RNAi-based Gene Therapy for Blood Genetic Diseases

Therapies for blood genetic diseases can be divided into different categories, including chemotherapy, radiotherapy, gene therapy, and hematopoietic stem cell transplantation. Among these treatments, gene targeting is progressively becoming a therapeutic alternative that offers the possibility of a permanent cure for certain blood genetic diseases. In recent years, gene therapy has played a more important role in curing genetic blood disorders. RNA interference (RNAi) is one of the directions for gene therapy, which was intensively studied in the past decades for its potentials in the treatment of diseases. In order to provide useful references and prospective directions for further studies concerning RNAi-based gene therapy for blood genetic diseases, current RNAi-based gene therapies for several typical blood genetic diseases have been summarized and discussed in this chapter

Cross-Regulation of Protein Stability by p53 and Nuclear Receptor SHP

We report here a novel interplay between tumor suppressor p53 and nuclear receptor SHP that controls p53 and SHP stability. Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway. Overexpressing SHP alone does not affect p53 stability. However, SHP destabilizes p53 by augmentation of Mdm2 ubiquitin ligase activity toward p53. The single amino acid substitution in the SHP protein SHPK170R increases SHP binding to p53 relative to SHP wild-type, whereas SHPG171A variant shows a diminished p53 binding. As a result of the cross-regulation, the tumor suppressor function of p53 and SHP in inhibition of colon cancer growth is compromised. Our findings reveal a unique scenario for a cross-inhibition between two tumor suppressors to keep their expression and function in check

Collective Human Opinions in Semantic Textual Similarity

Despite the subjective nature of semantic textual similarity (STS) and pervasive disagreements in STS annotation, existing benchmarks have used averaged human ratings as the gold standard. Averaging masks the true distribution of human opinions on examples of low agreement, and prevents models from capturing the semantic vagueness that the individual ratings represent. In this work, we introduce USTS, the first Uncertainty-aware STS dataset with ~15,000 Chinese sentence pairs and 150,000 labels, to study collective human opinions in STS. Analysis reveals that neither a scalar nor a single Gaussian fits a set of observed judgements adequately. We further show that current STS models cannot capture the variance caused by human disagreement on individual instances, but rather reflect the predictive confidence over the aggregate dataset.Comment: 16 pages, 7 figure

Biološka karakterizacija izolata golubljeg paramiksovirusa 1 i analiza njegove patogenosti u SPF pilića

Pigeon paramyxovirus type 1 (PPMV-1) is considered as an antigenic variant of Newcastle Disease leading to high mortality and significant economic losses to the poultry industry. However, the pathogenicity of PPMV-1 to chickens is still unclear. Herein, we reported the biological characterization of the isolated PPMV-1 from the diseased pigeons suspected to Newcastle Disease and studied its pathogenicity in SPF chickens. The phylogenetic tree and evolution distances revealed that the new isolate belonged to a VI.2.1.1.2.2 sub-genotype of NDV. Despite the cleavage motif of the F protein containing the 112RRQKR↓F117 sequence associated with virulent NDV strains, and the value of MDT and ICPI of the isolate showing mesogenic characteristics, the challenge trial showed that the isolate had weak pathogenicity to chickens while causing lesions in multiple tissues and organs in pigeons.Golublji paramiksovirus tipa 1 (PPMV-1) smatra se antigenskom varijantom njukaslske bolesti koja uzrokuje visoku smrtnost i znatne ekonomske gubitke u peradarskoj industriji. Patogenost virusa PPMV-1 u pilića međutim još uvijek nije jasna. U ovom je radu provedena biološka karakterizacija PPMV-1 izoliranog iz golubova za koje se sumnja da su oboljeli od njukaslske bolesti te je istražena njihova patogenost u SPF pilića. Filogenetsko stablo i evolucijske udaljenosti otkrili su da novi izolat pripada podgenotipu VI.2.1.1.2.2 virusa njukaslske bolesti (NDV). Unatoč motivu u mjestu cijepanja F-proteina koji sadržava sekvenciju 112RRQKR↓F117 povezanu s virulentnim sojevima NDV-a, vrijednosti MDT-a i ICPI-ja izolata pokazale su mezogene značajke. Ovo probno istraživanje je pokazalo da su izolati PPMV-1 slabo patogeni u pilića, dok u golubova uzrokuju lezije na više organa i tkiva

Proteomic Analysis of Serum in Lung Cancer Induced by 3-Methylcholanthrene

Lung cancer remains the leading cause of cancer-related mortality worldwide. Early detection of lung cancer is problematic due to the lack of a marker with high diagnosis sensitivity and specificity. To determine the differently expressed proteins in the serum of lung cancer and figure out the function of the proteins, two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to screen the serum proteins of lung cancer model induced by 3-methylcholanthrene (MCA). From optimized 2DE image, 455 spots in the normal sera and 716 spots in the lung cancers sera were detected. Among them, 141 protein spots were differentially expressed when comparing the serum from normal rat and serum from lung cancer model, including 82 overexpressed proteins and 59 underexpressed proteins. Changes of haptoglobin, transthyretin, and TNF superfamily member 8 (TNFRS8) were confirmed in sera from lung cancer by MALDI-TOF-MS. Proteomics technology leads to identify changes of haptoglobin, transthyretin, and TNFRS8 in serum of rat lung cancer model and represents a powerful tool in searching for candidate proteins as biomarkers

Resolving spin, valley, and moir\'e quasi-angular momentum of interlayer excitons in WSe2/WS2 heterostructures

Moir\'e superlattices provide a powerful way to engineer properties of electrons and excitons in two-dimensional van der Waals heterostructures. The moir\'e effect can be especially strong for interlayer excitons, where electrons and holes reside in different layers and can be addressed separately. In particular, it was recently proposed that the moir\'e superlattice potential not only localizes interlayer exciton states at different superlattice positions, but also hosts an emerging moir\'e quasi-angular momentum (QAM) that periodically switches the optical selection rules for interlayer excitons at different moir\'e sites. Here we report the observation of multiple interlayer exciton states coexisting in a WSe2/WS2 moir\'e superlattice and unambiguously determine their spin, valley, and moir\'e QAM through novel resonant optical pump-probe spectroscopy and photoluminescence excitation spectroscopy. We demonstrate that interlayer excitons localized at different moir\'e sites can exhibit opposite optical selection rules due to the spatially-varying moir\'e QAM. Our observation reveals new opportunities to engineer interlayer exciton states and valley physics with moir\'e superlattices for optoelectronic and valleytronic applications

n-Dodecyl­ammonium bromide monohydrate

In the title compound, C12H28N+·Br−·H2O, the ionic pairs formed by n-dodecyl­ammonium cations and bromide anions are arranged into thick layers; these layers are linked in a nearly perpendicular fashion [the angle between the layers is 85.84 (5)°] by hydrogen-bonding inter­actions involving the water mol­ecules. The methyl­ene part of the alkyl chain in the cation adopts an all-trans conformation. In the crystal structure, mol­ecules are linked by inter­molecular N—H⋯Br, O—H⋯Br and N—H⋯O hydrogen bonds