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Plasma membrane protein trafficking is of fundamental importance for cell function and cell integrity of neurons and includes regulated protein recycling. In this work, we report a novel role of the endoplasmic reticulum (ER) for protein recycling as discovered in trafficking studies of the ion channel TRPL in photoreceptor cells of Drosophila. TRPL is located within the rhabdomeric membrane from where it is endocytosed upon light stimulation and stored in the cell body. Conventional immunohistochemistry as well as stimulated emission depletion super-resolution microscopy revealed TRPL storage at the ER after illumination, suggesting an unusual recycling route of TRPL. Our results also imply that both phospholipase D (PLD) and retromer complex are required for correct recycling of TRPL to the rhabdomeric membrane. Loss of PLD activity in PLD3.1 mutants results in enhanced degradation of TRPL. In the retromer mutant vps35MH20 , TRPL is trapped in a Rab5-positive compartment. Evidenced by epistatic analysis in the double mutant PLD3.1 vps35MH20 , PLD activity precedes retromer function. We propose a model in which PLD and retromer function play key roles in the transport of TRPL to an ER enriched compartment.

Using a multicatheterized pig model, we identified the portal-drained viscera as the main releasing compartment of the short-chain fatty acids acetate, propionate, butyrate, isovalerate, and valerate in the fasted and postprandial states. Low hepatic acetate metabolism resulted in a high splanchnic release, whereas all other SCFAs were extensively cleared resulting in low but significant splanchnic releases. Muscle and kidneys are the main peripheral SCFA metabolizing organs during fasting and in the postprandial state.

A novel approach to inducing anion transport over the dialytic membrane was proposed and successfully tested using the dihydrogen phosphate anion. The anion receptor based on isophthalamide was anchored on a dendritic skeleton, resulting in a macromolecular structure with a limited possibility to cross the dialytic membrane. The dendritic receptor was placed in a compartment separated from a mother anion solution by a membrane. The resulting anion complexation reduced the actual concentration of the anion and induced the anion transfer across the membrane. The anion concentration in mother solution decreased, while it was found to be increased in the compartment with the dendritic receptor. This phenomenon was observed using dendritic receptors with four and eight complexation sites. A detailed analysis of a series of dialytic experiments by 1H NMR spectroscopy enabled an assessment of the complexation behavior of both receptors and an evaluation of the dendritic effect on the anion complexation.

In this study, an acidogenic compartment was attached to a dual-chambered MFC. Rice mill wastewater was acidified in the acidogenic chamber to enhance the biodegradation of complex organics before feeding to MFC. The system was operated under HRT of 12 h (A-MFC12) and 15 h (A-MFC15). The performance of the acidogenic chamber-MFC unit was compared with a conventional dual-chambered MFC (C-MFC15). The maximum total volatile fatty acid (VFA) accumulation was found to be mg 991.21 mg COD/L for A-MFC12, and 560 mg COD/L for A-MFC15, which corresponds to the acidification yield of 78.35 ± 1.19 % and 55.94 ± 1.36 %, respectively. The maximum volumetric power density achieved in A-MFC12 (4.08 ± 0.08 W/m3) was higher than that of A-MFC15 (2.34 ± 0.07 W/m3), and C-MFC15 (2.11 ± 0.04 W/m3). The findings suggest that integrating acidogenic pre-treatment induced a positive effect on bioelectricity generation and substrate removal efficiency of the MFC.

In contrast to water soluble enzymes which can be purified and studied while in solution, studies of solute carrier (transporter) proteins require both that the protein of interest is situated in a phospholipid membrane and that this membrane forms a closed compartment. An additional challenge to the study of transporter proteins has been that the transport depends on the transmembrane electrochemical gradients. Baruch I. Kanner understood this early on and first developed techniques for studying plasma membrane vesicles. This advanced the field in that the experimenter could control the electrochemical gradients. Kanner, however, did not stop there, but started to solubilize the membranes so that the transporter proteins were taken out of their natural environment. In order to study them, Kanner then had to find a way to reconstitute them (reinsert them into phospholipid membranes). The scope of the present review is both to describe the reconstitution method in full detail as that has never been done, and also to reveal the scientific impact that this method has had. Kanner’s later work is not reviewed here although that also deserves a review because it too has had a huge impact.

A systems chemistry approach is taken for compartmentalization of a continuous reaction medium (water and CO2) with induced creation of micro-heterogeneity in the medium by using a SOM (soft-oxometalate) catalyst. The first step involves compartmentalization of an assembled catalyst-photosensitizer duo catalysing the reduction of CO2 into formic acid in two reaction spaces: the interior of the compartment and the exterior of the compartment. The exterior compartment obeys typical surface activity driven nanocatalysis principles where the perturbation of the catalyst surface area inversely varies with product yield. The second step of disassembly to disrupt the SOM-catalyst, induced by addition of a base, releases the interior reaction product with total disappearance of the catalyst system. The assembly–disassembly cascade demonstrates the application of systems chemistry principles in perturbation, compartmentalization, catalysis and release of products with well-defined externally controlled stimuli such as concentration, light, and pH. The OSCR-catalyst reported here is an attempt to emulate Golgi bodies in the context of cellular chemistry on a functional level.

Creeping bentgrass (Agrostis stolonifera) is widely used in golf course settings for its desirable playing surface characteristics; however, it is highly susceptible to diseases that can disrupt surface integrity and cause significant losses despite preventative management. Understanding the influence of early plant growth and basic management practices on microbiome communities are crucial first steps to developing future efforts to harness the microbiome for plant health. This study investigated bacterial and fungal communities of creeping bentgrass foliage and rhizosphere through 6 months postemergence under a controlled environment to elucidate microbiome community dynamics in response to plant age. We hypothesized that plant compartments will host distinct community structures and exhibit different responses to plant age. Our results showed that predominant bacterial phyla and fungal classes remain consistent across time and plant compartment. However, genus-level classification revealed that bacterial taxa differed across plant compartment while fungal taxa remained consistent. Host influence over the microbiome manifests quickly, with the largest shift in both microbial communities occurring between emergence and 2 months postemergence. For example, Burkholderia and Penicillium spp. were present at high relative abundance at emergence but, by 2 months postemergence, both taxa decreased significantly. Bacterial communities continued to experience significant fluctuation in rare taxa from 2 months postemergence onward, while fungal community structure was driven by the fluctuation of the most common taxa. These results highlight the connection between plant age and microbial community structure in creeping bentgrass in addition to underscoring future research efforts in creeping bentgrass microbiome manipulation for plant health. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

The present study aimed to establish an animal model of the osteofascial compartment syndrome (OFCS) in hind legs of rabbits, and to repair an early nerve injury using the self-polymerized peptide nanofiber material that was laced with nerve growth factors (NGFs). An animal model of the compartment syndrome was established using the tourniquet method. The intrafascial pressure of rabbit legs at different time points was measured after successful modeling. Western blotting was used to assess the proliferation of nerve cells after injury. After incision and decompression, the repair group was implanted with the self-polymerized peptide nanofiber material in combination with NGFs at the nerve injury sites for repair of the injured nerves. Rabbit hind leg nerve specimens were collected from experimental rabbits (control group), rabbits 5 days after injury (unrepaired group), and rabbits 5 days after injury (repaired group), and hematoxylin-eosin (HE) staining analysis and immunofluorescence experiments were also performed. After loosening the tourniquet, the intra-fascial pressure peaked on the 1st day after injury and then gradually decreased. A western blot showed low expression of the proliferating cell nuclear antigens (PCNAs) in the control group, as it began to increase 4 h after injury, peaked 5 days after injury (P < 0.05), and then gradually decreased. Meanwhile, the tissue morphology of the repair group was better than that of the non-repair group. Fluorescence double labeling results showed that the proliferation of nerve cells in the repair group increased significantly, and S100 and DAPI co-labeling intensities increased significantly. The early application of the self-polymerizing peptide nanofiber material combined with NGF exhibited evident effects on the nerve injury treatment in the osteofascial compartment syndrome.

Late-stage functionalization (LSF) aids drug discovery efforts by introducing functional groups onto C-H bonds on pre-existing skeletons. We adopted the LSF strategy to synthesize analogues of the abundantly available triterpenoid, glycyrrhetinic acid (GA), by introducing aryl groups in the A-ring, expanding the A-ring and selectively activating one methyl group of the gem-dimethyl groups. Intriguingly, two compounds were found to preferentially accumulate in the mitochondrial compartment of MDA-MB-231 breast cancer cells, to cause depolarization of mitochondrial membrane potential and to induce antiproliferative and anti-invasive effects through enhanced mitochondrial superoxide production with parallel depletion of GSH levels. Furthermore, intraperitoneal administration of these two compounds, in comparison with GA, greatly regressed breast tumor growth and metastasis in a SCID mouse model bearing labeled MDA-MB-231 cells.

Dietary polyphenols are protective for chronic diseases. Their blood transport has not been well investigated. This work examines multiple classes of polyphenols and their interactions with albumin, lipoproteins, and red blood cell (RBC) compartments using four models and determines the % polyphenol in each compartment studied. The RBC alone model showed a dose-response polyphenol association with RBCs. A blood model with flavanones determined the % polyphenol that was inside RBCs and bound to the surface using a new albumin washing procedure. It was shown that RBCs can methylate flavanones. The whole blood model separated the polyphenol into four compartments with the aid of affinity chromatography. More polyphenols were found with albumin and lipoproteins (high-density lipoproteins and low-density lipoproteins) than with RBCs. In the plasma model, the polyphenols associated almost equally between lipoproteins and albumin. RBCs and lipoproteins are shown to be important reservoirs and transporters of polyphenols in blood.

The stage of design and technological preparation of production is the longest in the process of creating new types of aircraft. To improve the organizational structures of enterprises, consideration of their activities is required not from the point of view of the functioning of structural units, but from the point of view of the organization and course of business processes. The new organizational structure of the company is based on the management of business processes and production resources. In recent years, a tendency has arisen when certain parts of the aircraft are made in different cities, but in the case of IL-276, the most suitable for the production of the entire machine is Aviastar - SP JSC. This is due to the fact that this product will be manufactured on the basis of the existing IL-476 aircraft assembled at this enterprise. In fact, the IL-276 is simply a ―circumcised‖ IL-476. The car has a shortened fuselage in order to facilitate, and only two of the four (closest to the fuselage) engines are left, and the fuel supply is also reduced, which leads to a decrease in weight. The Ulyanovsk plant has large areas already equipped for aircraft of this type, a paint shop and platforms for flight tests, therefore, this company can produce a full production cycle of aircraft, which is economically viable. In addition, at this time, the company has a small workload, and the production of a new product will allow the use of free equipment and specialists.

Reconstructions of phylogenetic relationships in the flowering plant family Rubiaceae have up until now relied heavily on single- or multi-gene data, primarily from the plastid compartment. With th ...

Decitabine (DAC), a DNA methylation inhibitor, is transported into cancer cells mainly via equilibrative nucleoside transporter 1 (ENT1) and subsequently phosphorylated by deoxycytidine kinase (dCK). We previously reported that apparent DAC uptake into cells may be described using a simple compartment model with clearance for facilitated diffusion (PS) and subsequent phosphorylation (CLmet). In the present study, time course of apparent intracellular [3H]-DAC uptake was analyzed numerically, and PS and CLmet values were calculated using the compartment model in human colon cancer HCT116 cells. PS at 0.1 μM [3H]-DAC was markedly decreased in the presence of 100 μM irinotecan or etoposide, while CLmet was markedly decreased in the presence of 100 μM cytarabine or gemcitabine. CLmet at 0.1–10 μM [3H]-DAC varied in a concentration-dependent manner and was described by Michaelis-Menten parameters Km,met and Vmax,met. In conclusion, DAC uptake mainly via ENT1 may be described by a bidirectional first-order kinetic parameter, while phosphorylation by dCK may be described by Michaelis-Menten parameters.

The processes of demyelination and neurodegeneration in the central nervous system (CNS) of multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) are secondary to numerous pathophysiological mechanisms. One of the main cellular players is the Th17 lymphocyte. One of the major functions described for Th17 cells is the upregulation of pro-inflammatory cytokines, such as IL-17 at the level of peripheral and CNS inflammation. This review will focus on the newly described and unexpected, direct role played by the Th17 cells in the CNS of MS patients and EAE models. Th17 and their main cytokine, IL-17, are actively involved in the onset and maintenance of the immune cascade in the CNS compartment as Th17 were found to achieve brain-homing potential. Direct interaction of myelin oligodendrocyte glycoprotein - specific Th17 with the neuronal cells firstly induces demyelination and secondly, extensive axonal damage. The Th17 cells promote an inflammatory B cell response beyond the BBB through the presence of infiltrating Th follicles. Due to their role in preventing remyelination and direct neurotoxic effect, Th17 cells might stand for an important connection between neuroinflammation and neurodegeneration in a devastating disease like MS. The Th17 cell populations have different mechanisms of provoking an autoimmune attack not only in the periphery but also in the CNS of MS patients.

A designed two-compartment cell was applied to the degradation analysis of FeF3 having high theoretical energy density. Comparing with the result of the coin cell, the two-compartment cell gave us insight that the elution of Fe was responsible for the degradation of FeF3 and LiDFOB was found as an essentially effective additive for suppressing the degradation of FeF3.

The Toxoplasma gondii lytic cycle is a repetition of host cell invasion, replication, egress, and re-invasion into the next host cell. While the molecular players involved in egress have been studied in greater detail in recent years, the signals and pathways for triggering egress from the host cell have not been fully elucidated. A perforin-like protein, PLP1, has been shown to be necessary for permeabilizing the parasitophorous vacuole (PV) membrane or exit from the host cell. In vitro studies indicated that PLP1 is most active in acidic conditions, and indirect evidence using superecliptic pHluorin indicated that the PV pH drops prior to parasite egress. Using ratiometric pHluorin, a GFP variant that responds to changes in pH with changes in its bimodal excitation spectrum peaks, allowed us to directly measure the pH in the PV prior to and during egress by live-imaging microscopy. A statistically significant change was observed in PV pH during egress in both wild-type RH and Δplp1 vacuoles compared to DMSO-treated vacuoles. Interestingly, if parasites are chemically paralyzed, a pH drop is still observed in RH but not in Δplp1 tachyzoites. This indicates that the pH drop is dependent on the presence of PLP1 or motility. Efforts to determine transporters, exchangers, or pumps that could contribute to the drop in PV pH identified two formate-nitrite transporters (FNTs). Auxin-induced conditional knockdown and knockouts of FNT1 and FNT2 reduced the levels of lactate and pyruvate released by the parasites and lead an abatement of vacuolar acidification. While additional transporters and molecules are undoubtedly involved, we provide evidence of a definitive reduction in vacuolar pH associated with induced and natural egress and characterize two transporters that contribute to the acidification.Author SummaryToxoplasma gondii is a single celled intracellular parasite that infects many different animals, and it is thought to infect up to one third of the human population. This parasite must rupture out of its replicative compartment and the host cell to spread from one cell to another. Previous studies indicated that a decrease in pH occurs within the replicative compartment near the time of parasite exit from host cells, an event termed egress. However, it remained unknown whether the decrease in pH is directly tied to egress and, if so, what is responsible for the decrease in pH. Here we used a fluorescent reporter protein to directly measure pH within the replicative compartment during parasite egress. We found that pH decreases immediately prior to parasite egress and that this decrease is linked to parasite disruption of membranes. We also identified a family of transporters that release acidic products from parasite use of glucose for energy as contributing to the decrease in pH during egress. Our findings provide new insight that connects parasite glucose metabolism to acidification of its replicative compartment during egress from infected cells.

Artificial metalloenzymes with different protein scaffolds, cofactors and functions have been prepared to expand the natural enzymatic repertoire with abiotic reactions. However, due to the sensitivity of metal centers toward various biomolecules, especially glutathione, low activity and turnover of artificial metalloenzymes in vivo are systematic problems not fully solved. Apart from straightforward routes such as the use of neutralizing agents, metal cofactors modification and directed evolution, one may notice that nature can create isolated microenvironments for diverse biological processes within cells. Following this way, here we report the in vivo assembly of artificial metalloenzymes based on HaloTag-SNAPTag fusion protein. These metalloenzymes have metal cofactors bound on protein interfaces, and can trigger liquid-liquid phase separation to form liquid condensates inside Escherichia coli. These condensates serve as membraneless, isolated compartments for artificial metalloenzymes to efficiently perform intracellular catalysis, mediating abiotic unmasking, coupling and polymerization reactions. The cellular compartmentalization also enables spatial control of reactions, either facilitating a cascade reaction within the confined spaces, or concurrent reactions with spatial separation. Such engineered Escherichia coli can work as whole-cell catalyst with confined metal species, colonizing at mice intestine to effect in vivo abiotic transformations with a lower chance of heavy metal poisoning. These results represent a systematic strategy to stabilize and potentiate artificial metalloenzyme in vivo, with potential applications in fields such as non-natural metabolism, fermentation and drug delivery.

Excess excitation energy in the light-harvesting antenna of Photosystem II (PSII) can cause irreversible damage to the photosynthetic apparatus. In periods of high light intensity, a feedback mechanism known as non-photochemical quenching (NPQ), induces the formation of quenchers which can safely dissipate excess excitation energy as heat. Although quenchers have been identified in more than one compartment of the PSII supercomplex, there is currently no quantitative description of how much NPQ is occurring at each of these locations. Here, we perform time-resolved fluorescence measurements on WT and antenna mutants lacking LHCII (NoL) and all peripheral antenna (Ch1 and Ch1lhcb5). By combining the results with those of steady-state fluorescence experiments we are able to estimate the intrinsic rate of NPQ for each plant and each PSII compartment. It is concluded that 60-70% of quenching occurs in LHCII, 15-20% in the minor antenna and 15-20% in the PSII core.

The time-response behaviour of a group of oxytocin analogues structurally modified on potential sites of oxytocin splitting by tissue inactivation enzymes ("enzyme probes") was investigated ex vivo on the potassium depolarized rat myometrium (at 30°C) and compared with the data obtained in the in vivo experiments. The modified oil-immersion method by Kalsner and Nickerson was used to record time profiles after cessation of a steady state myometrium contraction triggered by analogues in a high potassium tissue medium. An exchange of the aqueous medium for mineral oil enables to suppress return diffusion of the peptide and to record its irreversible clearance near the corresponding receptor compartment. Response records were analysed by a nonlinear numeric procedure based on combination of steady state and kinetic terms that allows concomitant estimations of affinities from time-response measurements, in the given case for analogues on depolarized myometrium. Potential inactivation-sensitive sites in the oxytocin chain are the Ν-terminal peptide bond Cys1 -Tyr2 (aminopeptidase splitting), the intramolecular disulphide bridge (reduction and formation of the practically inactive linear peptide) and the C-terminal Leu8 -GlyNH2 9 or the Pro7 -Leu8 (postprolin cleaving enzyme) bond, respectively. Clearance rate constants of single peptides in the OXT-receptor compartment were in an interval of 0.025 to 0.28 min-1 . The fragment contribution analysis reveals a significant linear additivity of individual structural changes and thus a predictivity of irreversible inactivation rate in the receptor compartment. The most potent inactivation of oxytocin is associated with aminopeptidase splitting; other enzymes may play some though nondecisive role. Less significant differences within the peptide group were found for rate constants for peptide transport between receptor compartment and its external aqueous medium. Besides rate constants, the evaluation of time-response data yields affinity values of the tested peptides and indicates a 25-times desensitation of depolarized compared with a native state.

This chapter examines the interaction between tracer glucose uptake and phosphor-ylation in brain. It derives the equations for the use of labeled deoxyglucose, fluorodeoxyglucose, or glucose itself to calculate brain glucose phosphorylation. The chapter estimates the value of the “lumped constant” as a function of the glucose phosphorylation rate, the plasma glucose concentration, the maximal transport capacity of the cerebral capillary endothelium, and the plasma flow of the brain. The driving force of the loss of tracer from a compartment is the aqueous concentration of the tracer in the compartment, if the tracer is in aqueous solution. Compartmental analysis of tracer uptake in vivo serves to measure the size of the different compartments of the tracer, that is, the relative abundance of its different states, and the magnitude of the transfer coefficient or relaxation constant of each compartment. The brain has two kinetic compartments, the vascular space and an extra-vascular space, separated by a blood-brain barrier.

Lysosome-related organelles play evolutionarily conserved roles in zinc storage, but mechanisms that control zinc flow in and out are not well understood. In C. elegans intestinal cells, the CDF-2 transporter stores zinc in these organelles during excess. Here we identify ZIPT-2.3 as the transporter that releases zinc during deficiency. The expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated in zinc excess and deficiency, establishing a fundamental mechanism of homeostasis. Super-resolution microscopy demonstrated these organelles are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment inflates during zinc excess and deficiency by vesicle fusion delivering zinc transporters. These results identify an unexpected structural feature of lysosome-related organelles that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis.

International audience; Macroautophagy is a highly conserved eukaryotic cellular pathway involving the engulfment of macromolecules, organelles, and invading microbes by a double-membrane compartment and subsequent lysosomal degradation. The mechanisms that regulate macroautophagy, and the interaction of its components with other cellular pathways, have remained unclear. Here, we performed proximity-dependent biotin identification (BioID) on 39 core human macroautophagy proteins, identifying over 700 unique high confidence proximity interactors with new putative connections between macroautophagic and essential cellular processes. Of note, we identify members of the OSBPL (oxysterol binding protein like) family as Atg8-family protein interactors. We subsequently conducted comprehensive screens of the OSBPL family for LC3B-binding and roles in xenophagy and aggrephagy. OSBPL7 and OSBPL11 emerged as novel lipid transfer proteins required for macroautophagy of selective cargo. Altogether, our proximity interaction map provides a valuable resource for the study of autophagy and highlights the critical role of membrane contact site proteins in the pathway.

Loss of fatty acid β-oxidation (FAO) in the proximal tubule is a critical mediator of acute kidney injury and eventual fibrosis. However, transcriptional mediators of FAO in proximal tubule injury remain understudied. Krüppel-like factor 15 (KLF15), a highly enriched zinc-finger transcription factor in the proximal tubule, was significantly reduced in proximal tubule cells after aristolochic acid I (AAI) treatment, a proximal tubule-specific injury model. Proximal tubule specific knockout of Klf15 exacerbated proximal tubule injury and kidney function decline compared to control mice during the active phase of AAI treatment, and after ischemia-reperfusion injury. Furthermore, along with worsening proximal tubule injury and kidney function decline, knockout mice exhibited increased kidney fibrosis as compared to control mice during the remodeling phase after AAI treatment. RNA-sequencing of kidney cortex demonstrated increased transcripts involved in immune system and integrin signaling pathways and decreased transcripts encompassing metabolic pathways, specifically FAO, and PPARα signaling, in knockout versus control mice after AAI treatment. In silico and experimental chromatin immunoprecipitation studies collectively demonstrated that KLF15 occupied the promoter region of key FAO genes, CPT1A and ACAA2, in close proximity to transcription factor PPARα binding sites. While the loss of Klf15 reduced the expression of Cpt1a and Acaa2 and led to compromised FAO, induction of KLF15 partially rescued loss of FAO in AAI-treated cells. Klf15, Ppara, Cpt1a, and Acaa2 expression was also decreased in other mouse kidney injury models. Tubulointerstitial KLF15 independently correlated with eGFR, PPARA and CPT1A appearance in expression arrays from human kidney biopsies. Thus, proximal tubule-specific loss of Klf15 exacerbates acute kidney injury and fibrosis, likely due to loss of interaction with PPARα leading to loss of FAO gene transcription.

Compartmentalization is an attractive approach to enhance catalytic activity by retaining reactive intermediates and mitigating deactivating pathways. Such a concept has been well explored in biochemical and more recently, organometallic catalysis to ensure high reaction turnovers with minimal side reactions. However, a scarcity of theoretical framework towards confined organometallic chemistry impedes a broader utility for the implementation of compartmentalization. Herein, we report a general kinetic model and offer design guidance for a compartmentalized organometallic catalytic cycle. In comparison to a non-compartmentalized catalysis, compartmentalization is quantitatively shown to prevent the unwanted intermediate deactivation, boost the corresponding reaction efficiency (𝛾), and subsequently increase catalytic turnover frequency (𝑇𝑂𝐹). The key parameter in the model is the volumetric diffusive conductance (𝐹 ) that describes catalysts’ diffusion propensity across a compartment’s boundary. Optimal values of 𝐹 for a specific organometallic chemistry are needed to achieve maximal values of 𝛾 and 𝑇𝑂𝐹. Our model suggests a tailored compartment design, including the use of nanomaterials, is needed to suit a specific organometallic catalysis. This work provides justification and design principles for further exploration into compartmentalizing organometallics to enhance catalytic performance.

Study question Is progesterone receptor (PGR) downregulation disrupted within endometrial epithelial compartment, during embryo receptivity phase in assisted reproductive technology (ART) cycles? Summary answer PGR is not downregulated in endometrial epithelial cells from ART cycles during embryo receptivity phase. What is known already Progesterone (P4) promotes the downregulation of its own progesterone receptor (PGR). During the mid-luteal phase, PGR is downregulated in endometrial epithelial cells (EEC), a critical process for embryo implantation. Embryos are unable to attach to the maternal surface when PGR expression is sustained in EEC. Non-physiologic ovarian steroid produced or employed in ART cycles may alter endometrial development compromising its receptivity. Scarce information is available whether PGR is downregulated in EEC from ARTs including ovarian stimulation for in vitro fertilization (IVF) cycles or hormonal endometrial preparation for frozen thawed embryo transfer (HEP-FET). Study design, size, duration Cross sectional study including endometrial samples from fertile women during natural cycle (FNC, n = 23), from infertile women submitted to IVF (n = 19) and from infertile women who underwent mock HEP-FET (n = 35). Samples were obtained between 2018–2019. Sample size was calculated considering a power of 90%, alpha error=0.05, an expected PGR expression of 2 and 0.5 in ART and FNC groups, respectively, having a standard deviation=0.9. At least 9 patients would be necessary in each group. Participants/materials, setting, methods Endometrial samples were obtained during mid-luteal phase scheduled 7 days after ovulation in FNC, 5 days after oocyte retrieval in IVF without embryo transfer or 5 days after P4 supplementation in HEP-FET. Immunohistochemistry was employed to quantify PGR using histologic score (Hscore). PGR mRNA levels were determined by qRT-PCR from EEC dissected by laser capture microdissection. Anova test was used for comparing means of Hscore and mRNA among groups. Statistical significance was established as P Main results and the role of chance No statistical differences were found in demographic characteristics including age, body mass index or endometrial thickness. The PGR expression was reduced in FNC compared to IVF and HP-FET endometria (0.6 ± 0.1, 1.9 ± 0.9 and 2.2 ± 0.9 respectively; P Limitations, reasons for caution This is a descriptive study reporting failure of PGR downregulation in endometria from ART cycles with vaginal P4 supplementation during the luteal-phase. Whether interference or resistance to P4 signal is the mechanism involved in the failure of PGR down regulation in ART cycles needs to be determined Wider implications of the findings: PGR downregulation within EEC was shown in FNC. The retained PGR expression detected in most ART cycles may interfere with embryo implantation and might explain the restricted pregnancy success. Future studies might reveal whether PGR evaluation in EEC can predict embryo implantation. Trial registration number Not Aplicable

Serial membranes that operate through a common compartment, the cytosol for transport at the plasma membrane and tonoplast, are intrinsically connected and communicate through this pool of solutes.

Liposomes are used for systemic delivery of chemotherapeutic drugs to reduce their nonspecific side effects. Liposomes can encapsulate hydrophilic and lipophilic drugs in the water compartment and the lipid membrane, respectively. However, typical drug loading capacity of liposomes by passive loading method is less than 1%. The low drug loading efficiency is problematic because it necessitates the use of a large amount of carrier materials that may cause undesirable biological effects. To increase drug loading in liposomes, weusedsupersaturated drug solutionswith gemcitabine (GEM) and doxorubicin (Dox) as examples. The prepared liposomes showed higher drug loading compared with passive loading, maintainedstabilityand provided sustained drug release for 48 hrs.

In this work, silver nanohybrids (AgNHs) comprising of two different dimensions of nanostructures i.e., nanorods (zero dimensions) and nanoparticles (one dimensions), are synthesised. As a green chemical approach, we have used the leaf extracts of Cassia occidentalis (coffee senna) for the synthetic protocol of these variant dimensions of nanostructures. The as synthesized nanostructures were explored for the fabrication of a nano-hybrid based potentiometric glucose biosensor. A conducting polymer, polypyrrole (PPy) is used for the strong adsorption of the nanohybrid on the graphite (Gr) electrode. The resulting composite matrix (Gr/PPy/AgNHs) is further modified with glucose oxidase (GOx) enzyme to obtain Gr/PPy/AgNHs/GOx biosensor for the electrochemical detection of glucose. The synergetic effect of the materials employed in development of bio-electrode resulted in an efficient glucose biosensor with a low detection limit (55.3 μM), high sensitivity (69.72 μAmM –1cm–2) and a wide linear range of 0.2–29 mM. These results validate a successful electrochemical sensor with superior analytical performance in comparison to sensors cited in literature. The proposed biosensor also exhibits good storage stability, reproducibility and remains unaffected by some of the common interferents present in the biological sample. The developed biosensor is also evaluated for glucose analysis in real samples with a high percentage recovery (97%) thus validating the possibility of its usage in biomedical applications.

This work demonstrated a microfluidic preparation process for novel Janus microparticles with individual drug release properties in each compartment. A flow-focusing microfluidic chip was designed to produce oil-in-water droplets from a mixed solution of poly(lactic-co-glycolic acid) and a triglyceride type lipid. Based on solvent evaporation-induced phase separation, droplets evolved and were solidified into Janus particles, each of which had a polymer compartment and a lipid compartment. The ratio of the two compartments in a particle can be discretionarily regulated, and the particle structure can also be flexibly altered to Janus-patchy, triple, quadruple or core-shell type. Phase transition of the chosen lipid from solid to liquid would occur under physiological temperature, which was applied for rapid release of the loaded drug. The polymer compartment would undergo a slow degradation process in physiological environment, facilitating sustained drug release. Paclitaxel was loaded into Janus particles during preparation, and staged release was achieved, leading to a combination of rapid and sustained release, which is highly desired in target drug delivery. This study would start the application of hybrid Janus particles of polymer-lipid type with novel release kinetics in drug delivery systems.

Effects of the anxiolytic diazepam and nootropics piracetam and mexidol on passive avoidance conditioning (PAC) in rats were compared in experiments using a three-compartment apparatus. The latter consisted of a central, brightly lit compartment, a noxious dark compartment in which footshock was delivered to a rat, and a safe dark compartment, where the rat was not exposed to electric shock. Footshock during the acquisition of passive avoidance response in the control animals caused an abrupt increase in the latency to escape from the central compartment during testing but did not result in preference for a safe compartment. On the basis of these data on differential effects of footshock on PAC, we suggested that learning processes, which determined the motor response delay and the safe compartment preference, had a diverse associative nature. An increase in latency is associated with the classical fear conditioning regardless of the place of electric shock exposure. In contrast to this, the safe compartment preference is associated with the formation of the memory trace about the location of the footshock exposure. The use of pharmacological substances that affect fear and memory in different ways provided additional arguments in favor of the assumption about various associative processes determining passive avoidance learning. Reduction in the level of fear using diazepam decreased the latency of motor response compared to the control value but did not affect the preference for a safe compartment. In contrast, the mnemotropic properties of piracetam and mexidol increased the preference for a safe compartment without increasing the latency. These differential pharmacological effects confirm that PAC is based on the fear conditioning, which causes an increase in the latency to escape from the central compartment, and on the memory of the location of shock exposure, which provides the preference for the safe compartment.

A two-tissue reversible compartment model is solved by Laplace transform method for kinetic modelling of [18F]2-fluoro-2deoxy-D-glucose, in order to quantify amyloid in positron emission tomography...

To evaluate thiol/disulfide homeostasis in both maternal and fetal compartment in the presence of fetal growth restriction (FGR).A prospective case-control study was carried out in women with FGR (Native thiol, total thiol and disulfide amounts were decreased in the maternal serum and fetal cord blood of babies born to women with FGR (Maternal and fetal serum thiol/disulfide profiles may use prediction of FGR severity and its neonatal outcome.

Reactive oxygen species (ROS), such as the superoxide anion, the hydroxyl radical and singlet oxygen, can influence cellular processes in many ways. However, the molecular mechanisms of ROS action in cells are still poorly understood. As such, we need to develop tools that can better elucidate ROS behavior in the dynamic environment of a cell. Optogenetics provides one approach to this end. Using a genetically encoded protein-encased photosensitizer, one could produce a given ROS with a controllable yield in a specific intracellular domain or compartment. A palette of ROS sensitizing protein derivatives has emerged and, in this review, we use information gleaned from recent studies to discuss properties that define a 'good' singlet oxygen photosensitizing protein.

In immune-mediated glomerular diseases like crescentic glomerulonephritis (cGN), inflammatory CD4+T cells accumulate within the tubulointerstitial compartment in close contact to proximal and distal tubular epithelial cells and drive renal inflammation and tissue damage. However, whether renal epithelial cell populations play a role in the pathogenesis of cGN by modulating CD4+T cell responses is less clear. In the present study, we aimed to investigate the potential of renal epithelial cells to function as antigen-presenting cells, thereby stimulating CD4+T cell responses. Using a FACS-based protocol that allowed comparative analysis of cortical epithelial cell populations, we showed that particularly proximal tubular epithelial cells (PTECs) express molecules linked with antigen-presenting cell function, including major histocompatibility complex class II (MHCII), CD74, CD80, and CD86 in homeostasis and nephrotoxic nephritis, a murine model of cGN. Protein expression was visualized at the PTEC single cell level by imaging flow cytometry. Interestingly, we found inflammation-dependent regulation of epithelium-expressed CD74, CD80, and CD86, whereas MHCII expression was not altered. Antigen-specific stimulation of CD4+T cells by PTECs in vitro supported CD4+T cell survival and induced CD4+T cell activation, proliferation, and inflammatory cytokine production. In patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis, MHCII and CD74 were expressed by both proximal and distal tubules, whereas CD86 was predominantly expressed by proximal tubules. Thus, particularly PTECs have the potential to induce an inflammatory phenotype in CD4+T cells in vitro, which might also play a role in the pathology of immune-mediated kidney disease.

Stiff person syndrome (SPS) is a rare and disabling neurological disorder of autoimmune origin, characterized by progressive stiffness and muscle spasms affecting the axial and limb muscles, most frequently associated with antibodies against glutamic acid decarboxylase. We describe a patient who presented initially with compartment syndrome and was later diagnosed with SPS.This is the first case report of SPS possibly presenting initially with compartment syndrome. This case illustrates the importance of recognizing that patients with SPS may present with varied manifestations, including compartment syndrome, which by itself is a medical emergency.

In aerobic granular sludge (AGS) systems, different-sized microbial aggregates having different solids retention time (SRT) coexist in the same reactor compartment and are subjected to the same influent wastewater. Thus, the AGS system provides a unique ecosystem to study the importance of local (species sorting) and regional (immigration) processes in bacterial community assembly. The microbial communities of different-sized aggregates (flocs0.2 mm, small granules (0.2-1.0 mm) and large granules1.0 mm), influent wastewater, excess sludge and effluent of a full-scale AGS plant were characterized over a steady-state operation period of 6 months. Amplicon sequencing was integrated with mass balance to determine the SRT and net growth rate of operational taxonomic units (OTUs). We found strong evidence of species sorting as opposed to immigration, which was significantly higher at short SRT (i.e., flocs and small granules) than that at long SRT (large granules). Rare OTUs in wastewater belonging to putative functional groups responsible for nitrogen and phosphorus removal were progressively enriched with an increase in microbial aggregates size. In contrast, fecal- and sewage infrastructure-derived microbes progressively decreased in relative abundance with increase in microbial aggregate size. These findings highlight the importance of AGS as a unique model ecosystem to study fundamental microbial ecology concepts.

C4 photosynthesis evolved dozens of times, with a critical step being the engagement of a C4 metabolic cycle to concentrate CO2 into a bundle sheath-like compartment. While C3–C4 intermediate species show a progressive increase in the activity of a C4 metabolic cycle, the integration of the C4 and C3 biochemical cycles in enhancing photosynthetic carbon gain occurs in a punctuated manner, at an initial C4 cycle activity near 60%. Punctuated integration of the C4 cycle could result from the evolutionary acquisition of traits that coordinate the C3 and C4 biochemical cycles (for example, an enzymatic, regulatory or transport function) or from a sudden reduction in the mesophyll C3 cycle. Alternatively, a punctuated pattern could be an artifact of low numbers of C3–C4 intermediates in the evolutionary space where C4 cycle engagement occurs, due to incomplete sampling of natural diversity or evolutionary dynamics rendering such intermediates unstable. Understanding how the C4 cycle becomes integrated with the C3 cycle could reveal new avenues for engineering the C4 pathway into C3 plants. Such efforts would be facilitated by the generation of hybrids, or the discovery of additional intermediates, that span the transition from low to high C4 cycle engagement.

At the biochemical level, the plant peroxisome, which is a subcellular compartment surrounded by a single membrane, basically contains the antioxidant enzyme catalase and at least one HO-producing flavin oxidase. Over the last 25 years, considerable progress has been made in our understanding of basic processes such as β-oxidation, the glyoxylate cycle, and photorespiration. Novel experimental approaches have also enabled the discovery and identification of novel components of peroxisomes in different plant tissues, which has demonstrated potential new functions for these multipurpose organelles. Some of these enzymatic components, such as antioxidant systems like catalase, ascorbate peroxidase and superoxide dismutase, appear to be common to all tissue types, while others appear to be tissue-specific, i.e. glyoxylate cycle enzymes in oil-rich seedlings. This mini-review will provide a general overview of this fascinating plant organelle, in which hydrogen peroxide (HO) and the free radical nitric oxide (NO) are key molecules capable of regulating their own peroxisomal metabolism. Recent new experimental data show that virus proteins are imported into peroxisomes and also point to the presence of the gasotransmitter hydrogen sulfide (HS), which could represent a novel regulatory mechanism., Research in FJC laboratory is supported by the ERDF cofinanced grant from the Ministry of Economy and Competitiveness (AGL2015-65104-P) and Junta de Andalucía (group BIO 192), Spain

An hydroxythiophene-conjugated benzothiazole (T2(OH)B) was synthesized as a pH sensitive fluorescent probe. T2(OH)B displayed dual emission behavior due to the excited state intramolecular proton transfer (ESIPT) process, while the methoxy analogs, T2(OMe)B, did not. T2(OH)B showed strong fluorescence enhancement above physiological pHs. The applicability of T2(OH)B as a biological pH indicator was demonstrated by its use for staining mitochondrial compartment and H. pylori. Owing to its strong fluorescence emission with a large stokes shift and its effective response to pH, T2(OH)B serves as a platform for the design of new types of fluorescent probes.

A novel electrochemical membrane reactor integrated with a gas diffusion cathode (GDE) is proposed to improve oxygen utilization and energy efficiency for hydrogen peroxide (H2O2) electrogeneration...

Electrode cross-talk in lithium-ion batteries has been increasingly recognized in recent years as an explanation for several performance trends during cycling. However, little is known about the na...