3D collagen migration patterns reveal a SMAD3-dependent and TGF-β1-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma

The TGF-β1 transcription factor SMAD3 is epigenetically repressed in tumour-associated fibroblasts (TAFs) from lung squamous cell carcinoma (SCC) but not adenocarcinoma (ADC) patients, which elicits a compensatory increase in SMAD2 that renders SCC-TAFs less fibrotic. Here we examined the effects of altered SMAD2/3 in fibroblast migration and its impact on the desmoplastic stroma formation in lung cancer.We used a microfluidic device to examine descriptors of early protrusions and subsequent migration in 3D collagen gels upon knocking down SMAD2 or SMAD3 by shRNA in control fibroblasts and TAFs.High SMAD3 conditions as in shSMAD2 fibroblasts and ADC-TAFs exhibited a migratory advantage in terms of protrusions (fewer and longer) and migration (faster and more directional) selectively without TGF-β1 along with Erk1/2 hyperactivation. This enhanced migration was abrogated by TGF-β1 as well as low glucose medium and the MEK inhibitor Trametinib. In contrast, high SMAD2 fibroblasts were poorly responsive to TGF-β1, high glucose and Trametinib, exhibiting impaired migration in all conditions.The basal migration advantage of high SMAD3 fibroblasts provides a straightforward mechanism underlying the larger accumulation of TAFs previously reported in ADC compared to SCC. Moreover, our results encourage using MEK inhibitors in ADC-TAFs but not SCC-TAFs.© 2022. The Author(s)

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

Differential Regulation of Horizontally Acquired and Core Genome Genes by the Bacterial Modulator H-NS

Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization

Bovine Tuberculosis in Doñana Biosphere Reserve: The Role of Wild Ungulates as Disease Reservoirs in the Last Iberian Lynx Strongholds

Doñana National Park (DNP) in southern Spain is a UNESCO Biosphere Reserve where commercial hunting and wildlife artificial feeding do not take place and traditional cattle husbandry still exists. Herein, we hypothesized that Mycobacterium bovis infection prevalence in wild ungulates will depend on host ecology and that variation in prevalence will reflect variation in the interaction between hosts and environmental risk factors. Cattle bTB reactor rates increased in DNP despite compulsory testing and culling of infected animals. In this study, 124 European wild boar, 95 red deer, and 97 fallow deer were sampled from April 2006 to April 2007 and analyzed for M. bovis infection. Modelling and GIS were used to identify risk factors and intra and inter-species relationships. Infection with M. bovis was confirmed in 65 (52.4%) wild boar, 26 (27.4%) red deer and 18 (18.5%) fallow deer. In the absence of cattle, wild boar M. bovis prevalence reached 92.3% in the northern third of DNP. Wild boar showed more than twice prevalence than that in deer (p<0.001). Modelling revealed that M. bovis prevalence decreased from North to South in wild boar (p<0.001) and red deer (p<0.01), whereas no spatial pattern was evidenced for fallow deer. Infection risk in wild boar was dependent on wild boar M. bovis prevalence in the buffer area containing interacting individuals (p<0.01). The prevalence recorded in this study is among the highest reported in wildlife. Remarkably, this high prevalence occurs in the absence of wildlife artificial feeding, suggesting that a feeding ban alone would have a limited effect on wildlife M. bovis prevalence. In DNP, M. bovis transmission may occur predominantly at the intra-species level due to ecological, behavioural and epidemiological factors. The results of this study allow inferring conclusions on epidemiological bTB risk factors in Mediterranean habitats that are not managed for hunting purposes. Our results support the need to consider wildlife species for the control of bTB in cattle and strongly suggest that bTB may affect animal welfare and conservation

Coronal voids and their magnetic nature

Context: Extreme ultraviolet (EUV) observations of the quiet solar atmosphere reveal extended regions of weak emission compared to the ambient quiescent corona. The magnetic nature of these coronal features is not well understood. // Aims: We study the magnetic properties of the weakly emitting extended regions, which we name coronal voids. In particular, we aim to understand whether these voids result from a reduced heat input into the corona or if they are associated with mainly unipolar and possibly open magnetic fields, similar to coronal holes. // Methods: We defined the coronal voids via an intensity threshold of 75% of the mean quiet-Sun (QS) EUV intensity observed by the high-resolution EUV channel (HRIEUV) of the Extreme Ultraviolet Imager on Solar Orbiter. The line-of-sight magnetograms of the same solar region recorded by the High Resolution Telescope of the Polarimetric and Helioseismic Imager allowed us to compare the photospheric magnetic field beneath the coronal voids with that in other parts of the QS. // Results: The coronal voids studied here range in size from a few granules to a few supergranules and on average exhibit a reduced intensity of 67% of the mean value of the entire field of view. The magnetic flux density in the photosphere below the voids is 76% (or more) lower than in the surrounding QS. Specifically, the coronal voids show much weaker or no network structures. The detected flux imbalances fall in the range of imbalances found in QS areas of the same size. // Conclusions: We conclude that coronal voids form because of locally reduced heating of the corona due to reduced magnetic flux density in the photosphere. This makes them a distinct class of (dark) structure, different from coronal holes

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition

Objective: To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Methods: Forty-nine patients with severe and closed TBI and 10 healthy control subjects with 18F-FDG PET were studied. Patients were divided into three groups: MCS&VS group (n ¼ 17), patients in a vegetative or a minimally conscious state; In-PTA group (n ¼ 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group (n ¼ 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Results: Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions: The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI.Lull Noguera, N.; Noé, E.; Lull Noguera, JJ.; Garcia Panach, J.; Chirivella, J.; Ferri, J.; López-Aznar, D.... (2010). Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition. Brain Injury. 24(9):1098-1107. doi:10.3109/02699052.2010.494592S10981107249Gallagher, C. N., Hutchinson, P. J., & Pickard, J. D. (2007). Neuroimaging in trauma. Current Opinion in Neurology, 20(4), 403-409. doi:10.1097/wco.0b013e32821b987bWoischneck, D., Klein, S., Rei�berg, S., D�hring, W., Peters, B., & Firsching, R. (2001). Classification of Severe Head Injury Based on Magnetic Resonance Imaging. Acta Neurochirurgica, 143(3), 263-271. doi:10.1007/s007010170106Grados, M. A. (2001). Depth of lesion model in children and adolescents with moderate to severe traumatic brain injury: use of SPGR MRI to predict severity and outcome. Journal of Neurology, Neurosurgery & Psychiatry, 70(3), 350-358. doi:10.1136/jnnp.70.3.350Meythaler, J. M., Peduzzi, J. D., Eleftheriou, E., & Novack, T. A. (2001). Current concepts: Diffuse axonal injury–associated traumatic brain injury. Archives of Physical Medicine and Rehabilitation, 82(10), 1461-1471. doi:10.1053/apmr.2001.25137Scheid, R., Walther, K., Guthke, T., Preul, C., & von Cramon, D. Y. (2006). Cognitive Sequelae of Diffuse Axonal Injury. Archives of Neurology, 63(3), 418. doi:10.1001/archneur.63.3.418Brandstack, N., Kurki, T., Tenovuo, O., & Isoniemi, H. (2006). MR imaging of head trauma: Visibility of contusions and other intraparenchymal injuries in early and late stage. Brain Injury, 20(4), 409-416. doi:10.1080/02699050500487951Xu, J., Rasmussen, I.-A., Lagopoulos, J., & Håberg, A. (2007). Diffuse Axonal Injury in Severe Traumatic Brain Injury Visualized Using High-Resolution Diffusion Tensor Imaging. Journal of Neurotrauma, 24(5), 753-765. doi:10.1089/neu.2006.0208Levine, B., Fujiwara, E., O’connor, C., Richard, N., Kovacevic, N., Mandic, M., … Black, S. E. (2006). In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging. Journal of Neurotrauma, 23(10), 1396-1411. doi:10.1089/neu.2006.23.1396Metting, Z., Rödiger, L. A., De Keyser, J., & van der Naalt, J. (2007). 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Metabolic thalamocortical correlations during a verbal learning task and their comparison with correlations among regional volumes. Brain Research, 1114(1), 125-137. doi:10.1016/j.brainres.2006.07.043Laureys, S., Faymonville, M., Luxen, A., Lamy, M., Franck, G., & Maquet, P. (2000). Restoration of thalamocortical connectivity after recovery from persistent vegetative state. The Lancet, 355(9217), 1790-1791. doi:10.1016/s0140-6736(00)02271-6Laureys, S., Goldman, S., Phillips, C., Van Bogaert, P., Aerts, J., Luxen, A., … Maquet, P. (1999). Impaired Effective Cortical Connectivity in Vegetative State: Preliminary Investigation Using PET. NeuroImage, 9(4), 377-382. doi:10.1006/nimg.1998.0414Laureys, S., Owen, A. M., & Schiff, N. D. (2004). Brain function in coma, vegetative state, and related disorders. The Lancet Neurology, 3(9), 537-546. doi:10.1016/s1474-4422(04)00852-xGuye, M., Bartolomei, F., & Ranjeva, J.-P. (2008). Imaging structural and functional connectivity: towards a unified definition of human brain organization? Current Opinion in Neurology, 24(4), 393-403. doi:10.1097/wco.0b013e3283065cfbPrice, C. J., & Friston, K. J. (2002). Functional Imaging Studies of Neuropsychological Patients: Applications and Limitations. Neurocase, 8(5), 345-354. doi:10.1076/neur.8.4.345.16186Kim, J., Avants, B., Patel, S., Whyte, J., Coslett, B. H., Pluta, J., … Gee, J. C. (2008). Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study. NeuroImage, 39(3), 1014-1026. doi:10.1016/j.neuroimage.2007.10.005Maxwell, W. L., MacKinnon, M. A., Smith, D. H., McIntosh, T. K., & Graham, D. I. (2006). Thalamic Nuclei After Human Blunt Head Injury. Journal of Neuropathology & Experimental Neurology, 65(5), 478-488. doi:10.1097/01.jnen.0000229241.28619.75SIDAROS, A., SKIMMINGE, A., LIPTROT, M., SIDAROS, K., ENGBERG, A., HERNING, M., … ROSTRUP, E. (2009). Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates. NeuroImage, 44(1), 1-8. doi:10.1016/j.neuroimage.2008.08.030Ashburner, J., & Friston, K. J. (2000). Voxel-Based Morphometry—The Methods. NeuroImage, 11(6), 805-821. doi:10.1006/nimg.2000.0582Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001). A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains. NeuroImage, 14(1), 21-36. doi:10.1006/nimg.2001.0786Giacino, J. T., Ashwal, S., Childs, N., Cranford, R., Jennett, B., Katz, D. I., … Zasler, N. D. (2002). The minimally conscious state: Definition and diagnostic criteria. Neurology, 58(3), 349-353. doi:10.1212/wnl.58.3.349Gispert, J. ., Pascau, J., Reig, S., Martínez-Lázaro, R., Molina, V., García-Barreno, P., & Desco, M. (2003). 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Thalamic integrity underlies executive dysfunction in traumatic brain injury. Neurology, 74(7), 558-564. doi:10.1212/wnl.0b013e3181cff5d

Copernicus Marine Service ocean state report, issue 4

This is the final version. Available from Taylor & Francis via the DOI in this record. FCT/MCTE

A bone remodelling model coupling micro-damage growth and repair by 3D BMU-activity.

Bone as most of living tissues is able, during its entire lifetime, to adapt its internal microstructure and subsequently its associated mechanical properties to its specific mechanical and physiological environment in a process commonly known as bone remodelling. Bone is therefore continuously renewed and micro-damage, accumulated by fatigue or creep, is removed minimizing the risk of fracture. Nevertheless, bone is not always able to repair itself completely. Actually, if bone repairing function is slower than micro-damage accumulation, a type of bone fracture, usually known as "stress fracture", can finally evolve. In this paper, we propose a bone remodelling continuous model able to simulate micro-damage growth and repair in a coupled way and able therefore to predict the occurrence of "stress fractures". The biological bone remodelling process is modelled in terms of equations that describe the activity of basic multicellular units. The predicted results show a good correspondence with experimental and clinical data. For example, in disuse, bone porosity increases until an equilibrium situation is achieved. In overloading, bone porosity decreases unless the damage rate is so high that causes resorption or "stress fracture"