Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases

Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy

Planar polymer waveguides with a graded-index profile resulting from intermixing of methacrylates in closed microchannels

Graded-index waveguides are known to exhibit lower losses and considerably larger bandwidths compared to step-index waveguides. The present work reports on a new concept for realizing such waveguides on a planar substrate by capillary filling microchannels (cladding) with monomer solution (core). A graded-index profile is obtained by intermi xing between the core and cladding material at the microchannel interface. To this end, various ratios of methyl methacrylate (MMA) and octafluoropentyl methacrylate (OFPMA) were evaluated as starting monomers and the results showed that the polymers P50:50 (50:50 MMA:OFPMA) and P0:100 (100% OFPMA) were suitable to be applied as waveguide core and cladding material respectively. Light guiding in the resulting P50:50/P0:100 waveguides was demonstrated and the refractive-index profile was quantified and compared with that of conventional step-index waveguides. The results for both cases were clearly different and a gradual refractive index transition between the core and cladding was found for the newly developed waveguides. Although the concept has been demonstrated in a research environment, it also has potential for upscaling by employing drop-on-demand dispensing of polymer waveguide material in pre-patterned microchannels, for example in a roll-to-roll environment

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

A microphysiological model designed for the research of angiogenic sprouting in an extracellular matrix

Angiogenesis is an important biological process for vascular development, as well as being involved in different health problems such as cancer, inflammatory processes, infections, and some autoimmune diseases, among others. In recent years, microphysiological devices have been proposed to study angiogenesis due to their ability to accurately recreate in vivo microenvironmental conditions. This study presents a platform to study the early stages of angiogenesis together with an in-silico model, presenting an innovative approach that allows us to better analyze the dynamics of angiogenesis. The presented platform allows the formation of an angiogenic gradient through a porous hydrogel, thus provoking the angiogenic response of endothelial cells and therefore studying the process under the desired conditions. In addition, the use of the two-photon polymerization technique has allowed us to print 3D hydrogels with the desired structure within microfluidic devices. Our results show that this microphysiological device, together with the developed mathematical model, is a valuable tool for studying the complex process of angiogenesis.We gratefully acknowledge the financial support from the Spanish Ministry of Science and Innovation (MICINN) and the Spanish State Research Agency (AEI) through grants RTI2018-097038-B-C22, PID2021-124575OB-I00 and PDC2022-133918-C22, and the the financial support from the European Union’s Horizon Europe research & innovation program (EIC-2021-PATHFINDER-OPEN- 01-01-101047099 4DBR). Finally, we also appreciate the support of Research Foundation Flanders (FWO) (1SH3W24N)

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia (vol 32, pg 788, 2018)

Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 or JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an additional sheet has been added to Supplementary Table 2

Ultrasound stimulus to enhance the bone regeneration capability of gelatin cryogels

In the present study, gelatin-based cryogels have been seeded with human SAOS-2 osteoblasts. In order to overcome the drawbacks associated with in vitro culture systems, such as limited diffusion and inhomogeneous cell-matrix distribution, this work describes the application of ultrasounds (average power, 149 mW; frequency, 1.5 MHz) to physically enhance the cell culture in vitro. The results indicate that the physical stimulation of cell-seeded gelatin-based cryogels upregulates the bone matrix production

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens

Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse and human tissues

Protein histidine phosphorylation accounts for about 6% of the total protein phosphorylation in eukaryotic cells; still details concerning histidine phosphorylation and dephosphorylation are limited. A mammalian 14-kDa phosphohistidine phosphatase, also denominated PHPT1, was found 6 years ago that provided a new tool in the study of phosphohistidine phosphorylation. The localization of PHPT1 mRNA by Northern blot analysis revealed high expression in heart and skeletal muscle. The main object of the present study was to determine the PHPT1 expression on protein level in mouse tissues in order to get further information on the physiological role of the enzyme. Tissue samples from adult mice and 14.5-day-old mouse embryos were processed for immunostaining using a PHPT1-specific polyclonal antibody. The same antibody was also provided to the Swedish human protein atlas project (HPR) (http://www.proteinatlas.org/index.php). The results from both studies were essentially consistent with the previously reported expression of mRNA of a few human tissues. In addition, several other tissues, including testis, displayed a high protein expression. A salient result of the present investigation was the ubiquitous expression of the PHPT1 protein and its high expression in continuously dividing epithelial cells

Prognostic value of the neutrophil-to-lymphocyte ratio in advanced hepatocellular carcinoma: An exploratory analysis from the ARQ197-215 study

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