Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

Autophagy plays critical roles in the maintenance of endothelial cells in response to cellular stress caused by blood flow. There is growing evidence that both cell adhesion and cell detachment can modulate autophagy, but the mechanisms responsible for this regulation remain unclear. Immunoglobulin and proline-rich receptor-1 (IGPR-1) is a cell adhesion molecule that regulates angiogenesis and endothelial barrier function. In this study, using various biochemical and cellular assays, we demonstrate that IGPR-1 is activated by autophagy-inducing stimuli, such as amino acid starvation, nutrient deprivation, rapamycin, and lipopolysaccharide. Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220. The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. Thus, our data demonstrate that IGPR-1 is activated by autophagy-inducing stimuli and in response regulates autophagy, connecting cell adhesion to autophagy. These findings may have important significance for autophagy-driven pathologies such cardiovascular diseases and cancer and suggest that IGPR-1 may serve as a promising therapeutic target.

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

Liza Botros MD., Manon C. A. Pronk PhD., Jenny Juschten MD., John Liddle, Sofia K. S. H. Morsing, Jaap D. van Buul PhD., Robert H. Bates, Pieter R. Tuinman MD. PhD., Jan S. M. van Bezu, Stephan Huveneers PhD., Harm Jan Bogaard MD. PhD., Victor W. M. van Hinsbergh PhD., Peter L. Hordijk PhD., and Jurjan Aman MD. PhD.

Aims: Endothelial barrier dysfunction leads to edema and vascular leak, carrying high morbidity and mortality. Previously, Abl kinase inhibition was shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes.

Methods & Results: Bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented LPS-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, Mitogen-activated Protein 4 Kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signals via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Arg by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation.

Conclusion: MAP4K4 was identified as important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Inhibiting both Arg and MAP4K4, the clinically available drug bosutinib may form a viable strategy against vascular leakage syndromes.

Georgi Dimchev
Apr 9, 2020; 133:jcs239020-jcs239020
Articles

An adhesion promotion process and composition for enhancing adhesion between a copper conducting layer and a dielectric material during manufacture of a printed circuit board. The composition contains a corrosion inhibitor, an inorganic acid, and an alcohol which is effective to increase copper-loading in the composition.

A method is disclosed for curing ink printed images on golf balls by printing an image onto a golf ball and exposing the printed image to infrared radiation, then exposing the printed image to ultraviolet radiation.

In some embodiments, an improved mechanical adhesion of copper metallization to dielectric with partially cured epoxy fillers is presented. In this regard, a substrate build-up film is introduced having epoxy material and a plurality of epoxy microspheres, wherein an interior of the microspheres is not fully cured. Other embodiments are also disclosed and claimed.

This invention concerns a creepage control system for locomotives that optimizes adhesion while minimizing wasted energy, rail/wheel wear and shock loading on the drive train. The basis of the invention is to always maintain a small but positive value of the slope of the wheel-rail adhesion creep curve (or differential of adhesion versus creep) for all traction axles of the locomotive through microprocessor control. The value of the differential of adhesion versus creep is used to define an operating window for control and operation of motors continually in the optimum domain when high adhesion is demanded. When, due to a sudden increase in rail contamination, the value of the control function becomes negative, the microprocessor control reduces the generator excitation in stages until the function becomes positive and inside the operating window again. The microprocessor controls a rail cleaning system which is turned on or off depending on the cleanliness of the rail. It also controls a rail sanding system which is turned on or off depending on the magnitude of wheel creep.

The adhesion between a locomotive drive wheel and supporting rail can be substantially increased by application of a powder mixture that contains a hard particle constituent preferably including alumina, a soft particle constituent preferably including titania, and an iron oxide constituent. The mixture may be in the form of a dry powder, a paste with water or alcohol vehicle, or a metal composite that includes the powder.

If the wheel/rail adhesion for a railway vehicle is insufficient then the wheels may slip when braking. If slipping is detected, a control system may reduce the brake pressure to permit a controlled level of slip and so to optimize the braking force for the available adhesion. By determining the pressure supplied to the brake cylinder, a signal may be obtained which indicates the value of the adhesion. Alternatively the adhesion may be monitored by detecting any discrepancy between the braking deceleration demanded by the driver and the observed deceleration. The adhesion signal may activate a warning. It may also be used to adjust the rate at which sand is supplied by a sander to the wheel/rail interface. The rate at which sand is supplied may also be adjusted in accordance with other parameters such as the train speed.

A method of dynamically controlling traction of a locomotive (V) having a plurality of axles (A1–A6) on each of which are mounted wheels (W) for moving the locomotive over a set of rails (R). A creep control signal (creep_n) is provided to a controller (TMTC) for each axle to move the locomotive over the rails, the creep control signal being a function of adhesion operation characteristics (tractive effort, torque, creep) for that axle. An advisory signal (ccc_n) combining values representative of the adhesion quality of the two axles is provided to the controller to maximize the tractive effort of the axle if the adhesion quality of the other axle is a maximum for the current rail conditions. This reduces the amount of time for the axle to attain its maximum tractive effort when rail conditions change.

The present invention provides an adhesive composition that may improve both adhesiveness to a film layer and adhesiveness to a rubber layer, and an adhesion method using the same, as well as a laminate and a tire. The adhesive composition according to the present invention includes a rubber component, at least 80 mass % of which rubber component is an epoxidized natural rubber.

The method for surface inclusions detection, enhancement of endothelial and osteoblast cells adhesion and proliferation and sterilization of electropolished and magnetoelectropolished Nitinol implantable medical device surfaces uses an aqueous solution of chemical compounds containing halogenous oxyanions as hypochlorite (ClO−) and hypobromite (BrO−) preferentially 6% sodium hypochlorite (NaClO).

The galvannealed steel sheet includes: a galvannealed layer formed on at least one surface of a steel sheet and contains includes an amount of 0.05 mass % to 0.5 mass % of Al, an amount of 6 mass % of 12 mass % of Fe, and the balance composed of Zn and inevitable impurities; and a mixed layer formed on a surface of the galvannealed layer and includes a composite oxide of Mn, Zn, and P and an aqueous P compound, wherein the composite oxide includes 0.1 mg/m2 to 100 mg/m2 of Mn, an amount of 1 mg/m2 to 100 mg/m2 of P, and Zn, and a P/Mn ratio is 0.3 to 50, and wherein the total size of an area of the mixed layer in which an attached amount of P is equal to or more than 20 mg/m2 is 20% to 80% of a surface area of the mixed layer.

A temporary adhesive for reversibly bonding a silicon wafer to a silicon support contains a crosslinkable organopolysiloxanes composition and a fatty acid or salt thereof or fatty acid ester as a release regulator having a density different from the crosslinkable organopolysiloxanes composition of at least 0.1 g/cm3, which upon parting of the wafer from the substrate, the adhesive remains substantially adhered to the substrate.

An apparatus, according to one embodiment, comprises a near field transducer; an adhesion layer on a media facing side of the near field transducer, the adhesion layer comprising Ni and Cr; and a protective layer on a media facing side of the adhesion layer. Other apparatuses, systems and methods are described in additional embodiments.

In nanoimprinting processes, photo-cured products often separate from the substrate and stick to the mold due to insufficient adhesion between the photo-cured product and the substrate. This causes a defect of pattern separation. An adhesion layer composition used for forming an adhesion layer between a substrate and a photocurable composition includes a compound (A) having at least two functional groups, and a solvent (B). The functional groups include at least one functional group capable of being bound to the substrate, selected from the group consisting of hydroxy, carboxy, thiol, amino, epoxy, and (blocked) isocyanate, and at least one hydrogen donating group as a functional group capable of being bound to the photocurable composition.

The present invention relates to a process for producing an electrolytic capacitor, the process comprising process steps i) ii): i) providing a capacitor body (1) that comprises an electrode body (2) of an electrode material,a dielectric (3) which at least partially covers the surface of this electrode material, anda solid electrolyte (4) at least comprising an electrically conductive material which at least partially covers the dielectric surface; ii) applying a primer solution e) to the capacitor body (1), followed by an application of a solution or dispersion a) comprising a conjugated polymer b) and a solvent or dispersant d), followed by an at least partial removal of the solvent or dispersant d) for the formation of the polymeric outer layer (5) that is formed onto the capacitor body (1); wherein the primer solution e) comprises at least one monofunctional amine and at least one carboxylic acid.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

Flora Borne, Alexander Kovalev, Stanislav Gorb, and Virginie Courtier-Orgogozo

Insects produce a variety of adhesives for diverse functions such as locomotion, mating, and egg or pupal anchorage to substrates. Although they are important for the biology of organisms and potentially represent a great resource for developing new materials, insect adhesives have been little studied so far. Here, we examined the adhesive properties of the larval glue of Drosophila melanogaster. This glue is made of glycosylated proteins and allows the animal to adhere to a substrate during metamorphosis. We designed an adhesion test to measure the pull-off force required to detach a pupa from a substrate and to evaluate the contact area covered by the glue. We found that the pupa adheres with similar forces to a variety of substrates (with distinct roughness, hydrophilic and charge properties). We obtained an average pull-off force of 217 mN, corresponding to 15,500 times the weight of a pupa and an adhesion strength of 137–244 kPa. Surprisingly, the pull-off forces did not depend on the contact area. Our study paves the way for a genetic dissection of the components of D. melanogaster glue that confer its particular adhesive properties.

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