Bile duct ligation in the rat causes upregulation of ZO-2 and decreased colocalization of claudins with ZO-1 and occludin

As the only barrier between blood and bile compartments hepatocellular tight junctions play a crucial role in cholestasis-induced increase of biliary permeability. The molecular basis of this reversible defect is not known. We, therefore, examined expression, phosphorylation, distribution and colocalization of the junctional proteins occludin, claudin-1-3, ZO-1 and ZO-2 in rats after bile duct ligation and release of ligation. In control rats, claudin-1 and ZO-2 displayed a lobular gradient with highest expression levels in periportal cells, whereas claudin-2 showed a reciprocal distribution. Other proteins were evenly expressed in the liver lobule. Ligation resulted in upregulation of ZO-2 (2.7-fold), ZO-1 (1.4-fold) and occludin (1.2-fold) but not of claudins. Only ZO-2 showed increased phosphorylation. Distribution patterns were unchanged except for a strong accumulation of ZO-2 in perivenous hepatocytes. Colocalization analysis demonstrated that perivenous ZO-2 was the only protein examined revealing strongly increased overlap with occludin and ZO-1, whereas claudins and other proteins displayed a decrease. All changes were partially reversed by release of ligation. We conclude that differential expression of claudin-1-2 and ZO-2 has functional implications for bile formation. The moderately increased ZO-1 and occludin levels account for the known elongation of tight junction strands. The highly increased expression and changed distribution of ZO-2 suggests that ZO-1 is partly substituted by ZO-2, an alteration possibly causing impaired barrier functio

Mechanistic Regimes of Vibronic Transport in a Heterodimer and the Design Principle of Incoherent Vibronic Transport in Phycobiliproteins

Following the observation of coherent oscillations in non-linear spectra of photosynthetic pigment protein complexes, particularly phycobilliprotein such as PC645, coherent vibronic transport has been suggested as a design principle for novel light harvesting materials operating at room temperature. Vibronic transport between energetically remote pigments is coherent when the presence of a resonant vibration supports transient delocalization between the pair of electronic excited states. Here, we establish the mechanism of vibronic transport for a model heterodimer across a wide range of molecular parameter values. The resulting mechanistic map demonstrates that the molecular parameters of phycobiliproteins in fact support incoherent vibronic transport. This result points to an important design principle: incoherent vibronic transport is more efficient than a coherent mechanism when energetic disorder exceeds the coupling between the donor and vibrationally excited acceptor states. Finally, our results suggest that the role of coherent vibronic transport in pigment protein complexes should be reevaluated

Microtubule appendages mediating T-cell motility and polarity

© 2015 The Royal Society of Chemistry. Polarization of the centrosome and the Golgi apparatus in the T cell (TC) toward the antigen-presenting cell (APC) is essential for the specificity of the immune response on the cellular level. Previously we reported the existence of thin, long processes on the TC surface, which emanated predominantly from the area next to the Golgi apparatus. They appeared to be involved in the orientation of the TC during the initial phases of its attachment, which preceded the formation of the immunological synapse mediated by lamellipodia. Here we improve the visualization of the long, thin protrusions in the cultured TC and demonstrate using cytoskeleton inhibitors and immunofluorescence that microtubules form their cytoskeletal basis. The protrusions are seen prior to the attachment and the development of the broad lamellipodia (within a few minutes). We propose the term "tubulopodia" for this distinct type of cell appendage. Using an established experimental model that replaces the APC surface with a biomimetic substrate coated with antibodies against the TC receptor (TCR), we demonstrate that abrogation of the lamellipodium-mediated synapse formation does not impede the orientation of the TC Golgi apparatus and the centrosome to the contact area. Video microscopy reveals the spreading of the tubulopodia on the TCR-binding substrate, which results in the area of their emanation, and consequently the Golgi apparatus and the centrosome, being closely apposed (polarized) to the TCR-binding surface. Treatment with paclitaxel made the tubulopodia rigid, preventing their attachment to the TCR-binding surface and the reorientation of the cell body with the intracellular structures. We speculate that the motility and polarity of the TC in vivo may be mediated on a large scale by differential adhesion through the long, flexible tubulopodia

The pseudogap state in superconductors: Extended Hartree approach to time-dependent Ginzburg-Landau Theory

It is well known that conventional pairing fluctuation theory at the Hartree level leads to a normal state pseudogap in the fermionic spectrum. Our goal is to extend this Hartree approximated scheme to arrive at a generalized mean field theory of pseudogapped superconductors for all temperatures $T$. While an equivalent approach to the pseudogap has been derived elsewhere using a more formal Green's function decoupling scheme, in this paper we re-interpret this mean field theory and BCS theory as well, and demonstrate how they naturally relate to ideal Bose gas condensation. Here we recast the Hartree approximated Ginzburg-Landau self consistent equations in a T-matrix form. This recasting makes it possible to consider arbitrarily strong attractive coupling, where bosonic degrees of freedom appear at $T^*$ considerably above $T_c$. The implications for transport both above and below $T_c$ are discussed. Below $T_c$ we find two types of contributions. Those associated with fermionic excitations have the usual BCS functional form. That they depend on the magnitude of the excitation gap, nevertheless, leads to rather atypical transport properties in the strong coupling limit, where this gap (as distinct from the order parameter) is virtually $T$-independent. In addition, there are bosonic terms arising from non-condensed pairs whose transport properties are shown here to be reasonably well described by an effective time-dependent Ginzburg-Landau theory.Comment: 14 pages, 5 figures, REVTeX4, submitted to PRB; clarification of the diagrammatic technique added, one figure update

ПАТОГЕНЕЗ КОРОНАВІРУСНОЇ ІНФЕКЦІЇ COVID-19

Coronavirus SARS-CoV-2, penetrates through the mucous membranes of the respiratory tract and enterocytes of the small intestine through ACE2 receptors. Most ACE2 is expressed on the surface of cells of the respiratory tract, especially on type I and II alveolocytes, which explains the lung damage in infected people. Disruption of the gas exchange process associated with damage to the alveoli and capillaries leads to hypoxemia and secondary (indirect) damage to internal organs and systems. The pathogen SARS-CoV-2, which uses the ACE2 receptor to penetrate cells, is promoted by proteases that are inside these cells. ACE2 activity is due, in particular, IFN, the role and participation of which in the infectious process is being studied. The development of systemic vasculitis due to the tropism of the glycoprotein of coronavirus to endothelial cells that have the ACE receptor also indirectly leads to pathological changes in the lungs, heart, brain, kidneys, gastrointestinal tract. As a result of endothelial dysfunction and programmed necrotic cell death (apoptosis and piroptosis) in COVID-19, there is a systemic violation of microcirculation in the vascular bed of various organs and systems, which characterizes the clinical manifestations and consequences in infected. The autoimmune mechanism of defeat of internals is not excluded also. Binding of SARS-CoV-2 to receptors on the cell surface leads to an inflammatory process with the production of pro-inflammatory cytokines, the concentration of which can be extremely high in the form of the so-called “cytokine storm” that underlies ARDS and MODS. The risk of death is directly associated with high serum IL-6 levels. After 5-7 days from the onset of the disease there is interstitial pneumonia, initially focal, which quickly turns into drainage. The system of mononuclear phagocytes is affected; lymphopenia develops, IFN synthesis is suppressed. Coronavirus pneumonia can be complicated by the accession of bacterial flora, as evidenced by increased levels of procalcitonin in the serum, it also occurs when the patient’s condition worsens. In addition, the patient’s severity is accompanied by high levels of CRP, LDH, D-dimer, ferritin and the like. At the same time there are changes in the blood coagulation system. The level of hemoglobin decreases, which aggravates the hypoxic syndrome. Pathomorphological changes of ARDS include acute exudative and productive phases. In the first phase, signs of diffuse alveolar damage, acute bronchiolitis, edema and hemorrhage of interstitial tissue predominate. The productive phase is characterized by the development of fibrosing alveolitis with the organization of exudate in the lumen of the alveoli and bronchioles. coronavirus infection can also cause serious damage to other internal organs and systems. Thus, pathomorphological changes in infected SARS-CoV-2 are due to the direct action of nCoV, hyperactivity of the immune system, high levels of cytotoxicity of CD8 + T cells, autoimmune processes and the like.Коронавірус SARS-CoV-2 проникає через слизові оболонки дихальних шляхів (ДШ) і ентероцити тонкої кишки за допомогою рецепторів ангіотензин перетворюючого фактора 2 (АПФ2). У найбільшій кількості АПФ2 експресується на поверхні клітин дихального тракту, особливо на альвеолоцитах І і ІІ типу, що пояснює ураження легень у інфікованих. Порушення процесу газообміну, пов’язане з ураженням альвеол і капілярів, призводить до гіпоксемії і вторинних (опосередкованих) уражень внутрішніх органів і систем. Збуднику SARS-CoV-2 сприяють протеази, які знаходяться всередині цих клітин. Активність АПФ2 обумовлена інтерфероном (ІФН), роль і дольова участь яких в інфекційному процесі вивчається. Розвиток системного васкуліту у зв’язку з тропністю глікопротеїну коронавірусів (КВ) до ендотеліоцитів, які мають рецептор АПФ2, також опосередковано призводить до патологічних змін у легенях, серці, мозку, нирках, травному каналі (ТК). У результаті ендотеліальної дисфункції та запрограмованої некротичної загибелі клітин (апоптоз і піроптоз) при COVID-19 виникає системне порушення мікроциркуляції в судинному руслі різних органів і систем, що характеризує клінічні прояви та наслідки в інфікованих. Не виключається і автоімунний механізм ураження внутрішніх органів. Зв’язування SARS-CoV-2 з рецепторами на поверхні клітин призводить до запального процесу з продукцією прозапальних цитокінів, концентрація яких може бути надзвичайно високою у вигляді так званого «цитокінового шторму», який лежить в основі гострого респіраторного дистрес-синдрому (ГРДС) і сндрому поліорганної недостатності (СПОН). Ризик летального висліду асоційований безпосередньо з високим рівнем інтерлейкіну-6 (ІЛ-6) у сироватці крові. Через 5-7 діб від початку хвороби виникає інтерстиційна пневмонія, спочатку вогнищева, яка швидко перетворюється на зливну. Уражається система мононуклеарних фагоцитів; розвивається лімфопенія, пригнічується синтез ІФН. КВ пневмонія може ускладнитися приєднанням бактерійної флори, про що свідчить підвищення рівня прокальцитоніну в сироватці крові. Також це відбувається і при погіршенні стану хворого. Крім того, на тяжкість хвороби вказує високий рівень С-реактивного білка (СРБ), лактатдегідрогенази (ЛДГ), D-димеру, феритину тощо. Паралельно відбуваються зміни і в системі згортання крові. Знижується рівень гемоглобіну, що обтяжує гіпоксичний синдром. Патоморфологічні зміни ГРДС включають гостру ексудативну та продуктивну фази. У першій фазі переважають ознаки дифузного альвеолярного пошкодження, гострого бронхіоліту, набряку і геморагій інтерстиційної тканини. Для продуктивної фази властиві розвиток фіброзуючого альвеоліту з організацією ексудату в просвіті альвеол і бронхіол. Також КВ інфекція може спричиняти серйозні ураження в інших внутрішніх органах і системах. Таким чином, патоморфологічні зміни в інфікованих SARS-CoV-2 обумовлені безпосередньою дією nCoV, гіперактивністю імунної системи, високим рівнем цитотоксичності СD8+ Т-клітин, автоімунними процесами тощо

Magnetic Field Effects in the Pseudogap Phase: A Competing Energy Gap Scenario for Precursor Superconductivity

We study the sensitivity of T_c and T^* to low fields, H, within the pseudogap state using a BCS-based approach extended to arbitrary coupling. We find that T^* and T_c, which are of the same superconducting origin, have very different H dependences. This is due to the pseudogap, \Delta_{pg}, which is present at the latter, but not former temperature. Our results for the coherence length \xi fit well with existing experiments.We predict that very near the insulator \xi will rapidly increase.Comment: 4 pages, 4 figures, RevTe

Challenges for industrial robot applications in food manufacturing

The global food industry is facing many challenges due to the impact of climate change, ever-changing demands by consumers, and increasing legislative pressures by the government, which have resulted in several drivers for changes. Current large scale rigid manufacturing systems are increasingly seen as incapable of supporting the underlining requirements for implementation of such changes. In this context, one of the key requirements is the need for improved flexibility and reconfigurability of production facilities, often provided by adoption of Industrial Robots in other manufacturing sectors. However, despite their recent technological advancements, in particular the advent of the 4th industrial revolution (Industry 4.0), and significant reduction in overall implementation cost over the last two decades, the uptake of industrial robots in food processing has been slow. This paper explores the application of industrial robots in food manufacturing, the benefits of their use and the challenges currently hindering their uptake

Nernst Effect and Anomalous Transport in Cuprates: A Preformed-Pair Alternative to the Vortex Scenario

We address those puzzling experiments in underdoped high $T_c$ superconductors which have been associated with normal state "vortices" and show these data can be understood as deriving from preformed pairs with onset temperature $T^* > T_c$. For uncorrelated bosons in small magnetic fields, and arbitrary $T^*/T_c$, we present the exact contribution to \textit{all} transport coefficients. In the overdoped regime our results reduce to those of standard fluctuation theories ($T^*\approx T_c$). Semi-quantitative agreement with Nernst, ac conductivity and diamagnetic measurements is quite reasonable.Comment: 9 pages, 4 figures; Title, abstract and contents modified, new references added, figures changed, one more figure added; to be published on PR

Mechanism of pseudogap probed by a local impurity

The response to a local strong non-magnetic impurity in the pseudogap phase is examined in two distinctly different scenarios: phase-fluctuation (PF) of pairing field and d-density-wave (DDW) order. In the PF scenario, the resonance state is generally double-peaked near the Fermi level, and is abruptly broadened by vortex fluctuations slightly above the transition temperature. In the DDW scenario, the resonance is single-peaked and remains sharp up to gradual intrinsic thermal broadening, and the resonance energy is analytically determined to be at minus of the chemical potential.Comment: 4 pages, 2 figure

Superconducting transitions from the pseudogap state: d-wave symmetry, lattice, and low-dimensional effects

We investigate the behavior of the superconducting transition temperature within a previously developed BCS-Bose Einstein crossover picture. This picture, based on a decoupling scheme of Kadanoff and Martin, further extended by Patton, can be used to derive a simple form for the superconducting transition temperature in the presence of a pseudogap. We extend previous work which addressed the case of s-wave pairing in jellium, to explore the solutions for T_c as a function of variable coupling in more physically relevant situations. We thereby ascertain the effects of reduced dimensionality, periodic lattices and a d-wave pairing interaction. Implications for the cuprate superconductors are discussed.Comment: REVTeX, 11 pages, 6 EPS figures included, Replace with published versio