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The atypical chemokine receptor ACKR2 drives pulmonary fibrosis by tuning influx of CCR2+ and CCR5+ IFNγ-producing γδT cells in mice.

Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical … n and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras, and antibody-mediated leukocyte depletion. ACKR2 was upregulated acutely in response to bleomycin and normalized over time. ACKR2-/- mice showed reduced lethality and lung fibrosis. Bone marrow chimeras showed that lethality and fibrosis depended …

Разработка векторной вакцины аденовируса для целеопределения дендритных клеток.

Аденовиральные (Ад) векторные вакцины представляют собой одну из самых перспективных современных вакцинных платформ, и вакцины Ad в настоящее время изучаются в рамках клинических испытаний человека на инфекционные заболевания и рак. Наши исследования показали, что специфическая ориентация аденовируса на дендритные клетки значительно повысила эффективность вакцины. Однако это было достигнуто с использованием молекулярного адаптера, что потребовало двухкомпонентного векторного подхода. Для того чтобы выполнить задачи клинического перевода нашей стратегии, мы стремились достичь цели ДК с помощью

Совпадение в аннотации оригинала
Adenoviral (Ad) vector vaccines represent one of the most promising modern vaccine platforms, and Ad vector vaccines are currently being inv … o redirect the specificity of Ad vector vaccines, we replaced the Ad fiber knob with fiber-fibritin chimeras fused to DC1.8, a single-domain antibody (sdAb) specific for murine immature DC. We engineered a fiber-fibritin-sdAb chimeric molecule using the coding sequence for DC1.8, and then replaced the native Ad5 fiber knob sequence by homologous recombina …

Systematic analysis of viral genes responsible for differential virulence between American and Australian West Nile virus strains.

A variant Australian West Nile virus (WNV) strain, WNVNSW2011, emerged in 2011 causing an unprecedented outbreak of encephalitis in horses i … nes, non-structural genes and untranslated regions, as well as seven individual non-structural gene chimeras, using a modified circular polymerase extension cloning method. Our results showed that the complete non-structural region of WNVNSW2011, when substituted with that of WNVNY99, significantly enhanced viral replication and the ability to suppress ty …

[Determinants for iron overload in patients with acute leukemias and aplastic anemia].

AIM: to reveal the determinants of the development of iron overload in patients with acute leukemias (AL) and aplastic anemia (AA). SUBJECT … ates iron accumulation and is an additional risk factor for siderosis. In patients with transfusion chimeras and a rare phenotype in terms of rhesus antigens, packed red blood cell transfusion results in a much more increase in iron stores. CONCLUSION: The most important factor of iron overload acceleration is no specific choice of packed red blood cells …

Intergenotypic replacement of lyssavirus matrix proteins demonstrates the role of lyssavirus M proteins in intracellular virus accumulation.

Lyssavirus assembly depends on the matrix protein (M). We compared lyssavirus M proteins from different genotypes for their ability to support assembly and egress of genotype 1 rabies virus (RABV). Transcomplementation of M-deficient RABV with M from European bat lyssavirus (EBLV) types 1 and 2 reduced the release of infectious virus. Stable introduction of the heterogenotypic M proteins into RABV led to chimeric viruses with reduced virus release and intracellular accumulation of virus genomes. Although the chimeras indicated genotype-specific evolution of M, rapid selection of a compensatory…

Regions in the cytosolic C-terminus of the secretory Na(+)-K(+)-2Cl(-) cotransporter NKCC1 are required for its homodimerization.

The "secretory" Na+-K+-2Cl- cotransporter, NKCC1, is a member of a small gene family of electroneutral cation-chloride cotransporters (CCCs) with 9 homologues in vertebrates. A number of these transporters, including NKCC1 itself, have been shown to exist as homodimers in the membrane, suggesting that this may be a common feature of the CCCs. Here we employ chemical cross-linking studies, a novel co-immunoprecipition assay, and NKCC1/CCC chimeras to further explore the basis and significance of NKCC1 dimerization. An N-terminally truncated NKCC1 (nttNKCC1), in which the first 20 kDa of the 28 …

Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Graves' patients treated with antithyroid drugs.

Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from patients with untreated Graves' disease were compared with long-term response to antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras, wherein TSHR residues 9-165 or 90-165 had been substituted with comparable residues of the LH/chorionic gonadotropin receptor. Of 159 patients studied, 52 (32.7%) exhibited positive TSAb activity with one or both chimera lines (heterogeneous group), and 107 (67.3%) had no activity with e…

Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice.

Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of CBA and B6 strains, backcrossed with B6 females display reduction or loss of mandible, whereas those backcrossed with CBA females do not show noticeable phenotype at birth. The availability of phenotypically disparate strains renders identification of Otx2 modifier loci possible. In…

Expression of human F8B, a gene nested within the coagulation factor VIII gene, produces multiple eye defects and developmental alterations in chimeric and transgenic mice.

Factor VIII-associated gene B ( F8B ) is a small human gene of unknown function which is nested within the gene encoding coagulation factor VIII ( FVIII ) in chromosome band Xq28. The sequence of F8B includes the C2 cell adhesion motif of factor VIII, which has also been identified in numerous proteins known to play important roles during development. Here we have constructed both chimeric and transgenic mice expressing normal human F8B to investigate its possible developmental effects. The chimeras produced from embryonic stem cells transfected with normal F8B under control of a cytomegalovir…

Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from Bothrops asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide identifies its bactericidal region.

Mammalian group-II phospholipases A2 (PLA2) of inflammatory fluids display bactericidal properties, which are dependent on their enzymatic a … e myotoxin II-(115-129)-peptide than the corresponding moieties of resistant strains. Bacterial LPS chimeras indicated that LPS is a relevant target for myotoxin II-(115-129)-peptide. When heterologous LPS of the resistant strain was present in the context of susceptible bacteria, the chimera became resistant, and vice versa. Myotoxin II represents a grou …

A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).

The thyroid hormone (T3) receptor type alpha, the c-ErbA alpha proto-oncoprotein, stimulates transcription of T3-dependent promoters, interferes with AP-1 activity, and induces erythroid differentiation in a ligand-dependent manner. The v-ErbA oncoprotein does not bind hormone and has lost all of these activities. Using c-ErbA/v-ErbA chimeras, we found that a deletion of 9 amino acids, conserved among many members of the nuclear receptor superfamily, which are located at the extreme carboxy terminus of c-ErbA alpha is responsible for loss of both transactivation and transcriptional interferenc…

Sequences from myeloblastosis-associated virus MAV-2(O) and UR2AV involved in the formation of plaques and the induction of osteopetrosis, anemia, and ataxia.

Recombinant viruses were made between myeloblastosis-associated virus MAV-2(O) and UR2AV to examine the relationship between regions of the … ) gp37 and LTR except for construct pEU. When the viruses were inoculated into 10-day-old chickens, chimeras containing the env-LTR of gp37-LTR region of MAV-2(O) induced severe regenerative anemia similar to that induced by MAV-2(O). pEU was the exception, suggesting that the unique configuration of this chimera is responsible for its unusual pathogenic …

Graves' immunoglobulins activate phospholipase A2 by recognizing specific epitopes on thyrotropin receptor.

Thyroid-stimulating IgG from Graves' patients bind to the TSH receptor and activate both adenylyl cyclase (AC) and phospholipase A2 (PLA2) in FRTL5 thyroid cells. Both activities have been associated with increased thyroid cell growth and function; evidence exists that subpopulations of Graves' IgG can stimulate either AC or PLA2 cascades and that the activation of both is associated with the largest goiters in patients. Studies using chimeras of the human TSHR receptor (hTSHR) and the LH-CG receptor show that most patients with Graves' disease have cAMP-stimulating IgG that require epitopes o…

PROTAC as a Potential Toolbox for the Discovery of New Targets and Drugs.

With its event-driven degradation mechanism, proteolysis targeting chimera (PROTAC) is emerging as a powerful toolbox for novel drug discovery and target identification. In drug discovery, PROTAC enables the targeting of traditionally undruggable proteins, disrupts protein scaffolding functions, overcomes clinical drug resistance, and enhances target selectivity. In target identification, derivatizing bioactive molecules into PROTAC probes combined with proteomics permits precise identification of drug targets; furthermore, target-agnostic PROTAC libraries and tag-based degradation systems fac…

A General Photoredox Platform for the Hydroarylation of Olefins.

Alkene hydroarylation provides a direct strategy for merging aryl groups with alkene-derived C(sp3)-rich fragments, yet general methods that … erium incorporation, medium-ring formation, late-stage functionalization, and proteolysis-targeting chimera (PROTAC) library construction.

[Myocardial infiltration and formation of multiple granulocytic sarcoma of acute myeloid leukemia after cord blood transplantation].

A 57-year-old woman was diagnosed with acute myeloid leukemia (AML, M5a) with MLL rearrangement in August 2006. Cord blood transplantation (CBT) conditioned with a reduced-intensity regimen was carried out during second complete remission in March 2007. Marrow study on day 28 confirmed complete chimera and disappearance of minimal residual disease by RT-PCR. She complained of left chest pain around day 120. CT scan on day 127 showed left pleural effusion, tumors of the upper mediastinum and spleen, and pericardial effusion. She suddenly died of cardiogenic shock on day 129. Postmortem examinat…

[Does Ph'-negative chronic myeloleukemia exist?].

The authors have presented the current data on so-called Ph'-negative chronic myeloleukemia (CML). A detailed clinico-hematologic analysis has proved that most of patients with unchanged chromosome 22 have other myeloproliferative disease, most often it is chronic myelomonocytic leukemia. In some CML patients Ph'-chromosome is masked as a result of translocations, in other patients, although chromosome 22 is unchanged, the molecular-genetic marker of CML--chimera bcr/c-abl-gene, is detected on chromosome 22 or some other chromosome. It has been noted that only in rare cases of typical CML char…

Bone marrow origin of Ia molecules purified from epidermal cells.

Using radiation bone marrow chimeras, we have shown that Ia molecules purified from epidermal cell preparations of the mouse reflect the Ia phenotype of the bone marrow donor. This result strongly suggests that Ia molecules are synthesized by a bone-marrow-derived cell in the epidermis. Furthermore, results of peptide map analysis of immunoprecipitated biosynthetically labeled Ia suggest that the Ia molecules found in skin are identical to those found on B lymphocytes. These results support biochemical as well as serologic identity.

Luminescence-guided engineering of anti-idiotype nanobody-NanoLuc fusion reagents for sensitive monitoring of free therapeutic antibodies.

Therapeutic antibody monitoring requires bioanalytical platforms combining high sensitivity, specificity, and robustness in complex biologic … noLuc fusion level in Escherichia coli. This approach enabled early identification of highly active chimeras while preserving functional specificity, overcoming common nanobody-dependent expression bottlenecks during assay development. Selected binders were incorporated into a bridging assay format using a biotinylated nanobody as capture reagent and a na …

Cryo-EM structures of engineered Shiga toxin-based immunogens capable of eliciting neutralizing antibodies with therapeutic potential against hemolytic uremic syndrome.

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a serious disease that causes renal failure predom … espect to the BLS core. Additionally, we present structural evidence of the interaction between the chimeras and polyclonal Fab (pFab) fragments derived from INM004, demonstrating that the elicited neutralizing antibodies block most of the interaction surface of the toxins with their cellular receptors. These findings further validate this promising antib …