning calorimetry and confocal fluorescence microscopy of giant unilamellar vesicles concurred in showing that equimolar mixtures of linear and branched lipids gave rise to gel/fluid phase coexistence at room temperature. Mixtures containing DHPC evolved in time (0.5 h) from initial reticulated domains to extended solid ones when an equilibrium was achieved. The nanomechanical properties of supported planar bilayers formed by each of the four lipids studied by atomic force microscopy revealed average breakdown forces F_b decreasing in the order DHPC ≥ DPPC > DPhoPC >> DPhPC. Moreover, except for DPPC, two different F_b values were found for each lipid. Atomic force microscopy imaging of DHPC was peculiar in showing two coexisting phases of different heights, probably corresponding to an interdigitated gel phase that gradually transformed, over a period of 0.5 h, into a regular tilted gel phase. Permeability to nonelectrolytes showed that linear-chain phospholipids allowed a higher rate of solute + water diffusion than branched-chain phospholipids, yet the former supported a smaller extent of swelling of the corresponding vesicles. Ether or ester bonds appeared to have only a minor effect on permeability.     

Ether- versus Ester-Linked Phospholipid Bilayers Containing either Linear or Branched Apolar Chains

We studied the properties of bilayers formed by ether-and ester-containing phospholipids, whose hydrocarbon chains can be either linear or branched, using sn-1,2 dipalmitoyl, dihexadecyl, diphytanoyl, and diphytanyl phosphatidylcholines (DPPC, DHPC, DPhoPC, and DPhPC, respectively) either pure or in binary mixtures. Differential scanning calorimetry and confocal fluorescence microscopy of giant unilamellar vesicles concurred in showing that equimolar mixtures of linear and branched lipids gave rise to gel/fluid phase coexistence at room temperature. Mixtures containing DHPC evolved in time (0.5 h) from initial reticulated domains to extended solid ones when an equilibrium was achieved. The nanomechanical properties of supported planar bilayers formed by each of the four lipids studied by atomic force microscopy revealed average breakdown forces F_b decreasing in the order DHPC ≥ DPPC > DPhoPC >> DPhPC. Moreover, except for DPPC, two different F_b values were found for each lipid. Atomic force microscopy imaging of DHPC was peculiar in showing two coexisting phases of different heights, probably corresponding to an interdigitated gel phase that gradually transformed, over a period of 0.5 h, into a regular tilted gel phase. Permeability to nonelectrolytes showed that linear-chain phospholipids allowed a higher rate of solute + water diffusion than branched-chain phospholipids, yet the former supported a smaller extent of swelling of the corresponding vesicles. Ether or ester bonds appeared to have only a minor effect on permeability.     

Effects of ether vs. ester linkage on lipid bilayer structure and water permeability

The structure and water permeability of bilayers composed of the ether-linked lipid, dihexadecylphosphatidylcholine (DHPC), were studied and compared with the ester-linked lipid, dipalmitoylphosphaditdylcholine (DPPC). Wide angle X-ray scattering on oriented bilayers in the fluid phase indicate that the area per lipid A is slightly larger for DHPC than for DPPC. Low angle X-ray scattering yields A = 65.1 Å² for DHPC at 48 °C. LAXS data provide the bending modulus, K_C = 4.2 × 10⁻¹³ erg, and the Hamaker parameter H = 7.2 × 10⁻¹⁴ erg for the van der Waals attractive interaction between neighboring bilayers. For the low temperature phases with ordered hydrocarbon chains, we confirm the transition from a tilted L_β′ gel phase to an untilted, interdigitated L_βI phase as the sample hydrates at 20 °C. Our measurement of water permeability, P_f = 0.022 cm/s at 48 °C for fluid phase DHPC is slightly smaller than that of DPPC (P_f = 0.027 cm/s) at 50 °C, consistent with our triple slab theory of permeability.     

Production,thermodynamic characterization,and fruit juice quality improvement characteristics of an Exo-polygalacturonase from Penicillium janczewskii

Exo-polygalacturonase (Exo-PG), an extracellular pectinolytic enzyme with great potential in the food industry, was produced from Penicillium janczewskii under solid-state fermentation using wheat bran as a lignocellulosic substrate. Optimization of various fermentation process variables revealed that a moisture level of 70%, d-mannitol (carbon source), yeast extract (nitrogen source) and ZnSO₄/NiCl₂ as metal salt inducers generated the maximum yield of Exo-PG. After ammonium sulfate precipitation (70% saturation level), the enzyme was characterized in terms of various kinetic (i.e., temperature, pH, inhibitors, Michaelis-Menten constants) and thermodynamic parameters (i.e., Ea, ΔH*, ΔS* and ΔG*). The temperature and pH optima were 45 °C and 6.0, respectively, and the Exo-PG presented stability at a wider range of temperature and pH values. Metal ions Mn⁺² markedly improved the enzyme activity, while exposure to urea and ethylenediaminetetraacetic acid drastically inhibited the biocatalytic performance. The kinetic parameters i.e., k_m and V_max were computed to be 10 mM and 41.67 U/mL, respectively. A profound increase in clarity, yield, and reduction in viscosity was achieved for different fruit juices (apple, mango, and peach) after treatment with Exo-PG. Total antioxidant and total phenolic contents were also ameliorated. In conclusion, the catalytic activity, thermal steadiness, and fruit juices clarification performance of Exo-PG manifests a great prospect for bio-industrial exploitation.     

Direct observation and characterization of DMPC/DHPC aggregates under conditions relevant for biological solution NMR

We have used cryo-transmission electron microscopy (cryo-TEM) for inspection of aggregates formed by dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in aqueous solution at total phospholipid concentrations c_L≤5% and DMPC/DHPC ratios q≤4.0. In combination with ocular inspections, we are able to sketch out this part of phase-diagram at T=14-80 °C. The temperature and the ratio q are the dominating variables for changing sample morphology, while c_L to a lesser extent affects the aggregate structure. At q=0.5, small, possibly disc-shaped, aggregates with a diameter of ∼6 nm are formed. At higher q-values, distorted discoidal micelles that tend to short cylindrical micelles are observed. The more well-shaped discs have a diameter of around 20 nm. Upon increasing q or the temperature, long slightly flattened cylindrical micelles that eventually branch are formed. A holey lamellar phase finally appears upon further elevation of q or temperature. The implications for biological NMR work are two. First, discs prepared as membrane mimics are frequently much smaller than predicted by current “ideal bicelle” models. Second, the q≈3 preparations used for aligning water-soluble biomolecules in magnetic fields consist of perforated lamellar sheets. Furthermore, the discovered sequence of morphological transitions may have important implications for the development of bicelle-based membrane protein crystallization methods.     

Bat thermoregulation in the heat: Limits to evaporative cooling capacity in three southern African bats

High environmental temperatures pose significant physiological challenges related to energy and water balance for small endotherms. Although there is a growing literature on the effect of high temperatures on birds, comparable data are scarcer for bats. Those data that do exist suggest that roost microsite may predict tolerance of high air temperatures. To examine this possibility further, we quantified the upper limits to heat tolerance and evaporative cooling capacity in three southern African bat species inhabiting the same hot environment but using different roost types (crevice, foliage or cave). We used flow-through respirometry and compared heat tolerance limits (highest air temperature (T_a) tolerated before the onset of severe hyperthermia), body temperature (T_b), evaporative water loss, metabolic rate, and maximum cooling capacity (i.e., evaporative heat loss/metabolic heat production). Heat tolerance limits for the two bats roosting in more exposed sites, Taphozous mauritianus (foliage-roosting) and Eptesicus hottentotus (crevice-roosting), were T_a = ~44 °C and those individuals defended maximum T_b between 41 °C and 43 °C. The heat tolerance limit for the bat roosting in a more buffered site, Rousettus aegyptiacus (cave-roosting), was T_a = ~38 °C with a corresponding T_b of ~38 °C. These interspecific differences, together with a similar trend for higher evaporative cooling efficiency in species occupying warmer roost microsites, add further support to the notion that ecological factors like roost choice may have profound influences on physiological traits related to thermoregulation.     

Atomistic Simulations of Bicelle Mixtures

Mixtures of long- and short-tail phosphatidylcholine lipids are known to self-assemble into a variety of aggregates combining flat bilayerlike and curved micellelike features, commonly called bicelles. Atomistic simulations of bilayer ribbons and perforated bilayers containing dimyristoylphosphatidylcholine (DMPC, di-C₁₄ tails) and dihexanoylphosphatidylcholine (DHPC, di-C₆ tails) have been carried out to investigate the partitioning of these components between flat and curved microenvironments and the stabilization of the bilayer edge by DHPC. To approach equilibrium partitioning of lipids on an achievable simulation timescale, configuration-bias Monte Carlo mutation moves were used to allow individual lipids to change tail length within a semigrand-canonical ensemble. Since acceptance probabilities for direct transitions between DMPC and DHPC were negligible, a third component with intermediate tail length (didecanoylphosphatidylcholine, di-C₁₀ tails) was included at a low concentration to serve as an intermediate for transitions between DMPC and DHPC. Strong enrichment of DHPC is seen at ribbon and pore edges, with an excess linear density of ∼3 nm⁻¹. The simulation model yields estimates for the onset of edge stability with increasing bilayer DHPC content between 5% and 15% DHPC at 300 K and between 7% and 17% DHPC at 323 K, higher than experimental estimates. Local structure and composition at points of close contact between pores suggest a possible mechanism for effective attractions between pores, providing a rationalization for the tendency of bicelle mixtures to aggregate into perforated vesicles and perforated sheets.     

A centrifugal ultrafiltration strategy for isolating the low-molecular weight (≤ 25 K) component of human plasma proteome

The low-molecular weight fraction (LMF) of the human plasma proteome is an invaluable source of biological information, especially in the context of identifying plasma-based biomarkers of disease. In this study, a separation and enrichment strategy based on centrifugal ultrafiltration was developed for the LMF (i.e., ≤ 25 K) of plasma routinely prepared from normal, healthy volunteers. Four commercially-available filter membranes of similar nominal molecular weight cut-off (NMWC), but differing membrane chemistries and filter orientations (Microcon®, Millipore; Centrisart®, Sartorius; Amicon Ultra®, Millipore; Vivaspin®, Sartorius), were evaluated. Of these filtration devices, only the Sartorius Vivaspin® tangential membrane, NMWC 20 K was effective in the non-retention of M_r > 50 K, and recovery and enrichment of low-M_r components from human plasma. This filter membrane device was further optimized with respect to plasma buffer composition, centrifugal force, duration and temperature. Optimal ultrafiltration conditions were obtained using 100 µL of normal plasma in 10% acetonitrile, and a centrifugation force of 4000 × g for 35 min at 20 °C. In this LMF, 44 proteins (from 266 unique peptides) were identified using a combination of 1D-SDS-PAGE / nano-LC-MS/MS and a stringent level of identification (FDR < 1%). We report the identification of several proteins (e.g., protein KIAA0649 (Q9Y4D3), rheumatoid factor D5, serine protease inhibitor A3, and transmembrane adapter protein PAG) previously not reported in extant high-confidence Human Proteome Organization (HUPO) Plasma Proteome Project datasets. When compared with the low-M_r human plasma/serum proteome datasets of Zhou et al. (Electrophoresis, 2004. 25, 1289–98), Gundry et al. (Proteomics Clin. Appl., 2007. 1, 73–88) and Villanueva et al. (Anal Chem, 2004. 76, 1560–70), 64% of our identifications (28 proteins) were novel; these include cofilin-1, PPIase A, and the SH3 domain-binding glutamic acid-rich-like protein 3. In addition to intact proteins, many peptide fragments from high-abundance proteins (e.g., fibrinogen, clusterin, Factor XIIIa, transferrin, kinogen-1, and inter-alpha-trypsin inhibitor), presumably derived by ex vivo proteolysis, were observed.     

The effects of temperature,salinity, concentration and PEGylated lipid on the spontaneous nanostructures of bicellar mixtures

The self-assembling morphologies of low-concentration (mostly 1 and 10 mg/mL) bicellar mixtures composed of zwitterionic dipalmitoyl (di-C₁₆) phosphatidylcholine (DPPC), dihexanoyl (di-C₆) phosphatidylcholine (DHPC), and negatively charged dipalmitoyl (di-C₁₆) phosphatidylglycerol (DPPG) were investigated using small angle neutron scattering, dynamic light scattering and transmission electron microscopy. A polyethylene glycol conjugated (PEGylated) lipid, distearoyl phosphoethanolamine-[methoxy (polyethyleneglycol)-2000] (PEG2000-DSPE), was incorporated in the system at 5 mol% of the total lipid composition. The effects of several parameters on the spontaneous structures were studied, including temperature, lipid concentration, salinity, and PEG2000-DSPE. In general, nanodiscs (bicelles) were observed at low temperatures (below the melting temperature, T_M of DPPC) depending on the salinity of the solutions. Nanodisc-to-vesicle transition was found upon the elevation of temperature (above T_M) in the cases of low lipid concentration in the absence of PEG2000-DSPE or high salinity. Both addition of PEG2000-DSPE and high lipid concentration stabilize the nanodiscs, preventing the formation of multilamellar vesicles, while high salinity promotes vesiculation and the formation of aggregation. This study suggests that the stability of such nanodiscs is presumably controlled by the electrostatic interactions, the steric effect induced by PEG2000-DSPE, and the amount of DHPC located at the disc rim.     

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, φ_m, 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 φ_m-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 |φ_m| up to 118 mV, and its dependence on |φ_m| 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 φ_m 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, V_entry, increased with an increase in |φ_m|. The rim intensity due to CF-TP10 increased with an increase in |φ_m|, indicating that the CF-TP10 concentration in the inner leaflet of the GUV increased with |φ_m|. These results indicate that the φ_m-induced elevation in V_entry can be explained by the increase in CF-TP10 concentration in the inner leaflet with |φ_m|. 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.     

Phospholipids Enhance Nucleation but Not Elongation of Apolipoprotein C-II Amyloid Fibrils

Amyloid fibrils and their oligomeric intermediates accumulate in several age-related diseases where their presence is considered to play an active role in disease progression. A common characteristic of amyloid fibril formation is an initial lag phase indicative of a nucleation-elongation mechanism for fibril assembly. We have investigated fibril formation by human apolipoprotein (apo) C-II. ApoC-II readily forms amyloid fibrils in a lipid-dependent manner via an initial nucleation step followed by fibril elongation, breaking, and joining. We used fluorescence techniques and stopped-flow analysis to identify the individual kinetic steps involved in the activation of apoC-II fibril formation by the short-chain phospholipid dihexanoyl phosphatidylcholine (DHPC). Submicellar DHPC activates fibril formation by promoting the rapid formation of a tetrameric species followed by a slow isomerisation that precedes monomer addition and fibril growth. Global fitting of the concentration dependence of apoC-II fibril formation showed that DHPC increased the overall tetramerisation constant from 7.5 × 10^− 13 to 1.2 × 10^− 6 μM^− 3 without significantly affecting the rate of fibril elongation, breaking, or joining. Studies on the effect of DHPC on the free pool of apoC-II monomer and on fibril formation by cross-linked apoC-II dimers further demonstrate that DHPC affects nucleation but not elongation. These studies demonstrate the capacity of small lipid compounds to selectively target individual steps in the amyloid fibril forming pathway.     

In situ soil net nitrogen mineralization in coastal salt marshes (Suaeda salsa) with different flooding periods in a Chinese estuary

Flooding periods can be one of the most important factors influencing nitrogen (N) biogeochemical processes in wetlands ecosystem. We conducted a field study using in situ incubation method to investigate the seasonal dynamics of soil net N mineralization in three coastal salt marshes (Suaeda salsa) with different flooding periods (i.e., short-term (STF), seasonal (SF), and tidal (TF) flooding wetland) in the Yellow River Delta. Selected soil inorganic N pools (ammonium, nitrate and inorganic N) and N transformation (mineralization, nitrification and ammonification) rates in the top 0–10 cm soils were repeatedly quantified from April to October. Clear seasonal patterns in inorganic N pools and transformation rates were observed in accord with the seasonal variations of temperature and moisture. Generally, higher levels of soil inorganic nitrogen, ammonium nitrogen (NH₄⁺-N) and nitrate nitrogen (NO₃^－-N) occurred in the early-growing season (April), and NH₄⁺-N contents got a small accumulative peak in midsummer (September). The lower rates (negative) of net mineralization (R_min), nitrification (R_nit) and ammonification (R_amm) were observed in the early-growing season (April–June) and fall (September–October), whereas higher values (positive) in midsummer (August–September). Flooding had a significant influence on inorganic N pools (except for NH₄⁺-N) and transformation rates (p < 0.05). R_min values in SF wetland were significantly higher in the August-September period than those in other incubation periods. R_nit values in TF wetland exhibited a small variation and the highest value occured in the June–August period. The results of principal component analysis showed that soil samples were clearly divided into two groups before and after flow-sediment regulation. After flooding events, the R_min and R_amm values generally increased in the three wetlands, whereas a significant decrease in R_nit values was observed in SF wetland (p < 0.05), thus the differences in NO₃^－-N among these wetlands were eliminated. These results suggested that seasonal variations in temperature and moisture are important factors influencing inorganic N pools and transformation rates.     

The structural definition of some novel adducts of stoichiometry CuX:dpex:MeCN (2:1:1)(n), X = (pseudo-) halogen,dppx = Ph2E(CH2)xEPh2, E = P,As, Sb

Single-crystal X-ray studies have defined the structures of a number of novel adducts of the form CuX:dpex (2:1), X = (pseudo-)halide, dpex = bis(diphenylpnicogeno)alkane, Ph₂E(CH₂)_xEPh₂, E = P, As, of diverse types, solvated with acetonitrile. CuBr:dpem (2:1)₂. 2MeCN (E = both P, As) are tetranuclear, derivative of the familiar ‘step’ structure, while CuCl:dpph (MeCN solvate) and CuBr:dppe (MeCN solvate) yield one-dimensional polymers (i.e., x = 1, 2, 6 for dppx, x = m, e, h), as also does CuSCN:dpam (MeCN solvate). In CuI:dpsm:MeCN (3:1:2) (‘dpsm’ = Ph₂Sb(CH₂)SbPh₂), CuI:dpsm (2:1)₂ ‘step’ units are connected into an infinite ‘stair’ polymer by interspersed (MeCN)CuI linkers.     

Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase,nor β-amyloid content

The activity of positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (AChRs), including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and 3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) α7, rat (r) α9α10, hα3-containing AChRs, mouse (m) 5-HT_3AR, and several glutamate receptors (GluRs)] and voltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and β-amyloid (Aβ) content. The functional results indicate that PAM-2 inhibits hα3-containing AChRs (IC₅₀ = 26 ± 6 μM) with higher potency than that for NR1aNR2B and NR1aNR2A, two NMDA-sensitive GluRs. PAM-2 affects neither the activity of m5-HT_3ARs, GluR5/KA2 (a kainate-sensitive GluR), nor AChE, and PAM-4 does not affect agonist-activated rα9α10 AChRs. Relevant clinical concentrations of PAM-2–4 do not inhibit Na_v1.2 and K_v3.1 ion channels. These PAMs slightly enhance the activity of GluR1 and GluR2, two AMPA-sensitive GluRs. PAM-2 does not change the levels of A_β42 in an Alzheimer’s disease mouse model (i.e., 5XFAD). The molecular docking and dynamics results using the hα7 model suggest that the active sites for PAM-2 include the intrasubunit (i.e., PNU-120596 locus) and intersubunit sites. These results support our previous study showing that these PAMs are selective for the α7 AChR, and clarify that the procognitive/promnesic/antidepressant activity of PAM-2 is not mediated by other targets.     

Thermal energetics of the New-Guinean moss-forest rat (Rattus niobe) in comparison with other tropical murid rodents

The thermal energetics of rodents from cool, wet tropical highlands are poorly known. Metabolic rate, body temperature and thermal conductance were measured in the moss-forest rat, Rattus niobe (Rodentia), a small murid endemic to the highlands of New Guinea. These data were evaluated in the context of the variation observed in the genus Rattus and among tropical murids. In 7 adult R. niobe, basal metabolic rate (BMR) averaged 53.6±6.6 mL O₂ h⁻¹, or 103% of the value predicted for a body mass of 42.3±5.8 g. Compared to other species of Rattus, R. niobe combines a low body temperature (35.5±0.6 °C) and a moderately low minimal wet thermal conductance c_min (5.88±0.7 mL O₂ h⁻¹ °C⁻¹, 95% of predicted) with a small size, all of which lead to reduced energy expenditure in a constantly cool environment. The correlations of mean annual rainfall and temperature, altitude and body mass with BMR, body temperature and c_min were analyzed comparatively among tropical Muridae. Neither BMR, nor c_min or body temperature correlated with ambient temperature or altitude. Some of the factors which promote high BMR in higher latitude habitats, such as seasonal exposure to very low temperature and short reproductive season, are lacking in wet montane tropical forests. BMR increased with rainfall, confirming a pattern observed among other assemblages of mammals. This correlation was due to the low BMR of several desert adapted murids, while R. niobe and other species from wet habitats had a moderate BMR.     

Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression

Compounds possessing more than one functional activity incorporated into the same molecule may have advantages in treating complex disease states. Balanced serotonin/norepinephrine reuptake inhibitors (SNRIs) (i.e., (R)- and (S)-norduloxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) showed moderately potent serotonin reuptake inhibition (IC₅₀ values of 442 and 404 nM, respectively) but low reuptake inhibition of norepinephrine (IC₅₀ values of 2097 and 2190 nM, respectively) in vitro. The dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) also inhibited PDE4D2 (i.e., K_i values of 23 and 45 nM, respectively). Due to their synergistic functional activity, SNRI/PDE4 inhibitors may be effective in treating diseases such as depression.     

Partitioning of perfluorooctanoate into phosphatidylcholine bilayers is chain length-independent

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature T_m while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA's effect on T_m and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC and DSPC liposomes at 37 °C in the DLS experiments, which suggests that PFOA partitions more readily into bilayers in the fluid phase. These findings suggest that PFOA's effect on the phase behavior of phosphatidylcholines depends on the cooperativity and state (i.e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios > 1, which suggests the formation of mixed PFOA–lipid micelles.     

High carbon storage and oxygen (O2) release potential of Mahagony (Swietenia macrophylla) woodlot plantation in Bangladesh

Woodlot plantation takes our attention nowadays because of having high wood value, biomass and carbon stock. It also has considerable potential for regulating climate change by sinking CO₂. This study investigated the market value of Swietenia macrophylla woodlots concerning the current carbon trade mechanism, local timber and oxygen value. The carbon-di-oxide equivalence (CO_2e) and release oxygen (O_{2 Release}) ranged from 125.5 to 1004.5 Mg/ha (mean 436.3 Mg/ha) and 91.25–730.26 Mg/ha (mean 317.2 Mg/ha), respectively. Form carbon trade, the Swietenia macrophylla woodlots owner will earn 4,285–34,470 BDT/ha (mean 14,900 BDT/ha). It also seemed that the present market value of release oxygen (O_{2 Release}) ranged from 3.2 to 25.5 million BDT/ha (average 11.1 million BDT/ha). However, the study area's average DBH, height, density, and basal area were 18.9 cm, 12.6 m, 1233 stem/ha, and 36.6 m²/ha, respectively. The above-ground biomass, below-ground biomass, and total biomass ranged from 45.9 to 389.7 Mg/ha (mean 166.5 Mg/ha), 22.5–157.7 Mg/ha (mean 71.2 Mg/ha), and 68.4–547.4 Mg/ha (mean 237.7 Mg/ha) correspondingly. Besides, the produced wood volume ranged from 64.95-1225.19 m³/ha (average 481.48 m³/ha). While the price of wood ranged from 0.8 to 15.14 million BDT/ha (mean 5.95 million BDT/ha). However, the above-ground, below-ground, and total carbon ranged 22.97–194.85 Mg/ha (mean 87.27 Mg/ha, 11.23–78.85 Mg/ha (35.61 Mg/ha), and 34.2–273.7 Mg/ha (118.89 Mg/ha) independently. Moreover, our three developed basal area-based allometric models are fit for calculating the carbon stock of Swietenia macrophylla woodlots. This study explores the potentiality of woodlots in Bangladesh. Policymakers should encourage the farmers to create more woodlots that actively participate in climate change mitigation.