Vacuum Structure and Dark Energy

We consider that the universe is trapped in an excited vacuum state and the resulting excitation energy provides the observed dark energy. We explore the conditions under which this situation can arise from physics already known. Considering the example of how macroscopic QED fields alter the vacuum structure, we find that the energy scale 1 meV --- 1 eV is particularly interesting. We discuss how dark energy of this form is accessible to laboratory experiments.Comment: 5 pages, 2 figures; recognized for Honorable Mention in 2010 Gravity Research Foundation Awards for Essays on Gravitation, in press with Int. J. Mod. Phys.

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

ВЛИЯНИЕ ДОПОЛНИТЕЛЬНОГО ВИБРАЦИОННОГО ВОЗДЕЙСТВИЯ НА ЭФФЕКТИВНОСТЬ ПРОВЕДЕНИЯ ПРОЦЕДУРЫ ЭЛЕКТРОСТИМУЛЯЦИИ

An experimental instrument complex which includes hardware for performing complex procedures using electrical shock massager frictional action was performed. The aim of the study was to influence the additional vibration effect on the efficiency of the procedure of electrostimulation.In order to increase the efficiency of the procedure electrostimulation authors proposed to carry it out with using of massager shock-friction action. The changes of muscular indicator on different stimulation treatments was shown after a series of seven treatments .Results of the processing of the experimental data and its subsequent analysis found that the use of the vibration exposure is accompanied by increase of load parameters in untrained volunteers. The increase in contact area due to decrease in the distance between the nozzle and the axis of rotation of the tumbler body surface, increases the electrical efficiency of the procedure.On the basis of a generalized analysis of data reflecting the effect of inappropriate electrical stimulation, it was established that, in order to achieve the best results, oscillatory systems providing shock-friction mode of its interaction with the skin surface, in particular a shock-frictional massager, were used.Целью работы являлось изучение влияния дополнительного вибрационного эффекта на эффективность процедуры электростимуляции. Описан экспериментальный приборный комплекс, который включает в себя аппаратный комплекс для выполнения процедуры электростимуляции с использованием массажера ударно-фрикционного действия.С целью повышения эффективности выполнения процедуры электростимуляции авторами предложено осуществлять ее с использованием массажера ударно-фрикционного действия. Рассмотрены изменения динамометрических характеристик у волонтеров до начала процедур стимуляции и по окончании серии из семи процедур.В результате обработки полученных экспериментальных данных и их последующего анализа установлено, что применение вибрационного воздействия сопровождается приростом динамометрических параметров у нетренированных волонтеров. Также отмечено, что увеличение частоты вращения насадки при ударно-фрикционном воздействии с 20 до 30 Гц положительно влияет на результативность процедуры.На основании обобщенного анализа полученных данных, отражающих влияние сообщаемых электроду вынужденных колебаний на протекание процедуры электростимуляции, установлено, что для достижения ее наибольшей эффективности следует использовать колебательные системы, обеспечивающие ударно-фрикционный режим его взаимодействия с поверхностью кожи, в частности массажер ударно-фрикционного действия

ВЛИЯНИЕ НАПРАВЛЕНИЯ СООБЩАЕМЫХ ЭЛЕКТРОДУ КОЛЕБАНИЙ НА ХАРАКТЕР МОДУЛЯЦИИ ЭЛЕКТРОСТИМУЛЯЦИОННЫХ ТОКОВ ПРИ ИСПОЛЬЗОВАНИИ МОДЕЛИ-ИМИТАТОРА КОЖНОГО ПОКРОВА ЧЕЛОВЕКА

The experimental complex of apparatus of electrical stimulation with combination of active electrode vibration of original design was developed. It has a possibility to use various mechanical and electrical parameters of vibration influence and electrical stimulation. In particular it has a possibility to apply various directions of vibrations to an active electrical stimulation electrode. The results of experiments have shown that the use of vibration-combined electrical stimulation procedure has an advantage in efficiency over traditional non-vibrating regime of procedure. Moreover, percussive-frictional mode is superior due to opportunities it has to change the modes of action.Описан экспериментальный приборный комплекс, который включает в себя массажер ударно-фрикционного действия с функцией электростимуляции и аппаратных средств, обеспечивающих осуществление данного вида комплексного воздействия при различных механических и электрических параметрах и имитатор кожного покрова человека. Рассмотрено влияние направления сообщаемых электроду колебаний на форму импульсного тока

Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models

publishedVersio

Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana.

BACKGROUND: In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown. RESULTS: A set of stigma-expressed pseudokinase genes, termed BRASSIKINs (BKNs), were identified and found to be present in only core Brassicaceae genomes. In Arabidopsis thaliana Col-0, BKN1 displayed stigma-specific expression while the BKN2 gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linked BKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on the bkn1/2 mutant stigmas. In further analyses, the predominant transcript for the stigma-specific BKN1 was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001 Arabidopsis genomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossing Arabidopsis species, A. lyrata and A. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes. CONCLUSION: In this study, we have characterized the novel Brassicaceae-specific family of BKN pseudokinase genes, and examined the function of BKN1 and BKN2 in the context of pollen-stigma interactions in A. thaliana Col-0. Additionally, premature stop codons were identified in the predicted stigma specific BKN1 gene in a number of the 1001 A. thaliana ecotype genomes, and this was in contrast to the out-crossing Arabidopsis species which carried intact copies of BKN1. Thus, understanding the function of BKN1 in other Brassicaceae species will be a key direction for future studies

LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies

Loss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases

Reversing SKI-SMAD4-mediated suppression is essential for TH17 cell differentiation

T helper 17 (TH17) cells are critically involved in host defence, inflammation, and autoimmunity. Transforming growth factor β (TGFβ) is instrumental in TH17 cell differentiation by cooperating with interleukin-6 (refs 6, 7). Yet, the mechanism by which TGFβ enables TH17 cell differentiation remains elusive. Here we reveal that TGFβ enables TH17 cell differentiation by reversing SKI-SMAD4-mediated suppression of the expression of the retinoic acid receptor (RAR)-related orphan receptor γt (RORγt). We found that, unlike wild-type T cells, SMAD4-deficient T cells differentiate into TH17 cells in the absence of TGFβ signalling in a RORγt-dependent manner. Ectopic SMAD4 expression suppresses RORγt expression and TH17 cell differentiation of SMAD4-deficient T cells. However, TGFβ neutralizes SMAD4-mediated suppression without affecting SMAD4 binding to the Rorc locus. Proteomic analysis revealed that SMAD4 interacts with SKI, a transcriptional repressor that is degraded upon TGFβ stimulation. SKI controls histone acetylation and deacetylation of the Rorc locus and TH17 cell differentiation via SMAD4: ectopic SKI expression inhibits H3K9 acetylation of the Rorc locus, Rorc expression, and TH17 cell differentiation in a SMAD4-dependent manner. Therefore, TGFβ-induced disruption of SKI reverses SKI-SMAD4-mediated suppression of RORγt to enable TH17 cell differentiation. This study reveals a critical mechanism by which TGFβ controls TH17 cell differentiation and uncovers the SKI-SMAD4 axis as a potential therapeutic target for treating TH17-related diseases