Frustrated peptide chains at the fibril tip control the kinetics of growth of amyloid-ß fibrils.

Amyloid fibrillization is an exceedingly complex process in which incoming peptide chains bind to the fibril while concertedly folding. The coupling between folding and binding is not fully understood. We explore the molecular pathways of association of Aß40 monomers to fibril tips by combining time-resolved in situ scanning probe microscopy with molecular modeling. The comparison between experimental and simulation results shows that a complex supported by nonnative contacts is present in the equilibrium structure of the fibril tip and impedes fibril growth in a supersaturated solution. The unraveling of this frustrated state determines the rate of fibril growth. The kinetics of growth of freshly cut fibrils, in which the bulk fibril structure persists at the tip, complemented by molecular simulations, indicate that this frustrated complex comprises three or four monomers in nonnative conformations and likely is contained on the top of a single stack of peptide chains in the fibril structure. This pathway of fibril growth strongly deviates from the common view that the conformational transformation of each captured peptide chain is templated by the previously arrived peptide. The insights into the ensemble structure of the frustrated complex may guide the search for suppressors of Aß fibrillization. The uncovered dynamics of coupled structuring and assembly during fibril growth are more complex than during the folding of most globular proteins, as they involve the collective motions of several peptide chains that are not guided by a funneled energy landscape.

Mesoscopic protein-rich clusters host the nucleation of mutant p53 amyloid fibrils.

The protein p53 is a crucial tumor suppressor, often called "the guardian of the genome"; however, mutations transform p53 into a powerful cancer promoter. The oncogenic capacity of mutant p53 has been ascribed to enhanced propensity to fibrillize and recruit other cancer fighting proteins in the fibrils, yet the pathways of fibril nucleation and growth remain obscure. Here, we combine immunofluorescence three-dimensional confocal microscopy of human breast cancer cells with light scattering and transmission electron microscopy of solutions of the purified protein and molecular simulations to illuminate the mechanisms of phase transformations across multiple length scales, from cellular to molecular. We report that the p53 mutant R248Q (R, arginine; Q, glutamine) forms, both in cancer cells and in solutions, a condensate with unique properties, mesoscopic protein-rich clusters. The clusters dramatically diverge from other protein condensates. The cluster sizes are decoupled from the total cluster population volume and independent of the p53 concentration and the solution concentration at equilibrium with the clusters varies. We demonstrate that the clusters carry out a crucial biological function: they host and facilitate the nucleation of amyloid fibrils. We demonstrate that the p53 clusters are driven by structural destabilization of the core domain and not by interactions of its extensive unstructured region, in contradistinction to the dense liquids typical of disordered and partially disordered proteins. Two-step nucleation of mutant p53 amyloids suggests means to control fibrillization and the associated pathologies through modifying the cluster characteristics. Our findings exemplify interactions between distinct protein phases that activate complex physicochemical mechanisms operating in biological systems.

Spin-Selective Electron Transport Through Single Chiral Molecules.

The interplay between chirality and magnetism is a source of fascination among scientists for over a century. In recent years, chirality-induced spin selectivity (CISS) has attracted renewed interest. It is observed that electron transport through layers of homochiral molecules leads to a significant spin polarization of several tens of percent. Despite the abundant experimental evidence gathered through mesoscopic transport measurements, the exact mechanism behind CISS remains elusive. This study reports spin-selective electron transport through single helical aromatic hydrocarbons that are sublimed in vacuo onto ferromagnetic cobalt surfaces and examined with spin-polarized scanning tunneling microscopy (SP-STM) at a temperature of 5 K. Direct comparison of two enantiomers under otherwise identical conditions revealed magnetochiral conductance asymmetries of up to 50% when either the molecular handedness is exchanged or the magnetization direction of the STM tip or Co substrate is reversed. Importantly, the results rule out electron-phonon coupling and ensemble effects as primary mechanisms responsible for CISS.

Interaction of spindle assembly factor TPX2 with importins-α/ß inhibits protein phase separation.

The microtubule-based mitotic spindle is responsible for equally partitioning the genome during each cell division, and its assembly is executed via several microtubule nucleation pathways. Targeting Protein for XKlp2 (TPX2) stimulates the branching microtubule nucleation pathway, where new microtubules are nucleated from preexisting ones within mitotic or meiotic spindles. TPX2, like other spindle assembly factors, is sequestered by binding to nuclear importins-α/ß until the onset of mitosis, yet the molecular nature of this regulation remains unclear. Here we demonstrate that TPX2 interacts with importins-α/ß with nanomolar affinity in a 1:1:1 monodispersed trimer. We also identify a new nuclear localization sequence in TPX2 that contributes to its high-affinity interaction with importin-α. In addition, we establish that TPX2 interacts with importin-ß via dispersed, weak interactions. We show that interactions of both importin-α and -ß with TPX2 inhibit its ability to undergo phase separation, which was recently shown to enhance the kinetics of branching microtubule nucleation. In summary, our study informs how importins regulate TPX2 to facilitate spindle assembly, and provides novel insight into the functional regulation of protein phase separation.

RPE65 and retinal dystrophy: Report of new and recurrent mutations.

BACHGROUND: Leber congenital amaurosis (LCA) is a severe and congenital or early onset form of inherited retinitis pigmentosa (RP). To date, approximately 25 genes have been introduced in relation to LCA. In this regard, retinal pigment epithelium-specific 65 kDa (RPE65) is a well-known gene mutation that plays a role in the pathogenesis of 5-10% of LCA cases. METHOS: Two individuals fromseparate families were subjected to ehole exome sequencing (WES). Causativevariants were searched further assessed using Sanger sequencing. RESULTS: Here, two families with mutations in the RPE65 gene show severe and early onset LCA, as expected. In addition to the characterization of the phenotype, by reporting a new mutation (c.1451-1G>A), we further expand the mutation spectrum of RPE65. Likewise, as an interesting aspect of our study, we report on a previously reported RP-linked mutation associated with severe early onset LCA (c.T200G:p.L67R). CONCLUSIONS: Considering this variant in different populations, it is likely that it represents a hotspot and affects the function of the coded protein. The variable expressivity of the phenotype can be assumed by the presence of the modifier allele(s) as a result of a different genetic background or the effect of different environments on phenotype expression.

Neutral DNA-avidin nanoparticles as ultrasensitive reporters in immuno-PCR.

We have developed an immuno-PCR based diagnostic platform which couples detection antibodies to self-assembled, ultra-detectable DNA-avidin nanoparticles stabilized with poly(ethylene glycol) to link DNA amplification to target protein concentration. Electrostatic neutralization and cloaking of the PCR-amplifiable DNA labels by avidin and PEG coating reduces non-specific "stickiness" and enhances assay sensitivity. We further optimized the detectability of the nanoparticles by incorporating four repeats of a unique synthetic DNA PCR target into each nanoparticle. Using human chorionic gonadotropin hormone (hCG) as a model analyte, this platform was able to quantitate the target hCG protein in femtomolar concentrations using only standard laboratory equipment.

Survey of the microbiological count of the milk collected from livestock ancient city of Garmsar, Semnan Province, Iran.

Milk has a high nutritional value and can affect human health. Therefore, it is important to know the factors affecting its quality. The purpose of this study was to evaluate the raw milk microbial quality and factors affecting it. A total of 4260 raw cow milk samples, which were collected from villages around Garmsar city, Iran, and their microbial load were registered at Garmsar Dairy Cow Association between 2013 and 2014, was used in the present study. The total average ± SD of microbial load concentration was 3.02 × 105 ± 2.75 × 105 (CFU/ml). The average concentration of total bacteria in 2013 was 2.73 × 105 ± 1.58 × 105 (CFU/ml) and in 2014 it was 3.32 × 105 ± 3.93 × 105(CFU/ml). Seasonally, it was 2.94 × 105 ± 1.72 × 105 (CFU/ml), 3.69 × 105 ± 4.55 × 105 (CFU/ml), 2.91 × 105 ± 1.62 × 105 (CFU/ml), and 2.63 × 105 ± 1.67 × 105 (CFU/ml) for spring, summer, autumn, and winter, respectively. There was a significant difference in seasonal average microbial concentration of milk samples (p < 0.05). The present study concludes that microbial load of milk can be affected by environmental and hygienic conditions. Ranchers need to pay more attention to hygiene especially in warm seasons. Because in case of high microbial load in raw milk, even after milk pasteurization, it is not possible to have a high-quality and desirable product. Milk producers and distributors need also awareness in order to reduce the incidence of secondary contamination. But, the main correction is to establish direct supervision of the Ministry of Health onto the health of dairy cow farmers by structural integrity of Veterinary Medical Organization as the global one health.

Expression Pattern of Long Non-coding RNAs in Schizophrenic Patients.

The role of long non-coding RNAs (lncRNAs) in the pathogenesis of neurological disorders including schizophrenia has been highlighted by independent studies. In the present study, we compared peripheral blood expression of seven lncRNAs between schizophrenic patients and sex- and age-matched controls using quantitative real-time PCR technique. FAS-AS1, PVT1 and TUG1 were significantly down-regulated in schizophrenic patients compared with healthy individuals (P = 0.007, 0.003 and 0.001, respectively). The association between FAS-AS1 expression and schizophrenia was significant in male subjects aged more than 50 but not in other subgroups. GAS5, NEAT1 and OIP5-AS1 expressions were not significantly different between patients and controls (P = 0.523, 0.739 and 0.267, respectively). The associations between GAS5, NEAT1 and OIP5-AS1 expressions and schizophrenia were significant in female subjects but not in male subjects. THRIL was up-regulated in schizophrenic patients compared with healthy subjects. Based on the results of bootstraped median regression, and after controlling for the effects of age and sex, the difference in its expression between cases and controls was significant (P = 0.014), while the interaction between group and sex was not significant. The expression of lncRNAs was not correlated with age in any study subgroups. In addition, we found sex-based pairwise correlations between PVT1 expression and expression levels of OIP5-AS1, THRIL and NEAT1. We also demonstrated high sensitivity and specificity of GAS5 for diagnosis of schizophrenia in female patients. The current study provides further evidence for the participation of lncRNAs in the pathogenesis of schizophrenia. Future studies are needed to confirm the suitability of lncRNAs as peripheral biomarkers for this psychiatric disorder.

Towards a novel small animal proton irradiation platform: the SIRMIO project.

Background: Precision small animal radiotherapy research is a young emerging field aiming to provide new experimental insights into tumor and normal tissue models in different microenvironments, to unravel complex mechanisms of radiation damage in target and non-target tissues and assess efficacy of novel therapeutic strategies. For photon therapy, modern small animal radiotherapy research platforms have been developed over the last years and are meanwhile commercially available. Conversely, for proton therapy, which holds potential for an even superior outcome than photon therapy, no commercial system exists yet. Material and methods: The project SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology) aims at realizing and demonstrating an innovative portable prototype system for precision image-guided small animal proton irradiation, suitable for installation at existing clinical treatment facilities. The proposed design combines precise dose application with in situ multi-modal anatomical image guidance and in vivo verification of the actual treatment delivery. Results and conclusions: This manuscript describes the status of the different components under development, featuring a dedicated beamline for degradation and focusing of clinical proton beams, along with novel detector systems for in situimaging and range verification. The foreseen workflow includes pre-treatment proton transmission imaging, complemented by ultrasonic tumor localization, for treatment planning and position verification, followed by image-guided delivery with on site range verification by means of ionoacoustics (for pulsed beams) and positron-emission-tomography (PET, for continuous beams). The proposed compact and cost-effective system promises to open a new era in small animal proton therapy research, contributing to the basic understanding of in vivo radiation action to identify areas of potential breakthroughs for future translation into innovative clinical strategies.

Microwave-assisted extraction of hempseed oil: studying and comparing of fatty acid composition, antioxidant activity, physiochemical and thermal properties with Soxhlet extraction.

This work aimed to investigate the effects of the microwave-assisted extraction (MAE) on the hempseed (Cannabis sativa L.) oil yield, oxidation stability, and antioxidant activity. Power (300, 450, and 600 W) and time (5, 10, and 15 min) were independent variables while oil extraction yield, peroxide value (PV), p-anisidine value (AV), TOTOX value (TV), and DPPH scavenging activity were considered as dependent ones. Optimization was conducted by response surface methodology where the optimum point was 450 W and 7.19 min. In this point, the extraction yield obtained 33.91% w/w and the oil showed acceptable oxidation quality (PV of 2.5 meq/kg, AV of 0.67, and TV of 5.67) and antioxidant activity with the IC50 value of 30.82 mg/mL. The Soxhlet extraction (SE) method was carried out to be compared with MAE. It showed relatively higher oil extraction yield (37.93% w/w) but lower oil oxidation stability with PV of 6.4 meq/kg, AV of 3.69, TV of 16.49, and higher amount of IC50 32.47 mg/mL which showed lower antioxidant activity. Any significant difference between fatty acid compositions was not observed with the dominant amounts of linoleic acid and α-linolenic acid. Also, the tocopherol contents and thermal properties were studied by HPLC and DSC, respectively. MAE showed higher total tocopherol content (929.67 mg/kg) than SE (832.61 mg/kg) and γ-tocopherol was dominant. Moreover, DSC analysis showed that both profiles (crystallization and melting transitions) are likely influenced mostly by the triglyceride compositions and crystals structure.

Valorisation of untreated cane molasses for enhanced phytase production by Bacillus subtilis K46b and its potential role in dephytinisation.

BACKGROUND: The high cost of phytase production is the most limiting factor in its application in animal feeds. The present study aimed to develop a low-cost medium for production of a novel phytase in submerged fermentation using inexpensive agro-industrial by-products. The applicability of phytase in dephytinisation of commonly used food/feed ingredients, i.e. soybean meal and wheat bran, was also investigated. RESULTS: Using a one-factor-at-a-time approach, soybean meal and cane molasses were identified as significant agro-industrial by-products and these factors were subsequently optimised using response surface methodology (RSM). A central composite design was employed to further enhance phytase yield. Under optimum conditions of soybean meal 22.3 g L-1 , cane molasses 100 g L-1 and 39 h fermentation, phytase production increased to 56.562 U mL-1 , indicating more than 28-fold enhancement. The enzyme efficiently dephytinised wheat bran and soybean meal after 24 h incubation at 56.5 °C and increased inorganic phosphate content by 240% and 155%, respectively. CONCLUSION: Soybean meal and cane molasses were successfully used for enhancement of phytase production as economical carbon, nitrogen and phytic acid sources using RSM. The phytase showed a good capability to dephytinise wheat bran and soybean meal, demonstrating that the enzyme can be considered as a potential candidate for industrial food and feed applications. © 2016 Society of Chemical Industry.

Valorization of tomato waste proteins through production of antioxidant and antibacterial hydrolysates by proteolytic Bacillus subtilis: optimization of fermentation conditions.

In this study, protein-rich waste of tomato processing industries was fermented by Bacillus subtilis A14h to produce hydrolysates with antioxidant and antibacterial activities. The effects of different levels of initial pH, incubation temperature, fermentation time, protein concentration and inoculum size on proteolytic activity, release of amino acids and peptides, antioxidant and antibacterial activities of hydrolysates were evaluated and optimized by using response surface methodology (RSM). Results showed that all the evaluated variables significantly influenced the hydrolysis and bioactivities of hydrolysates in polynomial models. Hydrolysates showed remarkable 2, 2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (up to 70 %), ferric ion reducing power, and inhibitory activity against B. cereus (up to 69.8 %) and E. coli (up to 29.8 %). Overall, good correlation between the concentration of amino acids and peptides, and antioxidant as well as antibacterial activities (in particular for B. cereus inhibition activity) was observed. Finally, optimum conditions for fermentative conversion of tomato waste proteins to antioxidant and antibacterial hydrolysates were established. Results of this study showed that tomato waste protein can be valorized to produce antioxidant and antibacterial hydrolysates in a fermentative system using B. subtilis A14h.

Socket Interface Pressure and Amputee Reported Outcomes for Comfortable and Uncomfortable Conditions of Patellar Tendon Bearing Socket: A Pilot Study.

The objectives of the current study were to compare intra-socket pressure differences between comfortable and uncomfortable socket conditions, and the usefulness of subject perception of satisfaction, activity limitations, and socket comfort in distinguishing between these two socket conditions. Five unilateral trans-tibial amputees took part in the study. They answered the Socket Comfort Score (SCS) and Trinity Amputation and Prosthetic Experience Scale (TAPES) questionnaires before the interface pressure (in standing and walking) was measured for the uncomfortable socket condition at five regions of the residual limb. Participants were then provided with a comfortable socket and wore it for two weeks. Participants who were satisfied with the socket fit after two weeks repeated the SCS and TAPES questionnaires and interface pressure measurements. The differences between the test results of the two conditions were not statistically significant, except for the interface pressure at the popliteal region during the early stance phase, TAPES socket fit subscale, and the SCS. Due to large variability of the data and the lack of statistical significance, no firm conclusion can be made on the possible relationship between the interface pressure values and the patient-reported outcomes of the two socket conditions. A larger sample size and longer acclimation period are required to locate significant differences.

Bioconversion enhancement of conjugated linoleic acid by Lactobacillus plantarum using the culture media manipulation and numerical optimization.

The ability of different Lactobacillus strains to produce conjugated linoleic acid (CLA) from linoleic acid was evaluated. Preliminary experiments revealed that L. plantarum among the screened strains had the highest CLA-producing potential (95.25 µg/mL). The cell growth of this bacterium was studied in three media of MRS broth, skim milk and skim milk supplemented with yeast extract and glucose. Results showed that the use of yeast extract and glucose could significantly increase the cell growth and CLA production. Response surface methodology (RSM) was applied to investigate the effects of three independent variables; linoleic acid (LA), yeast extract concentrations and inoculum size on the CLA formation. A second-order polynomial model with high R (2) value (0.981) was developed using multiple linear regression analysis. The optimum conditions to achieve the highest CLA production (240.69 µg/mL) was obtained using 3 mg/mL LA, 4 g/L yeast extract and inoculum size of 4 % v/v. CLA concentration of the optimal sample was analyzed by Gas Chromatography (GC). The cis-9, trans-11 CLA was the major CLA isomer of total CLA detected.

Novel surface biochemical modifications of urinary catheters to prevent catheter-associated urinary tract infections.

More than 70% of hospital-acquired urinary tract infections are related to urinary catheters, which are commonly used for the treatment of about 20% of hospitalized patients. Urinary catheters are used to drain the bladder if there is an obstruction in the tube that carries urine out of the bladder (urethra). During catheter-associated urinary tract infections, microorganisms rise up in the urinary tract and reach the bladder, and cause infections. Various materials are used to fabricate urinary catheters such as silicone, polyurethane, and latex. These materials allow bacteria and fungi to develop colonies on their inner and outer surfaces, leading to bacteriuria or other infections. Urinary catheters could be modified to exert antibacterial and antifungal effects. Although so many research have been conducted over the past years on the fabrication of antibacterial and antifouling catheters, an ideal catheter needs to be developed for long-term catheterization of more than a month. In this review, we are going to introduce the recent advances in fabricating antibacterial materials to prevent catheter-associated urinary tract infections, such as nanoparticles, antibiotics, chemical compounds, antimicrobial peptides, bacteriophages, and plant extracts.

Enantioselective Adsorption on Magnetic Surfaces.

From the beginning of molecular theory, the interplay of chirality and magnetism has intrigued scientists. There is still the question if enantiospecific adsorption of chiral molecules occurs on magnetic surfaces. Enantiomer discrimination was conjectured to arise from chirality-induced spin separation within the molecules and exchange interaction with the substrate's magnetization. Here, it is shown that single helical aromatic hydrocarbons undergo enantioselective adsorption on ferromagnetic cobalt surfaces. Spin and chirality sensitive scanning tunneling microscopy reveals that molecules of opposite handedness prefer adsorption onto cobalt islands with opposite out-of-plane magnetization. As mobility ceases in the final chemisorbed state, it is concluded that enantioselection must occur in a physisorbed transient precursor state. State-of-the-art spin-resolved ab initio simulations support this scenario by refuting enantio-dependent chemisorption energies. These findings demonstrate that van der Waals interaction should also include spin-fluctuations which are crucial for molecular magnetochiral processes.

Hands-off and hands-on casting consistency of amputee below knee sockets using magnetic resonance imaging.

Residual limb shape capturing (Casting) consistency has a great influence on the quality of socket fit. Magnetic Resonance Imaging was used to establish a reliable reference grid for intercast and intracast shape and volume consistency of two common casting methods, Hands-off and Hands-on. Residual limbs were cast for twelve people with a unilateral below knee amputation and scanned twice for each casting concept. Subsequently, all four volume images of each amputee were semiautomatically segmented and registered to a common coordinate system using the tibia and then the shape and volume differences were calculated. The results show that both casting methods have intra cast volume consistency and there is no significant volume difference between the two methods. Inter- and intracast mean volume differences were not clinically significant based on the volume of one sock criteria. Neither the Hands-off nor the Hands-on method resulted in a consistent residual limb shape as the coefficient of variation of shape differences was high. The resultant shape of the residual limb in the Hands-off casting was variable but the differences were not clinically significant. For the Hands-on casting, shape differences were equal to the maximum acceptable limit for a poor socket fit.

Carbon-based biosensors from graphene family to carbon dots: A viewpoint in cancer detection.

According to the latest report by International Agency for Research on Cancer, 19.3 million new cancer cases and 10 million cancer deaths were globally reported in 2020. Early diagnosis can reduce these numbers significantly, and biosensors have appeared to be a solution to this problem as, unlike the traditional methods, they have low cost, rapid process, and do not need experts present on site for use. These devices have been incorporated to detect many cancer biomarkers and measure cancer drug delivery. To design these biosensors, a researcher must know about their different types, properties of nanomaterials, and cancer biomarkers. Among all types of biosensors, electrochemical and optical biosensors are the most sensitive and promising sensors for detecting complicated diseases like cancer. The carbon-based nanomaterial family has attracted lots of attention due to their low cost, easy preparation, biocompatibility, and significant electrochemical and optical properties. In this review, we have discussed the application of graphene and its derivatives, carbon nanotubes (CNTs), carbon dots (CDs), and fullerene (C60), for designing different electrochemical and optical cancer-detecting biosensors. Furthermore, the application of these carbon-based biosensors for detecting seven widely studied cancer biomarkers (HER2, CEA, CA125, VEGF, PSA, Alpha-fetoprotein, and miRNA21) is reviewed. Finally, various fabricated carbon-based biosensors for detecting cancer biomarkers and anticancer drugs are comprehensively summarized as well.

Implemented indoor airborne transmission mitigation strategies during COVID-19: a systematic review.

The COVID-19 pandemic has inflicted major economic and health burdens across the world. On the other hand, the potential airborne transmission of SARS-COV-2 via air can deeply undermine the effectiveness of countermeasures against spreading the disease. Therefore, there is an intense focus to look for ways to mitigate the COVID-19 spread within various indoor settings. This work systematically reviewed articles regarding airborne transmission of SARS-COV2 in various indoor settings since the onset of the pandemic. The systematic search was performed in Scopus, Web of Science, and PubMed databases and has returned 19 original articles carefully screened with regard to inclusion and exclusion criteria. The results showed that the facilities, such as dormitories and classrooms, received the most attention followed by office buildings, healthcare facilities, residential buildings, and other potential enclosed spaces such as a metro wagon. Besides, the majority of the studies were conducted experimentally while other studies were done using computer simulations. United States (n = 5), Spain (n = 4) and China (n = 3) were the top three countries based on the number of performed research. Ventilation rate was the most influential parameter in controlling the infection spread. CO2 was the primary reference for viral spread in the buildings. The use of natural ventilation or a combination of mechanical and natural ventilations was found to be highly effective in the studies. The current work helps in furthering research on effective interventions to improve indoor air quality and control the spread of COVID-19 and other respiratory diseases. Supplementary information: The online version contains supplementary material available at 10.1007/s40201-023-00847-0.

Design study of a novel geometrical arrangement for an in-beam small animal positron emission tomography scanner.

Objective.We designed a geometrical solution for a small animal in-beam positron emission tomography (PET) scanner to be used in the project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology). The system is based on 56 scintillator blocks of pixelated LYSO crystals. The crystals are arranged providing a pyramidal-step shape to optimize the geometrical coverage in a spherical configuration.Approach.Different arrangements have been simulated and compared in terms of spatial resolution and sensitivity. The chosen setup enables us to reach a good trade-off between a solid angle coverage and sufficient available space for the integration of additional components of the first design prototype of the SIRMIO platform. The possibility of moving the mouse holder inside the PET scanner furthermore allows for achieving the optimum placement of the irradiation area for all the possible tumor positions in the body of the mouse. The work also includes a study of the scintillator material where LYSO and GAGG are compared with a focus on the random coincidence noise due to the natural radioactivity of Lutetium in LYSO, justifying the choice of LYSO for the development of the final system.Main results.The best imaging performance can be achieved with a sub-millimeter spatial resolution and sensitivity of 10% in the center of the scanner, as verified in thorough simulations of point sources. The simulation of realistic irradiation scenarios of proton beams in PMMA targets with/without air gaps indicates the ability of the proposed PET system to detect range shifts down to 0.2 mm.Significance.The presented results support the choice of the identified optimal design for a novel spherical in-beam PET scanner which is currently under commissioning for application to small animal proton and light ion irradiation, and which might find also application, e.g. for biological image-guidance in x-ray irradiation.