Comparison of L- and D-Amino Acids for Bacterial Imaging in Lung Infection Mouse Model.

The effectiveness of L- and D-amino acids for detecting the early stage of infection in bacterial imaging was compared. We evaluated the accumulation of H-L-methionine (Met), H-D-Met, H-L-alanine (Ala), and H-D-Ala in EC-14 and HaCaT cells. Biological distribution was assessed in control and lung-infection-model mice with EC-14 using H-L- and D-Met, and F-FDG.

Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits.

Prion diseases are fatal neurodegenerative diseases characterized by the deposition of abnormal prion protein aggregates (PrP) in the brain. In this study, we developed hydroxyethylamino-substituted styrylchromone (SC) and 2-(2-(pyridin-3-yl)vinyl)-4H-chromen-4-one (VPC) derivatives for single-photon emission computed tomography (SPECT) imaging of PrP deposits in the brain. The binding affinity of these compounds was evaluated using recombinant mouse prion protein (rMoPrP) aggregates, which resulted in the inhibition constant (K) value of 61.

The CagA Oncoprotein Induces DNA Double Strand Breaks through Fanconi Anemia Pathway Downregulation and Replication Fork Collapse.

The proteins from the Fanconi Anemia (FA) pathway of DNA repair maintain DNA replication fork integrity by preventing the unscheduled degradation of nascent DNA at regions of stalled replication forks. Here, we ask if the bacterial pathogen exploits the fork stabilisation machinery to generate double stand breaks (DSBs) and genomic instability. Specifically, we study if the virulence factor CagA generates host genomic DSBs through replication fork destabilisation and collapse.

Discovery of a Novel Aminocyclopropenone Compound That Inhibits BRD4-Driven Nucleoporin NUP210 Expression and Attenuates Colorectal Cancer Growth.

Epigenetic deregulation plays an essential role in colorectal cancer progression. Bromodomains are epigenetic "readers" of histone acetylation. Bromodomain-containing protein 4 (BRD4) plays a pivotal role in transcriptional regulation and is a feasible drug target in cancer cells.

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans.

Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion.

Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine.

ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.

Predominance of ST8 and CC1/spa-t1784 methicillin-resistant Staphylococcus aureus isolates in Japan and their genomic characteristics.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious epidemiologic problem worldwide. In this study, we aimed to investigate recently isolated MRSA types and determine their characteristics.

Methods: We collected 164 strains isolated from 13 hospitals located in Tokyo and surrounding prefectures.

Skin microbiome profile of healthy Cameroonians and Japanese.

The commensal microbes of the skin have a significant impact on dermal physiology and pathophysiology. Racial and geographical differences in the skin microbiome are suggested and may play a role in the sensitivity to dermatological disorders, including infectious diseases. However, little is known about the skin microbiome profiles of people living in Central Africa, where severe tropical infectious diseases impose a burden on the inhabitants.

Development of Radiohalogenated Osimertinib Derivatives as Imaging Probes for Companion Diagnostics of Osimertinib.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for treating non-small-cell lung cancer (NSCLC) with EGFR mutations. Genetic testing is required to detect the mutation for selecting patients who can use osimertinib. Here, we report an attempt to develop nuclear imaging probes that detect the EGFR mutations.

Synthesis and evaluation of radiogallium-labeled long-chain fatty acid derivatives as myocardial metabolic imaging agents.

Since long-chain fatty acids work as the primary energy source for the myocardium, radiolabeled long-chain fatty acids play an important role as imaging agents to diagnose metabolic heart dysfunction and heart diseases. With the aim of developing radiogallium-labeled fatty acids, herein four fatty acid-based tracers, [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA, which are [67Ga]Ga-HBED-CC and [67Ga]Ga-DOTA conjugated with pentadecanoic acid (PDA) and 3-methylhexadecanoic acid (MHDA), were synthesized, and their potential for myocardial metabolic imaging was evaluated. Those tracers were found to be chemically stable in 0.

Investigation of Degradation Mechanism of Y6-Based Inverted Organic Solar Cells and Their Utilization in Durable Near-Infrared Photodetection.

The device durability of inverted organic solar cells (OSCs) is investigated based on Y6, which is an effective nonfullerene acceptor for high-performance OSCs. The durability of Y6-based inverted OSCs is poor and it can be caused by aggregation of Y6 in the bulk-heterojunction layer due to heating by continuous photo-irradiation (≈65 °C, 100 mW cm , and 72 h). It is found that the aggregation of Y6 is suppressed at a low temperature (≈50 °C), and that the Y6-based devices can be useful as a photodurable near-infrared detector upon continuous laser irradiation.

Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives.

Antimicrobial peptides that act by disrupting bacterial membranes are attractive agents for treating drug-resistant bacteria. This study investigates a membrane-disrupting peptide mimic made of a cyclic oligosaccharide cyclodextrin scaffold that can be chemically polyfunctionalized. An antibacterial functional group on the peptide was simplified to an alkylamino group that combines cationic and hydrophobic moieties, the former to interact with the anionic bacterial membrane and the latter with the membrane interior.

NSP9 of SARS-CoV-2 attenuates nuclear transport by hampering nucleoporin 62 dynamics and functions in host cells.

Nuclear pore complexes (NPC) regulate molecular traffics on nuclear envelope, which plays crucial roles during cell fate specification and diseases. The viral accessory protein NSP9 of SARS-CoV-2 is reported to interact with nucleoporin 62 (NUP62), a structural component of the NPC, but its biological impact on the host cell remain obscure. Here, we established new cell line models with ectopic NSP9 expression and determined the subcellular destination and biological functions of NSP9.

Feasibility of I-RGD uptake as a marker of angiogenesis after myocardial infarction.

Objective: Angiogenesis is an important process facilitating the healing process after myocardial infarction. I-RGD imaging may be a promising candidate to image angiogenesis but may also detect inflammation.

Methods: Left coronary artery was occluded for 30 min, followed by reperfusion in a rat model (n = 31).

Macrocyclic Peptide-Conjugated Tip for Fast and Selective Molecular Recognition Imaging by High-Speed Atomic Force Microscopy.

Fast and selective recognition of molecules at the nanometer scale without labeling is a much desired but still challenging goal to achieve. Here, we show the use of high-speed atomic force microscopy (HS-AFM) for real-time and real-space recognition of unlabeled membrane receptors using tips conjugated with small synthetic macrocyclic peptides. The single-molecule recognition method is validated by experiments on the human hepatocyte growth factor receptor (hMET), which selectively binds to the macrocyclic peptide aMD4.

Visualisation of helical structures of poly(diphenylacetylene)s bearing chiral amide pendants by atomic force microscopy.

The helical structures of poly(diphenylacetylene)s bearing optically active substituents linked through amide bonds and with a helicity memory have been visualised using atomic force microscopy. The polymers self-assembled into an ordered 2D monolayer on highly oriented pyrolytic graphite upon exposure to solvent vapour, whose helical pitch and handedness (right- and left-handed) were for the first time directly revealed at molecular resolution.

Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens.

We recently developed I- and At-labeled monomer RGD peptides using a novel radiolabeling method. Both labeled peptides showed high accumulation in the tumor and exhibited similar biodistribution, demonstrating their usefulness for radiotheranostics. This study applied the labeling method to a dimer RGD peptide with the aim of gaining higher accumulation in tumor tissues based on improved affinity with αβ integrin.

The membrane-linked adaptor FRS2β fashions a cytokine-rich inflammatory microenvironment that promotes breast cancer carcinogenesis.

Although it is held that proinflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we demonstrate that FRS2β, an adaptor protein expressed in a small subset of epithelial cells, triggers the proinflammatory changes that induce stroma in premalignant mammary tissues and is responsible for the disease onset. FRS2β deficiency in mouse mammary tumor virus (MMTV)-ErbB2 mice markedly attenuated tumorigenesis.

Mathematical modeling of Notch dynamics in neural development.

Notch signalling is a well-conserved signalling pathway that regulates cell fate through cell-cell communication. A typical feature of Notch signalling is 'lateral inhibition', whereby two neighbouring cells of equivalent state of differentiation acquire different cell fates. Recently, mathematical and computational approaches have addressed the Notch dynamics in neural development.

Dimer Interface in Natural Variant NK1 Is Dispensable for HGF-Dependent Met Receptor Activation.

NK1, a splicing variant of hepatocyte growth factor (HGF), binds to and activates Met receptor by forming an NK1 dimer and 2:2 complex with Met. Although the structural mechanism underlying Met activation by HGF remains incompletely resolved, it has been proposed that the NK1 dimer structure participates in this activation. We investigated the NK1 dimer interface's role in Met activation by HGF.

Association of Skin Microbiome with the Onset and Recurrence of Pressure Injury in Bedridden Elderly People.

Pressure injuries have been identified as one of the main health hazards among bedridden elderly people. Bedridden elderly people often stay in the same position for a long time, because they cannot switch positions; thus, the blood flow in the part of the body that is being compressed between the bed and their own weight is continuously blocked. As a result, redness and ulcers occur due to lacking oxygen and nutrients in the skin tissues, and these sites are often infected with microorganisms and, thus, become suppurative wounds, a condition commonly determined as pressure injuries.

New Activities of the Nuclear Pore Complexes.

Nuclear pore complexes (NPCs) at the surface of nuclear membranes play a critical role in regulating the transport of both small molecules and macromolecules between the cell nucleus and cytoplasm via their multilayered spiderweb-like central channel. During mitosis, nuclear envelope breakdown leads to the rapid disintegration of NPCs, allowing some NPC proteins to play crucial roles in the kinetochore structure, spindle bipolarity, and centrosome homeostasis. The aberrant functioning of nucleoporins (Nups) and NPCs has been associated with autoimmune diseases, viral infections, neurological diseases, cardiomyopathies, and cancers, especially leukemia.