Intrinsic Susceptibility Research Articles

Enhanced susceptibility of pediatric airway epithelium to respiratory syncytial virus infection.

Immature innate and adaptive immunity and vulnerability of narrower airways to obstruction increase the susceptibility of infants to severe respiratory syncytial virus (RSV) disease. In this issue of the JCI, Zhao et al. illustrated greater intrinsic susceptibility of pediatric versus adult airway epithelial cells to RSV-induced cytopathology. Using precision cut lung slices (PCLS) and air-liquid interface (ALI) airway epithelial cell cultures, the authors showed that impaired STAT3 activation in RSV-infected pediatric multiciliated cells increased cell apoptosis and viral shedding, which enhanced the spread of infection. Bolstering STAT3 activation and treatment of neonatal mice with apoptosis inhibitors suppressed virus spread, suggesting that enhancing STAT3 activation may provide therapeutic benefit.

An anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression

Previously, we showed that the germ cell-specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility (Ehrmann et al., 2019). Here, we show that in somatic cells the similar yet ubiquitously expressed RBMX protein has similar functions. RBMX regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. The RBMX gene is silenced during male meiosis due to sex chromosome inactivation. To test whether RBMXL2 might replace the function of RBMX during meiosis we induced expression of RBMXL2 and the more distantly related RBMY protein in somatic cells, finding each could rescue aberrant patterns of RNA processing caused by RBMX depletion. The C-terminal disordered domain of RBMXL2 is sufficient to rescue proper splicing control after RBMX depletion. Our data indicate that RBMX and RBMXL2 have parallel roles in somatic tissues and the germline that must have been conserved for at least 200 million years of mammalian evolution. We propose RBMX family proteins are particularly important for the splicing inclusion of some ultra-long exons with increased intrinsic susceptibility to cryptic splice site selection.

Credit card default prediction using ML and DL techniques

The banking sector is widely acknowledged for its intrinsic unpredictability and susceptibility to risk. Bank loans have emerged as one of the most recent services offered over the past several decades. Banks typically serve as intermediaries for loans, investments, short-term loans, and other types of credit. The usage of credit cards is experiencing a steady increase, thereby leading to a rise in the default rate that banks encounter. Although there has been much research investigating the efficacy of conventional Machine Learning (ML) models, there has been relatively less emphasis on Deep Learning (DL) techniques. The application of DL approaches to credit card default prediction has not been extensively researched despite their considerable potential in numerous fields. Moreover, the current literature frequently lacks particular information regarding the DL structures, hyperparameters, and optimization techniques employed. To predict credit card default, this study evaluates the efficacy of a DL model and compares it to other ML models, such as Decision Tree (DT) and Adaboost. The objective of this research is to identify the specific DL parameters that contribute to the observed enhancements in the accuracy of credit card default prediction. This research makes use of the UCI ML repository to access the credit card defaulted customer dataset. Subsequently, various techniques are employed to preprocess the unprocessed data and visually present the outcomes through the use of exploratory data analysis (EDA). Furthermore, the algorithms are hypertuned to evaluate the enhancement in prediction. We used standard evaluation metrics to evaluate all the models. The evaluation indicates that the AdaBoost and DT exhibit the highest accuracy rate of 82 ​% in predicting credit card default, surpassing the accuracy of the ANN model, which is 78 ​%.

Molecular Evaluation of the mRNA Expression of the ERG11, ERG3, CgCDR1, and CgSNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population.

The study of Candida glabrata genes associated with fluconazole resistance, from a molecular perspective, increases the understanding of the phenomenon with a view to its clinical applicability. We sought to establish the predictive molecular profile of fluconazole resistance in Candida glabrata by analyzing the ERG11, ERG3, CgCDR1, and CgSNQ2 genes. Expression was quantified using RT-qPCR. Metrics were obtained through molecular docking and Fisher discriminant functions. Additionally, a predictive classification was made against the susceptibility of C. glabrata to fluconazole. The relative expression of the ERG3, CgCDR1, and CgSNQ2 genes was higher in the fluconazole-resistant strains than in the fluconazole-susceptible, dose-dependent strains. The gene with the highest relative expression in the fluconazole-exposed strains was CgCDR1, and in both the resistant and susceptible, dose-dependent strains exposed to fluconazole, this was also the case. The molecular docking model generated a median number of contacts between fluconazole and ERG11 that was lower than the median number of contacts between fluconazole and ERG3, -CgCDR1, and -CgSNQ2. The predicted classification through the multivariate model for fluconazole susceptibility achieved an accuracy of 73.5%. The resistant strains had significant expression levels of genes encoding efflux pumps and the ERG3 gene. Molecular analysis makes the identification of a low affinity between fluconazole and its pharmacological target possible, which may explain the lower intrinsic susceptibility of the fungus to fluconazole.

Rational design of robust Cu@Ag core-shell nanowires for wearable electronics applications

Copper nanowires (CuNWs) have shown great potential as transparent electrodes for cost-effective wearable electronics. However, its unsatisfactory electrical conductivity and intrinsic susceptibility to oxidation hinder practical applications. To address these issues, herein, ultra-stable Cu@Ag core–shell NWs have been designed via a facile galvanic replacement method for wearable applications. The thermal stability of the NWs is significantly enhanced after introducing Ag, and superior stability is achieved with a more uniform Ag coating. The structural integrity of the percolation networks is basically maintained after 5 days’ annealing treatment at a high temperature (≥150 °C). The devices based on core–shell NWs show reliable heating performance, and can further be used for defrosting and heating water/ice applications. Owing to optimized contact between Ag-coated NWs, the devices exhibit excellent mechanical performance under repetitive bending. Based on above structural design, the resultant strain sensors show high sensitivity, good repeatability and a wide sensing range, which are capable to detect various hand gestures and communicate with Morse code. Furthermore, the fabricated core–shell NWs show robust antibacterial activity, which is essential for wearable healthcare applications, outperforming that of pristine CuNWs. This work provides a promising way for the design of high-performance metal NWs for advanced wearable electronics.

Multi-functionalization and recycling of basalt fibre/polypropylene laminated composites based on mixed plain-woven fabric and related interfacial decorations

The development of laminated composites of thermoplastic polypropylene (PP)/continuous basalt fabric is limited by poor mutual infiltration and weak interfacial interactions between the matrix and fabric, as well as the intrinsic flammability and susceptibility of the PP matrix to ultraviolet (UV) aging. To solve the above shortcomings in a high-efficiency manner, a multi-functional transition layer was constructed between the PP matrix and long basalt fibres (LBFs) based on a hybrid plain-woven fabric composed of LBFs weft yarns and PP warp yarns. After hot-laminating these hybrid plain-woven prepregs, the mechanical performance of the resultant laminates was optimised and strengthened by selecting the compositions of the multi-functional transition layers (comprising flexible alkyl glycidyl ether chains, various rigid inorganic nanoparticles, or a flexible-rigid hybrid layer). Among these different transition layers, the interface between the LBFs-g-MWCNTs-OH and the PP matrix presented better mutual infiltration due to the lower interfacial energy, stronger mechanical engagement effect derived from the rougher fibre surface, and higher interfacial modulus. Therefore, the fewer structural defects and more effective transfer of the applied load at the interface caused the tensile strength/modulus and flexural strength/modulus of the related hybrid weaving laminates (HWLs) to reach 278.1 MPa/31.8 GPa and 264.2 MPa/12.4 GPa, respectively. The rigid interfaces formed by the deposited nanoparticles also accelerated heat transfer from the matrix to the fibre and the absorption of UV-light inside composite, then improving the flame-retardancy and anti-UV aging performances of the corresponding HWLs. Finally, recyclability evaluations indicated that the waste LBFs-g-SiO2/PP HWLs can be used as anti-UV aging and flame-retardant agents to fabricate new modified PP pellets with multiple functions.

Refined Understanding of the Impact of the Mycobacterium tuberculosis Complex Diversity on the Intrinsic Susceptibility to Pretomanid

Refined Understanding of the Impact of the Mycobacterium tuberculosis Complex Diversity on the Intrinsic Susceptibility to Pretomanid

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Organosilicon-Based Ligand Design for High-Performance Perovskite Nanocrystal Films for Color Conversion and X-ray Imaging.

Perovskite nanocrystals (PNCs) bear a huge potential for widespread applications, such as color conversion, X-ray scintillators, and active laser media. However, the poor intrinsic stability and high susceptibility to environmental stimuli including moisture and oxygen have become bottlenecks of PNC materials for commercialization. Appropriate barrier material design can efficiently improve the stability of the PNCs. Particularly, the strategy for packaging PNCs in organosilicon matrixes can integrate the advantages of inorganic-oxide-based and polymer-based encapsulation routes. However, the inert long-carbon-chain ligands (e.g., oleic acid, oleylamine) used in the current ligand systems for silicon-based encapsulation are detrimental to the cross-linking of the organosilicon matrix, resulting in performance deficiencies in the nanocrystal films, such as low transparency and large surface roughness. Herein, we propose a dual-organosilicon ligand system consisting of (3-aminopropyl)triethoxysilane (APTES) and (3-aminopropyl)triethoxysilane with pentanedioic anhydride (APTES-PA), to replace the inert long-carbon-chain ligands for improving the performance of organosilicon-coated PNC films. As a result, strongly fluorescent PNC films prepared by a facile solution-casting method demonstrate high transparency and reduced surface roughness while maintaining high stability in various harsh environments. The optimized PNC films were eventually applied in an X-ray imaging system as scintillators, showing a high spatial resolution above 20 lp/mm. By designing this promising dual organosilicon ligand system for PNC films, our work highlights the crucial influence of the molecular structure of the capping ligands on the optical performance of the PNC film.

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth.

Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

High-resolution digital mapping of soil erodibility in China

Soil erodibility (K) is the intrinsic susceptibility of a soil to water erosion. Currently, its detailed and accurate spatial distribution information especially over large areas is urgently required for national and regional soil erosion assessment and soil conservation decision making. This study combined pedotransfer function with digital soil mapping techniques to develop a high-resolution map of soil erodibility across China. The First, based on a recent national soil survey, we adopted the erosion-productivity impact calculator (EPIC) to calculate soil erodibility values at 4710 soil sampling points. Then, with the caclulated values of points, we used five techniques including polygon linking (PL), ordinary kriging (OK), Cubist, extreme gradient boosting (XGBoost), and random forests (RF) to generate spatial distribution of soil erodibility. The three latter machine learning techniques modeled the quantitative relationships between soil erodibility and a set of environmental covariates. The results showed that machine learning methods exhibited much more spatial details than the PL and OK did. Among the five techniques the RF achieved the highest accuracy with R2 of 0.49 and RMSE of 0.0077 t ha h ha−1 MJ−1 mm−1 based on 10-fold cross-validation. Spatial uncertainty analysis of the RF predictions showed that high uncerntainty occurred in northwestern China and low uncertainty in the center and southeast. We found that topographical and climatic variables are major environmental factors indirectly controlling spatial variation of soil erodibility while the soil particle composition and SOC contents directly influence the variation.

Refined understanding of the impact of the Mycobacterium tuberculosis complex diversity on the intrinsic susceptibility to pretomanid.

This study confirmed that the Mycobacterium tuberculosis complex lineage 1, responsible for 28% of global tuberculosis cases, is less susceptible to pretomanid (Pa). It also refined the understanding of the intrinsic susceptibilities of lineages 5 and 6, most frequent in West Africa, and lineages 8 and 9. Regulators must review whether these in vitro differences affect the clinical efficacy of the WHO-recommended BPaL(M) regimen and set breakpoints for antimicrobial susceptibility testing accordingly. Notably, regulators should provide detailed justifications for their decisions to facilitate public scrutiny.

Susceptibility to mycobacterial infection in VEXAS syndrome.

VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency. Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites. patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3 vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients. VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.

Possible quantum-spin-liquid state in van der Waals cluster magnet Nb3Cl8

The cluster magnet Nb3Cl8 consists of Nb3 trimmers that form an emergent S = 1/2 two-dimensional triangular layers, which are bonded by weak van der Waals interactions. Recent studies show that its room-temperature electronic state can be well described as a single-band Mott insulator. However, the magnetic ground state is non-magnetic due to a structural transition below about 100 K. Here we show that there exists a thickness threshold below which the structural transition will not happen. For a bulk crystal, a small fraction of the sample maintains the high-temperature structure at low temperatures and such remnant gives rise to linear-temperature dependence of the specific heat at very low temperatures. This is further confirmed by the measurements on ground powder sample or c-axis pressed single crystals, which prohibits the formation of the non-magnetic state. Moreover, the intrinsic magnetic susceptibility also tends to be constant with decreasing temperature. Our results suggest that Nb3Cl8 with the high-temperature structure may host a quantum-spin-liquid ground state with spinon Fermi surfaces, which can be achieved by making the thickness of a sample smaller than a certain threshold.

Ti3C2Tx@Co(OH)2/Co3O4 nanocomposites with heterojunction enhancement effect for toluene detection at room temperature

Ti3C2Tx MXene possesses excellent conductivity, tunable electronic structure, and large surface area, thereby ideal for use in gas sensors. However, Ti3C2Tx MXene is limited by low sensitivity linked to its low intrinsic activity and susceptibility to oxidation. Herein, Ti3C2Tx@Co(OH)2/Co3O4 nanocomposites were prepared by self-assembly strategy. High sensitivity to toluene at room temperature can be obtained by adjusting the input ratio of Ti3C2Tx MXene (MXCo-40). MXCo-40 obtained with 40 mg of Ti3C2Tx MXene input exhibited a remarkable response of 514 % to 100 ppm toluene, 737 times higher than Ti3C2Tx MXene, with response and recovery times of 9 s and 5 s. Ultraviolet photoelectron spectrometer, ultraviolet–visible absorbance spectroscopy, and diffuse reflection infrared fourier transform spectroscopy analyses revealed the heterojunction structure and monitored the gas-sensing reaction. The results suggested that the improved performance can be attributed to the formation of enhanced heterojunction structure, the electron-supplying ability of Co low-lying 3d orbitals, and high local charge concentration facilitating toluene polarization and bond breaking. In summary, the proposed composite structure looks promising for the preparation of Ti3C2Tx MXene-based gas sensors for enhanced gas-sensing applications.

Abstract 19064: Sex Specific Gene Profile in Canine Sinoatrial Node

Introduction: Biological sex plays an important role in cardiac function and occurrence of cardiac arrhythmias. Clinical reports show that adult females have faster resting and intrinsic heart rate (HR) while males have faster HR peak and larger HR reserve. Furthermore, inappropriate sinus tachycardia primarily occurs in females, suggesting sex-specific function and/or structure of the sinoatrial node (SAN). The aim of the study is to define sex-specific molecular features of the SAN complex. Methods: mRNA was isolated from SAN pacemaker tissue of healthy adult canines (male=4, female=4). Differential RNA expression patterns of &gt;400 genes, including fibrosis, inflammation, and metabolism markers were quantified with nCounter Nanostring fibrosis panel. Quantitative PCR was used to compare mRNAs of key ion channels related to SAN pacemaker function. Results: Nanostring panel revealed sex-specific and SAN-specific gene profiles of inflammation and fibrotic markers with multiple mRNAs higher in male (e.g. NLRP3, CD86, COL3A1, TGFB1) and several higher in females (e.g. MARCOL, IL20RB). mRNAs responsible for SAN pacemaking e.g. HCN1, HCN4, Cav1.3, and GIRK4 are higher expressed in female SAN. Sex-specific retrospective analysis of published gene profiles from non-failing human hearts showed a similar pattern to canine with HCN1, HCN4, Cav1.3 expression higher in female SAN. Conclusions: The study revealed significantly different gene expressions of fibrosis, inflammation, and pacemaking in male vs female SAN. The higher expression of HCN1/4 and Cav1.3 may explain the faster intrinsic sinus rhythm and susceptibility to SAN arrhythmias in females. The elevated fibrosis and inflammation genes in male SAN may suggest higher vulnerability to fibrotic remodeling during cardiac disease.

Piston-cylinder cell made of Ni–Cr–Al alloy for magnetic susceptibility measurements under high pressures in pulsed high magnetic fields

We developed a metallic pressure cell made of 56Ni–40Cr–4Al (Ni–Cr–Al) alloy for use with a non-destructive pulse magnet and a magnetic susceptibility measurement apparatus with a proximity detector oscillator (PDO) in pulsed magnetic fields of up to 51 T under pressures of up to 2.1 GPa. Both the sample and sensor coil of the PDO were placed in the cell so that the magnetic signal from Ni–Cr–Al would not overlay the intrinsic magnetic susceptibility of the sample. A systematic investigation of the Joule heating originating from metallic parts of the pressure cell revealed that the increase in sample temperature is negligible at 1.4 K in magnetic fields of up to 40 T in the field-ascending process for the maximum applied magnetic field of 51 T. The effectiveness of our apparatus was demonstrated by investigating the pressure dependence of the magnetization process of the triangular-lattice antiferromagnet Ba3CoSb2O9.

MRI‐Compatible, Transparent PEDOT:PSS Neural Implants for the Alleviation of Neuropathic Pain with Motor Cortex Stimulation

AbstractSimultaneous monitoring of electrophysiology and magnetic resonance imaging (MRI) could guide the innovative diagnosis and treatment of various neurodegenerative diseases that are previously impossible. However, this technique is difficult because the existing metal‐based implantable neural interface for electrophysiology is not free from signal distortions from its intrinsic magnetic susceptibility while performing an MRI of the implanted area of the neural interface. Moreover, brain tissue heating from neural implants generated by the radiofrequency field from MRI poses potential hazards for patients. Previous studies with soft polymer‐based electrode arrays provide relatively suitable MRI compatibility but does not guarantee high‐resolution electrophysiological signal acquisition and stimulation performance. Here, MRI compatible, optically transparent flexible implantable device capable of electrophysiological multichannel mapping and electrical stimulation is introduced. Using the device, neuropathic pain (NP) relief with a 30‐channel electrophysiological mapping of the somatosensory area before and after motor cortex stimulation (MCS) in allodynia rats after noxious stimulation is confirmed. Additionally, artifact‐free manganese‐enhanced MRI of dramatic relief of pain‐related region activity by MCS is demonstrated. Furthermore, artifact‐free optogenetics with transgenic mice is also investigated by recording light‐evoked potentials. These results suggest a promising neuro‐prosthetic for analyzing and modulating spatiotemporal neurodynamic without MRI or optical modality resolution constraints.

Obtaining extended insight into molecular systems by probing multiple pathways in second-order nonlinear spectroscopy.

Second-order nonlinear spectroscopy is becoming an increasingly important technique in the study of interfacial systems owing to its marked ability to study molecular structures and interactions. The properties of such a system under investigation are contained within their intrinsic second-order susceptibilities which are mapped onto the measured nonlinear signals (e.g. sum-frequency generation) through the applied experimental settings. Despite this yielding a plethora of information, many crucial aspects of molecular systems typically remain elusive, for example the depth distributions, molecular orientation and local dielectric properties of its constituent chromophores. Here, it is shown that this information is contained within the phase of the measured signal and, critically, can be extracted through measurement of multiple nonlinear pathways (both the sum-frequency and difference-frequency output signals). Furthermore, it is shown that this novel information can directly be correlated to the characteristic vibrational spectra, enabling a new type of advanced sample characterization and a profound analysis of interfacial molecular structures. The theory underlying the different contributions to the measured phase of distinct nonlinear pathways is derived, after which the presented phase disentanglement methodology is experimentally demonstrated for model systems of self-assembled monolayers on several metallic substrates. The obtained phases of the local fields are compared to the corresponding phases of the nonlinear Fresnel factors calculated through the commonly used theoretical model, the three-layer model. It is found that, despite its rather crude assumptions, the model yields remarkable similarity to the experimentally obtained values, thus providing validation of the model for many sample classes.

Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells.

Metastatic dissemination is still one of the major causes of death of melanoma's patients. KiSS1 is a metastasis suppressor originally identified in melanoma cells, known to play an important physiological role in mammals' development and puberty. It has been previously shown that expression of KiSS1 could be increased in lung cancer cells using epigenetic agents, and that KiSS1 could have a pro-apoptotic action in combination with cisplatin. Thus, the aim of the present study was to examine in human melanoma vemurafenib sensitive- and -resistant BRAF mutant cells characterized by different mutational profiles and KiSS1, KiSS1 receptor and KiSS1 drug-induced release, if peptides derived from KiSS1 cleavage, i.e., kisspeptin 54, could increase the sensitivity to vemurafenib of human melanoma, using cellular, molecular and biochemical approaches. We found that kisspeptin 54 increases vemurafenib pro-apoptotic activity in a statistically significant manner, also in drug resistant cellular models. The efficacy of the combination appears to reflect the intrinsic susceptibility of each cell line to PLX4032-induced apoptosis, together with the different mutational profile as well as perturbation of proteins regulating the apoptotic pathway, The results presented here highlight the possibility to exploit KiSS1 to modulate the apoptotic response to therapeutically relevant agents, suggesting a multitasking function of this metastasis suppressor.