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The synthesis of nucleobases in natural environments, especially in interstellar molecular clouds, is the focus of a long-standing debate regarding prebiotic chemical evolution. Here we report the simultaneous detection of all three pyrimidine (cytosine, uracil and thymine) and three purine nucleobases (adenine, xanthine and hypoxanthine) in interstellar ice analogues composed of simple molecules including H 2 O, CO, NH 3 and CH 3 OH after exposure to ultraviolet photons followed by thermal processes, that is, in conditions that simulate the chemical processes accompanying star formation from molecular clouds. Photolysis of primitive gas molecules at 10 K might be one of the key steps in the production of nucleobases. The present results strongly suggest that the evolution from molecular clouds to stars and planets provides a suitable environment for nucleobase synthesis in space. The formation of nucleobases can take place in extraterrestrial environments. Here the authors show the simultaneous synthesis of three purine nucleobases and three pyrimidine from interstellar ice analogues that suggest the evolution from molecular clouds to stars and planets provide suitable environment for nucleobase synthesis in space.

Molecular clouds (MCs) in space are the birthplace of various molecular species. Chemical reactions occurring on the cryogenic surfaces of cosmic icy dust grains have been considered to play important roles in the formation of these species. Radical reactions are crucial because they often have low barriers and thus proceed even at low temperatures such as ∼10 K. Since the 2000s, laboratory experiments conducted under low-temperature, high-vacuum conditions that mimic MC environments have revealed the elementary physicochemical processes on icy dust grains. In this review, experiments conducted by our group in this context are explored, with a focus on radical reactions on the surface of icy dust analogues, leading to the formation of astronomically abundant molecules such as H , H O, H CO, and CH OH and deuterium fractionation processes. The development of highly sensitive, non-destructive methods for detecting adsorbates and their utilization for clarifying the behavior of free radicals on ice, which contribute to the formation of complex organic molecules, are also described.

The clinical characteristics of Alistipes bacteremia remain insufficiently understood. We retrospectively analyzed 13 cases of Alistipes bacteremia at a tertiary care center in Japan. Of the 13 patients, 7 were male and 6 female; 10 were >65 years of age. Of 9 patients with comorbidities, 7 had solid tumors or hematological malignancies and 11 had gastrointestinal symptoms. Isolates identified were Alistipes finegoldii in 4 cases, A. onderdonkii in 4, A. putredinis in 3, A. indistinctus in 2, and A. ihumii in 1. Ten strains exhibited low MICs against β-lactam/β-lactamase inhibitors and metronidazole. We observed high MICs against penicillin, ceftriaxone, and minocycline. Several strains harbored antimicrobial resistance genes, including adeF, tet(Q), cfxA3, cfxA4, and ermG. Twelve patients received β-lactam/β-lactamase inhibitors; 2 patients with solid tumors experienced septic shock and died. Alistipes bacteria can translocate from the gastrointestinal tract into the bloodstream, particularly in cases of inflammation, obstruction, or perforation, leading to severe infections.

H 2 O exists in two spin isomers, ortho and para, in a ratio of 3:1 at room temperature. Some astronomical observations have found water with a ratio of less than 3, thought to be due to water being photodesorbed from ice that had been formed at very low temperatures (≾30 K). Hama et al. tested this idea in the laboratory, by forming water ice at low temperature and then photodesorbing it to measure the ortho:para ratio. They found a ratio of 3, even at 10 K. Thus, another explanation for the low ratios in some astronomical objects must be found. Science , this issue p. 65 The ortho-para ratio of water desorbed from ice does not reflect its formation temperature. The anomalously low ortho-to-para ratios (OPRs) exhibited by gaseous water in space have been used to determine the formation temperature (<50 kelvin) of ice on cold interstellar dust. This approach assumes that the OPR of water desorbed from ice is related to the ice formation temperature on the dust. However, we report that water desorbed from ice at 10 kelvin shows a statistical high-temperature OPR of 3, even when the ice is produced in situ by hydrogenation of O 2 , a known formation process of interstellar water. This invalidates the assumed relation between OPR and temperature. The necessary reinterpretation of the low OPRs will help elucidate the chemical history of interstellar water from molecular clouds and processes in the early solar system, including comet formation.

The study of Klebsiella quasipneumoniae, Klebsiella variicola, and AmpC production in extended-spectrum β-lactamase (ESBL)-producing Klebsiella in Japan is limited, and existing data are insufficient. This study aims to characterize Klebsiella species, determine AmpC production rates, and analyze antimicrobial resistance patterns in ESBL-producing Klebsiella isolates in Japan. A total of 139 clinical isolates of ESBL-producing Klebsiella were collected in Japan, along with their corresponding antimicrobial susceptibility profiles. The isolates were identified using a web-based tool. ESBL genes within the isolates were identified using multiplex PCR. Screening for AmpC-producing isolates was performed using cefoxitin disks, followed by multiplex PCR to detect the presence of AmpC genes. Antimicrobial resistance patterns were analyzed across the predominant ESBL genotypes. The web-based tool identified 135 isolates (97.1%) as Klebsiella pneumoniae and 4 (2.9%) as K. quasipneumoniae subsp. similipneumoniae, with no instances of K. variicola detected. Among K. pneumoniae, the CTX-M-1 group emerged as the predominant genotype (83/135, 61.5%), followed by K. quasipneumoniae subsp. similipneumoniae (3/4, 75.0%). The CTX-M-9 group was the second most prevalent genotype in K. pneumoniae (45/135, 33.3%). The high resistance rates were observed for quinolones (ranging from 46.7% to 63.0%) and trimethoprim/sulfamethoxazole (78.5%). The CTX-M-1 group exhibited higher resistance to ciprofloxacin (66/83, 79.5%) compared to the CTX-M-9 group (18/45, 40.0%), a trend also observed for levofloxacin and trimethoprim/sulfamethoxazole. Among the 16 isolates that tested positive during AmpC screening, only one K. pneumoniae isolates (0.7%) were confirmed to carry the AmpC gene. Klebsiella pneumoniae with the CTX-M-1 group is the most common ESBL-producing Klebsiella in Japan and showed a low proportion of AmpC production. These isolates are resistant to quinolones and trimethoprim/sulfamethoxazole, highlighting the challenge of managing this pathogen. The findings underscore the importance of broader research and continuous monitoring to address the resistance patterns of ESBL-producing Klebsiella.

The presence of Corynebacterium in blood samples can indicate true bacteremia or contamination, thus complicating the diagnosis of true bacteremia. We aimed to evaluate the usefulness of time to positivity (TTP) in diagnosing true bacteremia and contamination in cases where Corynebacterium was isolated from blood samples. We compared the TTP of the true-bacteremia group (n = 77) with that of the contamination group (n = 88). For the true-bacteremia cases that had only one set of positive blood cultures (n = 14), considering clinical and bacteriological data, additional cultures were performed on blood or other specimens. The same Corynebacterium spp. as in blood were isolated from these specimens. Receiver operating characteristic curves were generated, and the sensitivity and specificity of TTP were calculated for diagnosing true bacteremia. The median TTP of the true-bacteremia group (26.8 h) was shorter than that of the contamination group (43.3 h) (P < 0.0001). When considering TTP ≤ 25.0 h as true bacteremia, the sensitivity and specificity were 44.2% and 95.5%, respectively. Moreover, when considering TTP ≤ 69.4 h as true bacteremia, the sensitivity and specificity were 96.1% and 20.5%, respectively. Among the true-bacteremia groups with one set of positive blood cultures (n = 14), no case exhibited a TTP > 69.4 h. Only three cases showed TTP ≤ 25.0 h in the true-bacteremia group with one set of positive blood cultures. TTP > 69.4 h is likely to indicate contamination and may be useful to exclude true bacteremia in cases with one set of positive blood cultures. Meanwhile, diagnosing true bacteremia using the threshold of TTP 25.0 h would be difficult. Therefore, the clinical and bacteriological data are important for diagnosing bacteremia, especially in cases with TTP ≤ 69.4 h.

Force transmission at integrin-based adhesions is important for cell migration and mechanosensing. Talin is an essential focal adhesion (FA) protein that links F-actin to integrins. F-actin constantly moves on FAs, yet how Talin simultaneously maintains the connection to F-actin and transmits forces to integrins remains unclear. Here we show a critical role of dynamic Talin unfolding in force transmission. Using single-molecule speckle microscopy, we found that the majority of Talin are bound only to either F-actin or the substrate, whereas 4.1% of Talin is linked to both structures via elastic transient clutch. By reconstituting Talin knockdown cells with Talin chimeric mutants, in which the Talin rod subdomains are replaced with the stretchable β-spectrin repeats, we show that the stretchable property is critical for force transmission. Simulations suggest that unfolding of the Talin rod subdomains increases in the linkage duration and work at FAs. This study elucidates a force transmission mechanism, in which stochastic molecular stretching bridges two cellular structures moving at different speeds. Focal adhesion proteins transmit intracellular forces to the extracellular matrix (ECM). Here, the authors show a force transmission by elastic transient clutch of Talin between ECM and constantly flowing F-actin at focal adhesions.

Classical transition-state theory is fundamental to describing chemical kinetics; however, quantum tunneling is also important in explaining the unexpectedly large reaction efficiencies observed in many chemical systems. Tunneling is often indicated by anomalously large kinetic isotope effects (KIEs), because a particle’s ability to tunnel decreases significantly with its increasing mass. Here we experimentally demonstrate that cold hydrogen (H) and deuterium (D) atoms can add to solid benzene by tunneling; however, the observed H/D KIE was very small (1–1.5) despite the large intrinsic H/D KIE of tunneling (≳100). This strong reduction is due to the chemical kinetics being controlled not by tunneling but by the surface diffusion of the H/D atoms, a process not greatly affected by the isotope type. Because tunneling need not be accompanied by a large KIE in surface and interfacial chemical systems, it might be overlooked in other systems such as aerosols or enzymes. Our results suggest that surface tunneling reactions on interstellar dust may contribute to the deuteration of interstellar aromatic and aliphatic hydrocarbons, which could represent a major source of the deuterium enrichment observed in carbonaceous meteorites and interplanetary dust particles. These findings could improve our understanding of interstellar physicochemical processes, including those during the formation of the solar system. Significance Quantum tunneling, an important phenomenon in many surface and interfacial chemical processes, is strongly dependent on the isotope of the tunneling atom. However, surface tunneling during the hydrogenation/deuteration of solid benzene at 15–25 K is accompanied by an almost semiclassical kinetic isotope effect (KIE) of 1–1.5, which is much lower than that intrinsic to tunneling (≳100), because isotopically insensitive surface diffusion of the adsorbed atoms controls the chemical kinetics. Our results suggest that tunneling has been unrecognized in studies of the chemistry of condensed phases, and small-KIE tunneling may account for the unexplained fast reactions of hydrogen and deuterium observed in surface/interface chemical systems such as aerosols, enzymes, and interstellar dust grains.

Over recent decades, considerable effort has been made to understand how mechanical stress applied to the actin network alters actin assembly and disassembly dynamics. However, there are conflicting reports concerning the issue both in vitro and in cells. In this review, we discuss concerns regarding previous quantitative live-cell experiments that have attempted to evaluate myosin regulation of filamentous actin (F-actin) turnover. In particular, we highlight an error-generating mechanism in quantitative live-cell imaging, namely convection-induced misdistribution of actin-binding probes. Direct observation of actin turnover at the single-molecule level using our improved electroporation-based Single-Molecule Speckle (eSiMS) microscopy technique overcomes these concerns. We introduce our recent single-molecule analysis that unambiguously demonstrates myosin-dependent regulation of F-actin stability in live cells. We also discuss the possible application of eSiMS microscopy in the analysis of actin remodeling in striated muscle cells.

Evaluations of the lateral properties of timber joints are necessary to ensure the safety of timber buildings. The yield load is an important property that is usually obtained using authorized engineering techniques. Although yield loads have been easily obtained using authorized techniques, events that have occurred in the joint during yielding have not been clarified. This study experimentally obtains elastic limit data using nailed joints. Mechanical tests measuring the residual displacement after various lateral loads with six-joint specimen specifications were conducted. In this study, the load at which the residual displacement reached 5% of the nail diameter was defined as the elastic limit. The experimentally obtained elastic limits were compared with the yield loads obtained using authorized engineering techniques. The ratios of elastic limits to the yield loads obtained using the perfect elasto-plastic model, method described in EN, and 5% offset method were 0.554–0.743, 0.557–0.834, and 0.648–0.801, respectively. The results numerically revealed that residual displacements occurred at a much lower load than the yield loads.