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Clinical and microbiological analysis of risk factors for breakthrough bloodstream infection during Tigecycline Therapy

A pentatomomorpha-specific salivary protein activates plant immunity and is critical for insect feeding

The stinkbug Riptortus pedestris , notorious for inducing soybean staygreen-like syndrome, employs a range of salivary proteins to manipulate the host plant for its benefit. Here, we show that RpSP1, a salivary protein specific to Pentatomomorpha, triggers plant defense responses in multiple plant species. RpSP1 interacts with and stabilizes a HSP40 family protein GmSPIP1 and is dependent on GmSPIP1 to induce cell death. We show that a critical 22-amino acid peptide within RpSP1 acts as an intracellular insect-derived elicitor. Furthermore, RpSP1 enhances insect-feeding efficiency. The dual functionality of RpSP1 is highlighted by the significant reduction of soybean staygreen-like syndrome following its overexpression in soybean plants or knockdown in insects. Our findings elucidate the complex molecular interactions between plants and herbivores, positioning RpSP1 as a crucial target for developing advanced pest management strategies with broad implications for agricultural biology.

Quality of routine malaria data captured at primary health facilities in the Hohoe Municipality, Ghana

Extremal structures with embedded prefailure indicators

Preemptive identification of potential failure under loading of engineering structures is a critical challenge. Our study presents an innovative approach to design built-in prefailure indicators within multiscale structural designs with optimized load carrying capabilities utilizing the design freedom of topology optimization. The indicators are engineered to visibly signal load conditions approaching the global critical buckling load at predefined locations. By showing noncritical local buckling when activated, the indicators provide early warning without compromising the overall structural integrity of the design. This proactive safety feature enhances structural reliability. The method is particularly beneficial for offshore wind turbines, where many sensors are located below sea level and are inaccessible for maintenance. By allowing the placement of indicators in accessible predetermined locations, our method can reduce the number of required sensors and improve structural health monitoring. Additionally, the potential use of memory overload indicators exploiting plasticity offers a reliable means of detecting overloads during offline periods. Experimental testing of 3D-printed designs confirms a strong correlation between measurements and numerical simulations, demonstrating the feasibility of creating structures that can signal the need for load reduction or maintenance at predetermined locations. This research contributes to the design of safer structures by introducing built-in early-warning failure systems.

Related studies on measuring the normal values of optic nerve sheath diameter in healthy Chinese adults based on CT scans

Cost-reduction strategy to culture patient derived bladder tumor organoids

SIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants

HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination. Each mAb was administered at 15 mg/kg, and both mAb-treated groups received ITS103.01, a highly potent CD4-binding site targeting antibody. mAb treatment delayed viral rebound, lowered rebound viremia setpoint and viral diversity, and extended animal lifespan. Compared to controls, for which viremia rebounded 2 wk following ATI, mAb infusion delayed rebound for both groups ( P = 0.0003). Animals that received the 4-mAb regimen rebounded 3 to 6 wk post-ATI while the 2-mAb regimen rebounded 5 to 22 wk post-ATI. Envelope escape mutations emerged in rebound virus of mAb-treated animals that abrogated neutralization by ITS103.01, the most potent in the cocktail. These data demonstrate in vivo antiviral activity of SIV mAbs in the context of ATI via immune pressure dominated by the most potent mAb and highlight their potential in adjunctive therapeutic studies.

Multicentre case-control study on the association between COVID-19 vaccines and neurological disorders (COVIVAX)

An analysis of the cultivation, consumption and composition of home-grown cannabis following decriminalisation in the Australian Capital Territory

Plastic responses to past environments shape adaptation to novel selection pressures

Phenotypic plasticity may pave the way for rapid adaptation to newly encountered environments. Although it is often contested, there is growing evidence that initial plastic responses of ancestral populations to new environmental cues may promote subsequent adaptation. However, we do not know whether plasticity to cues present in the ancestral habitat (past-cue plasticity) can facilitate adaptation to novel cues. Conceivably, this could occur if plastic responses are coincidentally optimal to both past and novel cues (i.e., are preadaptive) or if they are transferred to novel cues during adaptation. Past plastic phenotype values could also become fixed during adaptation to the new environment. To uncover the role of past-cue plasticity in adaptation, we tested gene expression plasticity responses of two parallel mine-waste-adapted Silene uniflora populations and their closest coastal relatives. Plants were exposed to the past and novel cues of salt and zinc, which revealed that during adaptation to mine waste, plasticity to salt diminishes. Despite this, our results show that ancestral plasticity to salt has a substantial impact on subsequent adaptation to zinc. For a third of genes that have evolved zinc plasticity in mine populations, salt plasticity has been transferred to the zinc response. Furthermore, a quarter of fixed expression differences between mine and coastal populations were similar to ancestral salt responses. Alongside evidence that ancestral plasticity to novel cues can facilitate adaptation, our results provide a clear indication that ancestral past-cue plasticity can also play a key role in rapid, parallel adaptation to novel habitats.

Chest CT characterization of children with necrotizing pneumonia due to Mycoplasma pneumoniae infection

Optimal strategies for correcting merotelic chromosome attachments in anaphase

Accurate chromosome segregation in mitosis depends on proper connections of sister chromatids, through microtubules, to the opposite poles of the early mitotic spindle. Transiently, many inaccurate connections are formed and rapidly corrected throughout the mitotic stages, but a small number of merotelic connections, in which a chromatid is connected to both spindle poles, remain lagging at the spindle’s equator in anaphase. Most of the lagging chromatids are eventually moved to one or the other pole, likely by a combination of microtubules’ turnover and the brute force of pulling by the microtubules’ majority from the one pole against the microtubules’ minority from the other pole. We use computer simulations from two stochastic models (1D and full 3D CellDynaMo model) combining force balances and microtubules’ dynamics for the lagging chromatids to investigate what maximizes the percentage of segregated laggards. We find that a) brute force tug-of-war with slow (< 0.0001 s −1 ) microtubules’ detachment rate can move asymmetric laggards to the poles in limited time, b) rapid (> 0.01 s −1 ) microtubules’ detachment rate leads to a significant loss of the laggards, and c) intermediate (~ 0.001 s −1 ) microtubules’ detachment rate ensures higher than 90% accuracy of segregation. The simulations also shed light on the waiting time required to correct the merotelic errors in anaphase and on the roles of chromatid-attached microtubule number and Aurora B–mediated, spatially graded regulation of microtubule kinetics in anaphase.

Prevalence and associated factors of epiretinal membrane using spectralis OCT in Fujian Eye Study

Errors are robustly tamed in cumulative knowledge processes

As knowledge accumulates in science and society in a distributed fashion, erroneous derivations can be introduced into the corpus of knowledge. Such derivations can compromise the validity of any units of knowledge that rely on them in the future. Can societal knowledge maintain some level of integrity given simple distributed error-checking mechanisms? In this paper, we investigate the following formulation of the question: assuming that a constant fraction of the new derivations is wrong, is it possible for simple error-checking mechanisms that apply when a new unit of knowledge is derived to maintain the integrity of the corpus of knowledge? This question was introduced by Ben-Eliezer et al. [“Is this correct? Let’s check!” in 14th Innovations in Theoretical Computer Science Conference (ITCS, 2023)], who gave a robust affirmative answer in a specific probabilistic model for knowledge accumulation. Namely, this model required that new units depend on just one existing unit and join the process according to a preferential attachment rule. In this work, we consider much more general families of processes of knowledge accumulation, where new units may depend on multiple existing units and join according to varied attachment mechanisms. We also consider models with a (random) fraction of insertions of adversarial nodes. We give a robust affirmative answer to the above question by showing that for all of these models, as long as many of the units follow simple local heuristics for checking a bounded number of units they depend on, all errors will be eventually eliminated.

Nonlinear relationship between hepatic steatosis index and reversion to normal glucose regulation in Chinese adults with prediabetes

Design of a light and Ca ²⁺ switchable organic–peptide hybrid

The design of organic–peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca 2+ -binding organic–peptide hybrid. The designed molecule, designated Ca 2+ -binding switch (CaBS), combines an EF-hand motif from classical Ca 2+ -binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light. The MC/SP group acts both as a photoswitch as well as an optical sensor of Ca 2+ binding. Photoconversion of the SP to the corresponding MC unmasks an acidic phenol, which CaBS uses as an integral part of both its Ca 2+ -binding site as well as its tertiary and quaternary structure. By design, the SP state of CaBS is monomeric, while the Ca 2+ -bound form of the MC state is an obligate dimer, with two Ca 2+ -binding sites formed at the interface of a domain-swapped dimer. Thus, light and Ca 2+ were expected to serve as an “AND gate” that powers a change in backbone structure/dynamics, oligomerization state, and fluorescence properties of the designed molecule. CaBS was designed using Rosetta and molecular dynamics simulations, and experimentally characterized by nuclear magnetic resonance, isothermal titration calorimetry, and optical titrations. These data illustrate the potential of combining small molecule engineering with de novo protein design to develop sensors whose conformation, association state, and optical properties respond to multiple environmental cues.

N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex

Integrative bioinformatic approach reveals novel melatonin-related biomarkers for Alzheimer’s disease

Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug

Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named meteor ( met ), harboring a mutation in the Werner syndrome RecQ - like helicase ( wrn ) gene. Loss of wrn leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration. Therefore, we conducted a screening of antiaging drugs using the met mutant and revealed that sapanisertib effectively ameliorated most of the aging phenotypes of the mutant. Mechanistically, the geroprotective effects of sapanisertib may be attributed to inhibition of mTORC1/2. Furthermore, sapanisertib also attenuated chronological aging in wild-type aged zebrafish and replicative-senescence in human foreskin fibroblasts. Taken together, our study introduces a unique and efficient model for large-scale antiaging drug screening in vertebrates and suggests sapanisertib as a potential therapeutic option for treating premature aging and promoting healthy aging.

PET imaging of AAV9 and AAVBR1 trafficking in normal mice