A human colonic crypt culture system to study regulation of stem cell-driven tissue renewal and physiological function

The intestinal epithelium is one of the most rapidly renewing tissues in the human body and fulfils vital physiological roles such as barrier function and transport of nutrients and fluid. Investigation of gut epithelial physiology in health and disease has been hampered by the lack of ex vivo models of the native human intestinal epithelium. Recently, remarkable progress has been made in defining intestinal stem cells and in generating intestinal organoid cultures. In parallel, we have developed a 3D culture system of the native human colonic epithelium that recapitulates the topological hierarchy of stem cell-driven tissue renewal and permits the physiological study of native polarized epithelial cells. Here we describe methods to establish 3D cultures of intact human colonic crypts and conduct real-time imaging of intestinal tissue renewal, cellular signalling, and physiological function, in conjunction with manipulation of gene expression by lentiviral or adenoviral transduction. Visualization of mRNA- and protein-expression patterns in cultured human colonic crypts, and cross-validation with crypts derived from fixed mucosal biopsies, is also described. Alongside studies using intestinal organoids, the near-native human colonic crypt culture model will help to bridge the gap that exists between investigation of colon cancer cell lines and/or animal (tissue) studies, and progression to clinical trials. To this end, the near native human colonic crypt model provides a platform to aid the development of novel strategies for the prevention of inflammatory bowel disease and cancer

Multimodal imaging of mild traumatic brain injury and persistent postconcussion syndrome

Background: Persistent postconcussion syndrome (PCS) occurs in around 5– 10% of individuals after mild traumatic brain injury (mTBI), but research into the underlying biology of these ongoing symptoms is limited and inconsistent. One reason for this could be the heterogeneity inherent to mTBI, with individualized injury mechanisms and psychological factors. A multimodal imaging study may be able to characterize the injury better. Aim: To look at the relationship between functional (fMRI), structural (diffusion tensor imaging), and metabolic (magnetic resonance spectroscopy) data in the same participants in the long term (>1 year) after injury. It was hypothesized that only those mTBI participants with persistent PCS would show functional changes, and that these changes would be related to reduced structural integrity and altered metabolite concentrations. Methods: Functional changes associated with persistent PCS after mTBI (>1 year postinjury) were investigated in participants with and without PCS (both n = 8) and non-head injured participants (n = 9) during performance of working memory and attention/processing speed tasks. Correlation analyses were performed to look at the relationship between the functional data and structural and metabolic alterations in the same participants. Results: There were no behavioral differences between the groups, but participants with greater PCS symptoms exhibited greater activation in attention-related areas (anterior cingulate), along with reduced activation in temporal, default mode network, and working memory areas (left prefrontal) as cognitive load was increased from the easiest to the most difficult task. Functional changes in these areas correlated with reduced structural integrity in corpus callosum and anterior white matter, and reduced creatine concentration in right dorsolateral prefrontal cortex. Conclusion: These data suggest that the top-down attentional regulation and deactivation of task-irrelevant areas may be compensating for the reduction in working memory capacity and variation in white matter transmission caused by the structural and metabolic changes after injury. This may in turn be contributing to secondary PCS symptoms such as fatigue and headache. Further research is required using multimodal data to investigate the mechanisms of injury after mTBI, but also to aid individualized diagnosis and prognosis

Preliminary results using a P300 brain-computer interface speller: a possible interaction effect between presentation paradigm and set of stimuli

Fernández-Rodríguez Á., Medina-Juliá M.T., Velasco-Álvarez F., Ron-Angevin R. (2019) Preliminary Results Using a P300 Brain-Computer Interface Speller: A Possible Interaction Effect Between Presentation Paradigm and Set of Stimuli. In: Rojas I., Joya G., Catala A. (eds) Advances in Computational Intelligence. IWANN 2019. Lecture Notes in Computer Science, vol 11506. Springer, ChamSeveral proposals to improve the performance controlling a P300-based BCI speller have been studied using the standard row-column presentation (RCP) par-adigm. However, this paradigm could not be suitable for those patients with lack of gaze control. To solve that, the rapid serial visual presentation (RSVP) para-digm, which presents the stimuli located in the same position, has been proposed in previous studies. Thus, the aim of the present work is to assess if a stimuli set of pictures that improves the performance in RCP, could also improve the per-formance in a RSVP paradigm. Six participants have controlled four conditions in a calibration task: letters in RCP, pictures in RCP, letters in RSVP and pictures in RSVP. The results showed that pictures in RCP obtained the best accuracy and information transfer rate. The improvement effect given by pictures was greater in the RCP paradigm than in RSVP. Therefore, the improvements reached under RCP may not be directly transferred to the RSVP.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Variability and constraint of vertebral formulae and proportions in colugos, tree shrews, and rodents, with special reference to vertebral modification by aerodynamic adaptation

Background: The aim of the present study is to provide the first large data set on vertebral formulae and proportions, and examine their relationship with different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and rodents (Rodentia), which have been considered less variable because they were thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. Materials and methods: The data included 33 colugos and 112 tree shrews, which are phylogenetically sister taxa, and 288 additional skeletons from 29 other mammalian species adapted to different locomotive modes, flying, gliding, arboreal, terrestrial, digging, and semi-aquatic habitats. Results: The following results were obtained: (1) intra-/interspecies variability and geographical variation in thoracic, lumbar, and thoracolumbar counts were present in two gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our examined mammals, some aerodynamic mammals, such as colugos, southern flying squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar gliders and some semi-aquatic rodents also showed some variation; (3) longer thoracic and shorter lumbar vertebrae were typically shared traits among the examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed squirrels (Anomaluridae). Conclusions: Our study reveals that aerodynamic adaptation could potentially lead to strong selection and modification of vertebral formulae and/or proportions based on locomotive mode despite evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44–56) Background: The aim of the present study is to provide the first large data set on vertebral formulae and proportions, and examine their relationship with different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and rodents (Rodentia), which have been considered less variable because they were thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. Materials and methods: The data included 33 colugos and 112 tree shrews, which are phylogenetically sister taxa, and 288 additional skeletons from 29 other mammalian species adapted to different locomotive modes, flying, gliding, arboreal, terrestrial, digging, and semi-aquatic habitats. Results: The following results were obtained: (1) intra-/interspecies variability and geographical variation in thoracic, lumbar, and thoracolumbar counts were present in two gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our examined mammals, some aerodynamic mammals, such as colugos, southern flying squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar gliders and some semi-aquatic rodents also showed some variation; (3) longer thoracic and shorter lumbar vertebrae were typically shared traits among the examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed squirrels (Anomaluridae). Conclusions: Our study reveals that aerodynamic adaptation could potentially lead to strong selection and modification of vertebral formulae and/or proportions based on locomotive mode despite evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44–56

Soils of the Hawaii Agricultural Experiment Station, University of Hawaii: Soil Survey, Laboratory Data, and Soil Descriptions

Benchmark Soils Project technical report 4Soils of 16 research sites in the University of Hawaii's agricultural research station network are described in detail. The sites are on the islands of Kauai, Oahu, Maui, and Hawaii. Soil series in the soil orders Mollisols, Oxisols, Vertisols, Inceptisols, Ultisols, Histisols, and Entisols are described. Soil maps of the stations are shown. Tables provide a soil profile description and laboratory data for the predominant soil series at each site, the text discusses the characteristics of the soil types within the series, along with their capability classifications, and related soils or variants at the sites are described

Signal peptide peptidases and gamma-secretase: Cousins of the same protease family?

Signal peptide peptidase (SPIP) is an unusual aspartyl protease, which mediates clearance of signal peptides by proteolysis within the endoplasmic reticulum (ER). Like presenilins, which provide the proteolytically active subunit of the,gamma-secretase complex, SPP contains a conserved GxGD motif in its C-terminal domain which is critical for its activity. While SPIP is known to be an aspartyl protease of the GxGD type, several presenilin homologues/SPP-like proteins (PSHs/ SPPL) of unknown function have been identified by database searches. In contrast to SPP and SPPL3, which are both restricted to the endoplasmic reticulum, SPPL2b is targeted through the secretory pathway to endosomes/lysosomes. As suggested by the differential subcellular localization of SPPL2b and SPPL3 distinct phenotypes were found upon antisense gripNA-mediated knockdown in zebrafish. spp and sppl3 knockdowns in zebrafish result in cell death within the central nervous system, whereas reduction of sppl2b expression causes erythrocyte accumulation in an enlarged caudal vein. Moreover, expression of D/A mutants of the putative C-terminal active sites of spp, sppl2, and spp13 produced phenocopies of the respective knockdown phenotypes. These data suggest that all investigated PSHs/SPPLs are members of the novel family of GxGD aspartyl proteases. More recently, it was shown that SPPL2b utilizes multiple intramembrane cleavages to liberate the TNF(x intracellular domain into the cytosol and to release the C-terminal counterpart into the lumen. These findings suggest common principles of intramembrane proteolysis by GxGD type aspartyl proteases. In this article,we will review the similarities of SPPs and gamma-secretase based on recent findings by us and others

Neuromuscular Responses during Knee Extension Exercise in Combination with Different Blood Flow Restriction Initial Pressures

Specifications of blood flow restriction training technique have been widely discussed to create a valid and reliable protocol. One of the unexplored variables is the effect of different initial restrictive pressures (tightness of cuffs, IRP) in combination with resistance exercise on neuromuscular responses and strength. PURPOSE: The purpose of this study was to determine any differences in amplitude (RMS) and median frequency (MDF) of electromyography (EMG) signals, as well as changes in strength during knee extension exercises with IRPs of 40-45 mmHg and 60-65 mmHg. METHODS: Twenty male subjects (age = 25.7 ± 4.3 yrs), participated in this study. They were required to attend the lab on 3 different occasions, with the first one being a familiarization session. On the subsequent sessions, participant\u27s upper leg was measured starting from the lateral epicondyle to the greater trochanter of the femur. An EMG electrode was placed at one-third the distance over the longitudinal axis of the vastus lateralis (VL) after shaving, abrading and cleaning with isopropyl alcohol. Initial restrictive pressure was randomly selected and participants completed a pre-exercise maximum voluntary contraction (MVC) test to determine their torque. For dynamic exercises, load was set at 20% MVC and each participant performed one set of 30 repetitions and three sets of 15 repetitions, separated by one minute rest. Post-exercise MVC was performed to assess the changes in leg strength following exercises. RESULTS: Results showed significant main effects (p\u3c0.01) in leg strength for condition (40-45 mmHg vs. 60-65 mmHg) and trial (pre vs. post MVC). A significant main effect was observed for condition for MVC EMG amplitude (p\u3c0.01). In addition, there were significant main effects for contractions (p\u3c0.01) in both EMG amplitude and MDF during dynamic exercises. CONCLUSION: The significant decreases in knee extension strength at IRP of 60-65 mmHg compared to IRP of 40-45mmHg from pre- to post-exercise suggest that subjects experienced more fatigue at 60-65 mmHg because of the decreased availability of oxygen to the working muscle. The use of different IRP will affect the level of blood flow and oxygen supply to skeletal muscle possibly causing variation in neuromuscular adaptation due to changes in total and type of muscle fiber recruitment

ATLAS Z Excess in Minimal Supersymmetric Standard Model

Recently the ATLAS collaboration reported a 3 sigma excess in the search for the events containing a dilepton pair from a Z boson and large missing transverse energy. Although the excess is not sufficiently significant yet, it is quite tempting to explain this excess by a well-motivated model beyond the standard model. In this paper we study a possibility of the minimal supersymmetric standard model (MSSM) for this excess. Especially, we focus on the MSSM spectrum where the sfermions are heavier than the gauginos and Higgsinos. We show that the excess can be explained by the reasonable MSSM mass spectrum.Comment: 13 pages, 7 figures; published versio

Generalised G2G_2-manifolds

We define new Riemannian structures on 7-manifolds by a differential form of mixed degree which is the critical point of a (possibly constrained) variational problem over a fixed cohomology class. The unconstrained critical points generalise the notion of a manifold of holonomy $G_2$, while the constrained ones give rise to a new geometry without a classical counterpart. We characterise these structures by the means of spinors and show the integrability conditions to be equivalent to the supersymmetry equations on spinors in supergravity theory of type IIA/B with bosonic background fields. In particular, this geometry can be described by two linear metric connections with skew torsion. Finally, we construct explicit examples by using the device of T-duality.Comment: 27 pages. v2: references added. v3: wrong argument (Theorem 3.3) and example (Section 4.1) removed, further examples added, notation simplified, all comments appreciated. v4:computation of Ricci tensor corrected, various minor changes, final version of the paper to appear in Comm. Math. Phy