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Endogenous biomolecular condensates, comprised of a multitude of proteins and RNAs, can organize into multiphasic structures, with compositionally-distinct phases. This multiphasic organization is generally understood to be critical for facilitating their proper biological function. However, the biophysical principles driving multiphase formation are not completely understood. Here, we utilizein vivocondensate reconstitution experiments and coarse-grained molecular simulations to investigate how oligomerization and sequence interactions modulate multiphase organization in biomolecular condensates. We demonstrate that increasing the oligomerization state of an intrinsically disordered protein region (IDR) results in enhanced immiscibility and multiphase formation. Interestingly, we found that oligomerization tunes the miscibility of IDRs in an asymmetric manner, with the effect being more pronounced when the IDR exhibiting stronger homotypic IDR interactions is oligomerized. Our findings suggest that oligomerization is a flexible biophysical mechanism which cells can exploit to tune the internal organization of biomolecular condensates and their associated biological functions.

Our understanding of how novel warning color traits evolve in natural populations is largely based on studies of reproductive stages and organisms with endogenously produced pigmentation. In these systems, genetic drift is often required for novel alleles to overcome strong purifying selection stemming from frequency-dependent predation and positive assortative mating. Here, we integrate data from field surveys, predation experiments, population genomics, and phenotypic correlations to explain the origin and maintenance of geographic variation in a diet-based larval pigmentation trait in the redheaded pine sawfly (Neodiprion lecontei), a pine-feeding hymenopteran. Although our experiments confirm that N. lecontei larvae are indeed aposematic-and therefore likely to experience frequency-dependent predation-our genomic data do not support a historical demographic scenario that would have facilitated the spread of an initially deleterious allele via drift. Additionally, significantly elevated differentiation at a known color locus suggests that geographic variation in larval color is currently maintained by selection. Together, these data suggest that the novel white morph likely spread via selection. However, white body color does not enhance aposematic displays, nor is it correlated with enhanced chemical defense or immune function. Instead, the derived white-bodied morph is disproportionately abundant on a pine species with a reduced carotenoid content relative to other pine hosts, suggesting that bottom-up selection via host plants may have driven divergence among populations. Overall, our results suggest that life stage and pigment source can have a substantial impact on the evolution of novel warning signals, highlighting the need to investigate diverse aposematic taxa to develop a comprehensive understanding of color variation in nature.

Objectives Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)–based heritability estimate (h2SNP) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10−9), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10−45) and Wnt signaling (adjusted P = 9.5 × 10−58). The heritability of PsA in this cohort was found to be moderate (h2SNP = 0.63), which was similar to the heritability of PsC (h2SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Objective: Telepsychology represents a promising approach to treatment for individuals and families encountering barriers to traditional face-to-face health care, especially in the challenging context of the 2019 coronavirus disease (COVID-19). Implementing the necessary infrastructure to sustain telepsychology programs within health care institutions requires detailed attention to a variety of domains. Despite the growing use of telepsychology, logistical considerations for the development of such programs are often unclear. Method: In order to clarify considerations regarding the use of telepsychology within partnering health care institutions, we describe the process of developing a telepsychology group intervention with parents of pediatric patients. Results: The development of a telepsychology program for parents at a large children's health care institution is discussed across four developmental phases: (a) curriculum development, (b) clinical framework, (c) program logistics, and (d) protocol and training infrastructure. Conclusion: Due to the growing need for telepsychological interventions for parents, both practitioners and health care institutions are tasked with collaborating to develop well-designed programs that are aligned with clinical best practices.

Movement of the lower jaw, a common behavior observed among vertebrates, is required for eating and processing food. This movement is controlled by signals sent from the trigeminal motor nerve through neuromuscular junctions (NMJs) to the masticatory muscles. Dysfunctional jaw movements contribute to craniomandibular disorders, yet the pathophysiology of these disorders is not well understood, as limited studies have been conducted on the molecular mechanisms of jaw movement.Using erc1b/kimWe identified Erc1b/ERC1 as a novel component of a genetic pathway contributing to muscle organization, trigeminal nerve outgrowth, and NMJ spatial distribution during development that is required for jaw movement.

Background Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. Methods Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. Results Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p 0.86). Conclusions The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.

Cells compartmentalize their intracellular environment to orchestrate countless simultaneous biochemical processes. Many intracellular tasks rely on membrane-less organelles, multicomponent condensates that assemble by liquid-liquid phase separation. A decade of intensive research has provided a basic understanding of the biomolecular driving forces underlying the form and function of such organelles. Here we review the technologies enabling these developments, along with approaches to designing spatiotemporally actuated organelles based on multivalent low-affinity interactions. With these recent advances, it is now becoming possible both to modulate the properties of native condensates and to engineer entirely new structures, with the potential for widespread biomedical and biotechnological applications.

Background Cigarette smoking remains the leading cause of preventable illness and death, underscoring ongoing need for evidence-based solutions. Pivot, a US Clinical Practice Guideline–based mobile smoking cessation program, comprises a personal carbon monoxide breath sensor; a smartphone app; in-app, text-based human-provided coaching; nicotine replacement therapy; and a moderated web-based community. Promising Pivot cohort studies have established the foundation for comparative assessment. Objective This study aimed to compare engagement, retention, attitudes toward quitting smoking, smoking behavior, and participant feedback between Pivot and QuitGuide, a US Clinical Practice Guideline–based smoking cessation smartphone app from the National Cancer Institute. Methods In this remote pilot randomized controlled trial, cigarette smokers in the United States were recruited on the web and randomized to Pivot or QuitGuide. Participants were offered 12 weeks of free nicotine replacement therapy. Data were self-reported via weekly web-based questionnaires for 12 weeks and at 26 weeks. Outcomes included engagement and retention, attitudes toward quitting smoking, smoking behavior, and participant feedback. The primary outcome was self-reported app openings at 12 weeks. Cessation outcomes included self-reported 7- and 30-day point prevalence abstinence (PPA), abstinence from all tobacco products, and continuous abstinence at 12 and 26 weeks. PPA and continuous abstinence were biovalidated via breath carbon monoxide samples. Results Participants comprised 188 smokers (94 Pivot and 94 QuitGuide): mean age 46.4 (SD 9.2) years, 104 (55.3%) women, 128 (68.1%) White individuals, and mean cigarettes per day 17.6 (SD 9.0). Engagement via mean “total app openings through 12 weeks” (primary outcome) was Pivot, 157.9 (SD 210.6) versus QuitGuide, 86.5 (SD 66.3; P Conclusions In this randomized controlled trial comparing the app-based smoking cessation programs Pivot and QuitGuide, Pivot participants had higher engagement and biovalidated cessation rates and more favorable user feedback at 12 and 26 weeks. These findings support Pivot as an effective, durable mobile smoking cessation program. Trial Registration ClinicalTrials.gov NCT04955639; https://clinicaltrials.gov/ct2/show/NCT04955639

Genetic screens are used to identify genes involved in specific biological processes. An EMS mutagenesis screen in Drosophila melanogaster identified growth control phenotypes in the developing eye. One mutant line from this screen, H.3.2, was phenotypically characterized using the FLP/FRT system and genetically mapped by complementation analysis and genomic sequencing by undergraduate students participating in the multi-institution Fly-CURE consortium. H.3.2 was found to have a nonsense mutation in short stop (shot), anortholog of the mammalian spectraplakin dystonin (DST). shot and DST are involved in cytoskeletal organization and play roles during cell growth and proliferation.

Background: Arthrodesis of the first metatarsophalangeal (MTP) joint has been shown to be effective in alleviating pain and correcting deformity in hallux rigidus. However, outcomes in specific sports and physical activities remain unclear. The aim of this study was to assess sports and physical activities in young patients following first MTP joint arthrodesis and to compare these results with clinical outcomes. Methods: Patients between ages 18 and 55 years who underwent MTP arthrodesis were identified by review of a prospective registry. Fifty of 73 eligible patients (68%) were reached for follow-up at a mean of 5.1 (range, 2.2-10.2) years with a mean age at surgery of 49.7 (range, 23-55) years. Physical activity was evaluated with a previously developed sports-specific, patient-administered questionnaire. Clinical outcomes were evaluated with the Foot and Ankle Outcome Score (FAOS). Results: Patients participated in 22 different sports and physical activities. The most common were walking, biking, weightlifting, swimming, running, and golf. Compared to preoperatively, patients rated 27.4% of activities as less difficult, 51.2% as the same, and 21.4% as more difficult. Patients returned to 44.6% of preoperative physical activities in less than 6 months and reached their maximal level of participation in 88.6% of physical activities. Ninety-six percent of patients (48/50) were satisfied with the procedure regarding return to sports and physical activities. Improvements in the FAOS Symptoms subscore were associated with increased postoperative running and walking duration, and improvements in FAOS Pain subscores were associated with greater patient satisfaction. Conclusion: Patients were able to participate in a wide variety of sports and physical activities postoperatively. Some patients reported increased difficulty, but were nonetheless satisfied with the procedure regarding physical activity participation. These findings suggest that first MTP joint arthrodesis is a reasonable option in young, active patients, and may be used to guide postoperative expectations. Level of Evidence: Level IV, retrospective case series.

Neuronal activity is a potent extrinsic regulator of oligodendrocyte generation and central nervous system myelination. Clinically, repetitive transcranial magnetic stimulation (rTMS) is delivered to noninvasively modulate neuronal activity; however, the ability of rTMS to facilitate adaptive myelination has not been explored. By performing cre‐lox lineage tracing, to follow the fate of oligodendrocyte progenitor cells in the adult mouse brain, we determined that low intensity rTMS (LI‐rTMS), administered as an intermittent theta burst stimulation, but not as a continuous theta burst or 10 Hz stimulation, increased the number of newborn oligodendrocytes in the adult mouse cortex. LI‐rTMS did not alter oligodendrogenesis per se, but instead increased cell survival and enhanced myelination. These data suggest that LI‐rTMS can be used to noninvasively promote myelin addition to the brain, which has potential implications for the treatment of demyelinating diseases such as multiple sclerosis., Main Points The impact that low intensity repetitive transcranial magnetic stimulation (LI‐rTMS) has on cells of the oligodendrocyte lineage is stimulation frequency and cell‐stage specific.LI‐rTMS does not affect oligodendrocyte progenitor cell proliferation or density.LI‐rTMS, delivered in an intermittent theta burst pattern, promotes the survival of premyelinating oligodendrocytes and enhances myelin internode extension by newly myelinating oligodendrocytes.

Background: In synergy with the mounting scientific evidence for the capacity of recovery after spinal cord injury (SCI) and training, new evidence-based therapies advancing neuromuscular recovery are emerging. There is a parallel need for outcome instruments that specifically address recovery. The Pediatric Neuromuscular Recovery Scale (Pediatric NRS) is one example with established content validity to assess neuromuscular capacity within task performance. Objective: The objective of this study was to determine interrater reliability of the Pediatric NRS to classify motor capacity in children after SCI. Methods: Pediatric physicians (3), occupational therapists (5), and physical therapists (6) received standardized training in scoring the scale, then rated video assessments of 32 children post SCI, 2–12 years of age, 78% non-ambulatory. Interrater reliability was analyzed using Kendall coefficient of concordance for individual Pediatric NRS items and overall score. Results: The interrater reliability coefficient was determined to be near 1 for the overall Pediatric NRS score (ICC = 0.966; 95% CI, 0.89–0.98). Twelve of 16 individual items exhibited high concordance coefficients (Kendall's W ≥ 0.8) and four items demonstrated concordance coefficients, < 0.8 and > 0.69. Interrater reliability was equivalent among groups defined by age and neurological level, but lower among non-ambulatory individuals. Conclusion: Strong interrater reliability was demonstrated by pediatric clinicians who scored children with SCI using the Pediatric NRS.

Background: Activity-based therapies aim to improve neuromuscular capacity after spinal cord injury (SCI). Objective: The purpose of this prospective study was to report the impact of Activity-based Locomotor Training (AB-LT) on neuromuscular capacity in pediatric patients with SCI. Methods: Participants were enrolled for their first episode of AB-LT for a minimum of 60 daily, 1.5-hour sessions. The Segmental Assessment of Trunk Control (SATCo) and the Pediatric Neuromuscular Recovery Scale (Pediatric NRS) were assessed initially, every 20 sessions, and post 60 sessions. Results: Twenty-six consecutive patients, mean age 5 years (SD = 3), completed a mean 55 sessions (SD = 4) within 63 weekdays (SD = 9). The Pediatric NRS total score improved significantly, adjusted mean 11.4, from initial to post-60 sessions (p < .05) with an average adjusted evaluation-to-evaluation 3.7 change. SATCo scores improved significantly across 60 sessions, mean change 5.2, an estimated 1.7 change between evaluations (p < .05). Age at enrollment and chronicity had no effect; however, initial neuromuscular capacity scores were negatively correlated with change scores (p < .05). Conclusion: Sixty AB-LT sessions significantly improved trunk and neuromuscular capacity in children with SCI, regardless of age or chronicity at enrollment. Patients with lower initial scores made greater improvements than patients with higher initial neuromuscular capacity. Anecdotal parent reports of their child's functional change in the home and community highlight the synergy between quantitative change in neuromuscular capacity and meaningful, improved quality of life and the need for formal investigation of this relationship.

Background People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs. Objectives To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI. Methods Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes. Result Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD. Conclusions In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.

The development of new control strategies for quadrotor types of unmanned aerial systems is important in meeting the existing research needs to handle undesired uncertainties for more satisfactory control systems. A Neural Network-Proportional plus Velocity (NN-PV) controller is proposed for improved stability and robustness in the presence of external disturbances and model parametric uncertainty. The experimental validation is conducted using Quanser's Autonomous Vehicles Research Studio (AVRS) for multiple-vehicle testing. The developed controller is validated through indoor flight tests. The experimental approach provides understanding and the manipulation of the controller (Angle Mode) of the QDrone. The performance of the control system demonstrates improvement of the speed and stability for the formation flight of two drones. The work presented produces a flexible, robust, and effective control system model that leads to expanded stability and reduces the effect of disturbances.

Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a prior trauma history, including child abuse, and the severity of initial trauma reactions. Participants (N = 81) were recruited and assessed at the emergency department of a large urban hospital in Miami and serum levels of common drugs of abuse were measured. Although substance use appeared to be a risk factor for trauma exposure, neither self-reported nor blood toxicology influenced the development of PTSD. Positive toxicology screens were more likely to be associated with a diagnosis of substance abuse or dependence, χ2 (1) = 4.11, p = .04. Participants with a history of physical abuse were more likely to have a positive toxicology screen, χ2 (1) = 4.03, p = .05. The majority of our trauma-exposed subjects (66%) were found to be positive for one or more illicit substances at presentation at the ED. The current findings provide support for the “high risk” hypothesis in which substance use is associated with increased trauma exposure.

Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.