Prepulse Inhibition of Auditory Cortical Responses in the Caudolateral Superior Temporal Gyrus in Macaca mulatta

Prepulse inhibition (PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials (LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses (alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus (STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone (ALONE) and while another monkey was present in the same room (ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. These findings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.Peer reviewe

Inductively Coupled Split Ring Resonator as Small RFID Pressure Sensor for Biomedical Applications

We present an inductively coupled split-ring resonator based small passive RFID pressure sensor for wireless intracranial pressure measurement. The proposed sensor has a volume as small as π×(4 mm) 2 ×1 mm. In the simulation, the proposed sensor can provide nearly 1 m operation distance when implanted in the intracranial environment. In our preliminary measurement in the air, the sensor has a resolution of 3 cmH2O.acceptedVersionPeer reviewe

Application of mild autohydrolysis to facilitate the dissolution of wood chips in direct-dissolution solvents

Wood is not fully soluble in current non-derivatising direct-dissolution solvents, contrary to the many reports in the literature quoting wood 'dissolution' in ionic liquids. Herein, we demonstrate that the application of autohydrolysis, as a green and economical wood pre-treatment method, allows for a massive increase in solubility compared to untreated wood. This is demonstrated by the application of two derivitising methods (phosphitylation and acetylation), followed by NMR analysis, in the cellulose-dissolving ionic liquids 1-allyl-3-methylimidazolium chloride ([amim]Cl) and 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH][OAc]. In addition, the non-derivitising tetrabutylphosphonium acetate ([P-4444][OAc]) : DMSO-d6 electrolyte also allowed for dissolution of the autohydrolysed wood samples. By combination of different particle sizes and P-factors (autohydrolysis intensity), it has been clearly demonstrated that the solubility of even wood chips can be drastically increased by application of autohydrolysis. The physiochemical factors affecting wood solubility after autohydrolysis are also discussed.Peer reviewe

Synapse Clusters Are Preferentially Formed by Synapses with Large Recycling Pool Sizes

Synapses are distributed heterogeneously in neural networks. The relationship between the spatial arrangement of synapses and an individual synapse's structural and functional features remains to be elucidated. Here, we examined the influence of the number of adjacent synapses on individual synaptic recycling pool sizes. When measuring the discharge of the styryl dye FM1–43 from electrically stimulated synapses in rat hippocampal tissue cultures, a strong positive correlation between the number of neighbouring synapses and recycling vesicle pool sizes was observed. Accordingly, vesicle-rich synapses were found to preferentially reside next to neighbours with large recycling pool sizes. Although these synapses with large recycling pool sizes were rare, they were densely arranged and thus exhibited a high amount of release per volume. To consolidate these findings, functional terminals were marked by live-cell antibody staining with anti-synaptotagmin-1-cypHer or overexpression of synaptopHluorin. Analysis of synapse distributions in these systems confirmed the results obtained with FM 1–43. Our findings support the idea that clustering of synapses with large recycling pool sizes is a distinct developmental feature of newly formed neural networks and may contribute to functional plasticity

Exome-wide somatic mutation characterization of small bowel adenocarcinoma

Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe

Mactinin, a fragment of cytoskeletal α-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

<p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-α, interleukin (IL)-1α and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein α-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1α, IL-1β and TNF-α, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p

Interplay of Cultures Studio – Sámi: Architecture that leaves no trace in the environment, Master's level course in Architecture

Who are the Sámi? What is Sámi culture? What is Sápmi? What can be called Sámiarchitecture? Who has the right to design in Sápmi? What is cultural appropriation? How can one experience Sápmi? Who has the right to own the land? How can we learn about indigenous culture, here Sámi, without perpetuating colonization? What have we learned about the way Sámi cultures relate to our material reality and how could this inform the way we build today in Western culture as we strive for a sustainable way to live on the planet? During the beginning of the year 2022 the multidisciplinary architecture master studio,Interplay of Culture introduced 16 students to Sámi culture. Here are a few questions that we asked ourselves, and tried to answer with more questions than definite answers. The focus of this course is on the thematic area of Global Sustainability and Cultural Locality. The aim was to gain insight on sustainable building solutions and culturally sensitive architecture in indigenous northern cultures context. This publication is the summary of our exploration on the extremely broad and fascinatingSámi cultures. It gives diversified insight on what students explored, learned and understood of Sámi culture and building knowledge.Peer reviewe

CCL28 Induces Mucosal Homing of HIV-1-Specific IgA-Secreting Plasma Cells in Mice Immunized with HIV-1 Virus-Like Particles

Mucosae-associated epithelial chemokine (MEC or CCL28) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs) in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1IIIB Virus-like particles (VLPs). Mice receiving either HIV-1IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19+ splenocytes of HIV-1IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines

Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation

Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE2) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20–30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation

Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H

Peer reviewe