Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM.     

SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin—Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases

The immune response to SARS-CoV-2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti-spike and anti-nucleocapsid antibodies, patient plasma proteins binding to pre-fusion stabilised complete spike and nucleocapsid proteins were isolated and analysed by matrix-assisted laser desorption ionisation–time of flight (MALDI-ToF) mass spectrometry. Amongst the immunoglobulins, a high affinity for human serum albumin was evident in the anti-spike preparations. Careful mass comparison revealed the preferential capture of advanced glycation end product (AGE) forms of glycated human serum albumin by the pre-fusion spike protein. The ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process. The preference of SARS-CoV-2 for AGE forms of glycated serum albumin may in part explain the severity and pathology of acute respiratory distress and the bias towards the elderly and those with (pre)diabetic and atherosclerotic/metabolic disease.     

Did Sleeping Papers in nursing research miss their target audience?

Scientometrics - Various factors have been attributed for delayed recognition of Sleeping Papers, for example introducing new technologies which didn’t yet exist, or proposing ideas that were...     

Dual representation of spatial rational Pythagorean-hodograph curves

In this paper, the dual representation of spatial parametric curves and its properties are studied. In particular, rational curves have a polynomial dual representation, which turns out to be both theoretically and computationally appropriate to tackle the main goal of the paper: spatial rational Pythagorean-hodograph curves (PH curves). The dual representation of a rational PH curve is generated here by a quaternion polynomial which defines the Euler–Rodrigues frame of a curve. Conditions which imply low degree dual form representation are considered in detail. In particular, a linear quaternion polynomial leads to cubic or reparameterized cubic polynomial PH curves. A quadratic quaternion polynomial generates a wider class of rational PH curves, and perhaps the most useful is the ten-parameter family of cubic rational PH curves, determined here in the closed form.     

Relative efficiency of police directorates in Slovenia: A non-parametric analysis

The main purpose of the paper is to apply a non-parametric methodology for measuring public police performance in Slovenia. The paper considers how previous studies have modeled the role of policing in their specifications of inputs and output. In particular, the multiple-stage Data Envelopment Analysis (DEA) technique is presented and then applied to measure the relative efficiency of police-work-related data for eleven Police Directorates (PDs) in 2010 and also compared with the efficiency scores in 2005. The data obtained from the police databases is analyzed through the Frontier Analyst 4.0 and SPSS 19.0 statistical package software. The results show that the technical efficiency varies significantly across the police directorates and across the selected years, even when we allow for environmental factors and control for these non-discretionary inputs. Most police directorates in Slovenia could attain a higher output if they were fully efficient. Indeed, all of the inefficient police directorates can learn how to ensure a “good” performance from the efficient ones (i.e. the Maribor PD and the Novo mesto PD) by observing how they are processing their inputs and outputs. Finally, the empirical results of the paper are important indicators of the relative efficiency (or inefficiency) of police directorates that can serve as a guide to the General Police Directorate when further investigating how to enhance the performance efficiency of the various units.     

Conclusions and Recommendations from the Pentagon Crash

The devastation in the September 11, 2001 terrorist attack on the Pentagon was reduced by the building’s resilient structural system. The continuity, redundancy, and energy-absorbing capacity embodied in this system should be incorporated in structures whose resistance to progressive collapse is important. Research should be conducted in the practical implementation of these measures for mitigation.     

Staying on your feet: the effectiveness of posture and handles in counteracting balance perturbation

Stairways, public transport and inclined walkways are often considered as sites with higher likelihood of falls due to a sudden loss of balance. Such sites are usually marked with warning signs, equipped with non-slip surfaces and handles or handrails to avert or decrease this likelihood. Especially, handles are supposed to provide additional support in cases of a sudden loss of balance. However, the mechanisms of using handles for balance at different heights are not yet fully disclosed. We simulated full body perturbations by applying an anterior force to the waist and investigated effectiveness and mechanisms of balance recovery in five different postures: step stance and normal stance with or without holding handles at different heights. Results indicate that both step stance and holding handles at different vertical positions sufficiently assist balance recovery, compared to normal stance. While there was no significant effect of handle in CoM displacement, the shoulder height handle required the lowest handle force, indicating a difference in using the handle.

Practitioner summary: To investigate handle use for balance recovery, we perturbed healthy young adults in different standing positions. Even though the use of different handles had a similar effect, the lowest forces were exerted on the shoulder height handle indicating a preferred handle position for balance recovery.

Abbreviation: AP: antero-posterior; CNS: Central nervous system; CoM: Center of Mass; CoMmax: Maximal displacement of the center of mass; CoP: Center of pressure; FHmax: Maximal resultant force exerted on the handle; hFHmax: Maximal horizontal force exerted on the handle; vFHmax; Maximal vertical force exerted on the handle; M1-M8: Perturbation force magnitude     

Development of New Microsatellite Markers for Salvia officinalis L. and Its Potential Use in Conservation-Genetic Studies of Narrow Endemic Salvia brachyodon Vandas

Nine new microsatellite markers (SSR) were isolated from Salvia officinalis L. A total of 125 alleles, with 8 to 21 alleles per locus, were detected in a natural population from the east Adriatic coast. The observed heterozygosity, expected heterozygosity, and polymorphic information content ranged from 0.46 to 0.83, 0.73 to 0.93 and 0.70 to 0.92, respectively. New microsatellite markers, as well as previously published markers, were tested for cross-amplification in Salvia brachyodon Vandas, a narrow endemic species known to be present in only two localities on the Balkan Peninsula. Out of 30 microsatellite markers tested on the natural S. brachyodon population, 15 were successfully amplified. To obtain evidence of recent bottleneck events in the populations of both species, observed genetic diversity (H_E) was compared to the expected genetic diversity at mutation-drift equilibrium (H_EQ) and calculated from the observed number of alleles using a two-phased mutation model (TPM). Recent bottleneck events were detected only in the S. brachyodon population. This result suggests the need to reconsider the current threat category of this endemic species.     

Experimental evidence for the interaction of C-60 fullerene with lipid vesicle membranes

There are some molecular dynamic simulations but a paucity of experimental evidence of the effects of C-60 fullerene on lipid bilayers. The aim of this study is to assess the potential for disruption of the lipid bilayer by C-60 suspended in water. We selected a C-60 suspension that has previously been shown to provoke cell membrane destabilisation in vivo. Electromobility measurements show significant negative surface charge on the C-60 nanoparticles suspended in a glucose solution and a zeta potential of ?26 mV. The prevalent C-60 clusters have hydrodynamic radii of approximately 2 nm. Phase contrast microscopy and computer aided image analysis results show that C-60 causes shape transformations and rupture of unilamellar phospholipid vesicles, indicative of changes in their average mean curvature. Small-angle X-ray scattering reveals that C-60 provokes disruptions of external membranes of multilamellar vesicles only after freeze and thaw cycles. Here, the liposomes undergo breakage and annealing steps which increase the probability for fullerenes to insert into the MLVs. Our experimental findings confirm the potential of C-60 to reconstruct lipids in biological membranes. This research enhances our understanding of the impact of engineered nanoparticles on cell membranes.