Small Protrusions Research Articles

Erosion of stainless steel electrodes in a high-repetition-rate gas spark switch

Abstract High-repetition-rate gas spark switches are widely used in the field of nanosecond pulses. A discharge experimental platform has been established to investigate the erosion process of the electrodes in a high-repetition-rate gas spark switch. The surface morphology of the electrodes after different numbers of discharges at a repetition rate of 100 Hz is observed using a confocal laser scanning microscope. The results show that three different morphologies are presented on the electrode surface. Compared with the anode, the cathode surface has a higher roughness. There are irregular protrusions in the central area of the cathode, and small dot-like protrusions in the central area of the anode. The erosion process of the electrode at a high repetition rate can be divided into two stages. In the first stage, the roughness of the electrode increases with the discharge number. In the second stage, the arithmetic mean deviation of the central area of the cathode is maintained at around 4 μm, and on the central area of the anode, it is maintained at around 1 μm. The maximum profile peak height of the electrode continues to increase with the discharge number. This research has significant implications for the design of long-life gas spark switches.

Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.

Alzheimer's disease (AD) is the most common type of dementia worldwide. The etiopathogenesis of this disease remains unknown. Currently, several hypotheses attempt to explain its cause, with the most well-studied being the cholinergic, beta-amyloid (Aβ), and Tau hypotheses. Lately, there has been increasing interest in the role of immunological factors and other proteins such as alpha-synuclein (α-syn) and transactive response DNA-binding protein of 43 kDa (TDP-43). Recent studies emphasize the role of tunneling nanotubes (TNTs) in the spread of pathological proteins within the brains of AD patients. TNTs are small membrane protrusions composed of F-actin that connect non-adjacent cells. Conditions such as pathogen infections, oxidative stress, inflammation, and misfolded protein accumulation lead to the formation of TNTs. These structures have been shown to transport pathological proteins such as Aβ, Tau, α-syn, and TDP-43 between central nervous system (CNS) cells, as confirmed by in vitro studies. Besides their role in spreading pathology, TNTs may also have protective functions. Neurons burdened with α-syn can transfer protein aggregates to glial cells and receive healthy mitochondria, thereby reducing cellular stress associated with α-syn accumulation. Current AD treatments focus on alleviating symptoms, and clinical trials with Aβ-lowering drugs have proven ineffective. Therefore, intensifying research on TNTs could bring scientists closer to a better understanding of AD and the development of effective therapies.

Amyloid-β Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling.

Neuronal excitatory synapses are primarily located on small dendritic protrusions called spines. During synaptic plasticity underlying learning and memory, Ca2+ influx through postsynaptic NMDA-type glutamate receptors (NMDARs) initiates signaling pathways that coordinate changes in dendritic spine structure and synaptic function. During long-term potentiation (LTP), high levels of NMDAR Ca2+ influx promote increases in both synaptic strength and dendritic spine size through activation of Ca2+-dependent protein kinases. In contrast, during long-term depression (LTD), low levels of NMDAR Ca2+ influx promote decreased synaptic strength and spine shrinkage and elimination through activation of the Ca2+-dependent protein phosphatase calcineurin (CaN), which is anchored at synapses via the scaffold protein A-kinase anchoring protein (AKAP)150. In Alzheimer's disease (AD), the pathological agent amyloid-β (Aβ) may impair learning and memory through biasing NMDAR Ca2+ signaling pathways toward LTD and spine elimination. By employing AKAP150 knock-in mice of both sexes with a mutation that disrupts CaN anchoring to AKAP150, we revealed that local, postsynaptic AKAP-CaN-LTD signaling was required for Aβ-mediated impairment of NMDAR synaptic Ca2+ influx, inhibition of LTP, and dendritic spine loss. Additionally, we found that Aβ acutely engages AKAP-CaN signaling through activation of G-protein-coupled metabotropic glutamate receptor 1 (mGluR1) leading to dephosphorylation of NMDAR GluN2B subunits, which decreases Ca2+ influx to favor LTD over LTP, and cofilin, which promotes F-actin severing to destabilize dendritic spines. These findings reveal a novel interplay between NMDAR and mGluR1 signaling that converges on AKAP-anchored CaN to coordinate dephosphorylation of postsynaptic substrates linked to multiple aspects of Aβ-mediated synaptic dysfunction.

Morphology, Glycan Pattern, Heat Shock Proteins, and Sex Steroid Receptors Expression in the Tubal Fimbria Epithelium of the Baboon Papio hamadryas during the Menstrual Cycle.

The oviductal fimbria is the first extraovarian anatomical structure that the cumulus-oocyte complex (COC) encounters, and is sensitive to sex hormone changes. The morphology, glycan pattern, expression of heat shock proteins (HSPs), estradiol receptor (ER), and progesterone receptor (PR) were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. The morphology was investigated by light and scanning electron microscopy; the glycopattern was characterized using conventional and lectin histochemistry; HSPs (60, -70, -90), ER, and PR were localized immunohistochemically. Well-differentiated ciliated and nonciliated cells were present only during the preovulatory phase. The nonciliated cells contained small apical protrusions and thin microvilli. During the preovulatory phase (1) the luminal surface of the fimbria displayed acidic glycans, complex N-glycans containing fucose, and oligolactosamine residues; (2) nonciliated cells expressed HSP60 and HSP90 in the apical blebs, HSP70 in the nucleus and cytoplasm, as well as nuclear ERα and PR; (3) ciliated cells showed HSP70 in the nucleus, cytoplasm, and cilia that also expressed HSP90 and PR. These results are related to the function of the fimbria where the early COC-oviduct crosstalk occurs and may represent a benchmark for translational studies of other primates.

(Invited) Application of Nanostructure for Improving the Interfacial Interactions between Sensing Surface and Targeted Particles

Various interfacial interactions, encompassing screened Coulomb (electrostatic double layer) forces, Lifshitz-van der Waals forces, hydrophobic/hydrophilic interactions, as well as steric, chemical, morphological, and roughness effects, have been confirmed to play a crucial role in governing the interaction between target particles and the sensing surface. Small protrusions on the sensing surface can induce substantial variations in the surface’s interaction with the target analytes based on the extended Derjauin-Landau-Verwey-Overbeek (DLVO) theory. 1 Here, indium tin oxide coated vertical nanowires served as nanostructure to investigate interfacial interactions between the sensing surface and targeted analytes. Analyzing the ratio of particle size to asperity size on the sensing surface within the extended DLVO theory revealed that surface roughness can provide sufficient interfacial interactions with target analytes, thereby enhancing the electrical sensing performance. Upon immersing the nanostructural sensing surface in an analyte solution, electrical signals undergo a significant shift owing to alterations in the surface potential at the interface between the functionalized sensing surface (such as antibodies or chemical functional groups) and the analyte solution. 2, 3 These observations highlight the critical role of nanostructure on the sensing surface, particularly with adequate surface roughness, in significantly improving sensing performance by facilitating effective interaction of the surface with the target analyte based on the extended DLVO theory.

Voltage mapping in subcellular nanodomains using electro-diffusion modeling.

Voltage distribution in sub-cellular micro-domains such as neuronal synapses, small protrusions, or dendritic spines regulates the opening and closing of ionic channels, energy production, and thus, cellular homeostasis and excitability. Yet how voltage changes at such a small scale in vivo remains challenging due to the experimental diffraction limit, large signal fluctuations, and the still limited resolution of fast voltage indicators. Here, we study the voltage distribution in nano-compartments using a computational approach based on the Poisson-Nernst-Planck equations for the electro-diffusion motion of ions, where inward and outward fluxes are generated between channels. We report a current-voltage (I-V) logarithmic relationship generalizing Nernst law that reveals how the local membrane curvature modulates the voltage. We further find that an influx current penetrating a cellular electrolyte can lead to perturbations from tens to hundreds of nanometers deep, depending on the local channel organization. Finally, we show that the neck resistance of dendritic spines can be completely shunted by the transporters located on the head boundary, facilitating ionic flow. To conclude, we propose that voltage is regulated at a subcellular level by channel organization, membrane curvature, and narrow passages.

Comparing jet-shaped point symmetry in cluster cooling flows and supernovae

I point out similarities between point-symmetric X-ray morphologies in cooling flow groups and clusters of galaxies, which are observed to be shaped by jets, and point-symmetric morphologies of eight core-collapse supernova (CCSN) remnants. I identify these similarities by qualitative eye inspection of multiwavelength images. I use these similarities to strengthen the jittering jet explosion mechanism (JJEM) of CCSNe, which predicts that the last pairs of jets to be launched by the newly born neutron star might shape some CCSN remnants to point-symmetric morphology. The point-symmetric morphologies in both types of objects are composed of two or more pairs of opposite bubbles (cavities), nozzles, some clumps, small protrusions (termed ears), and rims. The typically large volume of a CCSN remnant shaped by jets implies that the shaping jets carry an energy comparable to that of the ejecta, which in turn implies that jets exploded the remnant’s massive star progenitor. The morphological similarities studied here add to the similarity of CCSN remnants, not only point-symmetric ones, to planetary nebulae shaped by jets. Together, these similarities solidify the JJEM as the main explosion mechanism of CCSNe. I consider the identification of point-symmetry in CCSNe, as expected by jet-shaping in the JJEM, to be the most severe challenge to the competing neutrino-driven explosion mechanism. I reiterate my earlier claim, but in a more vocal voice, that the main explosion mechanism of CCSNe is the JJEM.

Mechanical Properties, Tissue Structure, and Elemental Composition of the Walking Leg Tips of Coconut Crabs

The coconut crab, Birgus latro, has black protrusions on the tops of its walking legs and claw fingers. In addition, there are regularly aligned small black protrusions on parts of the exoskeleton surface of the claws and leg. In this study, the elemental composition, crystal structure, tissue structure, and mechanical properties of these protrusions were studied using a materials science approach, and the results were compared with those of mineralized cuticle. These leg tips were found to be a non-calcified fibrous tissue of α-chitin connected to the mineralized cuticle. The tip of the second walking leg was elongated and had a pointed shape with an oval cavity at its center that was more than 1000 times larger than the pore tubes (100–350 nm) of the mineralized cuticle. It was very soft, with a hardness of 0.4 GPa, corresponding to 11–12% of the hardness of the hard exocuticle and 55–57% of the hardness of the soft endocuticle. The elastic modulus of 8.0 GPa obtained by means of nanoindentation testing was consistent with that of α-chitin fibers of shrimp shells obtained by means of tensile testing. These soft protrusions provide a secure grip on the surfaces of trees or rocks and protect the claw fingertips. It was concluded that the black protrusions are related to a unique ecological (engaging in vertical movements, entering and exiting limestone caves, and escape behavior) aspect of the coconut crab, the largest terrestrial crustacean.

Improving the functional properties of rice glutelin: impact of succinic anhydride modification

SummaryRice glutelin is poorly soluble which restricts its potential food application. Succinylation is a chemical modification that improves the solubility of proteins by derivatising the ɛ‐amino group of lysine residues. In this study, rice glutelin was modified by succinic anhydride at different succinic anhydride concentrations (10%, 20%, 30%, 40%, and 50%). The succinylated rice glutelin samples showed enhanced solubility, reduced particle size, and increased absolute zeta potential values. The emulsifying and foaming properties of succinylated rice glutelin were also significantly improved. Moreover, SEM revealed that the surface of succinylated rice glutelin had small pits and protrusions. These results suggest that succinylation can effectively improve the functional properties of rice glutelin, which will facilitate its application in the food industry.

Biophysical Modeling of Actin-Mediated Structural Plasticity Reveals Mechanical Adaptation in Dendritic Spines.

Synaptic plasticity is important for learning and memory formation; it describes the strengthening or weakening of connections between synapses. The postsynaptic part of excitatory synapses resides in dendritic spines, which are small protrusions on the dendrites. One of the key features of synaptic plasticity is its correlation with the size of these spines. A long-lasting synaptic strength increase [long-term potentiation (LTP)] is only possible through the reconfiguration of the actin spine cytoskeleton. Here, we develop an experimentally informed three-dimensional computational model in a moving boundary framework to investigate this reconfiguration. Our model describes the reactions between actin and actin-binding proteins leading to the cytoskeleton remodeling and their effect on the spine membrane shape to examine the spine enlargement upon LTP. Moreover, we find that the incorporation of perisynaptic elements enhances spine enlargement upon LTP, exhibiting the importance of accounting for these elements when studying structural LTP. Our model shows adaptation to repeated stimuli resulting from the interactions between spine proteins and mechanical forces.

The possible transport and exclusion mode of lipofuscin in rat myocardium under electron microscopy

Lipofuscin accumulation has been observed in human coronary arteries but whether or not myocardial tissue can release lipofuscin generated within cardiomyocytes must be clarified, as this may provide indicators for future anti-ageing research. The hearts of Sprague Dawley rats, aged 6–24 months, were embedded in resin and ultrathin sections cut for electron microscopy. Lipofuscin granules were abundant in cardiomyocytes. Cardiomyocytes were seen to release lipofuscin granules into the myocardial interstitium as cytoplasmic fragments with irregular protrusions on the sarcolemma surface. The cytoplasmic fragments entering the stroma fused directly with the endothelial cells of adjacent capillaries, delivering lipofuscin to the vessel wall. These fragments were also seen to be engulfed by stromal macrophages or fused with fibroblasts, which then combined with capillary endothelial cells to deliver lipofuscin to the vessel wall. Some cytoplasmic fragments disaggregated and formed membrane-like waste, which travelled to the vessel wall from the myocardial stroma as soluble fine particles via diffusion or pinocytosis of capillary endothelial cells. Lipofuscin entered the vascular wall and endothelial cells, forming large and small protrusions or folds that transported the lipofuscin to the vascular lumen and bloodstream.

Synthesis and Characterization of a Polystyrene-based Scintillator for Gamma Detection

This study aimed to create and examine plastic scintillators made from a polystyrene matrix, which are widely used in radiation detection due to their favorable properties such as rapid decay time, low cost, resistance to moisture, and ease of fabrication. The scintillators were doped with p-terphenyl (PTP) and 1,4-bis[2-(phenyloxazolyl)]-benzene (POPOP) using an injection method with an extruder machine. The materials were then characterized using various techniques. Fourier Transform Infrared Spectroscopy (FTIR) revealed the presence of aromatic chains which are essential for the scintillation process. Differential Scanning Calorimetry (DSC) analysis showed stable thermal properties with a glass transition temperature of approximately 100ºC. Scanning Electron Microscopy (SEM) showed that the surface of the polymer is amorphous with small bumps and protrusions likely caused by the PTP and POPOP dopants. The optical evaluation indicated that the sample could absorb UV photons up to 340 nm and emit photons in the wavelength range of 400-500 nm with a peak at 421 nm. Gamma spectra analysis indicated that the plastic scintillators performed well in gamma detection and could be used in a Radiation Portal Monitor (RPM).

Effects of the inhomogeneous microstructures on buffer layer ablation failure in high voltage cables

In recent years, growing attention has been paid to the buffer layer ablation failure in high voltage cables. The buffer layer was always regarded as a homogeneous material in previous studies, while in this paper, the effects of its structural inhomogeneity on failure is found unneglectable. The buffer layer is recognized to be a porous material comprising fibers and air pores through microscopic characterization. Its porosity is measured to be 85% by testing mercury intrusion porosimetry. Especially, some small fiber protrusions are observed on the surface of buffer layer, which are categorized and named as tip protrusions and arched protrusions. Subsequently, the influence of these fiber protrusions is investigated by quantitatively proposing their geometric models. The electric field distortion is observed at the fiber regions after finite element simulation. Under the extreme circumstances when the tip protrusions are vertical and close to the central area of air gap, the maximum electric field at tip site can reach to 28.5 kV/mm, which is 9.5 times of the breakdown threshold of air. And the maximum electric field of arched protrusions region can reach to 5.94 kV/mm, which is more moderate but still higher than the threshold. Therefore, it is demonstrated that the breakdown of air gap inner cables can be induced by the inhomogeneous fiber protrusions.

Rigid normograde rhinoscopy-assisted traction-avulsion removal of small middle ear polyps from the auditory tube in five cats.

This study aims to describe a novel minimally invasive technique for the removal of small middle ear polyps from the auditory tube openings in cats. Five cats with clinical signs of otitis externa and/or otitis media, and/or upper respiratory tract inflammation were included. All cats underwent pharyngolaryngoscopy under anaesthesia, CT scan of the head, neck and thoracic cavity, video-otoscopic examination, retrograde nasopharyngoscopy and normograde rhinoscopy. The five cats described in this study were all found to have significant respiratory tract inflammation (rhinitis, sinusitis, nasopharyngitis, otitis media) with small polypous protrusions from the auditory tube openings. A normograde rhinoscopy-assisted traction-avulsion (RATA) removal of these small polyps was performed in all cases without complications. The rostral nasopharynx was visualised by a unilaterally normograde advanced rigid endoscope passing the choana, and polyps were removed using a grasping forceps introduced in the contralateral nostril. Telephone follow-up revealed clear improvement in all cases. One of the cases was re-evaluated with a CT scan and endoscopy 4 weeks after treatment. The CT scan showed a significant improvement with no abnormalities in both external ear canals and air opacity in both tympanic bullae. Video-endoscopic examination revealed intact tympanic membranes with mild chronic abnormalities and patent auditory tube openings upon normograde rhinoscopy. Rigid normograde RATA is a novel, minimally invasive and effective technique for the removal of small middle ear polyps from auditory tube openings in cats with otitis media.

Extracellular vesicles budding from stromal macrophages from the blood circulating in patients with metastatic non-small cell lung cancer to predict clinical outcomes.

e14547 Background: Extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies, are involved in cellular communication, aiding tumor growth, and in metastasis of cancer. Recently, extracellular budding structures on Cancer Associated Macrophage-Like Cells (CAMLs), a subtype of phagocytic circulating stromal cells found in circulation, was observed in patients with metastatic non-small cell lung carcinoma (mNSCLC). In this prospective analysis of n=104 metastatic NSCLC (mNSCLC) patients, we enumerated EV budding on CAMLs to determine their clinical significance on Progression Free Survival (PFS) & Overall Survival (OS), further subtyping based on treatment with or without PD-L1 Immunotherapy (IMT) based on standard of care treatment. These preliminary data suggests that EV positive (EV+) CAMLs prognosticates for worse PFS & OS in mNSCLC. Methods: We initiated a single blind multi-year prospective study to investigate the relationship between EV budding in CAMLs to PFS & OS prior to start of new treatment lines for mNSCLC. Anonymized blood was procured from n=104 pathologically confirmed mNSCLC patients and filtered to isolate CAMLs to measure EV budding using tumor/EV markers (i.e. cytokeratin, CD63, or CD81) and an immune specific marker (PD-L1). Blood was filtered by CellSieve microfiltration and EV budding was characterized as small (≤1 µm) bulbous protrusions from the cell cytoplasm. EVs were quantified by presence (EV+) or absence (EV-), as well asPD-L1 positivity or negativity in EVs, to compare PFS & OS with hazard ratios (HRs) at 60 months by censored univariate and multivariate analyses. Results: CAMLs were identified in 93% (n=97/104) of all samples, with EV budding (EV+) identified in 62% (n=60/97) of CAMLs. At 60 month follow-up, it was determined that EV+ CAMLs was associated with significantly worse PFS (HR=1.67 95%CI=0.4-1.0, p=0.0410) and OS (HR=1.88, 95%CI=0.3-0.9, p=0.0108). Further, in patients not treated with IMT, EV+ CAMLs was associated with significantly worse PFS (HR=2.51, 95%CI=0.2-0.8, p=0.0251) and OS (HR=2.32, 95%CI=0.2-0.9, 0.0407). In contrast, in patients treated with IMT, EV+ CAMLs had no correlation to PFS (1.18, 95%CI=0.5-1.6, p=0.7050) or OS (HR=1.53, 95%CI=0.3-1.3, p=0.2858), suggesting a clinical benefit in treating EV+ patients with PD-L1 IMT. Conclusions: EV budding on phagocytic stromal cells found in the blood of mNSCLC patients appears to predict for poorer PFS and OS, which is reduced with additional of PD-L1 immunotherapies. Larger validation studies are ongoing in both mNSCLC and stage III NSCLC patients, along with analysis of PD-L1 EV staining.

A rare presentation of linea alba hernia involving fibrolipoma of the hepatic round ligament: a case report and literature review

BackgroundLinea alba hernias are relatively rare types of hernias. They manifest as small protrusions situated in the linea alba between the umbilicus and xiphoid cartilage. Usually, hernia contents comprise the pre-peritoneal fat, omentum, and gastrointestinal tract. However, very few cases of linea alba hernias involving the hepatic round ligament have been reported, to date.Case presentationAn 80-year-old woman presented with upper abdominal pain and a 1-week history of a mass in the upper midline. Abdominal computed tomography revealed adipose tissue protruding from the abdominal wall contiguous with the hepatic round ligament, suggesting a linea alba hernia. During surgery, the hernial sac content was found to be a mass, which was resected. A linea alba hernia defect measuring 20 mm was repaired using a mesh. Histopathological findings revealed that the mass included mature adipocyte proliferation with broad fibrous septa, which was diagnosed as fibrolipoma of the hepatic round ligament.ConclusionsWe report the first case of a linea alba hernia involving fibrolipoma of the hepatic round ligament worldwide and describe the clinical features, diagnosis, and surgical procedure with a literature review.

Abstract 3310: Extracellular vesicles budding from stromal macrophages in the blood of metastatic non-small cell lung cancer patients correlates with poor survival

Abstract Purpose: Cancer extracellular vesicles (EVs) are involved in cellular communication, tumor growth, progression, and metastasis in cancer. The origins of EVs, their formation, and potential clinical use as biomarkers are not well understood. Recently, budding of extracellular structures on Cancer Associated Macrophage-Like Cells [CAMLs] a specific subtype of phagocytic circulating stromal cells has been observed in metastatic non-small cell lung carcinoma (mNSCLC) patients. In this prospective analysis of n=40 mNSCLC samples, we enumerated EV budding on CAMLs to determine if their formation had an effect on clinical outcomes. These preliminary results suggest that EV budding from a specific subtype of circulating tumor associated macrophage prognosticates for worse clinical outcome which may serve as the mechanism for cancer EV formation and spread throughout the body. Patients and Methods: We initiated a single blind prospective pilot study to evaluate extracellular budding on the CAMLs of mNSCLC patients from blood samples obtained prior to therapy to determine their prevalence and clinical utility. Anonymized blood was procured and filtered to isolate CAMLs and stained for cytokeratin, CD45, CD31 and PD-L1. EV budding was observed as small (≤1 µm) bulbous protrusions from the cell periphery. EVs were quantified and compared against patient progression free survival (PFS) and overall survival (OS) with hazard ratios (HRs) at 24 months by censored univariate analysis. The imaged EVs were also characterized by their PD-L1 biomarker expression. Results: CAMLs were identified in 88% (n=35/40) of all samples, with EV budding identified in 60% (n=21/35) of CAMLs. These EVs appeared with tumor positive proteins (i.e. CD31, CD45, PD-L1 and cytokeratin). With a minimum of 24 months of follow-up, it was determined that the presence of EV budding in patients’ CAMLs was associated with significantly worse PFS (HR=4.00, 95%CI=1.4-12, p=0.0251) and borderline significant OS (HR=3.57, 95%CI=1.1-12, p=0.0747). Conclusions: EV budding found on phagocytic stromal cells found in the blood appear with tumor positive biomarkers and predict poor survival. These findings suggest that CAMLs are an origin cell for some cancer EVs. Larger validation studies and cross comparison of PD-L1 on EVs as it related to immunotherapy response is ongoing. Citation Format: Jillian A. Moran, Steven H. Lin, Martin J. Edelman, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Zhongxing Liao, Kirby P. Gardner, Cha-Mei Tang, Daniel L. Adams. Extracellular vesicles budding from stromal macrophages in the blood of metastatic non-small cell lung cancer patients correlates with poor survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3310.

Dual Function of 4-Aminothiophene in Surface-Enhanced Raman Scattering Application as an Internal Standard and Adsorbent for Controlling Au Nanocrystal Morphology.

The sensitivity and quantitative accuracy of surface-enhanced Raman scattering (SERS) are the main factors that restrict its application. Here, novel Au nanoscale convex polyhedrons (Au NCPs) were designed and fabricated to solve these problems via an embedded standard, including eight pods and six small protrusions. Spherical Au seeds regrew into different sizes of Au NCPs with a face-centered cubic structure. This morphology is due to the dual mechanism of the 4-aminothiophene (4-ATP) molecule that serves as an internal standard and a surface ligand regulator combined with the regulatory role of hexadecyl trimethyl ammonium chloride. The results show that Au NCPs were enclosed by high-index {12 9 1} facets, which greatly improved the local plasma resonance and reduced the lowest SERS detectable concentration of pyrene in standard seawater to 0.5 nM. An effective reference was produced by embedding 4-ATP with a relative standard deviation value less than 2.97% (in the same batch) and 3.92% (between different batches). Our research offers a new strategy for morphological regulation of metal nanocrystals, which is useful for the preparation of highly sensitive SERS substrates and trace analysis.

Blebs promote cell survival by assembling oncogenic signalling hubs.

Most human cells require anchorage for survival. Cell-substrate adhesion activates diverse signalling pathways, without which cells undergo anoikis-a form of programmed cell death1. Acquisition of anoikis resistance is a pivotal step in cancer disease progression, as metastasizing cells often lose firm attachment to surrounding tissue2,3. In these poorly attached states, cells adopt rounded morphologies and form small hemispherical plasma membrane protrusions called blebs4-11. Bleb function has been thoroughly investigated in the context of amoeboid migration, but it has been examined far less in other scenarios12. Here we show by three-dimensional imaging and manipulation of cell morphological states that blebbing triggers the formation of plasma membrane-proximal signalling hubs that confer anoikis resistance. Specifically, in melanoma cells, blebbing generates plasma membrane contours that recruit curvature-sensing septin proteins as scaffolds for constitutively active mutant NRAS and effectors. These signalling hubs activate ERK and PI3K-well-established promoters of pro-survival pathways. Inhibition of blebs or septins has little effect on the survival of well-adhered cells, but in detached cells it causes NRAS mislocalization, reduced MAPK and PI3K activity, and ultimately, death. This unveils a morphological requirement for mutant NRAS to operate as an effective oncoprotein. Furthermore, whereas some BRAF-mutated melanoma cells do not rely on this survival pathway in a basal state, inhibition of BRAF and MEK strongly sensitizes them to both bleb and septin inhibition. Moreover, fibroblasts engineered to sustain blebbing acquire the same anoikis resistance as cancer cells even without harbouring oncogenic mutations. Thus, blebs are potent signalling organelles capable of integrating myriad cellular information flows into concerted cellular responses, in this case granting robust anoikis resistance.

Actin filament sliding in CaMKII-actin bundles.

During learning and memory formation, neurons form synapses in the brain by connecting the axons of presynaptic neurons to the dendrites of postsynaptic neurons. Small protrusions in the postsynaptic neuron dendrites, called dendritic spines, form when the presynaptic neurons send high-frequency signals in a process known as long-term potentiation. The Calcium/calmodulin-dependent protein kinase II, CaMKII, is a critical protein in long-term potentiation, as it can decode the signals, trigger a phosphorylation cascade, and interact with actin filaments forming blunt-ended bundles. In this project, we modeled actin filaments using a previously reported coarse-grained model of 4 particles per actin protomer. We also modeled CaMKII and actin filaments based on docking simulations done in our group. We compare CaMKII bundles with bundles formed with other crosslinkers, such as α-actinin and fascin, and show that the geometry of CaMKII allows it to slide along actin filaments. We show how the sliding of the CaMKII monomers depends on the affinity and geometry of the CaMKII-actin interaction. Finally, we propose a mechanism that explains how CaMKII sliding may lead to the formation of blunt-ended actin bundles.