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Background: Women carrying a germline BRCA1 mutation, have 60% risk of developing breast cancer during their lifetime and frequently develop triple-negative, basal-like, aggressive breast tumors. Humans produce around 150,000 different proteins from their 25,000-30,000 genes. This is accomplished by alternative splicing (AS). We hypothesized that AS in BRCA1 mutation carriers is different from those women with wild type BRCA1, therefore, we examined AS, expression of genes encoding splicing factors, and enrichment of binding motifs for RNA-binding proteins in BRCA1 carriers (BRCA1mut/+) and controls (BRCA1 normal). Methods: Prophylactic mastectomy (BRCA1mut/+) and reduction mammoplasty (BRCA1 normal) specimens were collected at Prentice Women’s Hospital of Northwestern Medicine under approval by Northwestern’s Institutional Review Board (NU15B07). We isolated organoids from these tissues, and cryopreserved them for future use. We selected organoids of premenopausal women, age-matched (28-46) without oral contraceptive usage within 3 years: BRCA1mut/+ (n=12) and BRCA1 normal (n=4). Organoids were maintained in complete MammoCult medium in ultra-low attachment plates at 37 °C, 5% CO2 for 72 hrs, and harvested for RNA extraction (NucleoSpin RNA Plus, TaKaRa). 100 ng of total RNA (RIN 7+) were used for RNA sequencing assay with the KAPA mRNA Hyper Prep Kit (Roche Corporate) and NovaSeq 6000 for 100b paired-end sequencing (Illumina, Inc). The preprocessed reads were aligned to the human genome (hg38) using STAR. Differential expression analysis (DESeq2, nominal p-value < 0.05) and pathway analysis (GSEA, size ≥30, NES >2, FDR q-value Citation Format: Oukseub Lee, Mi-Ran Choi, Gannon Cottone, Priyam Patel, Susan E Clare, Seema A. Khan. Heterozygous BRCA1 mutation influences alternative splicing in human benign mammary organoids [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-13-03.

Pharmacological approaches to breast cancer risk-reduction for BRCA1 mutation carriers would provide an alternative to mastectomy. BRCA1-deficiency dysregulates progesterone signaling, promoting tumorigenesis. Selective progesterone receptor (PR) modulators (SPRMs) are therefore candidate prevention agents. However, their efficacy varies in different BRCA1-deficient mouse models. We examined chemopreventive efficacy of telapristone acetate (TPA), ulipristal acetate (UPA) and mifepristone (MFP) in mice with a conditional knockout of the Brca1 C-terminal domain. The SPRMs displayed a spectrum of efficacy: UPA was most effective, TPA less, and MFP ineffective. Compared to no-treatment controls, UPA reduced tumorigenesis (p = 0.04), and increased tumor latency (p = 0.03). In benign mammary glands, UPA decreased Ki67 (p 0.001) and increased PR expression (p 0.0001). RNA sequencing analysis revealed distinct gene expression in response to UPA and MFP. UPA downregulated glycolysis and extracellular matrix-inflammation genes (Fn1, Ptgs2, Tgfb2, Tgfb3) whereas MFP downregulated claudin genes and upregulated amino acid metabolism and inflammation genes. The anti-glucocorticoid effects of MFP appeared not to be tumor-protective, while altering estrogen receptor signaling and NF-kB activation. Our study points to an important role of epithelial PR and its paracrine action on the microenvironment in BRCA1-deficient mammary tumorigenesis, and prevention.

Deaths involving synthetic opioids other than methadone (synthetic opioids), which largely consist of illicitly manufactured fentanyl; psychostimulants with abuse potential (e.g., methamphetamine); and cocaine have increased in recent years, particularly since 2013 (1,2). In 2019, a total of 70,630 drug overdose deaths occurred, corresponding to an age-adjusted rate of 21.6 per 100,000 population and a 4.3% increase from the 2018 rate (20.7) (3). CDC analyzed trends in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids during 2013-2019, as well as geographic patterns in synthetic opioid- and psychostimulant-involved deaths during 2018-2019. From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted (3,105 to 36,359). The psychostimulant-involved death rate increased 317%, from 1.2 (3,627) in 2013 to 5.0 (16,167) in 2019. In the presence of synthetic opioid coinvolvement, death rates for prescription opioids, heroin, psychostimulants, and cocaine increased. In the absence of synthetic opioid coinvolvement, death rates increased only for psychostimulants and cocaine. From 2018 to 2019, the largest relative increase in the synthetic opioid-involved death rate occurred in the West (67.9%), and the largest relative increase in the psychostimulant-involved death rate occurred in the Northeast (43.8%); these increases represent important changes in the geographic distribution of drug overdose deaths. Evidence-based prevention and response strategies including substance use disorder treatment and overdose prevention and response efforts focused on polysubstance use must be adapted to address the evolving drug overdose epidemic.

We give an effective upper bound, for certain arithmetic hyperbolic 3-manifold groups obtained from a quadratic form construction, on the minimal index of a subgroup that embeds in a fixed 6-dimensional right-angled reflection group, stabilizing a totally geodesic subspace. In particular, for manifold groups in any fixed commensurability class we show that the index of such a subgroup is asymptotically smaller than any fractional power of the volume of the manifold. We also give effective bounds on the geodesic residual finiteness growths of closed hyperbolic manifolds that totally geodesically immerse in non-compact right-angled reflection orbifolds, extending work of the third author from the compact case. The first result gives examples to which the second applies, and for these we give explicit bounds on geodesic residual finiteness growth.

Tumor-initiating cells with reprogramming plasticity are thought to be essential for cancer development and metastatic regeneration in many cancers; however, the molecular mechanisms are not fully understood. This study reports that CD81, a tetraspanin protein marker of small extracellular vesicles (exosomes), functions as a binding partner of CD44 and facilitates self-renewal of tumor initiating cells. Using machine learning-assisted protein structure modeling, co-immunoprecipitation, and mutagenesis approaches, we further demonstrate that CD81 interacts with CD44 on the cellular membrane through their extracellular regions. In-depth global and phosphoproteomic analyses of clustering tumor cells unveils endocytosis-related signature pathways of proteins and phosphorylation patterns regulated by CD81 and CD44 specifically or shared between two. Notably, CRISPR Cas9-mediated depletion of either CD44 or CD81 results in loss of both proteins in cancer cell-secreted exosomes, a state which abolishes exosome-induced self-renewal of recipient cells for mammosphere formation. CD81 is expressed in >80% of human circulating tumor cells (CTCs) and specifically enriched in clustered CTCs along with CD44 isolated from breast cancer patients. Mimicking the phenotypes of CD44 deficiency, loss of CD81 also inhibits tumor cluster aggregation, tumorigenesis, and lung metastasis of triple negative breast cancer (TNBC), supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights the novel role of CD81 and its partnership with CD44 in cancer exosomes, self-renewal, CTC clustering, and metastasis initiation of TNBC.

Pediatric high-grade gliomas, specifically diffuse midline gliomas, account for only 20% of clinical cases but are 100% fatal. A majority of the DMG cases are characterized by the signature K27M mutation in histone H3. The H3K27M mutation opposes the function of enhancer of zeste homolog 2 (EZH2), the methyltransferase enzyme of the polycomb repressor complex 2. However, the role of EZH2 in DMG pathogenesis is unclear. In this study, we demonstrate a tumor suppressor function for EZH2 using Ezh2 loss- and gain-of-function studies in H3WT DMG mouse models. Genetic ablation of Ezh2 increased cell proliferation and tumor grade while expression of an Ezh2 gain-of-function mutation significantly reduced tumor incidence and increased tumor latency. Transcriptomic analysis revealed that Ezh2 deletion upregulates an inflammatory response with upregulation of immunoproteasome genes such as Psmb8, Psmb9, and Psmb10. Ezh2 gain-of-function resulted in enrichment of the oxidative phosphorylation/mitochondrial metabolic pathway namely the isocitrate dehydrogenase Idh1/2/3 genes. Pharmacological inhibition of EZH2 augmented neural progenitor cell proliferation, supporting the tumor suppressive role of EZH2. In vivo 7-day treatment of H3K27M DMG tumor bearing mice with an EZH2 inhibitor, Tazemetostat, did not alter proliferation or significantly impact survival. Together our results suggest that EZH2 has a tumor suppressor function in DMG and warrants caution in clinical translation of EZH2 inhibitors to treat patients with DMG.

Effective thermal management is critical for the operation of many modern technologies, such as electronic circuits, smart clothing, and building environment control systems. By leveraging the static infrared-reflecting design of the space blanket and drawing inspiration from the dynamic color-changing ability of squid skin, we have developed a composite material with tunable thermoregulatory properties. Our material demonstrates an on/off switching ratio of ~25 for the transmittance, regulates a heat flux of ~36 W/m2 with an estimated mechanical power input of ~3 W/m2, and features a dynamic environmental setpoint temperature window of ~8 °C. Moreover, the composite can manage one fourth of the metabolic heat flux expected for a sedentary individual and can also modulate localized changes in a wearer’s body temperature by nearly 10-fold. Due to such functionality and associated figures of merit, our material may substantially reduce building energy consumption upon widespread deployment and adoption., Thermoregulatory platforms that combine the advantages of passive and active thermal management systems have remained elusive. Here, the authors draw inspiration from the static infrared-reflecting space blanket and dynamic color-changing squid skin to develop a composite material that addresses this challenge.

Efficient manipulation of cell fate is important for regenerative engineering applications. Lineage-specific differentiation of stem cells is particularly challenging due to their inherent plasticity. Engineered topographies may alter cellular plasticity through contact guidance. However, the ability to rationally design topographies to regulate phenotypic outcomes has been hindered in part by the lack of tools to quantify nanoscale chromatin structure reorganization in live cells. Herein we use micropillars, molecular, and nanostructural quantification tools to investigate how nuclear morphology in human mesenchymal stem cells (hMSCs) affects chromatin conformation and osteogenic differentiation. We show that micropillar-induced contact guidance is transduced via the cytoskeleton and impacts nuclear architecture, lamin A/C multimerization, histone modifications, and the 3-D conformation of chromatin within packing domains, a key regulator of transcriptional responsiveness. Micropillars repressed expression of genes associated with developmental processes and enhanced lineage-specific responsiveness, thereby decreasing cell plasticity and off-target differentiation, and facilitating osteogenic differentiation of hMSCs. Altogether, these findings reveal that chromatin reprogramming through contact guidance-induced nuclear deformation can be an efficient way to manipulate cell fate.

Conventional breast imaging methods like Magnetic Resonance Imaging, ultrasound and X-Ray are relied upon by most clinics and doctors worldwide. Breast microwave imaging (BMI) is an alternative imaging technology which uses nonionizing radiation which safer for the body and has a lower cost. A pre-clinical BMI system using breast phantoms is used to create the open source University of Manitoba- BMI dataset (UM-BMID). In this paper, we explore the usability of the dataset, implement different machine learning classification algorithms for tumor detection on UM-BMID and compare our findings with the previously published results. The accuracy achieved was a maximum of 94% which shows great promise for use of machine learning techniques in breast microwave imaging.

Tumor-initiating cells with reprogramming plasticity and/or de-differentiation attributes have been thought to initiate primary tumor development as well as to regenerate secondary tumors in metastatic organs; however, the molecular mechanisms are not fully understood. We previously found that breast tumor-initiating cell marker, CD44, directs multicellular aggregation and cluster formation of circulating tumor cells (CTCs), which further enhance stemness and survival of such cells, enabling metastatic colonization to the lungs. To further elucidate the molecular network underlying CTC cluster formation, we performed global proteomic profiling and discovered that the tetraspanin protein CD81, which is normally enriched in exosomes (small extracellular vesicles), is a new driver of cancer initiation and metastasis as a facilitator and target of CD44. Loss of CD81 compromises tumorigenicity and mammosphere formation of triple negative breast cancer (TNBC) cells. Assisted by machine learning-based algorithms and mutagenesis approach, we found that CD81 interacts with CD44 on the cellular membrane through their extracellular regions. Notably, genetic knockout of CD44 or CD81 results in loss of both CD81 and CD44 in secreted exosomes, a state which abolishes exosome-induced self-renewal of recipient cells, such as mammosphere formation. In addition, RNA sequencing analysis showed that CD81 knockdown up-regulates expression of a cell differentiation marker, SEMA7a, whose down-regulation partially rescues mammosphere formation inhibition by CD81 depletion. Clinically, CD81 expression was observed in >80% of CTCs and specifically enriched and co-expressed along with CD44 in clustered CTCs of breast cancer patients. Mimicing the phenotypes of CD44 deficiency, loss of CD81 also inhibited tumor cell aggregation and lung metastasis of TNBC in both human and mouse tumor models, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights a new driving role of CD81 in cancer exosome-induced stemness, clustered CTCs, and metastasis initiation of TNBC, reported for the first time to our knowledge.

Pulmonary arterial hypertension (PAH) is a sex-biased disease. Increased expression and activity of the long-noncoding RNA X-inactive–specific transcript (Xist), essential for X-chromosome inactivation and dosage compensation of X-linked genes, may explain the sex bias of PAH. The present studies used a murine model of plexiform PAH, the intersectin-1s (ITSN) heterozygous knockout (KO(ITSN+/–)) mouse transduced with an ITSN fragment (EH(ITSN)) possessing endothelial cell proliferative activity, in conjunction with molecular, cell biology, biochemical, morphologic, and functional approaches. The data demonstrate significant sex-centered differences with regard to EH(ITSN)-induced alterations in pulmonary artery remodeling, lung hemodynamics, and p38/ETS domain containing protein/c-Fos signaling, altogether leading to a more severe female lung PAH phenotype. Moreover, the long-noncoding RNA–Xist is up-regulated in the lungs of female EH(ITSN)-KO(ITSN+/–) mice compared with that in female wild-type mice, leading to sex-specific modulation of the X-linked gene ETS domain containing protein and its target, two molecular events also characteristic to female human PAH lung. More importantly, cyclin A1 expression in the S and G(2)/M phases of the cell cycle of synchronized pulmonary artery endothelial cells of female PAH patients is greater versus controls, suggesting functional hyperproliferation. Thus, Xist up-regulation leading to female pulmonary artery endothelial cell sexual dimorphic behavior may provide a better understanding of the origin of sex bias in PAH. Notably, the EH(ITSN)-KO(ITSN+/–) mouse is a unique experimental animal model of PAH that recapitulates most of the sexually dimorphic characteristics of human disease.

Given a 2-manifold, a fundamental question to ask is which groups can be realized as the isometry group of a Riemannan metric of constant curvature on the manifold. In this paper, we give a nearly complete classification of such groups for infinite-genus 2-manifolds with no planar ends. Surprisingly, we show there is an uncountable class of such 2-manifolds where every countable group can be realized as an isometry group (namely, those with self-similar end spaces). We apply this result to obtain obstructions to standard group theoretic properties for the groups of homeomorphisms, diffeomorphisms, and the mapping class groups of such 2-manifolds. For example, none of these groups satisfy the Tits Alternative; are coherent; are linear; are cyclically or linearly orderable; or are residually finite. As a second application, we give an algebraic rigidity result for mapping class groups., 49 pages, 5 figures. v2: incorporates referee's comments, final version, accepted for publication

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome–mediated alterations of cerebral Aβ deposition.

We prove an effective version of a theorem relating curve complex distance to electric distance in hyperbolic 3-manifolds, up to errors that are polynomial in the complexity of the underlying surface. We use this to give an effective proof of a result regarding maps between curve complexes of surfaces induced by finite covers. As applications, we effectively relate the electric circumference of a fibered manifold to the curve complex translation length of its monodromy, and we give quantitative bounds on virtual specialness for cube complexes dual to curves on surfaces., Several edits including a streamlined proof of Lemma 5.2. Accepted for publication by the Journal of Topology

Cephalopods possess unrivaled camouflage and signaling abilities that are enabled by their sophisticated skin, wherein multiple layers contain chromatophore pigment cells (as part of larger chromatophore organs) and different types of reflective cells called iridocytes and leucophores. The optical functionality of these cells (and thus cephalopod skin) critically relies upon subcellular structures partially composed of unusual structural proteins known as reflectins. Herein, we highlight studies that have investigated reflectins as materials within the context of color-changing coatings. We in turn discuss these proteins' multi-faceted properties, associated challenges, and future potential. Through our presentation of selected case studies, we hope to stimulate additional dialogue and spur further research on photonic technologies based on and inspired by reflectins.

The incidence of breast cancer is amassed in the current era due to the advent in urbanization, increase in sophisticated vicissitude living, and espousal of western lifestyles. Alpha- fetoprotein, a serum glycoprotein produced during embryonic development tends to act as the curative mediator and has anti-estrotrophic properties to inhibit the growth of estrogen- dependent tumor’s in breast cancer and metastasis. This oncofetal protein exhibits pharmaceutical activity during en route cancer metastasis and pathways lead to tumor cell progression and proliferation. In this work, the maximal inhibitory action of the peptide derived from the active site segment, which was previously suggested in experimental works against mice xenografts (8-mer Peptide), was derived from the structural model generated by homology modelling that retains the inhibitory activity exhibited by the derived AFPep P489- P496 (EMTPVNPG). A comparable mutation study has been undertaken in the derived peptide region to maximize the inhibitory action of the above-said activities. Comparative molecular dynamics study of each mutation has been carried out to know the stability of the octapeptide 489-496 to ensure the curative perspective that is indulged in inhibiting the progression and proliferation of oncofetal proteins in breast cancer. Another modification to the derived peptide was done by addition of hydroxyproline group to the region selected that was previously suggested with the combined effect of tamoxifen and hydroxyproline associated peptide. Molecular docking studies have also been carried out for the octapeptide against Hsp70 which might help in stabilising the anti tumour associated peptide AFPep for better binding efficacy for maximal inhibitory action and treatment of breast cancer.

It is a classical result of Powell that pure mapping class groups of connected, orientable surfaces of finite type and genus at least three are perfect. In stark contrast, we construct nontrivial homomorphisms from infinite-genus mapping class groups to the integers. Moreover, we compute the first integral cohomology group associated to the pure mapping class group of any connected orientable surface of genus at least 2 in terms of the surface's simplicial homology. In order to do this, we show that pure mapping class groups of infinite-genus surfaces split as a semi-direct product., v2: Updated to include referees' comments, which includes a significant rewriting of the exposition in the introduction. To appear in Int. Math. Res. Not. IMRN. 23 pages, 5 figures. v1: 21 pages, 4 figures

Cephalopods (e.g., squid, octopuses, and cuttlefish) have long fascinated scientists and the general public alike due to their complex behavioral characteristics and remarkable camouflage abilities. As such, these animals are explored as model systems in neuroscience and represent a well-known commercial resource. Herein, selected literature examples related to the electrical properties of cephalopod-derived biopolymers (eumelanins, chitosans, and reflectins) and to the use of these materials in voltage-gated devices (i.e., transistors) are highlighted. Moreover, some potential future directions and challenges in this area are described, with the aim of inspiring additional research effort on ionic and protonic transistors from cephalopod-derived biopolymers.

Let $S$ be an orientable, connected surface with infinitely-generated fundamental group. The main theorem states that if the genus of $S$ is finite and at least 4, then the isomorphism type of the pure mapping class group associated to $S$, denoted $\mathrm{PMap}(S)$, detects the homeomorphism type of $S$. As a corollary, every automorphism of $\mathrm{PMap}(S)$ is induced by a homeomorphism, which extends a theorem of Ivanov from the finite-type setting. In the process of proving these results, we show that $\mathrm{PMap}(S)$ is residually finite if and only if $S$ has finite genus, demonstrating that the algebraic structure of $\mathrm{PMap}(S)$ can distinguish finite- and infinite-genus surfaces. As an independent result, we also show that $\mathrm{Map}(S)$ fails to be residually finite for any infinite-type surface $S$. In addition, we give a topological generating set for $\mathrm{PMap}(S)$ equipped with the compact-open topology. In particular, if $S$ has at most one end accumulated by genus, then $\mathrm{PMap}(S)$ is topologically generated by Dehn twists, otherwise the Dehn twists along with handle shifts topologically generate., 32 pages, 3 figures; v2 has several minor changes and corrections, including a more explicit treatment of the centers of big mapping class groups in Section 3

Let $G$ be a virtually special group. Then the residual finiteness growth of $G$ is at most linear. This result cannot be found by embedding $G$ into a special linear group. Indeed, the special linear group $\text{SL}_k(\mathbb{Z})$, for $k > 2$, has residual finiteness growth $n^{k-1}$., Updated version contains minor changes incorporating referee comments/suggestions and a simplified proof of Lemma 4.1

We quantify Peter Scott’s theorem that surface groups are locally extended residually finite (LERF) in terms of geometric data. In the process, we will quantify another result by Scott that any closed geodesic in a surface lifts to an embedded loop in a finite cover.

Purpose Single-cell RNA-sequencing (scRNA-seq) was used to interrogate the relatively rare stem (SC) and early transit amplifying (TA) cell populations in limbal/corneal epithelia from wild-type and autophagy-compromised mice. Methods We conducted scRNA-seq on ocular anterior segmental tissue from wild-type and beclin 1-deficient (beclin1+/-) mice, using a 10X Gemomics pipeline. Cell populations were distinguished by t-distributed stochastic neighbor embedding. Seurat analysis was conducted to compare gene expression profiles between these two groups of mice. Differential protein expression patterns were validated by immunofluorescence staining and immunoblotting. Results Unbiased clustering detected 10 distinct populations: three clusters of mesenchymal and seven clusters of epithelial cells, based on their unique molecular signatures. A discrete group of mesenchymal cells expressed genes associated with corneal stromal SCs. We identified three limbal/corneal epithelial cell subpopulations designated as stem/early TA, mature TA, and differentiated corneal epithelial cells. Thioredoxin-interacting protein and PDZ-binding kinase (PBK) were identified as novel regulators of stem/early TA cell quiescence. PBK arrested corneal epithelial cells in G2/M phase of the cell cycle. Beclin1+/- mice displayed a decrease in proliferation-associated (Ki67, Lrig1) and stress-response (H2ax) genes. The most increased gene in beclin1+/- mice was transcription factor ATF3, which negatively regulates limbal epithelial cell proliferation. Conclusions Establishment of a comprehensive atlas of genes expressed by stromal and epithelial cells from limbus and cornea forms the foundation for unraveling regulatory networks among these distinct tissues. Similarly, scRNA-seq profiling of the anterior segmental epithelia from wild-type and autophagy-deficient mice provides new insights into how autophagy influences proliferation in these tissues.

With an increasing interest in nanoparticulate delivery systems, there is a greater need to identify biomaterials that are biocompatible and safe for human applications. Protein polymers from animal and plant sources are promising materials for designing nanocarriers. Composition of the protein plays an important role for specific drug delivery applications such as drug release, targeting, and stimuli responsive drug release. An important issue in protein polymers is characteristics such as size, charge, and hydrophobicity may play a significant role in phagocytic uptake and initiating a subsequent immune response. This remains to be investigated systematically by analyzing factors that influence nanoparticle characteristics of protein and reduce phagocytic uptake and does not initiate immune response too. Although protein polymers are biodegradable, it is essential to ensure that there must not be premature enzymatic breakdown of the protein nanoparticles in the systemic circulation. Surface modification of the protein nanoparticles can be used to address this issue to propose the necessary modification in the surface of the protein would be great contribution in the nano particulate drug delivery systems (NPPDS). Of the various proteins, gelatin and albumin have been widely studied for drug delivery applications. Plant proteins are yet to be investigated widely for drug delivery applications so there is need to find out the plant proteins capable to act as nanoparticles. The commercial success of albumin-based nanoparticles has created an interest in other proteins. An increased understanding of the physicochemical properties coupled with the developments in rDNA technology will open up new opportunities for protein-based nanoparticulate systems. In the present studies several proteins currently useful for drug delivery system were structurally modeled and has been analyzed to propose the essential characteristics of protein for protein-based NPDDS.

The neurotransmitter nitric oxide (NO) has been implicated in the inhibitory control of metamorphosis of some marine gastropods, echinoderms, and ascidians. We have explored whether or not metamorphosis of metatrochophore larvae of the polychaete annelid Capitella teleta is also regulated by NO. Immunohistochemical analysis revealed a bilateral group of three large nitric oxide synthase (NOS) immunoreactive cells that lie dorsal to the pharynx and extend ventral processes toward the pharynx in the region of the dorsal pharyngeal pad. Smaller NOS-immunoreactive cells were distributed widely throughout the body but concentrated in the prostomium and pygidium. Histological analysis for NO, using the NO detector diaminofluorescein-FM, showed that NO concentration was high in the larval midgut, although diffuse amounts of NO were detected throughout the body. Inhibitors of NOS, including s-methylisothiourea sulfate, aminoguanidine hemisulfate, 7-nitroindazole, and N-methyl-L-arginine all induced settlement and...

We give a new, effective proof of the separability of cubically convex-cocompact subgroups of special groups. As a consequence, we show that if $G$ is a virtually compact special hyperbolic group, and $Q\leq G$ is a $K$-quasiconvex subgroup, then any $g\in G-Q$ of word-length at most $n$ is separated from $Q$ by a subgroup whose index is polynomial in $n$ and exponential in $K$. This generalizes a result of Bou-Rabee and the authors on residual finiteness growth and a result of the second author on surface groups., 12 pages, 5 figures. Revised in light of referee's comments. To appear in Pacific J. Math

We give a quantification of residual finiteness for the fundamental groups of hyperbolic manifolds that admit a totally geodesic immersion to a compact, right-angled Coxeter orbifold of dimension 3 or 4. Specifically, we give explicit upper bounds on residual finiteness that are linear in terms of geodesic length. We then extend the linear upper bounds to hyperbolic manifolds with a finite cover that admits such an immersion. Since the quantifications are given in terms of geodesic length, we define the geodesic residual finiteness growth and show that this growth is equivalent to the usual residual finiteness growth defined in terms of word length. This equivalence implies that our results recover the quantification of residual finiteness from \cite{BHP} for hyperbolic manifolds that virtually immerse into a compact reflection orbifold., Accepted for publication in Geometriae Dedicata. Significant improvements have been made due to referee comments/suggestions. The main theorems cover a much larger class of hyperbolic manifolds than was originally indicated. Section 6 of this version is also new. 18 pages, 9 figures

The main result of this article is a refinement of the well-known subgroup separability results of Hall and Scott for free and surface groups. We show that for any finitely generated subgroup, there is a finite dimensional representation of the free or surface group that separates the subgroup in the induced Zariski topology. As a corollary, we establish a polynomial upper bound on the size of the quotients used to separate a finitely generated subgroup in a free or surface group., Final version. To appear in Selecta Math