A 12.4-day periodicity in a close binary system after a supernova.

Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.

An infrared transient from a star engulfing a planet.

Planets with short orbital periods (roughly under 10 days) are common around stars like the Sun1,2. Stars expand as they evolve and thus we expect their close planetary companions to be engulfed, possibly powering luminous mass ejections from the host star3-5. However, this phase has never been directly observed. Here we report observations of ZTF SLRN-2020, a short-lived optical outburst in the Galactic disk accompanied by bright and long-lived infrared emission. The resulting light curve and spectra share striking similarities with those of red novae6,7-a class of eruptions now confirmed8 to arise from mergers of binary stars. Its exceptionally low optical luminosity (approximately 1035 erg s-1) and radiated energy (approximately 6.5 × 1041 erg) point to the engulfment of a planet of fewer than roughly ten Jupiter masses by its Sun-like host star. We estimate the Galactic rate of such subluminous red novae to be roughly between 0.1 and several per year. Future Galactic plane surveys should routinely identify these, showing the demographics of planetary engulfment and the ultimate fate of planets in the inner Solar System.

A rotating white dwarf shows different compositions on its opposite faces.

White dwarfs, the extremely dense remnants left behind by most stars after their death, are characterized by a mass comparable to that of the Sun compressed into the size of an Earth-like planet. In the resulting strong gravity, heavy elements sink towards the centre and the upper layer of the atmosphere contains only the lightest element present, usually hydrogen or helium1,2. Several mechanisms compete with gravitational settling to change a white dwarf's surface composition as it cools3, and the fraction of white dwarfs with helium atmospheres is known to increase by a factor of about 2.5 below a temperature of about 30,000 kelvin4-8; therefore, some white dwarfs that appear to have hydrogen-dominated atmospheres above 30,000 kelvin are bound to transition to be helium-dominated as they cool below it. Here we report observations of ZTF J203349.8+322901.1, a transitioning white dwarf with two faces: one side of its atmosphere is dominated by hydrogen and the other one by helium. This peculiar nature is probably caused by the presence of a small magnetic field, which creates an inhomogeneity in temperature, pressure or mixing strength over the surface9-11. ZTF J203349.8+322901.1 might be the most extreme member of a class of magnetic, transitioning white dwarfs-together with GD 323 (ref. 12), a white dwarf that shows similar but much more subtle variations. This class of white dwarfs could help shed light on the physical mechanisms behind the spectral evolution of white dwarfs.

Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics.

The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy. This underscores the urgent need to investigate alternative therapeutic approaches. Sigma receptors have been unexpectedly linked to the SARS-CoV-2 life cycle due to the direct antiviral effect of their ligands. Coronavirus-induced cell stress facilitates the formation of an ER-derived complex conducive to its replication. Sigma receptor ligands are believed to prevent the formation of this complex. Repurposing FDA-approved drugs for COVID-19 offers a timely and cost-efficient strategy to find treatments with established safety profiles. Notably, diphenhydramine, a sigma receptor ligand, is thought to counteract the virus by inhibiting the creation of ER-derived replication vesicles. Furthermore, lactoferrin, a well-characterized immunomodulatory protein, has shown antiviral efficacy against SARS-CoV-2 both in laboratory settings and in living organisms. In the present study, we aimed to explore the impact of sigma receptor ligands on SARS-CoV-2-induced mortality in ACE2-transgenic mice. We assessed the effects of an investigational antiviral drug combination comprising a sigma receptor ligand and an immunomodulatory protein. Mice treated with sigma-2 receptor ligands or diphenhydramine and lactoferrin exhibited improved survival rates and rapid rebound in mass following the SARS-CoV-2 challenge compared to mock-treated animals. Clinical translation of these findings may support the discovery of new treatment and research strategies for SARS-CoV-2.

Locus coeruleus toggles reciprocal prefrontal firing to reinstate fear.

The medial prefrontal cortex (mPFC) plays an essential role in regulating emotion, including inhibiting fear when danger has passed. The extinction of fear, however, is labile and a number of factors, including stress, cause extinguished fear to relapse. Here we show that fear relapse in rats limits single-unit activity among infralimbic (IL) neurons, which are critical for inhibiting fear responses, and facilitates activity in prelimbic (PL) neurons involved in fear expression. Pharmacogenetic activation of noradrenergic neurons in the locus coeruleus mimics this shift in reciprocal IL-PL spike firing, increases the expression of conditioned freezing behavior, and causes relapse of extinguished fear. Noradrenergic modulation of mPFC firing represents a mechanism for relapse and a potential target for therapeutic interventions to reduce pathological fear.

NMDA receptors in the CeA and BNST differentially regulate fear conditioning to predictable and unpredictable threats.

Considerable work demonstrates that Pavlovian fear conditioning depends on N-methyl-D-aspartate (NMDA) receptor-dependent plasticity within the amygdala. In addition, the bed nucleus of the stria terminalis (BNST) has also been implicated in fear conditioning, particularly in the expression of fear to poor predictors of threat. We recently found that the expression of backward (BW) fear conditioning, in which an auditory conditioned stimulus (CS) follows a footshock unconditioned stimulus (US), requires the BNST; the expression of forward (FW) fear conditioning was not disrupted by BNST inactivation. However, whether NMDA receptors within the BNST contribute to the acquisition of fear conditioning is unknown. Moreover, the central nucleus of the amygdala (CeA), which has extensive connections with the BNST, is critically involved in FW conditioning, however whether it participates in BW conditioning has not been explored. Here we test the specific hypothesis that the CeA and the BNST mediate the acquisition of FW and BW fear conditioning, respectively. Adult female and male rats were randomly assigned to receive bilateral infusions of the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), into the CeA or BNST prior to FW or BW fear conditioning. We found that intra-CeA APV impaired the acquisition of both FW and BW conditioning, whereas intra-BNST APV produced selective deficits in BW conditioning. Moreover, APV in the BNST significantly reduced contextual freezing, whereas CeA NMDA receptor antagonism impeded early but not long-lasting contextual fear. Collectively, these data reveal that CeA and BNST NMDA receptors have unique roles in fear conditioning.

Nucleus Reuniens Is Required for Encoding and Retrieving Precise, Hippocampal-Dependent Contextual Fear Memories in Rats.

The nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE before retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intrahippocampal infusions of the NMDA receptor antagonist aminophosphonovalerate. Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous contexts from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is expressed only when the RE is off-line.SIGNIFICANCE STATEMENT The midline thalamic nucleus reuniens (RE) coordinates communication between the hippocampus and medial prefrontal cortex, brain areas that are critical for contextual and spatial memory. Here we show that temporary pharmacological inactivation of RE impairs the acquisition and precision of contextual fear memories after pavlovian fear conditioning in rats. However, inactivating the RE before retrieval testing restored contextual memory in rats conditioned after RE inactivation. Critically, we show that imprecise contextual memories acquired under RE inactivation are learned independently of the hippocampus. These data reveal that the RE is required for hippocampal-dependent encoding of precise contextual memories to support the discrimination of safe and dangerous contexts.

Electrochemical Azidooxygenation of Alkenes Mediated by a TEMPO-N3 Charge-Transfer Complex.

We report a mild and efficient electrochemical protocol to access a variety of vicinally C-O and C-N difunctionalized compounds from simple alkenes. Detailed mechanistic studies revealed a distinct reaction pathway from those previously reported for TEMPO-mediated reactions. In this mechanism, electrochemically generated oxoammonium ion facilitates the formation of azidyl radical via a charge-transfer complex with azide, TEMPO-N3. DFT calculations together with spectroscopic characterization provided a tentative structural assignment of this charge-transfer complex. Kinetic and kinetic isotopic effect studies revealed that reversible dissociation of TEMPO-N3 into TEMPO• and azidyl precedes the addition of these radicals across the alkene in the rate-determining step. The resulting azidooxygenated product could then be easily manipulated for further synthetic elaborations. The discovery of this new reaction pathway mediated by the TEMPO+/TEMPO• redox couple may expand the scope of aminoxyl radical chemistry in synthetic contexts.

Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR.

The LasR regulator protein functions at the top of the Pseudomonas aeruginosa quorum-sensing hierarchy and is implicated in promoting bacterial virulence. Of note is recent evidence that this transcription factor may also respond to oxidative stress. Here, all cysteines in LasR were inspected to deduce their redox sensitivity and to probe the connection between stress response and LasR activity using purified LasR and individual LasR domains. Cys(79) in the ligand binding domain of LasR appears to be important for ligand recognition and folding of this domain to potentiate DNA binding but does not seem to be sensitive to oxidative stress when bound to its native ligand. Two cysteines in the DNA binding domain of LasR do form a disulfide bond when treated with hydrogen peroxide, and formation of this Cys(201)-Cys(203) disulfide bond appears to disrupt the DNA binding activity of the transcription factor. Mutagenesis of either of these cysteines leads to expression of a protein that no longer binds DNA. A cell-based reporter assay linking LasR function with ß-galactosidase activity gave results consistent with those obtained with purified LasR. This work provides a possible mechanism for oxidative stress response by LasR and indicates that multiple cysteines within the protein may prove to be useful targets for disabling its activity.

The dorsolateral striatum selectively mediates extinction of habit memory.

Previous research has indicated a role for the dorsolateral striatum (DLS) in acquisition and retrieval of habit memory. However, the neurobiological mechanisms guiding extinction of habit memory have not been extensively investigated. The present study examined whether the dorsolateral striatum (DLS) is involved in extinction of habit memory in a food-rewarded response learning version of the plus-maze in adult male Long-Evans rats (experiment 1). In addition, to determine whether the role of this brain region in extinction is selective to habit memory, we also examined whether the DLS is required for extinction of hippocampus-dependent spatial memory in a place learning version of the plus-maze (experiment 2). Following acquisition in either task, rats received two days of extinction training, in which the food reward was removed from the maze. The number of perseverative trials (a trial in which the rat made the same previously reinforced body-turn) and latency to reach the previously correct food well were used as measures of extinction. Animals were given immediate post-training intra-DLS administration of the sodium channel blocker bupivacaine or vehicle to determine the effect of DLS inactivation on consolidation of extinction memory in each task. In the response learning task, post-training DLS inactivation impaired consolidation of extinction memory. Injections of bupivacaine delayed 2 h post-training did not affect extinction, indicating a time-dependent effect of neural inactivation on consolidation of extinction memory in this task. In contrast, post-training DLS inactivation did not impair, but instead slightly enhanced, extinction memory in the place learning task. The present findings indicate a critical role for the DLS in extinction of habit memory in the response learning task, and may be relevant to understanding the neural mechanisms through which maladaptive habits in human psychopathologies (e.g. drug addiction) may be suppressed.

Complete enumeration of elementary flux modes through scalable demand-based subnetwork definition.

MOTIVATION: Elementary flux mode analysis (EFMA) decomposes complex metabolic network models into tractable biochemical pathways, which have been used for rational design and analysis of metabolic and regulatory networks. However, application of EFMA has often been limited to targeted or simplified metabolic network representations due to computational demands of the method. RESULTS: Division of biological networks into subnetworks enables the complete enumeration of elementary flux modes (EFMs) for metabolic models of a broad range of complexities, including genome-scale. Here, subnetworks are defined using serial dichotomous suppression and enforcement of flux through model reactions. Rules for selecting appropriate reactions to generate subnetworks are proposed and tested; three test cases, including both prokaryotic and eukaryotic network models, verify the efficacy of these rules and demonstrate completeness and reproducibility of EFM enumeration. Division of models into subnetworks is demand-based and automated; computationally intractable subnetworks are further divided until the entire solution space is enumerated. To demonstrate the strategy's scalability, the splitting algorithm was implemented using an EFMA software package (EFMTool) and Windows PowerShell on a 50 node Microsoft high performance computing cluster. Enumeration of the EFMs in a genome-scale metabolic model of a diatom, Phaeodactylum tricornutum, identified ∼2 billion EFMs. The output represents an order of magnitude increase in EFMs computed compared with other published algorithms and demonstrates a scalable framework for EFMA of most systems.

Ageing diminishes the modulation of human brain responses to visual food cues by meal ingestion.

BACKGROUND/OBJECTIVES: Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised. We therefore aimed to investigate changes in brain responses to food cues, and the modulatory effect of meal ingestion on such evoked neural activity, from young adulthood to middle age. SUBJECTS/METHODS: Twenty-four healthy, right-handed subjects, aged 19.5-52.6 years, were studied on separate days after an overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues. RESULTS: Across the group, meal ingestion reduced food cue-evoked activity of amygdala, putamen, insula and thalamus, and increased activity in precuneus and bilateral parietal cortex. Corrected for body mass index, ageing was associated with decreasing food cue-evoked activation of right dorsolateral prefrontal cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the fasted state. Ageing was also positively associated with the difference in food cue-evoked activation between fed and fasted states in the right DLPFC, bilateral amygdala and striatum, and negatively associated with that of the left orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal gyri, posterior cingulate and precuneus. There was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue-evoked regional brain activity with increasing age. CONCLUSIONS: Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.

Breast cancer metastasis: issues for the personalization of its prevention and treatment.

Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient's primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed.

Preventing Behavioral Human Immunodeficiency Virus Infections in Adolescents and Young Adults.

HIV prevention in adolescents and young adults (AYA) requires a multi-pronged strategy encompassing behavioral, biologic, and structural approaches. This article reviews the epidemiology of HIV infection in the United States and its pathogenesis and transmission. Prevention approaches are discussed in more detail, with an emphasis on how each approach is relevant to AYA populations. Information is summarized in a resource table with links to references and in-depth discussions of the topics reviewed in this article.

Cutaneous metastasis of transitional cell carcinoma in 12 dogs.

In humans, cutaneous metastasis of transitional cell carcinoma (TCC) has been attributed to direct extension, lymphatic or hematogenous dissemination, or surgical implantation. The purpose of this study was to characterize the clinical and histologic features of cutaneous TCC metastasis, confirmed by uroplakin-III immunohistochemistry, in dogs. The 12 cases were 9 spayed female and 3 neutered male dogs, 6 to 14 years old (mean, 11 years). Four dogs had a history of urinary incontinence. Three had undergone abdominal surgery for TCC diagnosis or treatment. The primary neoplasms were 7 papillary infiltrating and 5 nonpapillary infiltrating TCC. Cutaneous lesions were detected at a mean of 123 days (median, 38 days) after diagnosis of the primary TCC and appeared as plaques, papules, or nodules in, with 1 exception, perineal, inguinal, or ventral abdominal dermis or subcutis. Of 8 dogs with dermal TCC, 5 had epidermal erosion or ulceration. In 10 dogs, TCC was detected in cutaneous lymphatic vessels, identified by endothelial immunoreactivity for Prox1. Metastases were also detected in lymph nodes in all dogs and at distant noncutaneous sites, usually the lungs, in 10 dogs. Mean survival after diagnosis was 162 days (median, 90 days). Despite medical treatment of 10 dogs after the development of cutaneous metastasis, remission was not achieved; 4 dogs had stable disease. Although TCC could have spread to skin by direct extension or lymphatic or vascular dissemination, the proximity of most cutaneous metastases to the vulva or prepuce raises the additional possibility of transepidermal spread through urine-scalded skin.

Systems analysis of microbial adaptations to simultaneous stresses.

Microbes live in multi-factorial environments and have evolved under a variety of concurrent stresses including resource scarcity. Their metabolic organization is a reflection of their evolutionary histories and, in spite of decades of research, there is still a need for improved theoretical tools to explain fundamental aspects of microbial physiology. Using ecological and economic concepts, this chapter explores a resource-ratio based theory to elucidate microbial strategies for extracting and channeling mass and energy. The theory assumes cellular fitness is maximized by allocating scarce resources in appropriate proportions to multiple stress responses. Presented case studies deconstruct metabolic networks into a complete set of minimal biochemical pathways known as elementary flux modes. An economic analysis of the elementary flux modes tabulates enzyme atomic synthesis requirements from amino acid sequences and pathway operating costs from catabolic efficiencies, permitting characterization of inherent tradeoffs between resource investment and phenotype. A set of elementary flux modes with competitive tradeoffs properties can be mathematically projected onto experimental fluxomics datasets to decompose measured phenotypes into metabolic adaptations, interpreted as cellular responses proportional to the experienced culturing stresses. The resource-ratio based method describes the experimental phenotypes with greater accuracy than other contemporary approaches and further analysis suggests the results are both statistically and biologically significant. The insight into metabolic network design principles including tradeoffs associated with concurrent stress adaptation provides a foundation for interpreting physiology as well as for rational control and engineering of medically, environmentally, and industrially relevant microbes.

The feasibility and impact of implementing a computer-guided consultation to target health inequality in Asthma.

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management. Patients on asthma registers in Greater Manchester Primary Care Networks were identified and underwent remote review by nursing staff using the CGC linked directly to the GP clinical system. Three-hundred thirty-eight patients (mean age 59 (SD 17) years; 60% Female) were reviewed. The CGC reported the patient's asthma control to be "Good" in 22%, "Partial" in 6% and "Poor" in 72%. ACT scores were significantly higher in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. The number of steroid courses and hospital admissions in the previous 12 months was significantly lower in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. Nineteen percent were found not to have a personalised asthma management plan during CGC review, which was alerted by the CGC and subsequently, all but 3 patients had this created on review completion (McNemar's test; p < 0.001). 5% were found not to have been prescribed regular inhaled steroid therapy resulting in the operator being alerted by the CGC in all cases. Overall, 44% underwent alteration in asthma therapy following the CGC review with 82% of these representing treatment escalation. An end-to-end digital service solution is feasible for Asthma within primary care and the utilisation of a CGC when conducting primary care asthma reviews increases implementation of guideline-level management thus addressing healthcare inequality while enabling identification of "high risk" asthma patients and guiding appropriate therapy escalation and de-escalation.

Latitudes and attitudes: A multinational study of laparoscopic pyeloplasty in children.

PURPOSE: The Anderson-Hynes technique has been the treatment of choice for primary ureteropelvic junction obstruction in children. Laparoscopic approach has shown similar outcomes to open, with advantages of shorter hospital stay and less pain. We reviewed the experience of 11 geographically diverse, tertiary pediatric urology institutions focusing on the outcomes and complications of laparoscopic pyeloplasty. MATERIALS AND METHODS: A descriptive, retrospective study was conducted evaluating patients undergoing Anderson-Hynes dismembered laparoscopic pyeloplasty. Centers from four different continents participated. Demographic data, perioperative management, results, and complications are described. RESULTS: Over a 9-year period, 744 laparoscopic pyeloplasties were performed in 743 patients. Mean follow-up was 31 months (6-120m). Mean age at surgery was 82 months (1 w-19 y). Median operative time was 177 min. An internal stent was placed in 648 patients (87%). A catheter was placed for bladder drainage in 702 patients (94%). Conversion to open pyeloplasty was necessary in seven patients. Average length of hospital stay was 2.8 days. Mean time of analgesic requirement was 3.2 days. Complications, according to Clavien-Dindo classification, were observed in 56 patients (7.5%); 10 (1%) were Clavien-Dindo IIIb. Treatment failure occurred in 35 cases with 30 requiring redo pyeloplasty (4%) and 5 cases requiring nephrectomy (0.6%). CONCLUSION: We have described the laparoscopic pyeloplasty experience of institutions with diverse cultural and economic backgrounds. They had very similar outcomes, in agreement with previously published data. Based on these findings, we conclude that laparoscopic pyeloplasty is safe and successful in diverse geographics areas of the world.

The Elusive Coreceptors for the SARS-CoV-2 Spike Protein.

Evidence suggests that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein interacts with host coreceptors that participate in viral entry. Resolving the identity of coreceptors has important clinical implications as it may provide the basis for the development of antiviral drugs and vaccine candidates. The majority of characteristic mutations in variants of concern (VOCs) have occurred in the NTD and receptor binding domain (RBD). Unlike the RBD, mutations in the NTD have clustered in the most flexible parts of the spike protein. Many possible coreceptors have been proposed, including various sugars such as gangliosides, sialosides, and heparan sulfate. Protein coreceptors, including neuropilin-1 and leucine-rich repeat containing 15 (LRRC15), are also proposed coreceptors that engage the NTD.

Revision Anterior Cruciate Ligament, Lateral Collateral Ligament Reconstruction, and Osteochondral Allograft Transplantation for Complex Knee Instability.

Anterior cruciate ligament (ACL) injuries rarely occur as an isolated event and often include associated meniscal, subchondral bone, and collateral ligament injuries. Concomitant pathology frequently complicates primary and revision ACL reconstruction and must be addressed to ensure comprehensive diagnosis and treatment. In this Technical Note, we describe our method for treatment of complex knee instability following multiple failed ACL reconstruction using a multiligament reconstruction technique with an osteochondral allograft transplantation to the lateral femoral condyle. This comprehensive repair technique restores the anatomic load bearing forces of the cruciate and collateral ligaments and promotes biological repair through incorporation of cartilage resurfacing to ultimately achieve optimal kinematics of the knee joint.