Pitting the olive seed microbiome.

BACKGROUND: The complex and co-evolved interplay between plants and their microbiota is crucial for the health and fitness of the plant holobiont. However, the microbiota of the seeds is still relatively unexplored and no studies have been conducted with olive trees so far. In this study, we aimed to characterize the bacterial, fungal and archaeal communities present in seeds of ten olive genotypes growing in the same orchard through amplicon sequencing to test whether the olive genotype is a major driver in shaping the seed microbial community, and to identify the origin of the latter. Therefore, we have developed a methodology for obtaining samples from the olive seed's endosphere under sterile conditions. RESULTS: A diverse microbiota was uncovered in olive seeds, the plant genotype being an important factor influencing the structure and composition of the microbial communities. The most abundant bacterial phylum was Actinobacteria, accounting for an average relative abundance of 41%. At genus level, Streptomyces stood out because of its potential influence on community structure. Within the fungal community, Basidiomycota and Ascomycota were the most abundant phyla, including the genera Malassezia, Cladosporium, and Mycosphaerella. The shared microbiome was composed of four bacterial (Stenotrophomonas, Streptomyces, Promicromonospora and Acidipropionibacterium) and three fungal (Malassezia, Cladosporium and Mycosphaerella) genera. Furthermore, a comparison between findings obtained here and earlier results from the root endosphere of the same trees indicated that genera such as Streptomyces and Malassezia were present in both olive compartments. CONCLUSIONS: This study provides the first insights into the composition of the olive seed microbiota. The highly abundant fungal genus Malassezia and the bacterial genus Streptomyces reflect a unique signature of the olive seed microbiota. The genotype clearly shaped the composition of the seed's microbial community, although a shared microbiome was found. We identified genera that may translocate from the roots to the seeds, as they were present in both organs of the same trees. These findings set the stage for future research into potential vertical transmission of olive endophytes and the role of specific microbial taxa in seed germination, development, and seedling survival.

Thriving beneath olive trees: The influence of organic farming on microbial communities.

Soil health and root-associated microbiome are interconnected factors involved in plant health. The use of manure amendment on agricultural fields exerts a direct benefit on soil nutrient content and water retention, among others. However, little is known about the impact of manure amendment on the root-associated microbiome, particularly in woody species. In this study, we aimed to evaluate the effects of ovine manure on the microbial communities of the olive rhizosphere and root endosphere. Two adjacent orchards subjected to conventional (CM) and organic (OM) management were selected. We used metabarcoding sequencing to assess the bacterial and fungal communities. Our results point out a clear effect of manure amendment on the microbial community. Fungal richness and diversity were increased in the rhizosphere. The fungal biomass in the rhizosphere was more than doubled, ranging from 1.72 × 106 ± 1.62 × 105 (CM) to 4.54 × 106 ± 8.07 × 105 (OM) copies of the 18 S rRNA gene g-1 soil. Soil nutrient content was also enhanced in the OM orchard. Specifically, oxidable organic matter, total nitrogen, nitrate, phosphorous, potassium and sulfate concentrations were significantly increased in the OM orchard. Moreover, we predicted a higher abundance of bacteria in OM with metabolic functions involved in pollutant degradation and defence against pathogens. Lastly, microbial co-occurrence network showed more positive interactions, complexity and shorter geodesic distance in the OM orchard. According to our results, manure amendment on olive orchards represents a promising tool for positively modulating the microbial community in direct contact with the plant.

Phytochemical Analysis and Anti-Inflammatory Potential of Acanthus mollis L. Rhizome Hexane Extract.

The rhizomes of Acanthus mollis have traditionally been used for the treatment of several ailments involving inflammation. However, to the best of our knowledge, their chemical composition and pharmacological properties have not been studied until now. As a first approach, this study analyses the A. mollis rhizome hexane extract phytochemistry and its anti-inflammatory and antioxidant capacities in HepG2 and RAW 264.7 cell culture assays. Chemical profiling was performed with gas chromatography mass spectrometry without the modification of native molecules. Free phytosterols (such as ß-sitosterol) account for 70% of detected compounds. The anti-inflammatory capacity of the rhizome extract of A. mollis is mediated by the decrease in the NO production in RAW 264.7 that has previously been stimulated with lipopolysaccharide in a dose-dependent manner. Furthermore, HepG2 pre-treatment with the rhizome extract prevents any damage being caused by oxidative stress, both through ROS scavenge and through the antioxidant cellular enzyme system. In this respect, the extract reduced the activity of glutathione peroxidase and reductase, which were stimulated under oxidative stress conditions. Our results suggest that the extract from the rhizomes of A. mollis may constitute a potential source of natural products with anti-inflammatory activity and could validate the traditional use of A. mollis.

Primary somatosensory cortex bidirectionally modulates sensory gain and nociceptive behavior in a layer-specific manner.

The primary somatosensory cortex (S1) is a hub for body sensation of both innocuous and noxious signals, yet its role in somatosensation versus pain is debated. Despite known contributions of S1 to sensory gain modulation, its causal involvement in subjective sensory experiences remains elusive. Here, in mouse S1, we reveal the involvement of cortical output neurons in layers 5 (L5) and 6 (L6) in the perception of innocuous and noxious somatosensory signals. We find that L6 activation can drive aversive hypersensitivity and spontaneous nocifensive behavior. Linking behavior to neuronal mechanisms, we find that L6 enhances thalamic somatosensory responses, and in parallel, strongly suppresses L5 neurons. Directly suppressing L5 reproduced the pronociceptive phenotype induced by L6 activation, suggesting an anti-nociceptive function for L5 output. Indeed, L5 activation reduced sensory sensitivity and reversed inflammatory allodynia. Together, these findings reveal a layer-specific and bidirectional role for S1 in modulating subjective sensory experiences.

Bacterial inoculation of Quercus pyrenaica trees alters co-occurrence patterns but not the composition of the rhizosphere bacteriome in wild conditions.

Quercus pyrenaica is a woody species of high landscape value, however, its forests show an advanced state of degradation in the Iberian Peninsula. Afforestation typically has low success, thus, it is necessary to improve the fitness of oaks plantlets to be transplanted, for instance, by inoculating beneficial microorganisms. In adding microorganisms to ecosystems, there must be balanced efficacy with potential effects on native microbial communities. We addressed changes in diversity, richness, composition and co-occurrence networks of prokaryotic communities in the rhizosphere of inoculated and control trees outplanted to three different sites located in the Sierra Nevada National and Natural Park (Spain). After 18 months in wild conditions, we did not detect changes due to the inoculation in the richness, diversity and structure in none of the sites. However, we observed an increase in the complexity of the co-occurrence networks in two experimental areas. Modularization of the networks changed as a result of the inoculation, although the sense of the change depended on the site. Although it was impossible to unravel the effect of bacterial inoculation, our results highlighted that inoculation alters the association of rhizosphere bacteria without entailing other changes, so networks should be analysed prior to inoculating the plantlets.

Co-occurrence network analysis unveils the actual differential impact on the olive root microbiota by two Verticillium wilt biocontrol rhizobacteria.

BACKGROUND: Verticillium wilt of olive (VWO), caused by Verticillium dahliae Kleb, is one of the most threatening diseases affecting olive cultivation. An integrated disease management strategy is recommended for the effective control of VWO. Within this framework, the use of biological control agents (BCAs) is a sustainable and environmentally friendly approach. No studies are available on the impact that the introduction of BCAs has on the resident microbiota of olive roots. Pseudomonas simiae PICF7 and Paenibacillus polymyxa PIC73 are two BCAs effective against VWO. We examined the effects of the introduction of these BCAs on the structure, composition and co-occurrence networks of the olive (cv. Picual) root-associated microbial communities. The consequences of the subsequent inoculation with V. dahliae on BCA-treated plants were also assessed. RESULTS: Inoculation with any of the BCAs did not produce significant changes in the structure or the taxonomic composition of the 'Picual' root-associated microbiota. However, significant and distinctive alterations were observed in the topologies of the co-occurrence networks. The introduction of PIC73 provoked a diminution of positive interactions within the 'Picual' microbial community; instead, PICF7 inoculation increased the microbiota's compartmentalization. Upon pathogen inoculation, the network of PIC73-treated plants decreased the number of interactions and showed a switch of keystone species, including taxa belonging to minor abundant phyla (Chloroflexi and Planctomycetes). Conversely, the inoculation of V. dahliae in PICF7-treated plants significantly increased the complexity of the network and the number of links among their modules, suggestive of a more stable network. No changes in their keystone taxa were detected. CONCLUSION: The absence of significant modifications on the structure and composition of the 'Picual' belowground microbiota due to the introduction of the tested BCAs underlines the low/null environmental impact of these rhizobacteria. These findings may have important practical consequences regarding future field applications of these BCAs. Furthermore, each BCA altered the interactions among the components of the olive belowground microbiota in idiosyncratic ways (i.e. PIC73 strongly modified the number of positive relations in the 'Picual' microbiota whereas PICF7 mostly affected the network stability). These modifications may provide clues on the biocontrol strategies used by these BCAs.

Bacteriome dataset from the rhizosphere of trees in a Pinus pinaster and Pinus halepensis dominated forest subjected to drought conditions.

The Mediterranean basin is drastically affected by intense and frequent droughts, which jeopardize the diversity and survival of its forest, for example, Pinus pinaster forests. The dynamics of the bacterial communities inhabiting the rhizosphere of Pinus pinaster and other plants from a pine dominated forest under contrasting hydric conditions was monitored. The forest was located in Sierra de Oria (southeast Spain), and it was mainly composed by P. pinaster, P. halepensis, woody shrub species and herbaceous plants. 18 trees visually belonging to P. pinaster located along the perimeter and across the forest were selected for the analysis. All the trees were separated at least 50 m each other. Although all of them belonged to P. pinaster morphologically according to visual identification, the genotyping of the roots confirmed that they corresponded to P. pinaster, P. halepensis, and other plant species different from genus Pinus, although in the last case it was not possible to identify the plant species. At a distance less than 50 cm from the trunk, the litter and topsoil were removed, and the soil closely attached to non-suberified roots (rhizosphere soil) was collected (depth of 5-25 cm). Sampling was carried out in two seasons with contrasting temperature and rainfall patterns: on July 18, 2017 (summer) and April 24, 2018 (spring). After rhizosphere soil DNA and RNA extraction (and cDNA synthesis), a metabarcoding approach was followed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene and its derived transcripts by Illumina MiSeq platform. Sequencing reads were bioinformatically processed; specifically, they were filtered, trimmed, clustered into ASV (Amplicon Sequence Variants), and taxonomically identified. As a result, a total of 1,123,209 and 1,089,359 quality sequences were obtained from DNA and RNA-derived libraries, which resulted in 5,241 and 5,231 ASVs, respectively. Total communities (DNA) were mainly dominated by phyla Proteobacteria, Acidobacteria, Actinobacteria, Verrucomicrobia and Bacteroidetes in summer and spring, while potentially active populations (RNA libraries) were rich in Proteobacteria, Acidobacteria, Candidate division WPS-1, Actinobacteria and Verrucomicrobia both in summer and spring. On the other hand, DNA libraries were mainly dominated by genera Sphingomonas and acidobacterial groups Gp4 and Gp6, while potentially active bacteria (RNA) were rich in acidobacterial Gp3, Gp4, Gp6 and Phenylobacterium, although their relative abundance depended on the considered season. This dataset can provide valuable information about bacterial candidates which could be used as bioindicators of drought conditions. In addition to shifts in the bacterial relative abundance due to seasonal changes, the ratio RNA-based cDNA:DNA could be calculated as proxy of the potential activity of bacterial taxa. Moreover, these data could aid in developing bioformulations based on microorganisms which could be resistant to desiccation and involved in the drought resistance mechanisms of the host plant.

Timing, Energy, and Spatial Characterization of Highly Sampled Monolithic PET Detectors with Different Thicknesses.

The HyPET project proposes a hybrid dedicated TOF-PET for prostate imaging, with pixelated detector blocks in the front layer and monolithic blocks in the back layer. In this work, four detector configurations have been experimentally evaluated for the rear detector layer. The detector configuration consists of LYSO monolithic blocks with the same size (25.4 mm × 25.4 mm) but different thicknesses (5, 7.5, 10, and 15 mm) coupled to the same SiPM array. Each detector configuration has been experimentally characterized in terms of time, energy and spatial resolution by scanning the crystal surface using a fan beam in steps of 0.25 mm. Regarding spatial resolution, the interaction position was estimated using a Neural Network technique. All resolutions except energy, which remains nearly constant at 17% for all cases, show better values for the 5 mm detector thickness. We have achieved spatial resolution values of FWHM of 1.02 ± 0.10, 1.19 ± 0.13, 1.53 ± 0.17, 2.33 ± 0.55 mm, for the 5, 7.5, 10, and 15 mm blocks, respectively. The detector time resolution obtained was 275 ± 26, 291 ± 21, 344 ± 48, and 433 ± 45 ps respectively, using the energy weighted average method for the time stamps.

Corrigendum to "Coupling the endophytic microbiome with the host transcriptome in olive roots" [Comput. Struct. Biotechnol. J. 19 (2021) 4777-4789].

[This corrects the article DOI: 10.1016/j.csbj.2021.08.035.].

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

Performance evaluation of side-by-side optically coupled monolithic LYSO crystals.

BACKGROUND: Significant interest has been recently shown for using monolithic scintillation crystals in molecular imaging systems, such as positron emission tomography (PET) scanners. Monolithic-based PET scanners result in a lower cost and higher sensitivity, in contrast to systems based on the more conventional pixellated configuration. The monolithic design allows one to retrieve depth-of-interaction information of the impinging 511 keV photons without the need for additional hardware materials or complex positioning algorithms. However, the so-called edge-effect inherent to monolithic-based approaches worsens the detector performance toward the crystal borders due to the truncation of the light distribution, thus decreasing positioning accuracy. PURPOSE: The main goal of this work is to experimentally demonstrate the detector performance improvement when machine-learning artificial neural-network (NN) techniques are applied for positioning estimation in multiple monolithic scintillators optically coupled side-by-side. METHODS: In this work, we show the performance evaluation of two LYSO crystals of 33 × 25.4 × 10 mm3 optically coupled by means of a high refractive index adhesive compound (Meltmount, refractive index n = 1.70). A 12 × 12 silicon photomultiplier array has been used as photosensor. For comparison, the same detector configuration was tested for two additional coupling cases: (1) optical grease (n = 1.46) in between crystals, and (2) isolated crystals using black paint with an air gap at the interface (named standard configuration). Regarding 2D photon positioning (XY plane), we have tested two different methods: (1) a machine-learning artificial NN algorithm and (2) a squared-charge (SC) centroid technique. RESULTS: At the interface region of the detector, the SC method achieved spatial resolutions of 1.7 ± 0.3, 2.4 ± 0.3, and 2.6 ± 0.4 mm full-width at half-maximum (FWHM) for the Meltmount, grease, and standard configurations, respectively. These values improve to 1.0 ± 0.2, 1.2 ± 0.2, and 1.2 ± 0.3 mm FWHM when the NN algorithm was employed. Regarding energy performance, resolutions of 18 ± 2%, 20 ± 2%, and 23 ± 3% were obtained at the interface region of the detector for Meltmount, grease, and standard configurations, respectively. CONCLUSIONS: The results suggest that optically coupling together scintillators with a high refractive index adhesive, in combination with an NN algorithm, reduces edge-effects and makes it possible to build scanners with almost no gaps in between detectors.

Physical performance of adaptive axial FOV PET scanners with a sparse detector block rings or a checkerboard configuration.

Objective.Using Monte-Carlo simulations, we evaluated the physical performance of a hypothetical state-of-the-art clinical PET scanner with adaptive axial field-of-view (AFOV) based on the validated GATE model of the Siemens Biograph VisionTMPET/CT scanner.Approach.Vision consists of 16 compact PET rings, each consisting of 152 mini-blocks of 5 × 5 Lutetium Oxyorthosilicate crystals (3.2 × 3.2 × 20 mm3). The Vision 25.6 cm AFOV was extended by adopting (i) a sparse mini-block ring (SBR) configuration of 49.6 cm AFOV, with all mini-block rings interleaved with 16 mm axial gaps, or (ii) a sparse mini-block checkerboard (SCB) configuration of 51.2 cm AFOV, with all mini-blocks interleaved with gaps of 16 mm (transaxial) × 16 mm (axial) width in checkerboard pattern. For sparse configurations, a 'limited' continuous bed motion (limited-CBM) acquisition was employed to extend AFOVs by 2.9 cm. Spatial resolution, sensitivity, image quality (IQ), NECR and scatter fraction were assessed per NEMA NU2-2012.Main Results.All IQ phantom spheres were distinguishable with all configurations. SBR and SCB percent contrast recovery (% CR) and background variability (% BV) were similar (p-value > 0.05). Compared to Vision, SBR and SCB %CRs were similar (p-values > 0.05). However, SBR and SCB %BVs were deteriorated by 30% and 26% respectively (p-values < 0.05). SBR, SCB and Vision exhibited system sensitivities of 16.6, 16.8, and 15.8 kcps MBq-1, NECRs of 311 kcps @35 kBq cc-1, 266 kcps @25.8 kBq cc-1, and 260 kcps @27.8 kBq cc-1, and scatter fractions of 31.2%, 32.4%, and 32.6%, respectively. SBR and SCB exhibited a smoother sensitivity reduction and noise enhancement rate from AFOV center to its edges. SBR and SCB attained comparable spatial resolution in all directions (p-value > 0.05), yet, up to 1.5 mm worse than Vision (p-values < 0.05).Significance.The proposed sparse configurations may offer a clinically adoptable solution for cost-effective adaptive AFOV PET with either highly-sensitive or long-AFOV acquisitions.

Correlating the above- and belowground genotype of Pinus pinaster trees and rhizosphere bacterial communities under drought conditions.

Increasing temperatures along with severe droughts are factors that may jeopardize the survival of the forests in the Mediterranean basin. In this region, Pinus pinaster is a common conifer species, that has been used as a model species in evolutionary studies due to its adaptive response to changing environments. Although its drought tolerance mechanisms are already known, knowledge about the dynamics of its root microbiota is still scarce. We aimed to decipher the structural (bacterial abundance), compositional, functional and associative changes of the P. pinaster rhizosphere bacterial communities in spring and summer, at DNA and RNA level (environmental DNA, live and dead cells, and those synthesizing proteins). A fundamental aspect of root microbiome-based approaches is to guarantee the correct origin of the samples. Thus, we assessed the genotype of host needles and roots from which rhizosphere samples were obtained. For more than 50% of the selected trees, genotype discrepancies were found and in three cases the plant species could not be determined. Rhizosphere bacterial communities were homogeneous with respect to diversity and structural levels regardless of the host genotype in both seasons. Nonetheless, significant changes were seen in the taxonomic profiles depending on the season. Seasonal changes were also evident in the bacterial co-occurrence patterns, both in DNA and RNA libraries. While spring communities switched to more complex networks, summer populations resulted in more compartmentalized networks, suggesting that these communities were facing a disturbance. These results may mirror the future status of bacterial communities in a context of climate change. A keystone hub was ascribed to the genus Phenylobacterium in the functional network calculated for summer. Overall, it is important to validate the origin and identity of plant samples in any plant-microbiota study so that more reliable ecological analyses are performed.

Impacts of the Biocontrol Strain Pseudomonas simiae PICF7 on the Banana Holobiont: Alteration of Root Microbial Co-occurrence Networks and Effect on Host Defense Responses.

The impact of the versatile biocontrol and plant-growth-promoting rhizobacteria Pseudomonas simiae PICF7 on the banana holobiont under controlled conditions was investigated. We examine the fate of this biological control agent (BCA) upon introduction in the soil, the effect on the banana root microbiota, and the influence on specific host genetic defense responses. While the presence of strain PICF7 significantly altered neither the composition nor the structure of the root microbiota, a significant shift in microbial community interactions through co-occurrence network analysis was observed. Despite the fact that PICF7 did not constitute a keystone, the topology of this network was significantly modified-the BCA being identified as a constituent of one of the main network modules in bacterized plants. Gene expression analysis showed the early suppression of several systemic acquired resistance and induced systemic resistance (ISR) markers. This outcome occurred at the time in which the highest relative abundance of PICF7 was detected. The absence of major and permanent changes on the banana holobiont upon PICF7 introduction poses advantages regarding the use of this beneficial rhizobacteria under field conditions. Indeed a BCA able to control the target pathogen while altering as little as possible the natural host-associated microbiome should be a requisite when developing effective bio-inoculants.

Reducing Calibration Time in PET Systems Based on Monolithic Crystals.

In the past years, the gamma-ray detector designs based on the monolithic crystals have demonstrated to be excellent candidates for the design of high-performance PET systems. The monolithic crystals allow to achieve the intrinsic detector resolutions well below state-of-the-art; to increase packing fraction thus, increasing the system sensitivity; and to improve lesion detectability at the edges of the scanner field of view (FOV) because of their intrinsic depth of interaction (DOI) capabilities. The bottleneck to translate to the clinical PET systems based on a large number of monolithic detectors is eventually the requirement of mechanically complex and time-consuming calibration processes. To mitigate this drawback, several methods have been already proposed, such as using non-physically collimated radioactive sources or implementing the neuronal networks (NN) algorithms trained with simulated data. In this work, we aimed to simplify and fasten a calibration process of the monolithic based systems. The Normal procedure consists of individually acquiring a 11 × 11 22Na source array for all the detectors composing the PET system and obtaining the calibration map for each module using a method based on the Voronoi diagrams. Two reducing time methodologies are presented: (i) TEST1, where the calibration map of one detector is estimated and shared among all others, and (ii) TEST2, where the calibration map is slightly modified for each module as a function of their detector uniformity map. The experimental data from a dedicated prostate PET system was used to compare the standard calibration procedure with both the proposed methods. A greater similarity was exhibited between the TEST2 methodology and the Normal procedure; obtaining spatial resolution variances within 0.1 mm error bars and count rate deviations as small as 0.2%. Moreover, the negligible reconstructed image differences (13% deviation at most in the contrast-to-noise ratio) and almost identical contrast values were reported. Therefore, this proposed method allows us to calibrate the PET systems based on the monolithic crystals reducing the calibration time by approximately 80% compared with the Normal procedure.

Timing evaluation of a PET detector block based on semi-monolithic LYSO crystals.

PURPOSE: Detectors for positron emission tomography (PET) typically use two types of scintillation crystals, pixelated or monolithic. A variant of these types of scintillators are the so-called semi-monolithic crystals. They consist of a monolithic crystal segmented in one direction in pieces called slabs. These scintillators have the potential to successfully combine the benefits of pixelated and monolithic configurations, providing good timing and spatial resolutions as well as the capacity to decode the depth of interaction (DOI) information. In this work, the timing performance of a detector based on semi-monolithic crystals was studied in depth. The energy response was also evaluated. METHODS: The semi-monolithic detector consists of 1 × 24 LYSO slabs of 25.4 × 12 × 0.95 mm3 each. The bottom surface of the slabs is coupled to an array of 8 × 8 silicon photomultipliers (SiPMs) of 3 × 3 mm2 active area, 50 µm cell size and 3.2 mm pitch. The 64 output signals were independently readout by the TOFPET2 ASIC. In order to achieve the best coincidence time resolution (CTR), four different time walk corrections were tested. Additional work investigated the best method of combining the timestamps belonging to the same event. RESULTS: The resolvability of the slabs in the measured flood maps improves with the thickness of a light guide placed in between the scintillators and photosensors. The energy resolution does not change significantly with values as good as 13.7%. Regarding the CTR, values of 335.8, 363, 369.8, and 402.5 ps have been obtained for the whole detector for no light guide, 0.5, 1.0, and 1.5 mm thickness light guide cases, respectively. These values further improve to 276.1, 302.6, 305.6 and 336.2 ps, respectively, when energy-weighted averaging of timestamps is applied. CONCLUSIONS: We have shown both an excellent timing resolution and good energy resolution for a PET detector based on semi-monolithic crystals. The use of light guides of different thicknesses does not significantly affect the energy resolution of the whole detector, but the timing capabilities slightly worsen with the increasing thickness of the light guide.

Corticothalamic Pathways From Layer 5: Emerging Roles in Computation and Pathology.

Large portions of the thalamus receive strong driving input from cortical layer 5 (L5) neurons but the role of this important pathway in cortical and thalamic computations is not well understood. L5-recipient "higher-order" thalamic regions participate in cortico-thalamo-cortical (CTC) circuits that are increasingly recognized to be (1) anatomically and functionally distinct from better-studied "first-order" CTC networks, and (2) integral to cortical activity related to learning and perception. Additionally, studies are beginning to elucidate the clinical relevance of these networks, as dysfunction across these pathways have been implicated in several pathological states. In this review, we highlight recent advances in understanding L5 CTC networks across sensory modalities and brain regions, particularly studies leveraging cell-type-specific tools that allow precise experimental access to L5 CTC circuits. We aim to provide a focused and accessible summary of the anatomical, physiological, and computational properties of L5-originating CTC networks, and outline their underappreciated contribution in pathology. We particularly seek to connect single-neuron and synaptic properties to network (dys)function and emerging theories of cortical computation, and highlight information processing in L5 CTC networks as a promising focus for computational studies.

Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells.

A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Because of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

Coupling the endophytic microbiome with the host transcriptome in olive roots.

The connection between olive genetic responses to environmental and agro-climatic conditions and the composition, structure and functioning of host-associated, belowground microbiota has never been studied under the holobiont conceptual framework. Two groups of cultivars growing under the same environmental, pedological and agronomic conditions, and showing highest (AH) and lowest (AL) Actinophytocola relative abundances, were earlier identified. We aimed now to: i) compare the root transcriptome profiles of these two groups harboring significantly different relative abundances in the above-mentioned bacterial genus; ii) examine their rhizosphere and root-endosphere microbiota co-occurrence networks; and iii) connect the root host transcriptome pattern to the composition of the root microbial communities by correlation and co-occurrence network analyses. Significant differences in olive gene expression were found between the two groups. Co-occurrence networks of the root endosphere microbiota were clearly different as well. Pearson's correlation analysis enabled a first portray of the interaction occurring between the root host transcriptome and the endophytic community. To further identify keystone operational taxonomic units (OTUs) and genes, subsequent co-occurrence network analysis showed significant interactions between 32 differentially expressed genes (DEGs) and 19 OTUs. Overall, negative correlation was detected between all upregulated genes in the AH group and all OTUs except of Actinophytocola. While two groups of olive cultivars grown under the same conditions showed significantly different microbial profiles, the most remarkable finding was to unveil a strong correlation between these profiles and the differential gene expression pattern of each group. In conclusion, this study shows a holistic view of the plant-microbiome communication.

Role of metformin and other metabolic drugs in the prevention and therapy of endocrine-related cancers.

Metabolic syndrome is associated with chronic diseases, including type 2 diabetes, cardiovascular diseases, and cancer. This review summarizes the current evidence on the antitumor effects of some relevant drugs currently used to manage metabolic-related pathologies (i.e. insulin and its analogs, metformin, statins, etc.) in endocrine-related cancers including breast cancer, prostate cancer, pituitary cancer, ovarian cancer, and neuroendocrine neoplasms. Although current evidence does not provide a clear antitumor role of several of these drugs, metformin seems to be a promising chemopreventive and adjuvant agent in cancer management, modulating tumor cell metabolism and microenvironment, through both AMP-activated protein kinase-dependent and -independent mechanisms. Moreover, its combination with statins might represent a promising therapeutic strategy to tackle the progression of endocrine-related tumors. However, further studies are needed to endorse the clinical relevance of these drugs as adjuvants for cancer chemotherapy.