bluuebunny/crossref_metadata_2025 huggingface dataset:
Age- and Condition-Related Changes in Levels of Neuron Specific Enolase in Spiral Ganglion Neurons of C57BL/6 Mice
Authors: Cohen Glenn M
Published: July 2020

The mouse strain C57BL/6 suffers from the early onset of deafness. The deafness is attributable to sweeping degeneration of hair cells and the auditory nerve. Degeneration advances with age from the base to the apex of the cochlea. In the present study, neuronal condition was determined by linking relative levels of neuron specific enolase (NSE) in spiral ganglion neurons to their cytological appearances. NSE is an enolase isoform that is expressed only in nervous tissue and neuroendocrine glands.

Mice ranged in age from 3 days to 10 months. Inner ears were fixed with 2.5% paraformaldehyde in 0.1 M cacodylate buffer, decalcified for 24 hrs with EDTA, and then embedded in either paraffin or polyester wax. The latter, which melts at a lower temperature, caused much less neuronal shrinkage during routine processing. Deparaffinized sections were exposed first to rabbit anti-bovine NSE antibodies, then to biotinylated swine anti-rabbit antibodies, and finally to peroxidase-labelled avidin.
Catalase Gene Therapy in Experimental Optic Neuritis: Immunocytochemistry Study
Authors: Qi Xiaoping , Guy John
Published: July 2020

Catalase is one of the several important antioxidant enzymes that detoxifies hydrogen peroxide (H2O2) to nontoxic H2O+O2. While previous studies prove that catalase plays an important role in the mechanism of enzymatic antioxidant defenses, the basal level of catalase is inadequate to deal widi excessive generation of H2O2 during ischemia and inflammation of me central nervous system. Although administered exogenous catalase can significantly reduce free oxygen radical damage in inflammatory response and demyelination disorders, it does not eliminate H2O2. Moreover, catalase has to be administered daily to increase its level. Recently, viral mediated gene delivery has been successfully demonstrated in many mammalian tissues, including in vivo gene transfer into ocular tissue. Gene expression was observed in retinal photoreceptor, RPE, Corneal endothelial and trabecular meshwork. Although it has already been reported that in vitro human endothelial cells express a 2-4 fold increase in catalase level within 24 hours after administration of the viral-catalase cDNA complex, there is no information available regarding in vivo human catalase gene transfer.
Investigation of DNA Loop Domains using Fluorescent in Situ Hybridization (FISH) and Epifluorescence Microscopy
Authors: Klaus Angela V , McCarthy Siobhan , McCarrey John , Ward W Steven
Published: July 2020

The average sperm nucleus is only 8 micrometers long, but contains 1 meter of DNA. We have previously described how the sperm cell is able to package this DNA into the small volume of the sperm head. The only DNA structure that exists in both somatic cells and sperm nuclei is the organization of DNA loop domains that are attached at their bases to the nuclear skeleton, the nuclear matrix. We compared the structure of one gene in sperm nuclei to that of spermatogenic and adult cells.

Individual loop domains of the 5S rRNA gene cluster were visualized by fluorescent in situ hybridization (FISH). Nuclei were isolated from hamster spermatozoa, spermatogonia, pachytene spermatocytes, round spermatids, and adult liver cells. They were then extracted to remove the protamines or histones, fixed, hybridized to a biotinylated 5S rDNA probe, then viewed by epifluorescence microscopy.
Suppression of Gastrin Production after Cisplatin Treatment in Rats
Authors: Wang Y , Aggarwal S K
Published: July 2020

Cisplatin, a commonly used broad spectrum chemotherapeutic drug, has been proven effective in the treatments of bladder, lung, ovarian, head and neck, testicular and breast cancers. One of the major side effects of this drug is its gastrointestinal toxicity, which includes severe nausea, vomiting and in case of rats bloating of the stomach and gastric ulceration. In case of rats, it manifests as bloating of the stomach and gastric ulceration since the rats don't have vomiting reflex. This has been attributed to hypocalcemia induced by cisplatin treatment which results in the suppression of acetylcholine and constitutive nitric oxide release inducing a bloating of the stomach. This has further been shown to induce an increase in the acid content of the stomach. There are no studies available on any changes of gastric protection after cisplatin treatment Gastrin has been shown to have gastroprotective effects against injury by maintaining the gastric mucosal integrity and gastric mucosal blood flow.
Immunocytochemical Analysis of Murine Peritoneal Macrophages Treated with “Poly-Plat”, an in Vitro and in Vivo Study
Authors: Muenchen H J , Aggarwal SK
Published: July 2020

Poly-[(trans-1,2-diaminocyclohexane) platinumj-carboxyamylose (“poly-plat“) is a second generation analog of cisplatin which enhances the immune system with greater efficacy in vitro and in vivo “Poly-plat” contains 1/5 the platinum of CDDP and demonstrates less toxicity. In order to understand the mechanism of action of this compound an in vitro and in vivo study was performed. Swiss Webster mice and isolated murine peritoneal macrophages were treated with “poly-plat” (10 mg/kg). The Swiss Webster mice were given bolus injections and sacrificed at 2 and 12 days. Peritoneal macrophages were then isolated and allowed to incubate in culture for 24 h. Peritoneal macrophages were also isolated from normal mice and treated with the drugs for 2 h. After treatments the macrophages were placed in fresh media and allowed to incubate 24 h. Supematants were isolated at various times during culture for immunocytochemical analysis.

Both in vitro and in vivo studies showed enhanced immunostimulation after their respective treatments.
The Centriole-Centrosome Complex is Affected by Microgravity During Cell Division and in Cilia of Sea Urchin Embryos: Results from Space Flight Experiments
Authors: Schatten Heide , Chakrabarti Amitabha , Taylor Meghan , Crosser Michael , Mitchell Kirk
Published: July 2020

Sea urchins have been used for over a century as a remarkable animal model system in which to study cell, molecular, and developmental biology. The studies presented here have used sea urchin eggs and embryos for pioneering experiments to explore the effects of microgravity on the cytoskeleton during a space flight on the space shuttle Endeavor. The culture conditions followed those described previously utilizing the Aquatic Research Facility (ARF) to fertilize and culture eggs and embryos up to the pluteus stage under controlled temperature (12°C) and fixation conditions. To achieve a final fixation with 0.5% glutaraldehyde and 4μM taxol, concentrated fixation fluid was injected at preselected time points to preserve microtubules, centrioles, centrosomes, microfilaments, mitochondria, and cell membranes.

The analysis of the results revealed that the centriole-centrosome complex during cell division and cilia formation showed alterations in samples that had been exposed to microgravity while control cells cultured in a centrifuge at lg in space and those cultured on ground appeared normal.
Ultrastructure of Septa from the Filamentous Fungus Aspergillus Nidulans
Authors: Richardson Elizabeth A , Momany Michelle
Published: July 2020

The filamentous fungus Aspergillus nidulans partitions its cells by laying down septa at regularly spaced intervals in response to nuclear division. Physiological and genetic studies of the temperature-sensitive sep mutants have been especially useful in dissecting the regulation of septation. Electron microscopic studies of the sep mutants should be equally useful in dissecting the structural intermediates of septation. In preparation for ultrastructural studies of the sep mutants, we have examined septa in wild-type A. nidulans fixed by freeze substitution.

Dialysis membranes were placed on rich medium plates and inoculated with A. nidulans spore suspensions. After 12 hours at 30°C, the dialysis membranes with adhering fungal hyphae were cut into square pieces measuring approximately 5mm on each side. The pieces were plunged into liquid propane and processed according to the procedures of Hoch. Serial sections were cut using a diamond knife and post stained with uranyl acetate and lead citrate.
Ivermectin-Induced Hypertrophic Changes in Adult Canine Heartworm (Dirofilaria Immitis) Gut Epithelium
Authors: Steffens W L , McCall J W
Published: July 2020

Ivermectin is a drug widely utilized for its anthelminthic activity over a diverse range of animal parasites. It has proved to be particularly useful in the prophylaxis of infection by the heartworm (Dirofilaria immitis) in dogs and cats. Although its application in this respect has been as a filaricide in preventing early growth and maturation of naturally acquired larvae, it is known to have activity against young adults as well. Previous studies have shown that in vitro exposure to ivermectin induces somatic muscle paralysis in the nematode Haemonchus contortus, resulting in pharyngeal dysfunction and disruption of normal ingestion. Experiments were performed to determine the effect of in vivo exposure of adult canine heartworms to this drug.

Adult heartworms were harvested from groups of dogs treated monthly with ivermectin beginning four to five months after inoculation of infective larvae and from untreated control dogs. Live worms from both experimental and control dogs were fixed, embedded, and sectioned for conventional transmission electron microscopy.
Characterization of the Cell Surface of Perkinsus marinus, a Pathogen of the Eastern Oyster, Crassostrea virginica Utilizing Electron Microscopy, Light Microscopy and Epifluorescent Microscopy.
Authors: Neimark Julie
Published: July 2020

Perkinsus marinus is a protistan parasite that infects the Eastern Oyster, Crassostrea virginica, and is one factor responsible for the reduced productivity of oyster fisheries. This parasite (or related species) has a wide distribution and has also been found to infect the oysters in the Tampa Bay region. A significant aspect of this organism has been its enigmatic taxonomic position. Originally classified in two separate fungal genera, it currently is considered an Apicomplexan (Kingdom Protista) based on transmission electron microscopy studies of the zoospore revealing an apical complex. However, rRNA studies have shown that P. marinus may be more closely related to the dinoflagellates. The focus of my study has been on surface features of certain developmental stages that may aid in a definitive taxonomic placement of this organism.

Transmission electron microscopy observations of the trophozoite and hypnospore stages show variation in both the size of the organism and the presence of a cell wall.
Size and Density Variation in Microtriches from Bothriocephalus Species Found in Cyprinus Carpio from Lake Powell, UTAH.
Authors: Bingham I , Bingham L , Heckmann R A , Gardner J S
Published: July 2020

Absorption enhancing microtriches of Bothriocephalus sp. were studied in relation to location, size, density, structure, and possible function using SEM.

Carp, C. carpio, were collected by gill nets set in Lake Powell, Utah. Tapeworms were collected from the carp intestine and relaxed in a cold water bath for 12 hours, placed in 1% cacodylate buffered glutaraldehyde, washed in a cacodylate buffer, soaked overnight in 1% OsO4, washed in buffer, dehydrated in an ETOH series, critical point dried, attached to stubs, and sputter coated for four minutes with gold. Bothriocephalus was viewed at varying magnifications using the JEOL 6100 scanning electron microscope. Density counts and measurements were conducted using digitized images and the program Semafore. Images were collected from the scolex and 8 equal body sections. Microtriches were measured from the tip to the base.
Bioremediation: Utilization of Aircraft Paint Waste as a Nutrient Source by Pseudomonas SP. VM1
Authors: Thurmond J E , Norton WN , Howard GT
Published: July 2020

The standard organic coatings applied to Navy aircraft consist of an epoxy primer and a polyurethane topcoat. The old coatings are routinely stripped in order for new layers to be applied. The stripping process involves removing the coating by sandblasting the aircraft with small plastic pellets. Although unpublished, we have demonstrated an ability of Pseudomonas sp. VM1 to biodegrade the waste products associated with the sandblasting process. A primary objective of this investigation was to determine the growth kinetics associated with the utilization of paint waste products as a sole carbon source for Pseudomonas. Another objective was to ascertain the nature of morphologic changes that occur among the particles of paint during biodegradation. In addition, the study was designed to determine whether phenylmethylsulfonyl fluoride (PMSF), a recognized inhibitor of proteolytic enzymes, is capable of modifying the biodegradative process of paint waste by Pseudomonas.
Applications of Soft X-Ray and other Microscopy Techniques to Elucidate the Structure of Parasitic Metazoa
Authors: Kozek W J , Brown J , Meyer-Ilse W , Larabell C , Moronne M
Published: July 2020

The small size of many parasitic organisms requires the use of election microscopy for adequate elucidation of their structure. While both transmission and scanning electron microscopy can provide complementary results which allow considerable degree of structural correlation, each technique has its inherent limitations. Since previous studies have demonstrated that soft X-ray microscopy could be used to study parasitic protozoa and provide new information, the objective of this study was to determine whether soft X-ray microscopy could also be used to elucidate the morphology of small metazoa to complement the data obtained by other microscopy techniques.

Newborn larvae, approximately 7 μm × 110 μm in size, of parasitic nematode Trichinella spiralis were used as a model system. Some of the larvae, deposited by adult females maintained in vitro, were isolated and processed for examination by transmission and scanning electron microscopy as described in our previous studies, others were fixed in 4% glutaraldehyde (Millonig's buffer) and examined in the X-ray microscope XM-1, and in the BioRad MRC 1024 confocal laser (krypton/argon) microscope of the Advanced Light Source, Berkeley National Laboratory.
Fibrinogen Kurashiki (γ G268E) Fibrin Network Structure
Authors: DiOrio J P , Mosesson M W , Matsuda M
Published: July 2020

Upon thrombin-catalyzed proteolytic conversion of fibrinogen to fibrin, fibrinopeptide A release exposes an N-terminal polymerization site (‘EA’) in the central E domain that interacts with a constitutive complementary site in each outer D domain (‘Da’) to drive the molecular assembly process by end-to-middle domain non-covalent ‘Da:EA’ interactions. End-to-end aligned doublestranded fibrils are formed in coordination with another recently described constitutive self-association site (termed ‘D:D’)that is situated at the outer end of each D domain. The D:D site contributes to end-to-end molecular alignment of fibrin molecules within each fibril strand. Concomitant branching and lateral fibril associations to form thick fibers, lead to formation of the mature fibrin clot.

Fibrinogen ‘Kurashiki’ is a unique congenital dysfibrinogenemia that was identified in a homozygous father and his heterozygous son. The abnormality involves a γ chain amino acid mutation (γ G268E) and is characterized by delayed and abnormal fibrin polymerization.
Effect of Prematurity on the Presence of Weibel-Palade Bodies in Human Umbilical Vein Endothelial Cell In Situ
Authors: Tabatabaei N , Albertine KH , Wenhua L , Lorant DE
Published: July 2020

Newborn, premature infants have greater susceptibility to infection compared to older newborn infants. Although the reason for greater susceptibility to bacterial infection in premature infants is unknown, there are many reports that focus on polymorphonuclear leukocytes (neutrophils) as the defective cell type in the immature neonatal system. However, we have recently reported that in an rat model of inflammation, neutrophils from adult rats failed to migrate efficiently in neonatal rats. Furthermore, we found that this defect was associated with decreased expression of P-selectin on the surface of neonatal endothelial cells in situ. P-selectin is an adherence molecule that is expressed by activated endothelial cells and serves as the counterligand for CD11/CD18, the β2- integrin that is expressed by activated neutrophils.

We hypothesized that endothelial cell P-selectin expression would be less in human umbilical cord veins from prematurely born (preterm) infants compared to normal term infants. To test this hypothesis, we collected umbilical cords from preterm infants (<27 weeks gestation) and term infants (>38 weeks gestation).
Temporal and Spatial Expression Patterns of PDGF Receptors in Embryonic Rat Heart as Detected Through Confocal Scanning Laser Microscopy.
Authors: Thielen T , Carver W , Simpson DG , Borg TK , Terracio L , Price RL
Published: July 2020

The active form of platelet derived growth factor (PDGF) is a dimeric combination of two polypeptide chains: PDGF-A and PDGF-B. The protein can exist as a heterodimer (PDGF-AB) or as one of two homodimers (PDGF-AA, PDGF-BB), resulting in three isoforms. Two types of PDGF receptors also exist: PDGFRα and PDGFRß. The PDGFRß binds only the PDGF-B chain, while PDGFRα can bind both PDGF-A and -B chains. Both of these receptors show specific temporal and spatial expression patterns that are related to cellular responses including mitogenesis, cell migration, chemotaxis, adhesion and differentiation in a variety of cell types.

Spontaneous mutants in which the PDGFRα is absent exhibit fatal defects during fetal development in mice. Some of these malformities include cardiac septal, valve, and outflow tract defects. Similar defects occur when the function of PDGF-A is disrupted by blocking antibodies. Disruption of PDGF-B function, results in ventricular and atrial dilation, hyper-trabeculation and reduction of the ventricular wall to the thickness of a single cell layer.
A Scanning Electron Microscopic Study of Adhesive Pad Development in the Frog
Authors: Ba-Omar TA , Downie JR
Published: July 2020

We have been investigating the development of the toe-pads of the frog Phyllomedusa irinhuiis. Several families of frog appear to have evolved rather similar digits with expanded terminal pads where ventral surfaces are specialised for adhesion. Although toe-pad structure has been extensively studied, development - which may gives clues to evolution - has not.

Adult and eggs of P. Iriniialis were collected from Trinidad, West Indies. Tadpoles were grown in our aquarium in Glasgow. We fixed front and hind digits of tadpoles at Gosner (1960) stages 37-42, froglets at stage 43-46, and adults. Pads were then processed for SEM.

Adult toe pads have a specialised epidermis with a surface layer of hexagonallyshaped cells, separated by deep clefts into which mucus glands open. Each pad is separated from the rest of the digit by a circumferal groove (Fig. 1).
Ultrastructure and Elemental Distribution in Foliage of Manganese-Treated Sugar Maple Seedlings: Comparison of Freeze-substitution Fixatives
Authors: McQuattie C J , Schier G A , Burns S , Heckman J W
Published: July 2020

Trace metals, such as manganese (Mn) and aluminum (Al), show increased solubility as soil acidity increases. Uptake of these elements may approach toxic concentrations in some plant species growing in acid forest soils. Previously, we had excellent results when chromium trioxide (CrO3) was used as the freeze substitution fixative in examining Al-treated plant and fungal tissue.1-2 However, when the fixative was used to study Mn toxicity, peak overlap (CrK β and MnKα) made it difficult to determine the location of Mn. In contrast, osmium tetroxide (OsO4) has no overlapping peak with Mn and is an excellent freeze substitution fixative. This study compares the use of OsO4 and CrO3 as fixatives for energy dispersive x-ray microanalysis (EDS) of the effect of Mn on ultrastructure and element localization in sugar maple leaves.
Multiscale Tomographic Analysis for Micron-Sized Particulate Samples
Authors: Ditscherlein Ralf , Furat Orkun , de Langlard Mathieu , Martins de Souza e Silva Juliana , Sygusch Johanna , Rudolph Martin , Leißner Thomas , Schmidt Volker , Peuker Urs A.
Published: July 2020

The three-dimensional characterization of distributed particle properties in the micro- and nanometer range is essential to describe and understand highly specific separation processes in terms of selectivity and yield. Both performance measures play a decisive role in the development and improvement of modern functional materials. In this study, we mixed spherical glass particles (0.4–5.8μm diameter) with glass fibers (diameter 10μm, length 18–660μm) to investigate a borderline case of maximum difference in the aspect ratio and a significant difference in the characteristic length to characterize the system over several size scales. We immobilized the particles within a wax matrix and created sample volumes suitable for computed tomographic (CT) measurements at two different magnification scales (X-ray micro- and nano-CT). Fiber diameter and length could be described well on the basis of the low-resolution micro-CT measurements on the entire sample volume. In contrast, the spherical particle system could only be described with sufficient accuracy by combining micro-CT with high-resolution nano-CT measurements on subvolumes of reduced sample size. We modeled the joint (bivariate) distribution of fiber length and diameter with a parametric copula as a basic example, which is equally suitable for more complex distributions of irregularly shaped particles. This enables us to capture the multidimensional correlation structure of particle systems with statistically representative quantities.
Preferential Evaporation in Atom Probe Tomography: An Analytical Approach
Authors: Hatzoglou Constantinos , Rouland Solène , Radiguet Bertrand , Etienne Auriane , Costa Gérald Da , Sauvage Xavier , Pareige Philippe , Vurpillot François
Published: July 2020

Atom probe tomography (APT) analysis conditions play a major role in the composition measurement accuracy. Preferential evaporation (PE), which significantly biases the apparent composition, more than other well-known phenomena in APT, is strongly connected to those analysis conditions. One way to optimize them, in order to have the most accurate measurement, is therefore to be able to predict and then to estimate their influence on the apparent composition. An analytical model is proposed to quantify the PE. This model is applied to three different alloys such as NiCu, FeCrNi, and FeCu. The model explains not only the analysis temperature dependence, as in an already existing model, but also the dependence to the pulse fraction and the pulse frequency. Moreover, the model can also provide an energetic constant directly linked to the energy barrier required to field evaporate atom from the sample surface.
Selection Bias Encountered in the Systematic Linking of Historical Census Records
Authors: Antonie Luiza , Inwood Kris , Minns Chris , Summerfield Fraser
Published: July 2020

Linked historical records typically are unrepresentative of the population from which they are drawn even if the method of linking is restricted to time-invariant matching criteria. An example drawn from Canadian census records illustrates the nature of bias that may afflict even a carefully linked sample. The use of potentially time-varying match criteria doubles the size of a linked sample at a modest cost in terms of additional bias. This trade-off is attractive for some research purposes if care is taken in the uses to which the data are put. Reweighting to mitigate the effects of bias in visible characteristics is desirable.
The unequal distribution of household carbon footprints in Europe and its link to sustainability
Authors: Ivanova Diana , Wood Richard
Published: July 2020

Non-technical summary

The distribution of household carbon footprints is largely unequal within and across countries. Here, we explore household-level consumption data to illustrate the distribution of carbon footprints and consumption within 26 European Union countries, regions and social groups. The analysis further sheds light on the relationships between carbon footprints and socially desirable outcomes such as income, equality, education, nutrition, sanitation, employment and adequate living conditions.
Prospective Memory Development Across the Lifespan
Authors: Zuber Sascha , Kliegel Matthias
Published: July 2020

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.
Quantifying the Relationship Between Short‐Wavelength Dynamic Topography and Thermomechanical Structure of the Upper Mantle Using Calibrated Parameterization of Anelasticity
Authors: Richards Fred D. , Hoggard Mark J. , White Nicky , Ghelichkhan Siavash
Published: July 2020

Oceanic residual depth varies on
5,000 km wavelengths with amplitudes of ±1 km. A component of this short‐wavelength signal is dynamic topography caused by convective flow in the upper ∼300 km of the mantle. It exerts a significant influence on landscape evolution and sea level change, but its contribution is often excluded in geodynamic models of whole‐mantle flow. Using seismic tomography to resolve buoyancy anomalies in the oceanic upper mantle is complicated by the dominant influence of lithospheric cooling on velocity structure. Here, we remove this cooling signal from global surface wave tomographic models, revealing a correlation between positive residual depth and slow residual velocity anomalies at depths <300  km. To investigate whether these anomalies are of sufficient amplitude to account for short‐wavelength residual depth variations, we calibrate an experimentally derived parameterization of anelastic deformation at seismic frequencies to convert shear wave velocity into temperature, density, and diffusion creep viscosity. Asthenospheric temperature anomalies reach +150°C in the vicinity of major magmatic hot spots and correlate with geochemical and geophysical proxies for potential temperature along mid‐ocean ridges. Locally, we find evidence for a ∼150 km‐thick, low‐viscosity asthenospheric channel. Incorporating our revised density structure into models of whole‐mantle flow yields reasonable agreement with residual depth observations and suggests that ±30 km deviations in local lithospheric thickness account for a quarter of total amplitudes. These predictions remain compatible with geoid constraints and substantially improve the fit between power spectra of observed and predicted dynamic topography. This improvement should enable more accurate reconstruction of the spatiotemporal evolution of Cenozoic dynamic topography.
MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer’s disease pathogenesis
Authors: Cao Jiqing , Huang Min , Guo Lei , Zhu Li , Hou Jianwei , Zhang Larry , Pero Adriana , Ng Sabrina , El Gaamouch Farida , Elder Gregory , Sano Mary , Goate Alison , TCW Julia , Haroutunian Vahram , Zhang Bin , Cai Dongming
Published: July 2020

Our recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP2) homeostasis to the susceptibility of developing Alzheimer’s Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP2 pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4+/− patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4−/− subjects. In addition, brain miR-195 levels are reduced along with disease progression from normal aging to early AD, and cerebrospinal fluid (CSF) miR-195 levels of MCI subjects are positively correlated with cognitive performances as measured by mini-mental status examination (MMSE) and negatively correlated with CSF tau levels, suggesting the involvement of miR-195 in early development of AD with a potential impact on cognition. Similar differences in miR-195 levels are seen in ApoE4+/+ mouse hippocampal brain tissue and cultured neurons when compared to ApoE3+/+ counterparts. Over-expressing miR-195 reduces expression levels of its top predicted target synaptojanin 1 (synj1), a brain PIP2-degrading enzyme. Furthermore, elevating miR-195 ameliorates cognitive deficits, amyloid plaque burden, and tau hyper-phosphorylation in ApoE4+/+ mice. In addition, elevating miR-195 rescues AD-related lysosomal defects in inducible pluripotent stem cells (iPSCs)-derived brain cells of ApoE4+/+ AD subjects while inhibiting miR-195 exacerbates these phenotypes. Together, our data uncover a novel regulatory mechanism of miR-195 targeted at ApoE4-associated brain PIP2 dyshomeostasis, cognitive deficits, and AD pathology.
Topology predicts long-term functional outcome in early psychosis
Authors: Fournier Margot , Scolamiero Martina , Gholam-Rezaee Mehdi M. , Cleusix Martine , Jenni Raoul , Ferrari Carina , Golay Philippe , Baumann Philipp S. , Cuenod Michel , Conus Philippe , Do Kim Q. , Hess Kathryn
Published: July 2020

Early intervention in psychosis is crucial to improving patient response to treatment and the functional deficits that critically affect their long-term quality of life. Stratification tools are needed to personalize functional deficit prevention strategies at an early stage. In the present study, we applied topological tools to analyze symptoms of early psychosis patients, and detected a clear stratification of the cohort into three groups. One of the groups had a significantly better psychosocial outcome than the others after a 3-year clinical follow-up. This group was characterized by a metabolic profile indicative of an activated antioxidant response, while that of the groups with poorer outcome was indicative of oxidative stress. We replicated in a second cohort the finding that the three distinct clinical profiles at baseline were associated with distinct outcomes at follow-up, thus validating the predictive value of this new stratification. This approach could assist in personalizing treatment strategies.
Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer
Authors: Schumacher Oliver , Galvão Daniel A. , Taaffe Dennis R. , Chee Raphael , Spry Nigel , Newton Robert U.
Published: July 2020

Background

An increasing number of studies indicate that exercise plays an important role in the overall care of prostate cancer (PCa) patients before, during and after treatment. Historically, research has focused on exercise as a modulator of physical function, psychosocial well-being as well as a countermeasure to cancer- and treatment-related adverse effects. However, recent studies reveal that exercise may also directly influence tumour physiology that could beneficially affect the response to radiotherapy.

Methods

In this narrative review, we provide an overview of tumour vascular characteristics that limit the effect of radiation and establish a rationale for exercise as adjunct therapy during PCa radiotherapy. Further, we summarise the existing literature on exercise as a modulator of tumour perfusion and hypoxia and outline potential future research directions.

Results

Preclinical research has shown that exercise can reduce intratumoral hypoxia—a major limiting factor in radiotherapy—by improving tumour perfusion and vascularisation. In addition, preliminary evidence suggests that exercise training can improve radiotherapy treatment outcomes by increasing natural killer cell infiltration in a murine PCa model.

Conclusions

Exercise is a potentially promising adjunct therapy for men with PCa undergoing radiotherapy that may increase its effectiveness. However, exercise-induced tumour radiosensitisation remains to be confirmed in preclinical and clinical trials, as does the optimal exercise prescription to elicit such effects.
Publisher Correction: ‘TRAIL-based gene delivery and therapeutic strategies’ and ‘Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy’
Authors: Zhong Hui-ha , Wang Hui-yuan , Gao Jian , Huang Yong-zhuo , Gao Ang , Hu Xian-li , Saeed Madiha , Chen Bin-fan , Li Ya-ping , Yu Hai-jun
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2
Authors: Huang Nan , Xu Chang , Deng Liang , Li Xue , Bian Zhixuan , Zhang Yue , Long Shuping , Chen Yan , Zhen Ni , Li Guohui , Sun Fenyong
Published: July 2020

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an essential enzyme involved in de novo purine biosynthesis, is connected with formation of various tumors. However, the specific biological roles and related mechanisms of PAICS in gastric cancer (GC) remain unclear. In the present study, we identified for the first time that PAICS was significantly upregulated in GC and high expression of PAICS was correlated with poor prognosis of patients with GC. In addition, knockdown of PAICS significantly induced cell apoptosis, and inhibited GC cell growth both in vitro and in vivo. Mechanistic studies first found that PAICS was engaged in DNA damage response, and knockdown of PAICS in GC cell lines induced DNA damage and impaired DNA damage repair efficiency. Further explorations revealed that PAICS interacted with histone deacetylase HDAC1 and HDAC2, and PAICS deficiency decreased the expression of DAD51 and inhibited its recruitment to DNA damage sites by impairing HDAC1/2 deacetylase activity, eventually preventing DNA damage repair. Consistently, PAICS deficiency enhanced the sensitivity of GC cells to DNA damage agent, cisplatin (CDDP), both in vitro and in vivo. Altogether, our findings demonstrate that PAICS plays an oncogenic role in GC, which act as a novel diagnosis and prognostic biomarker for patients with GC.
TIGAR/AP-1 axis accelerates the division of Lgr5− reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation
Authors: Chen Fei , Zhang Yushuo , Hu Songling , Shi Xiaolin , Wang Zhongmin , Deng Zicheng , Lin Longxin , Zhang Jianghong , Pan Yan , Bai Yang , Liu Fenju , Zhang Haowen , Shao Chunlin
Published: July 2020

During radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve intestinal stem cells (ISCs) and secretory progenitor cells are both reported to replenish damaged cells and contribute to crypt regeneration. However, the suppressed β-catenin/c-MYC axis within these slow-cycling cells leads to limited regenerative response to restore intestinal integrity during fatal accidental injury. Current study demonstrates that post-IR overexpression of TIGAR, a critical downstream target of c-MYC in mouse intestine, mounts a hyperplastic response in Bmi1-creERT+ reserve ISCs, and thus rescues mice from lethal IR exposure. Critically, by eliminating damaging reactive oxygen species (ROS) yet retaining the proliferative ROS signals, TIGAR-overexpression enhances the activity of activator protein 1, which is indispensable for initiating reserve-ISC division after lethal radiation. In addition, it is identified that TIGAR-induction exclusively gears the Lgr5− subpopulation of reserve ISCs to regenerate crypts, and intestinal TIGAR-overexpression displays equivalent intestinal reconstruction to reserve-ISC-restricted TIGAR-induction. Our findings imply that precise administrations toward Lgr5− reserve ISCs are promising strategies for unpredictable lethal injury, and TIGAR can be employed as a therapeutic target for unexpected radiation-induced GIS.
Maximizing lentiviral vector gene transfer in the CNS
Authors: Humbel Morgane , Ramosaj Mergim , Zimmer Virginie , Regio Sara , Aeby Ludiwine , Moser Sylvain , Boizot Alexia , Sipion Mélanie , Rey Maria , Déglon Nicole
Published: July 2020

Gene transfer is a widely developed technique for studying and treating genetic diseases. However, the development of therapeutic strategies is challenging, due to the cellular and functional complexity of the central nervous system (CNS), its large size and restricted access. We explored two parameters for improving gene transfer efficacy and capacity for the selective targeting of subpopulations of cells with lentiviral vectors (LVs). We first developed a second-generation LV specifically targeting astrocytes for the efficient expression or silencing of genes of interest, and to better study the importance of cell subpopulations in neurological disorders. We then made use of the retrograde transport properties of a chimeric envelope to target brain circuits affected in CNS diseases and achieve a broad distribution. The combination of retrograde transport and specific tropism displayed by this LV provides opportunities for delivering therapeutic genes to specific cell populations and ensuring high levels of transduction in interconnected brain areas following local administration. This new LV and delivery strategy should be of greater therapeutic benefit and opens up new possibilities for the preclinical development of gene therapy for neurodegenerative diseases.
Contactless probing of polycrystalline methane hydrate at pore scale suggests weaker tensile properties than thought
Authors: Atig Dyhia , Broseta Daniel , Pereira Jean-Michel , Brown Ross
Published: July 2020

Methane hydrate is widely distributed in the pores of marine sediments or permafrost soils, contributing to their mechanical properties. Yet the tensile properties of the hydrate at pore scales remain almost completely unknown, notably the influence of grain size on its own cohesion. Here we grow thin films of the hydrate in glass capillaries. Using a novel, contactless thermal method to apply stress, and video microscopy to observe the strain, we estimate the tensile elastic modulus and strength. Ductile and brittle characteristics are both found, dependent on sample thickness and texture, which are controlled by supercooling with respect to the dissociation temperature and by ageing. Relating the data to the literature suggests the cohesive strength of methane hydrate was so far significantly overestimated.
Author Correction: Brainstem and spinal cord MRI identifies altered sensorimotor pathways post-stroke
Authors: Karbasforoushan Haleh , Cohen-Adad Julien , Dewald Julius P. A.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Proton-transfer-induced 3D/2D hybrid perovskites suppress ion migration and reduce luminance overshoot
Authors: Kim Hobeom , Kim Joo Sung , Heo Jung-Min , Pei Mingyuan , Park In-Hyeok , Liu Zhun , Yun Hyung Joong , Park Min-Ho , Jeong Su-Hun , Kim Young-Hoon , Park Jin-Woo , Oveisi Emad , Nagane Satyawan , Sadhanala Aditya , Zhang Lijun , Kweon Jin Jung , Lee Sung Keun , Yang Hoichang , Jang Hyun Myung , Friend Richard H. , Loh Kian Ping , Nazeeruddin Mohammad Khaja , Park Nam-Gyu , Lee Tae-Woo
Published: July 2020

Perovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation.
Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state
Authors: Kawabe Takeshi , Yi Jaeu , Kawajiri Akihisa , Hilligan Kerry , Fang Difeng , Ishii Naoto , Yamane Hidehiro , Zhu Jinfang , Jankovic Dragana , Kim Kwang Soon , Trinchieri Giorgio , Sher Alan
Published: July 2020

CD4+T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether MP CD4+T cells are functionally heterogeneous and, if so, what signals specify the differentiation of MP cell subpopulations under homeostatic conditions is still unclear. Here we characterize MP lymphocytes as consisting of T-bethigh, T-betlow, and T-bet−subsets, with innate, Th1-like effector activity exclusively associated with T-bethighcells. We further show that the latter population depends on IL-12 produced by CD8α+type 1 dendritic cells (DC1) for its differentiation. Finally, our data demonstrate that this tonic IL-12 production requires TLR-MyD88 signaling independent of foreign agonists, and is further enhanced by CD40-CD40L interactions between DC1 and CD4+T lymphocytes. We propose that optimal differentiation of T-bethighMP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels.
Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease
Authors: Doi Daisuke , Magotani Hiroaki , Kikuchi Tetsuhiro , Ikeda Megumi , Hiramatsu Satoe , Yoshida Kenji , Amano Naoki , Nomura Masaki , Umekage Masafumi , Morizane Asuka , Takahashi Jun
Published: July 2020

Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.
A flat carborane with multiple aromaticity beyond Wade–Mingos’ rules
Authors: Lu Wei , Do Dinh Cao Huan , Kinjo Rei
Published: July 2020

It is widely known that the skeletal structure of clusters reflects the number of skeletal bonding electron pairs involved, which is called the polyhedral skeletal electron pair theory (PSEPT) or Wade and Mingos rules. While recent computational studies propose that the increase of skeletal electrons of polyhedral clusters leads to the flat structure beyond the PSEPT, little experimental evidence has been demonstrated. Herein, we report the synthesis of a C2B4R4 carborane 2 featuring a flat ribbon-like structure. The C2B4 core of 2 bearing 16 skeletal electrons in the singlet-ground state defies both the [4n + 2] Hückel’s rule and Baird’s rule. Nevertheless, the delocalization of those electrons simultaneously induces two independent π- and two independent σ-aromatic ring currents, rendering quadruple aromaticity.
An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment
Authors: GeurtsvanKessel Corine H. , Okba Nisreen M. A. , Igloi Zsofia , Bogers Susanne , Embregts Carmen W. E. , Laksono Brigitta M. , Leijten Lonneke , Rokx Casper , Rijnders Bart , Rahamat-Langendoen Janette , van den Akker Johannes P. C. , van Kampen Jeroen J. A. , van der Eijk Annemiek A. , van Binnendijk Rob S. , Haagmans Bart , Koopmans Marion
Published: July 2020

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.
Long-term Parkinson’s disease quality of life after staged DBS: STN vs GPi and first vs second lead
Authors: Cernera Stephanie , Eisinger Robert S. , Wong Joshua K. , Ho Kwo Wei David , Lopes Janine Lobo , To Kevin , Carbunaru Samuel , Ramirez-Zamora Adolfo , Almeida Leonardo , Foote Kelly D. , Okun Michael S. , Gunduz Aysegul
Published: July 2020

Deep brain stimulation (DBS) for Parkinson’s disease (PD) improves quality of life (QoL), but longitudinal follow-up data are scarce. We sought to quantify long-term benefits of subthalamic nucleus (STN) vs globus pallidus internus (GPi), and unilateral vs staged bilateral PD-DBS on postoperative QoL. This is a retrospective, longitudinal, non-randomized study using the PD QoL questionnaire (PDQ)-39 in patients with STN- or GPi-DBS, and with unilateral (N = 191) or staged bilateral (an additional contralateral lead implant) surgery (N = 127 and 156 for the first and second lead, respectively). Changes in PDQ-39 summary index (PDQ-39SI) and subscores throughout 60 months of follow-up were used as the primary analysis. We applied mixed models that included levodopa and covariates that differed at baseline across groups. For unilateral implantation, we observed an initial improvement in PDQ-39SI of 15.55 ± 3.29% (µ ± SE) across both brain targets at 4 months postoperatively. Unilateral STN patients demonstrated greater improvement in PDQ-39SI than GPi patients at 4 and 18 months postoperatively. Analysis of patients with staged bilateral leads revealed an initial 25.34 ± 2.74% (µ ± SE) improvement in PDQ-39SI at 4 months after the first lead with further improvement until 18 months, with no difference across targets. Scores did not improve after the second lead with gradual worsening starting at 18 months postoperatively. STN-DBS provided greater short-term QoL improvement than GPi-DBS for unilateral surgery. For staged bilateral DBS, overall QoL improvement was explained primarily by the first lead. Decision-making for patients considering DBS should include a discussion surrounding the potential risks and benefits from a second DBS lead.