Monitoring response and resistance to kinase inhibitors is essential to precision cancer medicine, and is usually investigated by molecular profiling of a tissue biopsy obtained at progression. ...However, tumor heterogeneity and tissue sampling bias limit the effectiveness of this strategy. In addition, tissue biopsies are not always feasible and are associated with risks due to the invasiveness of the procedure. To overcome these limitations, blood-based liquid biopsy analysis has proven effective to non-invasively follow tumor clonal evolution.
We exploited urine cell-free, trans-renal DNA (tr-DNA) and matched plasma circulating tumor DNA (ctDNA) to monitor a metastatic colorectal cancer patient carrying a CAD-ALK translocation during treatment with an ALK inhibitor.
Using a custom next generation sequencing panel we identified the genomic CAD-ALK rearrangement and a TP53 mutation in plasma ctDNA. Sensitive assays were developed to detect both alterations in urine tr-DNA. The dynamics of the CAD-ALK rearrangement in plasma and urine were concordant and paralleled the patient's clinical course. Detection of the CAD-ALK gene fusion in urine tr-DNA anticipated radiological confirmation of disease progression. Analysis of plasma ctDNA identified ALK kinase mutations that emerged during treatment with the ALK inhibitor entrectinib.
We find that urine-based genetic testing allows tracing of tumor-specific oncogenic rearrangements. This strategy could be effectively applied to non-invasively monitor tumor evolution during therapy. The same approach could be exploited to monitor minimal residual disease after surgery with curative intent in patients whose tumors carry gene fusions. The latter could be implemented without the need of patient hospitalization since urine tr-DNA can be self-collected, is stable over time and can be shipped at specified time-points to central labs for testing.
AIMS: Facilitation has been reported in a wide range of plant communities, with evidence of positive interactions between beneficiary and nurse plants shifting during their ontogenetic development. ...This study explored the hypothesis that shrubs of Juniperus communis subsp. nana (thereafter Juniperus) play a crucial role in the successional sequence of plant communities acting as nurse for different species, but only after reaching a certain size. In addition, we examined whether plant–plant interaction changes during ontogenesis of these shrubs in the presence of contrasting disturbance regimes in terms of substrate stability. LOCATION: Sibillini National Park, central Italy. The vegetation is semi‐natural dry grasslands (92/43/EEC Habitats Directive: Habitat 6210 ‐ Festuco‐Brometalia). METHODS: Field measurements were carried out to assess the effects of Juniperus on (1) the distribution of co‐existing vascular species, (2) the above‐ and below‐ground microclimate, and (3) changes in soil fertility and hydrology. RESULTS: The capacity of Juniperus shrubs to facilitate heterospecific plants considerably increases during its ontogenetic development, i.e. small shrubs mainly compete for resources with local vegetation, whereas large shrubs act as nurse plants for herbaceous and especially for woody species. The facilitation effect was slight, albeit significantly higher in the disturbed area than in the more stable one. Juniperus was able to promote the formation of an island of fertility under its canopy by accumulating a considerable amount of organic matter, N, P, Ca²⁺, Mg²⁺ and K⁺ in a few decades. Juniperus shrubs improve soil hydrological properties and mitigate the daily range of soil temperature, reducing the exposure of co‐existing plants to high temperatures and water loss through soil evaporation, particularly during the growing periods in spring and summer. CONCLUSIONS: This study demonstrates that biogenic amelioration of soil quality, coupled with the mitigation of below‐canopy microclimatic conditions, control the establishment and growth of co‐existing plants during Juniperus shrub development.
•Rhizodeposition and turnover of vine roots are responsible for accumulating C and N at depth.•The grass-cover of the vineyard alleys favours the accumulation of stabilised soil organic matter.•In ...our vineyard soils, fulvic acids represent a degradation product of humic acids.•At depth, fine vine roots have longer turnover times in the grass-covered than in the harrowed vineyard soil.•The vine increases the organic C and total N stock in the deeper layers of vineyard soils.
To examine the effects of vineyard soil management on soil C and N content and quality, we studied harrowed and grass-covered vineyards on a soil developed on plio-pleistocene, marine sediments. A soil naturally covered by grasses adjacent to the vineyards served as control. To reach this goal, we assessed (1) the distribution of C and N and their 13C and 15N signatures in different soil organic matter pools, (2) the amount of C and N as live and dead vine fine roots and their 13C, 15N and 14C signatures, and (3) the stocks of C and N forms accumulated at two soil-depth intervals (0–50 and 50–100cm).
Independent of the soil management, the vines increased the total organic C and total N content in the deeper soil horizons because of root turnover and rhizodeposition processes. In the upper horizons, a greater organic matter accumulation was fostered by the presence of the grass cover and the absence of tillage. The grass cover favoured the organic C storage mainly in the form of particulate and highly stabilised organic matter (humic acids and humin), and reduced the soil N content by plant uptake, whereas the harrowing produced a greater abundance of fulvic acids, which were mainly ascribed to oxidative processes enhanced by the soil tillage. In both vineyard soils, decaying vine roots represented an important source of organic C and N, especially in the deepest horizons. Indeed, isotope analyses revealed a more intense degradation of the dead vine roots in the deeper soil portion, where they likely constituted the main substrate for soil microorganisms. In the deepest horizons of the grass-covered vineyard, the greater mean residence time of the decaying vine roots and the lower root production were attributed to the easily available energetic substrates supplied by grass root turnover and rhizodeposition, which were preferentially used by microorganisms. This fact fostered a larger C accumulation in the grass-covered than in the harrowed vineyard.
The Main Ethiopian Rift is a key sector of the East African Rift System that connects the Afar depression, at Red Sea–Gulf of Aden junction, with the Turkana depression and Kenya Rift to the South. ...It is a magmatic rift that records all the different stages of rift evolution from rift initiation to break-up and incipient oceanic spreading: it is thus an ideal place to analyse the evolution of continental extension, the rupture of lithospheric plates and the dynamics by which distributed continental deformation is progressively focused at oceanic spreading centres.
The first tectono-magmatic event related to the Tertiary rifting was the eruption of voluminous flood basalts that apparently occurred in a rather short time interval at around 30
Ma; strong plateau uplift, which resulted in the development of the Ethiopian and Somalian plateaus now surrounding the rift valley, has been suggested to have initiated contemporaneously or shortly after the extensive flood-basalt volcanism, although its exact timing remains controversial. Voluminous volcanism and uplift started prior to the main rifting phases, suggesting a mantle plume influence on the Tertiary deformation in East Africa. Different plume hypothesis have been suggested, with recent models indicating the existence of deep superplume originating at the core-mantle boundary beneath southern Africa, rising in a north–northeastward direction toward eastern Africa, and feeding multiple plume stems in the upper mantle. However, the existence of this whole-mantle feature and its possible connection with Tertiary rifting are highly debated.
The main rifting phases started diachronously along the MER in the Mio-Pliocene; rift propagation was not a smooth process but rather a process with punctuated episodes of extension and relative quiescence. Rift location was most probably controlled by the reactivation of a lithospheric-scale pre-Cambrian weakness; the orientation of this weakness (roughly NE–SW) and the Late Pliocene (post 3.2
Ma)-recent extensional stress field generated by relative motion between Nubia and Somalia plates (roughly ESE–WNW) suggest that oblique rifting conditions have controlled rift evolution. However, it is still unclear if these kinematical boundary conditions have remained steady since the initial stages of rifting or the kinematics has changed during the Late Pliocene or at the Pliocene–Pleistocene boundary.
Analysis of geological–geophysical data suggests that continental rifting in the MER evolved in two different phases. An early (Mio-Pliocene) continental rifting stage was characterised by displacement along large boundary faults, subsidence of rift depression with local development of deep (up to 5
km) asymmetric basins and diffuse magmatic activity. In this initial phase, magmatism encompassed the whole rift, with volcanic activity affecting the rift depression, the major boundary faults and limited portions of the rift shoulders (off-axis volcanism). Progressive extension led to the second (Pleistocene) rifting stage, characterised by a riftward narrowing of the volcano-tectonic activity. In this phase, the main boundary faults were deactivated and extensional deformation was accommodated by dense swarms of faults (Wonji segments) in the thinned rift depression. The progressive thinning of the continental lithosphere under constant, prolonged oblique rifting conditions controlled this migration of deformation, possibly in tandem with the weakening related to magmatic processes and/or a change in rift kinematics. Owing to the oblique rifting conditions, the fault swarms obliquely cut the rift floor and were characterised by a typical right-stepping arrangement. Ascending magmas were focused by the Wonji segments, with eruption of magmas at surface preferentially occurring along the oblique faults. As soon as the volcano-tectonic activity was localised within Wonji segments, a strong feedback between deformation and magmatism developed: the thinned lithosphere was strongly modified by the extensive magma intrusion and extension was facilitated and accommodated by a combination of magmatic intrusion, dyking and faulting. In these conditions, focused melt intrusion allows the rupture of the thick continental lithosphere and the magmatic segments act as incipient slow-spreading mid-ocean spreading centres sandwiched by continental lithosphere.
Overall the above-described evolution of the MER (at least in its northernmost sector) documents a transition from fault-dominated rift morphology in the early stages of extension toward magma-assisted rifting during the final stages of continental break-up. A strong increase in coupling between deformation and magmatism with extension is documented, with magma intrusion and dyking playing a larger role than faulting in strain accommodation as rifting progresses to seafloor spreading.
The Broadly Rifted Zone (BRZ) of southern Ethiopia is a long‐lived and structurally complex segment of the East African Rift System. However, due to poor surface exposure of early synrift strata and ...a dearth of subsurface data, the evolution of the BRZ remains poorly understood. We present new apatite (U‐Th‐Sm)/He and augmented apatite fission track low‐temperature thermochronology data from the Beto and Galana basin boundary fault systems to constrain the tectonothermal evolution of the western and eastern BRZ, respectively. Time‐temperature reconstructions suggest that East African Rift System‐related extension began concurrently across the BRZ in the early Miocene (20–17 Ma), at least 6 Myr prior to faulting in the Main Ethiopian Rift further north. Increased time‐temperature resolution provided by multithermochronometer analyses reveals contrasting along‐strike spatiotemporal variations in Beto and Galana margin cooling histories, which appear to mirror the disparate structural geometries of their basin‐bounding normal fault arrays. Longitudinal contrasts in basin architecture and rift‐related cooling histories across the BRZ may reflect the region's heterogeneous distribution of preexisting basement fabrics, namely, the presence of a previously reported N‐NNE trending Neoproterozoic suture zone beneath the eastern BRZ. Its influence may explain both the development of long, curvilinear faults and the gradual basinward migration of strain exhibited by the easternmost BRZ, absent further west. The anomalous evolution of the BRZ compared to the greater Ethiopian Rift, both in its earlier onset and its wider deformation zone, likely results from its inheritance of preattenuated lithosphere, thermomechanically modified by earlier Cretaceous‐Paleogene Anza‐South Sudan rifting and/or Eocene plume impingement.
Key Points
Apatite (U‐Th‐Sm)/He and augmented fission track data constrain early Miocene onset of rift‐related cooling in Beto and Galana basin margins
Contrasting along‐strike cooling histories of Beto and Galana margins appear to reflect disparate structural geometries of their basin‐bounding fault arrays
Longitudinal contrasts in structural evolution of Broadly Rifted Zone may result from east‐west differences in preexisting lithospheric heterogeneities
BACKGROUND AND AIMS: The activity of roots and associated microorganisms plays a key-role in soil formation and evolution, but we lack of knowledge on the quality and extent of the “rhizosphere ...effect” in the different soil horizons. The aim of this study was to assess the interactions between rhizosphere processes and genetic horizons in a forest (Quercus ilex L.) soil developed from limestone. Specifically, we tested (a) if the rhizosphere effect was significant in all the horizons of the soil profiles, and (b) if the intensity of the rhizosphere effect was associated to structure, composition and activity of the microbial community. METHODS: Bulk and rhizosphere soils were characterized by physical, mineralogical, chemical and biological (microbial activity and community structure) analyses. RESULTS: Throughout the soil profile, the rhizosphere processes affected properties like particle-size distribution and soil structure, mineralogy, pH, and organic C and total P content. Conversely, amounts of exchangeable Ca, Mg and K, iron oxides, available P, and total nitrogen showed no significant change. As for the microbial community, its structure and metabolic activity differed between rhizosphere and bulk only in the core of the solum (2Bwb and 3Bwb horizons). CONCLUSIONS: The main processes controlling the intensity of the rhizosphere effect on the soil horizons were root activity, soil faunal perturbation and slope dynamics. While root activity impacted the whole soil profile, although to a lesser extent at depth, the influence of fauna and slope was confined atop the profile. It follows that long-term changes due to root activity and associated microbial community were more strongly expressed in the core of the solum, not at the surface, of this limestone-derived soil.
Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of ...the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s’ wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e’ 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.
The upgraded Large Hadron Collider beauty (LHCb) detector will provide data taken in Run3 at the instantaneous luminosity of proton-proton collisions increased to 2⋅1033 cm-2s-1 at energies of up to ...14 TeV. To ensure the safe operation of the experiment, a new beam and background Radiation Monitoring System (RMS-R3) was built. RMS-R3 is based on metal-foil detector technology developed at the Institute for Nuclear Research, National Academy of Sciences of Ukraine (Kyiv, Ukraine). The system comprises four detector modules with two sensors in each. Their frequency response is proportional to the flux of incident charged particles. The modules are located around the beam pipe at a distance of 2.2 m from the interaction point. The results measured during the Run3 in 2022 testify to the reliable operation of the system. Applying the asymmetry method, high-accuracy data were obtained on the localization of the interactions region and the beam and background contribution.
•In drylands, organic amendments, irrigation, and plant activity improve soil fertility.•In drylands, enzymatic activity occurred also at soil depth.•Soil organic C storage occurred by the formation ...of organo-mineral encapsulation.•Chemical fertilization and drip irrigation favor organic matter mineralization at depth.
The progressive degradation of cultivated drylands has been mainly ascribed to adoption of intensive soil use, namely repeated soil cultivation with external inputs and disturbances. Consequently, soil managements in equilibrium with environmental and social constrains are required to conserve and improve the soil fertility. We evaluated the impact of soil cultivation and management on chemical and biochemical properties of dryland soils from the Tunisian Jeffara Plain. This study considered three sites (Chenini Nahel, Matmata Nouvelle, and Menzel Habib), with both non-cultivated and cultivated soils. These latter were subjected to different soil management: organic fertilization and irrigation by submersion, chemical fertilization and drip irrigation, no fertilization and sporadic watering. The results showed that the addition of organic matter as compost or manure combined with irrigation may favor pH reduction, with consequently higher enzymatic activity and organic matter storage. The latter occurred because of the encapsulation of organic particles into collars made of re-precipitated gypsum and calcite. In cases where chemical fertilization and drip irrigation were applied, the organic matter stabilization occurred only at the surface; at depth we observed a reduction of organics due to microbially-mediated mineralization processes. When neither organic amendment nor water was supplied, no substantial difference occurred between cultivated and non-cultivated soils. We concluded that, in drylands, agricultural managements providing the use of water and organic amendments is the way to increase soil organic matter storage and improve physical, chemical and biological properties so to enhance the soil fertility.
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