Kinetic energy release in electron-induced decay reactions of molecular ions: C3H8+ and C3H7+

We have measured the kinetic energy release (KER) distributions for electron-induced dissociation of mass-selected molecular parent and fragment ions of propane. They are compared with distributions determined for spontaneous (metastable) dissociation. The average KER for induced dissociation of C3H8+ into C3H7+ is 13.2 +/- 1.2 meV, about 42% larger than for the spontaneous reaction. This large difference is attributed to the dramatically reduced time at which the induced reaction can be sampled. In contrast, the KER for dissociation of C3H7+ into C3H5+, which is characterized by a large reverse activation energy, is hardly affected by the experimental time scale. (C) 2000 American Institute of Physics. [S0021-9606(00)00826-6]

High resolution measurements of kinetic energy release distributions of neon, argon, and krypton cluster ions using a three sector field mass spectrometer

Using a newly constructed three sector field mass spectrometer (resulting in a BE1E2 field configuration) we have measured the kinetic energy release distributions of neon, argon, and krypton cluster ions. In the present study we used the first two sectors, B and E1, constituting a high resolution mass spectrometer, to select the parent ions in terms of mass, charge, and energy, and studied the decay of those ions in the third field free region. Due to the improved mass resolution we were able to extend earlier studies carried out with a two sector field machine, where an upper size limit arose from the fact that several isotopomers contribute to a decaying parent ion beam when the cluster size exceeds a certain value. Furthermore we developed a new data analysis. It allows us to model also fragment ion peaks that are a superposition of different decay reactions and thus we can determine the average kinetic energy release for all decay reactions of a given cluster ion. In a further step we used these results to determine the binding energies of cluster ions Rg(n) (ngreater than or equal to10) by applying finite heat bath theory. The smaller sizes have not been included in this analysis, because the validity of finite heat bath theory becomes questionable below napproximate to10. The present average kinetic energy releases and binding energies are compared with other experiments and various calculations. (C) 2004 American Institute of Physics

Kinetic-energy release in Coulomb explosion of metastable C3H52+

C3H52+, formed by electron impact ionization of propane, undergoes metastable decay into C2H2++CH3+. We have monitored this reaction in a magnetic mass spectrometer of reversed geometry that is equipped with two electric sectors (BEE geometry). Three different techniques were applied to identify the fragment ions and determine the kinetic-energy release (KER) of spontaneous Coulomb explosion of C3H52+ in the second and third field free regions of the mass spectrometer. The KER distribution is very narrow, with a width of about 3% [root-mean square standard deviation]. An average KER of 4.58+/-0.15 eV is derived from the distribution. High level ab initio quantum-chemical calculations of the structure and energetics of C3H52+ are reported. The activation barrier of the reverse reaction, CH3++C2H2+ (vinylidene), is computed. The value closely agrees with the experimental average KER, thus indicating that essentially all energy available in the reaction is partitioned into kinetic energy. (C) 2003 American Institute of Physics

The impact of resistance training program on the muscle strength and bone density in adolescent athletes

© 2018 Saša Bubanj et al., published by Sciendo 2018. Strength training and other modes of physical activity may be beneficial in osteoporosis prevention by maximizing bone mineral accrual in childhood and adolescence. This study focuses on the impact of the nine-month long program of resistant exercises with different level of external loads (low, middle and high) on the lower limbs explosive strength and bone tissue density in athletes adolescents aged 17 to 18 years. Sixty healthy, male athletes and non-athletes, divided into experimental (ES, sprinters, N = 45) and control sub-sample (CS, non-athletes, N = 15), were included in study. ES examinees (EG1, EG2 and EG3) were subjected to the program of resistance exercises with low level (60% of the One Repetition Maximum-1RM), middle level (70% 1RM), and high level (85% 1RM) of external loads, respectively. Bone Density values were determined by the use of a clinical sonometer.,Sahara (Hologic, Inc., MA 02154, USA). Explosive strength values of hip extensors and flexors, knee extensors and flexors, and ankle plantar and dorsiflexors were determined by the use of accelerometer.,Myotest (Sion, Switzerland) and the means of Counter Movement Jump without arms swing (CMJ) and half squat. ANOVA method for repeated measures and ANCOVA method were used to determine significant differences and resistance program effects on the lower limbs explosive strength and bone tissue density. Resistance exercise does impact the explosive strength and bone parameters in a way to increase half squat 1RM values, but decreases CMJ values, and increases speed of sound (SOS), broadband ultrasound attenuation (BUA) and bone mineral density (BMD) values in athletes-adolescents, aged 17-18 years

Effect of the Monocyte Chemoattractant Protein-1/CC Chemokine Receptor 2 System on Nephrin Expression in Streptozotocin-Treated Mice and Human Cultured Podocytes

OBJECTIVE-Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes. RESEARCH DESIGN AND METHODS-Expression of nephrin was assessed in human podocytes exposed to rh-MCP-1 by immunofluorescence and real-time PCR. Glomerular CCR2 expression was studied in 10 kidney sections from patients with overt nephropathy and eight control subjects by immunohistochemistry. Both wild-type and MCP-1 knockout mice were made diabetic with streptozotocin. Ten weeks after the onset of diabetes, albuminuria and expression of nephrin, synaptopodin, and zonula occludens-1 were examined by immunofluorescence and immunoblotting. RESULTS-In human podocytes, MCP-1 binding to the CCR2 receptor induced a significant reduction in nephrin both mRNA and protein expression via a Rho-dependent mechanism. The MCP-1 receptor, CCR2, was overexpressed in the glomerular podocytes of patients with overt nephropathy. In experimental diabetes, MCP-1 was overexpressed within the glomeruli and the absence of MCP-1 reduced both albuminuria and downregulation of nephrin and synaptopodin. CONCLUSIONS-These findings suggest that the MCP-1/CCR2 system may be relevant in the pathogenesis of proteinuria in diabetes

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints

Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells

Background: The Duffy antigen receptor for chemokines (DARC) shows high affinity binding to multiple inflammatory CC and CXC chemokines and is expressed by erythrocytes and endothelial cells. Recent evidence suggests that endothelial DARC facilitates chemokine transcytosis to promote neutrophil recruitment. However, the mechanism of chemokine endocytosis by DARC remains unclear. Methodology/Principal Findings: We investigated the role of several endocytic pathways in DARC-mediated ligand internalization. Here we report that, although DARC co-localizes with caveolin-1 in endothelial cells, caveolin-1 is dispensable for DARC-mediated 125I-CXCL1 endocytosis as knockdown of caveolin-1 failed to inhibit ligand internalization. 125I-CXCL1 endocytosis by DARC was also independent of clathrin and flotillin-1 but required cholesterol and was, in part, inhibited by silencing Dynamin II expression. 125I-CXCL1 endocytosis was inhibited by amiloride, cytochalasin D, and the PKC inhibitor Gö6976 whereas Platelet Derived Growth Factor (PDGF) enhanced ligand internalization through DARC. The majority of DARC-ligand interactions occurred on the endothelial surface, with DARC identified along plasma membrane extensions with the appearance of ruffles, supporting the concept that DARC provides a high affinity scaffolding function for surface retention of chemokines on endothelial cells. Conclusions/Significance: These results show DARC-mediated chemokine endocytosis occurs through a macropinocytosis-like process in endothelial cells and caveolin-1 is dispensable for CXCL1 internalization. © 2011 Zhao et al

Systemic Delivery of an Adjuvant CXCR4-CXCL12 Signaling Inhibitor Encapsulated in Synthetic Protein Nanoparticles for Glioma Immunotherapy

Glioblastoma (GBM) is an aggressive primary brain cancer, with a 5 year survival of ∼5%. Challenges that hamper GBM therapeutic efficacy include (i) tumor heterogeneity, (ii) treatment resistance, (iii) immunosuppressive tumor microenvironment (TME), and (iv) the blood-brain barrier (BBB). The C-X-C motif chemokine ligand-12/C-X-C motif chemokine receptor-4 (CXCL12/CXCR4) signaling pathway is activated in GBM and is associated with tumor progression. Although the CXCR4 antagonist (AMD3100) has been proposed as an attractive anti-GBM therapeutic target, it has poor pharmacokinetic properties, and unfavorable bioavailability has hampered its clinical implementation. Thus, we developed synthetic protein nanoparticles (SPNPs) coated with the transcytotic peptide iRGD (AMD3100-SPNPs) to target the CXCL2/CXCR4 pathway in GBM via systemic delivery. We showed that AMD3100-SPNPs block CXCL12/CXCR4 signaling in three mouse and human GBM cell cultures in vitro and in a GBM mouse model in vivo. This results in (i) inhibition of GBM proliferation, (ii) reduced infiltration of CXCR4+ monocytic myeloid-derived suppressor cells (M-MDSCs) into the TME, (iii) restoration of BBB integrity, and (iv) induction of immunogenic cell death (ICD), sensitizing the tumor to radiotherapy and leading to anti-GBM immunity. Additionally, we showed that combining AMD3100-SPNPs with radiation led to long-term survival, with ∼60% of GBM tumor-bearing mice remaining tumor free after rechallenging with a second GBM in the contralateral hemisphere. This was due to a sustained anti-GBM immunological memory response that prevented tumor recurrence without additional treatment. In view of the potent ICD induction and reprogrammed tumor microenvironment, this SPNP-mediated strategy has a significant clinical translation applicability.Fil: Alghamri, Mahmoud S.. University Of Michigan Medical School; Estados UnidosFil: Banerjee, Kaushik. University Of Michigan Medical School; Estados UnidosFil: Mujeeb, Anzar A.. University Of Michigan Medical School; Estados UnidosFil: Mauser, Ava. University of Michigan; Estados UnidosFil: Taher, Ayman. University Of Michigan Medical School; Estados UnidosFil: Thalla, Rohit. University Of Michigan Medical School; Estados UnidosFil: McClellan, Brandon L.. University Of Michigan Medical School; Estados UnidosFil: Varela, Maria L.. University Of Michigan Medical School; Estados UnidosFil: Stamatovic, Svetlana M.. University Of Michigan Medical School; Estados UnidosFil: Martinez Revollar, Gabriela. University Of Michigan Medical School; Estados UnidosFil: Andjelkovic, Anuska V.. University Of Michigan Medical School; Estados UnidosFil: Gregory, Jason V.. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University Of Michigan Medical School; Estados UnidosFil: Calinescu, Alexandra. University Of Michigan Medical School; Estados UnidosFil: Jiménez, Jennifer A.. University of Michigan; Estados UnidosFil: Apfelbaum, April A.. University of Michigan; Estados UnidosFil: Lawlor, Elizabeth R.. University of Washington; Estados UnidosFil: Carney, Stephen. University of Michigan; Estados UnidosFil: Comba, Andrea. University Of Michigan Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faisal, Syed Mohd. University Of Michigan Medical School; Estados UnidosFil: Barissi, Marcus. University Of Michigan Medical School; Estados UnidosFil: Edwards, Marta B.. University Of Michigan Medical School; Estados UnidosFil: Appelman, Henry. University Of Michigan Medical School; Estados UnidosFil: Sun, Yilun. Case Western Reserve University; Estados UnidosFil: Gan, Jingyao. University of Michigan; Estados UnidosFil: Ackermann, Rose. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Olin, Michael R.. University of Minnesota; Estados UnidosFil: Lahann, Joerg. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido