Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity

Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies

Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications

The one dimensional Kondo lattice model at partial band filling

The Kondo lattice model introduced in 1977 describes a lattice of localized magnetic moments interacting with a sea of conduction electrons. It is one of the most important canonical models in the study of a class of rare earth compounds, called heavy fermion systems, and as such has been studied intensively by a wide variety of techniques for more than a quarter of a century. This review focuses on the one dimensional case at partial band filling, in which the number of conduction electrons is less than the number of localized moments. The theoretical understanding, based on the bosonized solution, of the conventional Kondo lattice model is presented in great detail. This review divides naturally into two parts, the first relating to the description of the formalism, and the second to its application. After an all-inclusive description of the bosonization technique, the bosonized form of the Kondo lattice hamiltonian is constructed in detail. Next the double-exchange ordering, Kondo singlet formation, the RKKY interaction and spin polaron formation are described comprehensively. An in-depth analysis of the phase diagram follows, with special emphasis on the destruction of the ferromagnetic phase by spin-flip disorder scattering, and of recent numerical results. The results are shown to hold for both antiferromagnetic and ferromagnetic Kondo lattice. The general exposition is pedagogic in tone.Comment: Review, 258 pages, 19 figure

Gene expression variability across cells and species shapes innate immunity.

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response

Neutron-diffraction study of the magnetic ordering in superconducting TmRh4B4

The results of neutron-diffraction measurements are reported which confirm that superconducting TmRh4B4 orders magnetically at TM0.7 K. The modulated antiferromagnetic structure deduced from the data is of particular interest, considering the similarity of certain other physical properties of TmRh4B4 to those of the ferromagnetic, reentrant superconductor ErRh4B4. © 1983 The American Physical Society

Vitamin D deficiency, skin, and sunshine: A review

The sunshine vitamin - “Vitamin D” is a subject of interest that attracted researcher’s attention in the past few decades. Vitamin D is a fat-soluble vitamin and also a nutrient which increases the calcium absorption and plays an important part in the maintenance of body’s immune system and bone formation. However, the deficiency of Vitamin D, also known as hypovitaminosis D, will affect various body parts such as the brain, heart, muscle, immune system, and bones. Thus, the deficiency leads to severe conditions such as osteopenia, osteoporosis, rickets (in children), hypertension, fractures and falls in adults, cancers, diabetes, autoimmune diseases, infections, and neurological disorders. An effective approach for the deficiency prevention is the thorough understanding of Vitamin D sources, Vitamin D serum levels, and deficiency symptoms, linked with different pathological conditions, requirement and maintenance in the body, sunlight exposure duration, and effective treatment dose. Therefore, the present review will lay an emphasis on the role of Vitamin D, the reasons for its deficiency, available sources, and treatment options reported so far

Surface modification with cross-linked random copolymers: Minimum effective thickness

International audienceUltrathin films of benzocyclobutene (BCB)-functionalized random copolymer with styrene and methyl methacrylate, P(S-r-BCB-r-MMA), with thicknesses ranging from 0 to 10.5 nm, were thermally cross-linked on Si substrates. The penetration of deuterated PMMA (dPMMA) into the P(S-r-BCB-r-MMA) films and the microdomain orientation of PS-b-PMMA diblock copolymers on P(S-r-BCB-r-MMA) coated substrates were investigated by neutron reflectivity (NR) and scanning force microscopy (SFM), respectively. NR measurements on bilayers of dPMMA on cross-linked P(S-r-BCB-r-MMA) showed that the neutron scattering length density (SLD) at the substrate was equal to that of P(S-r-BCB-r-MMA) if the P(S-r-BCB-r-MMA) film was thicker than 5.5 nm. With decreasing thickness of the P(S-r-BCB-r-MMA) film, the SLD at the substrate increased, characteristic of an increasing penetration of the dPMMA. When thin films of PS-b-PMMA diblock copolymer having cylindrical microdomains are placed on surfaces modified with cross-linked films of P(S-r-BCB-r-MMA) thinner than 5.5 nm, the cylindrical microdomains orient parallel to the surface, whereas for thicker films, the microdomains orient normal to the surface. Both of these results indicate that interfacial interactions are screened when the P(S-r-BCB-r-MMA) film is thicker than 5.5 nm

Pharmacological evaluation of bromelain in mouse model of Alzheimer's disease.

The current study elucidates pharmacological evaluation of bromelain as a bioactive compound obtain from pineapple stem belongs to family Bromeliaceae in AlCl3 and D - galactose induced mice. In mice, co-administration of AlCl3 at dose 5 mg/kg b.w., via the oral route, and D - galactose at dose 60 mg/kg b.w., via intraperitoneal route for 90 days resulted in cognitive impairment, spatial learning, and memory deficits, as well as neurotoxicity. However, 30 consecutive days, treatments via an intraperitoneal route with bromelain low dose (Brm L) at dose 10 mg/kg b.w., bromelain high dose (Brm H) at dose 20 mg/kg b.w., donepezil (Dnpz) at dose 2 mg/kg b.w., and Brm L + Dnpz at doses 10, 2 mg/kg b.w. were considerably reversed the effect of AlCl3 and D - galactose induced AD mice. Consequences of behavioral parameters (Morris water maze, elevated plus maze and locomotor), biochemical estimation (MDA, GSH, SOD, CAT, Nitrite and AChE), and ELISA tests (mouse BACE, Aβ1 - 42, TNF-α, IL-6, and BDNF) confirmed significant (p < 0.05) neuroprotective effect of treatments in AlCl3 and D - galactose induced mice. Additionally, hematoxylin and eosin staining of the cerebral cortex and the hippocampus exposed eosinophilic lesions and hyperchromatic nuclei in AD mice, but these neurodegenerative effects were eliminated by Brm L, Brm H, Dnpz, and Brm L + Dnpz treatments. Thus, bromelain alone and in combination with donepezil prevent AlCl3 and D - galactose induced spatial learning and memory deficits, as well as cognitive impairment, by increasing cholinergic activity and synaptic plasticity, as well as reducing oxidative damage, neuroinflammation, Aβ 1-42 aggregations, and histopathological damage, according to our findings. The present study consequences indicate that bromelain alone and in combination with donepezil appears to have neuroprotective properties. Henceforward, this may be a promising treatment option for Alzheimer's disease