In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria‐associated ER membranes (MAMs). Ca2+ ion and phospholipid transfer occurs at MAMs ...to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER‐anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid‐like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51–VAPB interaction is mediated by the FFAT‐like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM‐tethering function.
SYNOPSIS
The crystal structure and biochemical analyses of PTPIP51, a mitochondrial protein localized at the mitochondria‐associated ER membrane (MAM), revealed its phospholipid binding and transfer activity.
The crystal structure of the TPR domain of PTPIP51 at 1.45 Å resolution revealed the presence of a lipid‐like serpentine electron density.
PTPIP51 has phospholipid (especially phosphatidic acid) binding and transfer functions in vitro.
Mitochondrial cardiolipin levels are affected by PTPIP51.
The crystal structure and biochemical analyses of PTPIP51, a mitochondrial protein localized at the mitochondria‐associated ER membrane (MAM), revealed its phospholipid binding and transfer activity.
Developing new antibody assays for emerging SARS‐CoV‐2 variants is challenging. SARS‐CoV‐2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their ...performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT‐positive sera, we noticed that log‐transformed optical density (OD) ratio of wild‐type (WT) sVNT exhibited better titer‐correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer‐correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false‐negative rates (cPass‐BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F‐BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed‐effects model suggested superior titer‐correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.
Obesity is a major health problem and is known to be closely associated with metabolic diseases. Abnormal hepatic accumulation of fat causes fatty liver or hepatic steatosis, and long-term ...consumption of a high-fat diet is known to be a key obesity-causing factor. Recent studies have demonstrated that probiotics such as Lactobacillus strains, exert an anti-obesity effect by regulating adipogenesis. However, it is still unknown how the consumption of probiotics can reduce abdominal fat volume by regulating the hepatic expression of lipogenic genes. Therefore, we evaluated the effect of long-term ingestion of L. plantarum LMT1-48 on the expression of lipogenic genes in high-fat diet (HFD)-fed mice. We observed that treatment of 3T3-L1 adipocytes with L. plantarum LMT1-48 extract inhibited their differentiation and lipid accumulation by downregulating lipogenic genes, namely, PPARγ, C/EBPα, FAS, and FABP4. Interestingly, administration of L. plantarum LMT1-48 reduced liver weight and liver triglycerides concurrently with the downregulation of the lipogenic genes PPARγ, HSL, SCD-1, and FAT/CD36 in the liver, resulting in the reduction of body weight and fat volume in HFD-fed obese mice. Notably, we also observed that the administration of at least 10
CFU of L. plantarum LMT1-48 significantly lowered body weight and abdominal fat volume in modified diet-fed mouse models. Collectively, these data suggest that L. plantarum LMT1-48 is a potential healthy food for obese people.
Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as ...with lipid rafts or tetraspanin‐enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin‐enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L6 family member 5)‐enriched microdomains (T5ERMs) on the directionality of cell migration. Physical association of TM4SF5 with epidermal growth factor receptor (EGFR) and integrin α5 was visualized by live fluorescence cross‐correlation spectroscopy and higher‐resolution microscopy at the leading edge of migratory cells, presumably forming TM4SF5‐enriched microdomains. Whereas TM4SF5 and EGFR colocalized at the migrating leading region more than at the rear, TM4SF5 and integrin α5 colocalized evenly throughout cells. Cholesterol depletion and disruption in TM4SF5 post‐translational modifications, including N‐glycosylation and palmitoylation, altered TM4SF5 interactions and cellular localization, which led to less cellular migration speed and directionality in 2‐ or 3‐dimensional conditions. TM4SF5 controlled directional cell migration and invasion, and importantly, these TM4SF5 functions were dependent on cholesterol, TM4SF5 post‐translational modifications, and EGFR and integrin α5 activity. Altogether, we showed that TM4SF5 dynamically interacted with EGFR and integrin α5 in migratory cells to control directionality and invasion. —Kim, H.‐J., Kwon, S., Nam, S. H., Jung, J. W., Kang, M., Ryu, J., Kim, J. E., Cheong, J.‐G., Cho, C. Y., Kim, S., Song, D.‐G., Kim, Y.‐N., Kim, T. Y., Jung, M.‐K., Lee, K.‐M., Pack, C.‐G., Lee, J. W. Dynamic and coordinated single‐molecular interactions at TM4SF5‐enriched microdomains guide invasive behaviors in 2‐ and 3‐dimensional environments. FASEB J. 31, 1461–1481 (2017) www.fasebj.org
Thermal therapy is one of the most popular physiotherapies and it is particularly useful for treating joint injuries. Conventional devices adapted for thermal therapy including heat packs and wraps ...have often caused discomfort to their wearers because of their rigidity and heavy weight. In our study, we developed a soft, thin, and stretchable heater by using a nanocomposite of silver nanowires and a thermoplastic elastomer. A ligand exchange reaction enabled the formation of a highly conductive and homogeneous nanocomposite. By patterning the nanocomposite with serpentine-mesh structures, conformal lamination of devices on curvilinear joints and effective heat transfer even during motion were achieved. The combination of homogeneous conductive elastomer, stretchable design, and a custom-designed electronic band created a novel wearable system for long-term, continuous articular thermotherapy.
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•Dimethylglyoxime modified alginate bead(D-Ca-alg) was prepared for Ni2+ recovery.•D-Ca-alg shows superior Ni2+ adsorption capacity compared with pristine alginate bead.•D-Ca-alg ...could selectively adsorbs Ni2+ in the presence of Li+ and Co2+ at pH 3.•Continuous Ni2+ recovery was demonstrated using D-Ca-alg packed column experiments.•Ni2+ is successfully concentrated by consecutive elution of Ni2+ adsorbed D-Ca-alg column.
Nickel (Ni2+) plays a crucial role in the battery industry, but its high concentration in industrial wastewater poses significant health risks, necessitating an efficient removal process. Selective adsorption presents a promising technology for metal recycling from wastewater; however, there is currently no adsorbent that exhibits sufficient selectivity for Ni2+ over other divalent metals. In this study, we synthesized highly Ni2+ selective alginate beads modified with dimethylglyoxime (D-Ca-alg) and evaluated their Ni2+ separation and enrichment behavior. D-Ca-alg exhibited superior Ni2+ adsorption capacity (74.9 mg/g) compared to pristine alginate beads (Ca-alg) (50.6 mg/g). By increasing the solution pH, the Ni2+ uptake of D-Ca-alg proportionally increased and reached a maximum (61.6 mg/g at pH > 5). The physicochemical analysis revealed that both ion exchange and chelate formation are the main mechanisms of Ni2+ adsorption onto D-Ca-alg. Also, the selective Ni2+ separation ability of D-Ca-alg from other metal ions was evaluated in lithium-ion battery (LIB) recycling industry waste effluents. At pH 3, D-Ca-alg selectively separates Ni2+ from the solution without co-adsorption of Li+ and Co2+. In the continuous Ni2+ adsorption test, D-Ca-alg packed column treated more than 85 bed volumes (BV) of 20 mg/L Ni2+ solution with a flow rate of 1.0 mL/min. Finally, with 4 consecutive elutions of Ni2+ saturated D-Ca-alg packed columns, around 4000 ppm of Ni2+ enriched solution was obtained. Overall, our findings underscore the potential of D-Ca-alg as an effective adsorbent for Ni2+ recovery from LIB waste effluents, addressing environmental concerns and promoting sustainability in the battery industry.
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•Highly effective adsorbent is investigated to remove radioactive cesium(Cs) from seawater.•The adsorbent is metal hexacyanoferrate immobilized alginate bead (Me-HCF beads).•Me-HCF ...particles are formed on the alginate bead surface rather than inside of bead matrix.•Because Me-HCF particles are located on the surface of bead, it shows rapid reaction kinetics.•Me-HCF beads exhibit excellent feasibility for removal of 137Cs contaminated real seawater.
Metal hexacyanoferrates (Me-HCFs) are highly effective materials for removing radioactive Cs (137Cs) in seawater. For their practical application, granulation of Me-HCFs is necessary. However, conventional granulation techniques using a polymer as a binding material adversely affect the adsorption performance of Me-HCFs by blocking their adsorption sites. In the present work, to minimize the interference of the binding material, Me-HCF crystals were synthesized on an alginate bead surface in situ for the treatment of 137Cs+-contaminated seawater. Three different Me-HCFs immobilized on alginate beads (Fe-HCF, Cu-HCF, and Co-HCF) were prepared via a simple and rapid method involving a reaction between ionophorically crosslinked alginate beads (Fe3+, Cu2+, and Co2+ ions) and HCF solution. Among them, Fe-HCF crystals were successfully grown on the alginate bead surface; the other crystals were hardly synthesized despite a longer reaction time. The Fe-HCF crystals composed 15.0 % (w/w) of the beads and were located on the surface of the beads rather than being embedded in the alginate matrix. Because the Fe-HCF crystals were located at the surface of the alginate beads, Cs+ adsorption onto the Fe-HCF crystals showed fast reaction kinetics (achieving equilibrium in ∼ 3 h) and a high Cs+ adsorption capacity (∼33.5 mg/g). Also, a feasibility test was carried out for the removal of radioactive 137Cs+ in real seawater medium. Finally, a continuous Cs+ removal test was conducted in a packed column of the Fe-HCF beads. It was able to treat 65 bed volume of 50 mg/L of Cs+ solution with a flow rate of 1 mL/min.
ABSTRACT
Chiggers were collected from the central and southern parts of South Korea between April and November, 2009 with the aim of investigating the seasonal and geographical distribution of Or. A ...total of 1136 chiggers were identified. They included eight species belonging to four genera, as follows: Leptotrombidium scutellare (27.2%, n = 309), L. pallidum (54.6%, n = 621), L. orientale (6.25%, n = 71), L. palpale (1.59%, n = 18), L. zetum (2.0%, n = 23), Euschoengastia koreaensis (1.5%, n = 17), Cheladonta ikaoensis (0.08%, n = 1) and Neotrombicula japonica (1.05%, n = 12). The density of L. pallidum was high from April to May, whereas L. scutallare was not found in spring, being observed from October. Serotype‐specific nested PCR targeting the 56 kDa protein gene and sequencing analysis identified that the strains of 1136 O. tsutsugamushi in the chiggers as Boryong (6.8%), Kanda (0.4%), Oishi (0.3%), Jecheon (0.1%), Youngworl (0.1%) and Wonju (0.1%). Our findings indicate that L. pallidum and L. scutellare are dominant species in Korea and have geographical and seasonal variations.
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