A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect) to be a notable factor in their evolution. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum is typical of bodies in this part of the main belt.

The internal structure of Eris inferred from its spin and orbit evolution.

The large Kuiper Belt object Eris is tidally locked to its small companion Dysnomia. Recently obtained bounds on the mass of Dysnomia demonstrate that Eris must be unexpectedly dissipative for it to have despun over the age of the solar system. Here, we show that Eris must have differentiated into an ice shell and rocky core to explain the dissipation.

Profiling the Biophysical Developability Properties of Common IgG1 Fc Effector Silencing Variants.

Therapeutic antibodies represent the most significant modality in biologics, with around 150 approved drugs on the market. In addition to specific target binding mediated by the variable fragments (Fvs) of the heavy and light chains, antibodies possess effector functions through binding of the constant region (Fc) to Fcγ receptors (FcγR), which allow immune cells to attack and kill target cells using a variety of mechanisms. However, for some applications, including T-cell-engaging bispecifics, this effector function is typically undesired.

The distribution of CO on Europa indicates an internal source of carbon.

Jupiter's moon Europa has a subsurface ocean, the chemistry of which is largely unknown. Carbon dioxide (CO) has previously been detected on the surface of Europa, but it was not possible to determine whether it originated from subsurface ocean chemistry, was delivered by impacts, or was produced on the surface by radiation processing of impact-delivered material. We mapped the distribution of CO on Europa using observations obtained with the James Webb Space Telescope (JWST).

Hydrogen peroxide at the poles of Ganymede.

Ganymede is the only satellite in the solar system known to have an intrinsic magnetic field. Interactions between this field and the Jovian magnetosphere are expected to funnel most of the associated impinging charged particles, which radiolytically alter surface chemistry across the Jupiter system, to Ganymede's polar regions. Using observations obtained with JWST as part of the Early Release Science program exploring the Jupiter system, we report the discovery of hydrogen peroxide, a radiolysis product of water ice, specifically constrained to the high latitudes.

Structure-based engineering of a novel CD3ε-targeting antibody for reduced polyreactivity.

Bispecific antibodies continue to represent a growth area for antibody therapeutics, with roughly a third of molecules in clinical development being T-cell engagers that use an anti-CD3 binding arm. CD3 antibodies possessing cross-reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N-terminus of CD3 epsilon (CD3ε). Such antibodies have high isoelectric points and display problematic polyreactivity (correlated with poor pharmacokinetics for monospecific antibodies).

Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers.

Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life-extended monoclonal antibody (adintrevimab) provides about 50% protection against symptomatic COVID-19 in SARS-CoV-2-naïve adults at serum nAb titers on the order of 1:30.

Ethical conflict: Conceptualization, measurement, and an examination of consequences.

Previous research on workplace conflict has focused on disagreements about work tasks, processes, and personal relationships. However, conflicts often involve matters of right and wrong; yet, ethical conflict is notably absent from the literature. Informed by moral convictions theory, we introduce the construct of ethical conflict, create and validate a measure of it, and explore its unique effects on workplace outcomes.

Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency.

An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency.

Sodium chloride on the surface of Europa.

The potential habitability of Europa's subsurface ocean depends on its chemical composition, which may be reflected in that of Europa's geologically young surface. Investigations using Galileo Near-Infrared Mapping Spectrometer data led to the prevailing view that Europa's endogenous units are rich in sulfate salts. However, recent ground-based infrared observations have suggested that, while regions experiencing sulfur radiolysis may contain sulfate salts, Europa's more pristine endogenous material may reflect a chloride-dominated composition.

Isolation and characterization of abundantly-expressed cDNAs from the Harderian gland of the garter snake (Thamnophis sirtalis: Colubridae).

The Harderian gland (HG) is an orbital structure whose proteinaceous secretions pass through the nasolacrimal duct to the vomeronasal organ (VNO). Though these three structures occur in many tetrapod vertebrates, the garter snake (Thamnophis sirtalis) is one of the few vertebrates in which the passage of the proteinaceous secretions have been experimentally shown. Secreted proteins from the HG may function as transporters for chemical signals to the VNO epithelium.

Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors.

Zika virus (ZIKV) shares a high degree of homology with dengue virus (DENV), suggesting that preexisting immunity to DENV could affect immune responses to ZIKV. We have tracked the evolution of ZIKV-induced B cell responses in three DENV-experienced donors. The acute antibody (plasmablast) responses were characterized by relatively high somatic hypermutation and a bias toward DENV binding and neutralization, implying the early activation of DENV clones.

Labeling of neuronal morphology using custom diolistic techniques.

Background: Diolistic labeling is increasingly utilized in neuroscience as an efficient, reproducible method for visualization of neuronal morphology. The use of lipophilic carbocyanine dyes, combined with particle-mediated biolistic delivery allows for non-toxic fluorescent labeling of multiple neurons in both living and fixed tissue. Since first described, this labeling method has been modified to fit a variety of research goals and laboratory settings.

Remediating agitation-induced antibody aggregation by eradicating exposed hydrophobic motifs.

Therapeutic antibodies must encompass drug product suitable attributes to be commercially marketed. An undesirable antibody characteristic is the propensity to aggregate. Although there are computational algorithms that predict the propensity of a protein to aggregate from sequence information alone, few consider the relevance of the native structure.

A novel path for rapid transverse communication of vestibular signals in turtle cerebellum.

Voltage-sensitive dye activity within the thin, unfoliated turtle cerebellar cortex (Cb) was recorded in vitro during eighth cranial nerve (nVIII) stimulation. Short latency responses were localized to the middle of the lateral edges of both ipsilateral and contralateral Cb [vestibulocerebellum (vCb)]. Even with a severed contralateral Cb peduncle, stimulation of the nVIII ipsilateral to the intact peduncle evoked contralateral vCb responses with a mean latency of only 0.

Origin and timing of voltage-sensitive dye signals within layers of the turtle cerebellar cortex.

Optical recording techniques were applied to the turtle cerebellum to localize synchronous responses to microstimulation of its cortical layers and reveal the cerebellum's three-dimensional processing. The in vitro yet intact cerebellum was first immersed in voltage-sensitive dye and its responses while intact were compared to those measured in thick cerebellar slices. Each slice is stained throughout its depth, even though the pial half appeared darker during epi-illumination and lighter during trans-illumination.

No sodium in the vapour plumes of Enceladus.

The discovery of water vapour and ice particles erupting from Saturn's moon Enceladus fuelled speculation that an internal ocean was the source. Alternatively, the source might be ice warmed, melted or crushed by tectonic motions. Sodium chloride (that is, salt) is expected to be present in a long-lived ocean in contact with a rocky core.

Leader-follower values congruence: are socialized charismatic leaders better able to achieve it?

In a field study, the authors investigated the relationship between socialized charismatic leadership and values congruence between leaders and followers. Socialized charismatic leadership theory holds that charismatic leaders convey a values-based message and bring about values congruence between themselves and their followers. Yet, other research suggests that individuals' values are stable and closely linked to occupational membership and that employees' values are therefore likely to be quite difficult to change.

Pharmacokinetics and pharmacodynamics of linezolid in children with cystic fibrosis.

Unlabelled: Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF.

Objectives: (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance.

Topography and response timing of intact cerebellum stained with absorbance voltage-sensitive dye.

Physiological activity of the turtle cerebellar cortex (Cb), maintained in vitro, was recorded during microstimulation of inferior olive (IO). Previous single-electrode responses to such stimulation showed similar latencies across a limited region of Cb, yet those recordings lacked spatial and temporal resolution and the recording depth was variable. The topography and timing of those responses were reexamined using photodiode optical recordings.

Identification of 14-3-3zeta by chemical affinity with salicylanilide inhibitors of interleukin-12p40 production.

Salicylanilides were found as selective inhibitors of interleukin-12p40 production in stimulated dendritic cells. The conversion of one of these bioactive salicylanilides into a comparably bioactive, chemically labeled derivative was achieved using a facile and systematic functional group derivatization strategy. This resulted in a tool reagent that was then employed in an affinity chromatography approach that resulted in the identification of the protein 14-3-3zeta as having selective affinity for the chromatography matrix that was derivatized with a salicylanilide that inhibited IL-12p40 production.

Salicylanilides: selective inhibitors of interleukin-12p40 production.

Interleukin (IL)-12p40, a subunit component of both IL-12 and IL-23, is being widely studied for its role in inflammatory disease. As part of an effort to profile cellular signaling pathways across different cell types, we report salicylanilide inhibitors of IL-12p40 production in stimulated dendritic cells. Based on a hypothesis that a desirable therapeutic profile is one that could block IL-12p40 but not IL-6 production, we engaged in directed analoging.