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Cytoskeleton-associated protein 4 (CKAP4) is a cell surface receptor for Dickkopf 1 (DKK1), a secreted protein. The DKK1-CKAP4 pathway is activated in various malignant tumors, including pancreatic, lung, esophageal, and liver cancers, to promote tumor growth. Thus, CKAP4 has been expected to represent a novel molecular target of cancer therapy. Recombinant mouse anti-CKAP4 antibodies were generated based on an original mouse antibody (3F11-2B10) and inhibited DKK1-CKAP4 signaling and xenograft tumor formation induced by pancreatic cancer cells, which was comparable with 3F11-2B10. From the 3F11-2B10 nucleotide sequence, humanized anti-CKAP4 antibody (Hv1Lt1) was subsequently developed. The binding affinity of Hv1Lt1 for CKAP4 was superior to that of 3F11-2B10. Hv1Lt1 inhibited DKK1 binding to CKAP4, AKT activity, and sphere formation of pancreatic cancer cells, which was comparable with 3F11-2B10. Hv1Lt1 also suppressed xenograft tumor formation induced by human pancreatic cancer cells and tumor growth in murine cancer models, in which murine pancreatic cancer organoids were orthotopically transplanted into the pancreas. In resected tumor samples from mice treated with Hv1Lt1, anti-tumor immune reactions were modulated and cytotoxic T cells were highly infiltrated in the tumor microenvironment. Additionally, combination of Hv1Lt1 and other chemotherapy drugs exhibited stronger effects compared with monotherapy. These results suggest that Hv1Lt1 represents a promising anti-cancer therapy.
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BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.
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Cryptococcus deneoformans is a yeast-type fungus that causes fatal meningoencephalitis in immunocompromised patients and evades phagocytic cell elimination through an escape mechanism. Memory T (Tm) cells play a central role in preventing the reactivation of this fungal pathogen. Among these cells, tissue-resident memory T (TRM) cells quickly respond to locally invaded pathogens. This study analyzes the kinetics of effector T (Teff) cells and Tm cells in the lungs after cryptococcal infection. Emphasis is placed on the kinetics and cytokine expression of TRM cells in the early phase of infection. CD4+ Tm cells exhibited a rapid increase by day 3, peaked at day 7, and then either maintained their levels or exhibited a slight decrease until day 56. In contrast, CD8+ Tm cells reached their peak on day 3 and thereafter decreased up to day 56 post-infection. These Tm cells were predominantly composed of CD69+ TRM cells and CD69+ CD103+ TRM cells. Disruption of the CARD9 gene resulted in reduced accumulation of these TRM cells and diminished interferon (IFN) -γ expression in TRM cells. TRM cells were derived from T cells with T cell receptors non-specific to ovalbumin in OT-II mice during cryptococcal infection. In addition, TRM cells exhibited varied behavior in different tissues. These results underscore the importance of T cells, which produce IFN-γ in the lungs during the early stage of infection, in providing early protection against cryptococcal infection through CARD9 signaling.
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Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Criptococose , Cryptococcus , Interferon gama , Lectinas Tipo C , Pulmão , Animais , Criptococose/imunologia , Criptococose/microbiologia , Interferon gama/metabolismo , Interferon gama/imunologia , Camundongos , Antígenos de Diferenciação de Linfócitos T/metabolismo , Cryptococcus/imunologia , Antígenos CD/metabolismo , Antígenos CD/genética , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Pulmão/imunologia , Pulmão/microbiologia , Células T de Memória/imunologia , Células T de Memória/metabolismo , Camundongos Endogâmicos C57BL , Memória Imunológica , Imunidade Inata , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Linfócitos T CD4-Positivos/imunologiaRESUMO
We have investigated the 3d orbital excitations in CaCuO_{2} (CCO), Nd_{2}CuO_{4} (NCO), and La_{2}CuO_{4} (LCO) using high-resolution resonant inelastic x-ray scattering. In LCO they behave as well-localized excitations, similarly to several other cuprates. On the contrary, in CCO and NCO the d_{xy} orbital clearly disperses, pointing to a collective character of this excitation (orbiton) in compounds without apical oxygen. We ascribe the origin of the dispersion as stemming from a substantial next-nearest-neighbor (NNN) orbital superexchange. Such an exchange leads to the liberation of the orbiton from its coupling to magnons, which is associated with the orbiton hopping between nearest neighbor copper sites. Finally, we show that the exceptionally large NNN orbital superexchange can be traced back to the absence of apical oxygens suppressing the charge transfer energy.
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BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.
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Síndrome de Behçet , Periodontite , Feminino , Humanos , Fibrinolisina , Síndrome de Behçet/complicações , Síndrome de Behçet/genética , Doenças Raras/complicações , Periodontite/complicações , Periodontite/genética , Plasminogênio/genética , FibrinaRESUMO
With the rapid expansion of genomic medicine, more citizens are compelled to think about genetics in their daily lives. This study aims to explore appropriate types of educational media and methods to enlighten activities for genetics and hereditary cancer. We presented an 18-min YouTube video on genetics and hereditary cancer to participants at a scientific event, Science Agora 2020, and administered a web questionnaire to investigate their opinions about when and how citizens should start learning about genetics and hereditary cancer. We recruited 133 participants who watched the video, and 26.3% (35/133) responded to the questionnaire. Most of them were evaluated to understand and appreciate the contents of the video. They identified websites, or videos as suitable learning media, irrespective of their sex, age, or profession. They highlighted upper elementary school or junior high school as appropriate educational stages to start learning about genetics and hereditary cancer to facilitate collecting their own genetic information by themselves. Our findings show that educational institutions should provide opportunities to learn about genetics and hereditary cancers, especially for upper elementary school and junior high school students, using learning media, such as videos, depending on their level or demand.
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The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification.
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Cattle-related injuries are a significant contributing factor in 84.3% of livestock-related incidents in Hokkaido Japan. The specific countermeasures to respond to its characteristics are needed because cattle move freely. This study examined the JA Kyosai mutual aid payment claim form data of the agricultural work-related incidents that occurred from 1st January 2013 to 31st December 2016. We extracted incidents coded 'Cattle' term on the 'Causing Stuffs/Animals' column as cattle-related injuries and analysed them. In four years, there were 227 cattle-related incidents and all were non-fatal cases. The most common age group of victims were in their 60s (37.9%). The Therapy duration was 1 to 243 days, with one day being the most common (10.1%); however, in 51.5% of the cases it required more than 30 days. The most common Activity at the moment of the incident was 'bringing the cattle' (22.5%), of which 'leading the cattle by rope' (56.9% of bringing) was most frequently mentioned. Even farmers with significant experience with cattle cannot control cattle proficiently. Neither can they predict cattle behaviour. Hence, cattle should be kept under protected contact. Since prevention of incidents has limits, harm reduction to farmers must be considered. In the short-term planning, isolated pathways and shock-absorbing lead rope are effective in preventing injuries. However, a more long-term perspective must consider, a fully automated system that reduces human contact with cattle on farms.
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Acidentes de Trabalho , Agricultura , Animais , Humanos , Acidentes de Trabalho/prevenção & controle , Japão/epidemiologia , Fazendas , FazendeirosRESUMO
Background: Globally, lung cancer causes the most cancer death. While molecular therapy progress, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has provided remarkable therapeutic effects, some patients remain resistant to these therapies and therefore new target development is required. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the secretory protein Dickkopf-1 (DKK1) and the binding of DKK1 to CKAP4 promotes tumor growth via Ak strain transforming (AKT) activation. We investigated if CKAP4 functions as a diagnostic biomarker and molecular therapeutic target for lung cancer. Methods: CKAP4 secretion with exosomes from lung cancer cells and the effect of CKAP4 palmitoylation on its trafficking to the exosomes were examined. Serum CKAP4 levels were measured in mouse xenograft models, and 92 lung cancer patients and age- and sex-matched healthy controls (HCs). The lung cancer tissues were immunohistochemically stained for DKK1 and CKAP4, and their correlation with prognosis and serum CKAP4 levels were investigated. Roles of CKAP4 in the lung cancer cell proliferation were examined, and the effects of the combination of an anti-CKAP4 antibody and osimertinib, a third generation TKI, on anti-tumor activity were tested using in vitro and in vivo experiments. Results: CKAP4 was released from lung cancer cells with exosomes, and its trafficking to exosomes was regulated by palmitoylation. CKAP4 was detected in sera from mice inoculated with lung cancer cells overexpressing CKAP4. In 92 lung cancer patients, positive DKK1 and CKAP4 expression patients showed worse prognoses. Serum CKAP4 positivity was higher in lung cancer patients than in HCs. After surgical operation, serum CKAP4 levels were decreased. CKAP4 overexpression in lung cancer cells promoted in vitro cell proliferation and in vivo subcutaneous tumor growth, which were inhibited by an anti-CKAP4 antibody. Moreover, treatment with this antibody or osimertinib, a third generation TKI, inhibited AKT activity, sphere formation, and xenograft tumor growth in lung cancer cells harboring EGFR mutations and expressing both DKK1 and CKAP4, while their combination showed stronger inhibition. Conclusions: CKAP4 may represent a novel biomarker and molecular target for lung cancer, and combination therapy with an anti-CKAP4 antibody and osimertinib could provide a new lung cancer therapeutic strategy.
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Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy.
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Neoplasias Colorretais , Neoplasias Hepáticas , Metastasectomia , Humanos , Adenosina/genética , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Biomarcadores , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Medição de Risco , RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.
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Ácidos Nucleicos Livres , Neoplasias Ovarianas , Proteína BRCA2/genética , Neoplasias da Mama , Criança , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Linhagem , Inibidores de Poli(ADP-Ribose) PolimerasesRESUMO
Acute oral toxicity is primarily determined using animal testing, as stated in the Organization for Economic Cooperation and Development (OECD) Test Guideline (TG) 420, 423, and 425. Currently, regarding animal welfare, few alternatives to animal testing such as in vitro approaches have been evaluated. Therefore, in this preliminary study examining a new method to determine acute oral toxicity, we investigated whether UN Globally Harmonized System all categories can be predicted using the Hansen solubility parameter (HSP). In particular, Hansen spheres were produced based on oral toxicity information of the test substances and their HSP values, and the respective parameters were identified. A comparison of these potential parameters with the HSP value of each test substance showed an accuracy of 84.1% (53/63), 10.0% (3/30) false negatives, and 21.2% (7/33) false positives. By comparing the HSP of the resulting potential parameters with a test substance, it is possible to predict acute oral toxicity with high accuracy.
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Organização para a Cooperação e Desenvolvimento Econômico , Animais , Solubilidade , Testes de Toxicidade Aguda/métodosRESUMO
BACKGROUND: Hemodynamics and their clinical outcome of cerebral aneurysms treated with flow diverter (FD) stents have thus far been investigated using computational fluid dynamics (CFD) simulations. Although human blood is characterized as a non-Newtonian patientspecific fluid, non-patient-specific blood properties (PSBP) were applied in most extant studies. OBJECTIVE: To investigate the hemodynamic effects caused by PSBPs in aneurysms treated with FD stents. METHODS: We measured blood properties (density and viscosity) for 12 patients who underwent FD stent deployment. We conducted CFD simulations with the measured PSBPs and non-PSBPs quoted from previous studies. The average blood flow velocity and wall shear stress within the aneurysms were calculated and two simulation patterns were compared. RESULTS: The velocity and wall shear stress changed by 2.93% and 3.16% on average, respectively, without an FD stent deployed. Conversely, with the FD stents deployed, the change rates increased to 11.1% and 9.06% on average, respectively. CONCLUSIONS: The change in hemodynamic parameters if PSBPs are considered, may not be negligible when conducting CFD simulations of FD stent deployed aneurysms To obtain an adequate hemodynamic environment for cerebral aneurysms with FD stents deployed, it is recommended to use PSBPs for CFD simulations.
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Aneurisma Intracraniano , Simulação por Computador , Hemodinâmica , Humanos , Hidrodinâmica , StentsRESUMO
BACKGROUND: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. CASE PRESENTATION: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. CONCLUSIONS: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.
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Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment.
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Microambiente Celular/imunologia , Claudinas/deficiência , Criptococose/imunologia , Cryptococcus/imunologia , Pulmão/imunologia , Pneumonia/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Microambiente Celular/genética , Claudinas/imunologia , Criptococose/genética , Interferon gama/genética , Interferon gama/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Knockout , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Pneumonia/genética , Pneumonia/microbiologiaRESUMO
Microbial diversity in an apple orchard cultivated with natural farming practices for over 30 years was compared with conventionally farmed orchards to analyze differences in disease suppression. In this long-term naturally farmed orchard, major apple diseases were more severe than in conventional orchards but milder than in a short-term natural farming orchard. Among major fungal species in the phyllosphere, we found that Aureobasidium pullulans and Cryptococcus victoriae were significantly less abundant in long-term natural farming, while Cladosporium tenuissimum predominated. However, diversity of fungal species in the phyllosphere was not necessarily the main determinant in the disease suppression observed in natural farming; instead, the maintenance of a balanced, constant selection of fungal species under a suitable predominant species such as C. tenuissimum seemed to be the important factors. Analysis of bacteria in the phyllosphere revealed Pseudomonas graminis, a potential inducer of plant defenses, predominated in long-term natural farming in August. Rhizosphere metagenome analysis showed that Cordyceps and Arthrobotrys, fungal genera are known to include insect- or nematode-infecting species, were found only in long-term natural farming. Among soil bacteria, the genus Nitrospira was most abundant, and its level in long-term natural farming was more than double that in the conventionally farmed orchard.
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HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation.
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Infecções por HIV/genética , Sítios de Splice de RNA/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Desaminases APOBEC/metabolismo , Adaptação Fisiológica/genética , Antirretrovirais/uso terapêutico , Sequência de Bases/genética , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , DNA Viral/genética , Expressão Gênica/genética , Regulação Viral da Expressão Gênica/genética , Genoma Viral/genética , Genômica/métodos , Células HEK293 , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , RNA Viral/genética , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , Replicação Viral/fisiologia , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismoRESUMO
High-temperature superconductivity appears in cuprate materials that have been tuned in a way where the copper-oxygen bond configuration and coordination is in a state of minimal energy. In competition with the Jahn-Teller effect, which impedes the formation of infinitely connected CuO2 planes, the state of minimal energy persists for planar copper-oxygen bond length variations of up to 10%. We have synthesized the infinite-layer phases of CaCuO2 and SrCuO2 as single-crystalline films using molecular beam epitaxy and performed in-plane scanning transmission electron microscopy mapping. For the infinite-layer phase of CaCuO2 with a short Cu-O bond length, the CuO2 planes maintain their minimal energy by forming distinguished atomic stripes. In contrast, atomic stripe formation does not occur in the infinite-layer phase of SrCuO2, which has a larger Cu-O bond length. The polar field provided by the charge reservoir layer in cuprates with infinitely connected CuO2 planes holds the key over the emergence of superconductivity and is vital to maintain infinitely connected CuO2 planes themselves.