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BIS (Bcl-2-interacting cell death suppressor, or BAG-3), is a multifunctional co-chaperone that maintains protein quality control via autophagy and proteostasis. Following the central nervous system (CNS) injury, BIS expression is markedly upregulated in reactive astrocytes, suggesting a regulatory role of reactive astrogliosis. To investigate this, we generated astrocyte-specific BIS knockout (BIS-aKO) mice for the first time. While BIS-aKO mice exhibited normal growth and survival, the injury-induced upregulation of BIS expression was abolished in reactive astrocytes following excitotoxic injury. Using a photothrombotic stroke model, we found that astrocytic BIS deficiency resulted in significantly increased GFAP expression in scar-forming astrocytes at the infarct border and altered morphology in the peri-infarct region. Furthermore, we observed increased infiltration of amoeboid Iba1-positive cells in the astroglial scar, indicating enhanced neuroinflammation. Correlative light-and electron-microscopy following both stroke and stab wound injury revealed BIS-aKO astrocytes exhibited a greater density of intermediate filament filling in their soma and processes, along with relatively fewer cytoplasmic organelles, such as mitochondria. Collectively, these findings highlight a previously unrecognized role of BIS in modulating reactive gliosis during brain injury and our model provides a valuable tool for investigating the astrocyte-specific functions of BIS in CNS pathophysiology.

Identification of early adaptive and maladaptive neuronal stress responses is an important step in developing targeted neuroprotective therapies for degenerative disease. In glaucoma, retinal ganglion cells (RGCs) and their axons undergo progressive degeneration resulting from stress driven by sensitivity to intraocular pressure (IOP). Despite therapies that can effectively manage IOP many patients progress to vision loss, necessitating development of neuronal-based therapies. Evidence from experimental models of glaucoma indicates that early in the disease RGCs experience altered excitability and are challenged with dysregulated potassium (K+) homeostasis. Previously we demonstrated that certain RGC types have distinct excitability profiles and thresholds for depolarization block, which are associated with sensitivity to extracellular K+. Here, we used our inducible mouse model of glaucoma to investigate how RGC sensitivity to K+ changes with exposure to elevated IOP. In controls, conditions of increased K+ enhanced membrane depolarization, reduced action potential generation, and widened action potentials. Consistent with our previous work, 4 weeks of IOP elevation diminished RGC light-and current-evoked responses. Compared to controls, we found that IOP elevation reduced the effects of increased K+ on depolarization block threshold, with IOP-exposed cells maintaining greater excitability. Finally, IOP elevation did not alter axon initial segment dimensions, suggesting that structural plasticity alone cannot explain decreased K+ sensitivity. Thus, in response to prolonged IOP elevation RGCs undergo an adaptive process that reduces sensitivity to changes in K+ while diminishing excitability. These experiments give insight into the RGC response to IOP stress and lay the groundwork for mechanistic investigation into targets for neuroprotective therapy.

Throughout human history, the control of light, electricity and heat has evolved to become the cornerstone of various innovations and developments in electrical and electromagnetic technologies. Wireless communications, laser and computer technologies have all been achieved by altering the way light and other energy forms act naturally and how to manage them in a controlled manner. At the nanoscale, to control light and heat, matured nanostructure fabrication techniques have been developed in the last two decades, and a wide range of groundbreaking processes have been achieved. Photonic crystals, nanolithography, plasmonics phenomena and nanoparticle manipulation are the main areas where these techniques have been applied successfully and led to an emergent material sciences branch known as metamaterials. Metamaterials and functional material development strategies are focused on the structures of the matter itself, which has led to unconventional and unique electromagnetic properties through the manipulation of light-and in a more general picture the electromagnetic waves-in widespread manner. Metamaterial's nanostructures have precise shape, geometry, size, direction and arrangement. Such configurations are impacting the electromagnetic light waves to generate novel properties that are difficult or even impossible to obtain with natural materials. This review discusses these metamaterials and metasurfaces from the perspectives of materials, mechanisms and advanced metadevices in depth, with the aim to serve as a solid reference for future works in this exciting and rapidly emerging topic.

To evaluate the ophthalmic clinical features and functional outcomes for patients with malignant sinonasal tumors who initially presented with orbital symptoms. Retrospective chart review for patients seen at Moorfields Eye Hospital between 1997 and 2020. Patient demographics and clinical features, radiology, histology, and treatment outcomes were reviewed. Forty patients (22 females; 55%) with sinonasal cancers first presented to an ophthalmologist at an average age of 53.9 years (median 56; range 8-92 years), with their having had first symptoms at 53.6 years (median 55.8; range 7.8-91.9 years). The commonest symptoms were persistent periorbital ache (19/40; 48%), periocular swelling (18; 45%), proptosis (16; 40%), and diplopia (15; 38%). All midface tumors affected only 1 orbit, and 13 of 40 (33%) eyes presented with an acuity of 20/60 or worse-5 having no perception of light-and 10 eyes (25%) had a relative afferent pupillary defect. An average of 4.5 mm relative exophthalmos was present (median 4 mm; range 0-9 mm), and a palpable mass in 19 of 40 (48%) orbits. Reduced eye movements and nonaxial displacement were recorded in 29 (73%) and 34 (85%) patients, respectively, and 9 (23%) had an abnormal optic disc or fundus. Bone erosion affected 95% of orbits, and almost a half had involvement of the neighboring extraocular muscles, orbital apex, or intracranially. The commonest tumor groups were sinonasal carcinomas (45%), sarcomas (28%), or lymphomas (11%). Of 37 globe-sparing treatments, 25 (68%) had persistence of previously impaired ophthalmic functions and 6 of 37 (16%) developed new impairment; only 6 of 37 (16%) of affected orbits retained normal function, and 6 patients lost all vision on the affected side. Sinonasal malignancies that present with orbital invasion are probably at the more aggressive end of the cancer spectrum, might be expected to carry a worse prognosis, and usually arise from the ethmoid or maxillary sinuses. In our series, carcinomas and sarcomas were the commonest malignancies, with similar 5-year overall survivals (of just over 50%), and over three-quarters of patients developed permanent impairment of orbital function and/or visual loss.

Photon fluence rate-response curves at different wavelengths were generated for the light-induced inhibition of hypocotyl elongation in seedlings of wildtype and photomorphogenic mutants of Arabidopsis thaliana. (L.) Heynh. Treatment of wild-type seedlings with continuous low-fluence-rate light (< 1.0 &#x3bc;mol photons &#xb7; m(-2) &#xb7; s(-1)) induced some inhibition of hypocotyl elongation at all wavelengths tested, with maximum inhibition in blue light. At higher fluence rates, inhibition reached a maximum of 70-80% in UV-A, blue, and far-red light. Fluence rate-response curves for seedlings of blu1, a blue light-response mutant, showed a specific reduction in their response to blue light, but their response to UV-A, red, and far-red light was similar to that in wild-type seedlings. In contrast, the phytochromedeficient mutant hy6 showed a loss of response to lowfluence-rate light at all wavelengths, as well as to highfluence-rate far-red light. However, hy6 seedlings retained sensitivity to high-fluence-rate blue and UV-A light. The data support the conclusion that blue-lightand phytochrome-dependent photosensory systems regulate hypocotyl elongation independently and in an additive manner. Furthermore, hypocotyl inhibition in wild-type, blul, hy6 and blul-hy6 double mutants was indistinguishable in UV-A light, whereas marked differences were observed at other wavelengths, indicating the involvement of a third photosensory system with an absorption maximum in the UV-A.

Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

We propose and experimentally demonstrate a high efficient circularly polarizing dichroism waveplate (CPDW) using a Si-based all-dielectric 2Dchiral metasurface. We demonstrate that the CPDW exhibits a unique dichroism in that it functions as a transmissive quarter waveplate for one of either left-or right-handed circularly polarized incident lightand a reflective mirror for the opposite polarization. The circular polarization dichroism (CPD&#x2009;=&#x2009;IRCP&#x2009;-&#x2009;ILCP) in transmission at wavelength ~1.5&#x2009;&#x3bc;m reaches 97% and the extinction ratio (ER&#x2009;=&#x2009;IRCP/ILCP) is as high as 345:1. Experimental fabrications and measurements of the proposed all-dielectric metasurface are implemented and found to be in excellent agreement with the simulations. The proposed all-dielectric chiral metasurface is of advantages of high-dichroism, easy-fabrication and standard semiconductor fabrication techniques compatible, which could lead to enhanced security in fiber and free-space communications, as well as imaging and sensing applications for circularly polarized light with a highly integrated photonic platform.

A combined light-and electron microscopic study of thymic changes in the adult rats after di-n-butyltin dichloride (DBTC) administration has been made. A rapid depletion of thymocytes in the cortex of thymus and subsequent rapid recovery of the number of thymocytes occurred. In this process, at 1-3 days after DBTC treatment the number of necrotic thymocytes was maximal. At 3-6 days, reticular epithelial cells were predominantly phagocytizing and acid phosphatase-positive in the cortex and cortico-medullary regions, where they appeared to develop from macrophage-like cells. During acute involution, it was likely that reticular epithelial cells were phagocytic and remove the necrotic thymocytes. The proportion of CD4+ CD8+ cells in the cortex of thymus was maximally reduced from day 3 onwards and reached the lowest level at 6 days after single oral dose of DBTC. On these days, the proportions of CD4- CD8- and single positive cell (CD4- CD8+ or CD4+ CD8-) subsets were relatively increased. These data suggest that DBTC preferentially causes an initial depletion of CD4+ CD8+ cells in thymus, and both macrophages and reticular epithelial cells of the cortex may be involved in the rapid removal of damaged thymocytes from thymus.

Notophthalmus (Triturus) viridescens, a urodele amphibian (newt) common to the Eastern United States, is a promising subject for developmental and regeneration studies. We have available a monoclonal antibody shown to be specific in many vertebrates for rod opsin, the membrane apoprotein of the visual pigment rhodopsin. This antibody to an N-terminal epitope, by rigorous biochemical and immunological criteria, recognizes only rod photoreceptor cells of the retina in light-and electron-microscopic immunocytochemistry. To determine the ontogeny and localization of rhodopsin in developing rods as an indicator of function in the embryonic urodele retina, we have utilized this antibody in the immunofluorescence technique on sections of developing N. viridescens. It was applied to serial sections of the eye region of Harrison stage 28 (optic vesicle) through stage 43 (most adult retina histology complete) embryos, and subsequently visualized with biotinylated species antibody followed by extravidin fluorescein isothiocyanate. The first positive reaction to rhodopsin could be detected in two to four cells (total) of the stage 37 embryonic eye, in the region of the central retinal primordium where the photoreceptors will be found. Some indications of retinal outer nuclear and inner plexiform layers could be seen at this time. Later embryonic stages demonstrated increasing numbers of positive cells in the future photoreceptor outer nuclear layer and outer and inner segments, spreading even to the peripheral retina. Nevertheless, by stale 43, no positive cells could be found at the dorsal or ventral retinal margins. Thus, biochemical differentiation of a photoreceptor population in the urodele retina occurs at a stage before retinal histogenesis is complete. The total maturation of retinal rods occurs topographically over a long period until the adult distribution is achieved.

Pancreatic islet amyloid, formed from islet amyloid polypeptide, is found in 96% of Type II (non-insulin-dependent) diabetic patients. Islet amyloidosis is progressive and apparently irreversible. Fibrils immunoreactive for islet amyloid polypeptide are found in macrophages associated with amyloid, suggesting that deposits can be phagocytosed. To determine the mechanism for the recognition and internalisation of fibrils, mouse peritoneal macrophages were cultured with fibrillar synthetic human islet amyloid polypeptide. Fibrils did not exert a cytotoxic effect over 72 h of culture. The uptake and degradation of fibrils was analysed by quantitative light-and electron-microscopic immunocytochemistry and immunoreactivity was detectable in 86+/-3% cells within 6 h of culture. Neither polyinosinic acid (200 microg/ml) nor nocodazole (10 microg/ml) inhibited fibril uptake, suggesting that internalisation is not blocked by poly-ions and is independent of microtubule assembly. Inhibition of pseudopodia formation by cytochalasin B blocked fibriI uptake. Fibril aggregates became condensed in lysosomes to form protofilaments and were resistant to intracellular proteolysis. Fibrils can be phagocytosed by macrophages in vitro but amyloid-associated factors may block the recognition of fibrils in vivo preventing the removal of islet amyloid in diabetes.

The scientific study of natural products traditionally used in anticancer preparations has yielded several therapeutically relevant compounds. One of these traditional preparations with potentially beneficial properties is aqueous extracts of Sutherlandia frutescens, a shrub indigenous to the Western Cape region of South Africa. The aims of this study were to evaluate in vitro efficacy of these preparations on the MCF-7 breast adenocarcinoma and MCF-12A non-tumorigenic cell lines in terms of cell proliferation, cell morphology and possible induction of cell death. Crystal violet staining was used to evaluate cell proliferation, light-and fluorescence microscopy were used to investigate both intracellular and extracellular morphological features of apoptosis and autophagy (e.g. membrane blebbing, condensed chromatin and intracellular lysosomes), while flow cytometry quantified cell cycle changes and induction of apoptosis through analysis of the flip-flop translocation of phosphatidylserine. Crystal violet staining showed a time- and dose specific response to aqueous Sutherlandia frutescens extracts, revealing exposure to 1mg/ml aqueous extract for 48h to be ideal for comparing the differential effects of Sutherlandia frutescens in the MCF-7 and MCF-12A cell lines. Microscopy showed distinct morphological changes with hallmarks of apoptosis being observed in both cell lines. Flow cytometry revealed a decrease in actively cycling cells in both cell lines, and a 4.36% increase in phosphatidylserine translocation in the MCF-7 cell line, indicative of apoptosis induction, while fluorescence microscopy showed evidence of the induction of autophagy. Analyses revealed the carcinogenic MCF-7 cell line to be more susceptible to the cytostatic and cytotoxic effects of aqueous extracts of Sutherlandia frutescens when compared to the non-tumorigenic MCF-12A cell line, thus warranting further research into the exact cellular mechanisms involved and the possible synergistic activities of Sutherlandia frutescens ingredients.

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Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species. The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microconidia. Light induces the differentiation of conidia and apothecia, while sclerotia are exclusively formed in the absence of light. The relevance of light for virulence of the fungus is not obvious, but infections are observed under natural illumination as well as in constant darkness. By a random mutagenesis approach, we identified a novel virulence-related gene encoding a GATA transcription factor (BcLTF1 for light-responsive TF1) with characterized homologues in Aspergillus nidulans (NsdD) and Neurospora crassa (SUB-1). By deletion and over-expression of bcltf1, we confirmed the predicted role of the transcription factor in virulence, and discovered furthermore its functions in regulation of light-dependent differentiation, the equilibrium between production and scavenging of reactive oxygen species (ROS), and secondary metabolism. Microarray analyses revealed 293 light-responsive genes, and that the expression levels of the majority of these genes (66%) are modulated by BcLTF1. In addition, the deletion of bcltf1 affects the expression of 1,539 genes irrespective of the light conditions, including the overexpression of known and so far uncharacterized secondary metabolism-related genes. Increased expression of genes encoding alternative respiration enzymes, such as the alternative oxidase (AOX), suggest a mitochondrial dysfunction in the absence of bcltf1. The hypersensitivity of &#x394;bctlf1 mutants to exogenously applied oxidative stress--even in the absence of light--and the restoration of virulence and growth rates in continuous light by antioxidants, indicate that BcLTF1 is required to cope with oxidative stress that is caused either by exposure to light or arising during host infection.

Exposure to high light induced a quantitatively similar decrease in the rate of photosynthesis at limiting photon flux density (PFD) and of photosystem II (PSII) photochemical efficiency, FV/FM, in both green and blue-green algal lichens which were fully hydrated. Such depressions in the efficiency of photochemical energy conversion were generally reversible in green algal lichens but rather sustained in blue-green algal lichens. This greater susceptibility of blue-green algal lichens to sustained photoinhibition was not related to differences in the capacity to utilize light in photosynthesis, since the light-and CO2-saturated rates of photosynthetic O2 evolution were similar in the two groups. These reductions of PSII photochemical efficiency were, however, largely prevented in lichen thalli which were fully desiccated prior to exposure to high PFD. Thalli of green algal lichens which were allowed to desiccate during the exposure to high light exhibited similar recovery kinetics to those which were kept fully hydrated, whereas bluegreen algal lichens which became desiccated during a similar exposure exhibited greatly accelerated recovery compared to those which were kept fully hydrated. Thus, green algal lichens were able to recover from exposure to excessive PFDs when thalli were in either the hydrated or desiccated state during such an exposure, whereas in blue-green algal lichens the decrease in photochemical efficiency was reversible in thalli illuminated in the desiccated state but rather sustained subsequent to illumination of thalli in the hydrated state.

Peptide-FMRFamide-like immunoreactivity in the brain and suboesophageal ganglion of the honeybee Apis mellifera L. is demonstrated with the peroxidase-antiperoxidase technique. Immunoreactivity is found in about 120 perikarya of the brain and in about 30 of the suboesophageal ganglion. These cells are distributed in 13 paired clusters representing neurons of different types including neurosecretory neurons projecting to neurohemal organs. Immunoreactivity of different intensity is found in the non-glomerular neuropil around the mushroom bodies, in the lateral protocerebrum, the central body, the optic tubercles, the lobula and medulla of optic lobe, the ocellar neuropil, in multiglomerular elements of the antennal lobes and in the dorsal deuterocerebrum. In the mushroom bodies, immunoreactivity is located in layers of the lobes and stalks, corresponding to intrinsic fibre bundles of some Kenyon cell types. The somata of these intrinsic cells did not show FMRFamide-like immunoreactivity. Electron microscopy of immunostained somata and nerve fibres was performed employing a pre-embedding peroxidase-antiperoxidase technique. Fibres of optic lobes and the non-glomerular neuropil contain immunoreactive dense core vesicles (diameter 50-165 nm) accumulated in boutons besides small synaptic vesicles and synaptic membrane specializations. Immunoreactive layers of the mushroom body neuropil were analysed at the ultrastructural level. Axon profiles with dense-core vesicles of a small type (diameter 35-75 nm) show only faint immunoreactive products. Immunoreactivity of intrinsic mushroom body neurons does not appear to be specifically correlated with synaptic organelles. Our results indicate that FMRFamide or related peptides peptides may be neuroactive compounds in different classes of nerve cells in the bee brain.

The study on the effects of different cutting intensities on the eco-physiological characteristics and growth status of Stylosanthes guianensis showed that moderate cutting could promote the regrowth capacity of the grass. The total content of leaf chlorophyll had no significant difference between zero-, light-and heavy cutting, but the ratio of leaf chlorophyll a/b increased to 1.59: 1 and 1.52: 1 under light-and heavy cutting, respectively, compared with 1.22:1 under zero-cutting, which could be very helpful for the plant to over-compensate itself. Cutting also affected the growth status and activities of plant roots. At the earlier stage of heavy cutting, the total length, total surface area and mean diameter of plant roots decreased by 54.9%, 66.5% and 27.2%, respectively, and root activities also decreased greatly, in comparing with zero-cutting. But, the above-mentioned indices could be recovered to a higher level under different cutting treatments than under zero-cutting at the later growth period of the grass. As for the total annual yield of the grass, it was 3 179.8 g x m(-2) under light-cutting, 3006.1 g x m(-2) under heavy- cutting, and 2 936.98 g x m(-2) under zero-cutting, indicating that rational cutting could improve grass productivity.

Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to investigate the health effect of biodiesel as well as efficiency of DOC or other exhaust aftertreatment systems.

Renal dysfunction is often seen in patients with plasma cell dyscrasias. The abnormal light and heavy chains that are produced by the neoplastic plasma cells in these patients are responsible for the renal abnormalities that occur. The renal manifestations are heterogeneous and include alterations in all three renal compartments; sometimes more than one compartment is affected in a given case. It must be demonstrated that the renal abnormalities are directly related to the underlying plasma cell dyscrasia to make a definitive diagnosis of an associated lesion. Therefore, it becomes crucial to link the renal findings with the circulating nephrotoxic light or heavy chains. Immunofluorescence is very helpful and diagnostic in the majority of the cases, as it can localize the light or heavy chains to the various renal compartments showing alterations, and frequently confirm monoclonality. However, the antibodies that are used routinely do not necessarily label the abnormal light and heavy chains; the corollary of this is that a negative immunofluorescence workup does not rule out a light- or heavy-chain-related renal disorder. Electron microscopy is also important as it can depict crucial morphologic correlates to provide unique evidence or to simply confirm and clarify diagnostic findings. Ultrastructural immunolabeling combines the information obtained from immunofluorescence and electron microscopy by highlighting specific structures associated with the deposition of the pathogenic monotypical light and heavy chains.

The cytogenesis of motor neurons of the immature brain stem of the bovine has been examined by light-and electron microscopy from the periods of origin and migration of the motor neurons until their transformation into relatively mature neurons in their area of destination. Up to 2.7 cm CRL intensive cell migration occurs from the ventromedial cell column in a ventrolateral direction, leading to the formation of the definitive viscero-efferent nucleus of the facial nerve. Electron-optically these cells exhibit features of immature neurons which are extending leading processes in the direction of their destination. At 2.5 cm CRL a formation of vertical cell columns can be identified in the facial nucleus which has reached its final position. Its perikaryon areas come into contact with radial fibres. This morphological pattern marks the process of migration. An increased ultrastructural differentiation is typical for neurons which are localized in their ultimate position.