A splicing isoform of GPR56 mediates microglial synaptic refinement via phosphatidylserine binding.

Developmental synaptic remodeling is important for the formation of precise neural circuitry, and its disruption has been linked to neurodevelopmental disorders such as autism and schizophrenia. Microglia prune synapses, but integration of this synapse pruning with overlapping and concurrent neurodevelopmental processes, remains elusive. Adhesion G protein-coupled receptor ADGRG1/GPR56 controls multiple aspects of brain development in a cell type-specific manner: In neural progenitor cells, GPR56 regulates cortical lamination, whereas in oligodendrocyte progenitor cells, GPR56 controls developmental myelination and myelin repair. Here, we show that microglial GPR56 maintains appropriate synaptic numbers in several brain regions in a time- and circuit-dependent fashion. Phosphatidylserine (PS) on presynaptic elements binds GPR56 in a domain-specific manner, and microglia-specific deletion of Gpr56 leads to increased synapses as a result of reduced microglial engulfment of PS+ presynaptic inputs. Remarkably, a particular alternatively spliced isoform of GPR56 is selectively required for microglia-mediated synaptic pruning. Our present data provide a ligand- and isoform-specific mechanism underlying microglial GPR56-mediated synapse pruning in the context of complex neurodevelopmental processes.

Preservation of male fertility in patients undergoing pelvic irradiation.

As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy.

Computational simulations establish a novel transducer array placement arrangement that extends delivery of therapeutic TTFields to the infratentorium of patients with brainstem gliomas.

BACKGROUND AND PURPOSE: Tumor treating fields (TTFields) are a non-invasive, efficacious treatment modality currently approved for supratentorial glioblastomas. Despite their ability to improve overall survival in supratentorial tumors, the current placement of arrays is limited to the supratentorial head, precluding its use in infratentorial tumors. Infratentorial malignancies are in need of new therapy modalities given their poor prognoses in both children and adults. The aim of this research is to determine whether rearrangement of TTFields may allow for management of infratentorial tumors. MATERIALS AND METHODS: Delivery of TTFields using Novocure's prototype Optune™ device human male head model was simulated based on brain MRIs from patients with brainstem gliomas to develop a novel array layout designed to extend adequate infratentorial coverage. RESULTS: Array placement on the vertex, bilateral posterolateral occiput, and superior-posterior neck achieved intensities above 1.1 V/cm (average 1.7 V/cm; maximum 2.3 V/cm) in the vertical field direction and above 1 V/cm (average 2 V/cm; maximum 2.8 V/cm) in the horizontal field direction of the infratentorium. The calculated field intensity within the simulated tumors were in the therapeutic range and demonstrated the effective delivery of TTFields to the infratentorial brain. CONCLUSIONS: Our findings suggest that rearrangement of the TTFields standard array with placement of electrodes on the vertex, bilateral posterolateral occiput, and superior-posterior neck allows for adequate electric field distribution in the infratentorium that is within the therapeutic range.

Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells.

OBJECTIVES: The present study was carried out to determine if lyophilized açaí fruit pulp (genus, Euterpe), rich in polyphenols and other bioactive antioxidant and anti-inflammatory phytochemicals, is efficacious in reversing age-related cognitive deficits in aged rats. METHODS: The diets of 19-month-old Fischer 344 rats were supplemented for 8 weeks with 2% Euterpe oleracea (EO), Euterpe precatoria (EP), or a control diet. Rats were tested in the Morris water maze and then blood serum from the rats was used to assess inflammatory responses of BV-2 microglial cells. RESULTS: After 8 weeks of dietary supplementation with 2% EO or EP, rats demonstrated improved working memory in the Morris water maze, relative to controls; however, only the EO diet improved reference memory. BV-2 microglial cells treated with blood serum collected from EO-fed rats produced less nitric oxide (NO) than control-fed rats. Serum from both EO- and EP-fed rats reduced tumor necrosis factor-alpha (TNF-α). There is a relationship between performance in the water maze and the production of NO and TNF-α by serum-treated BV-2 cells, such that serum from rats with better performance was more protective against inflammatory signaling. DISCUSSION: Protection of memory during aging by supplementation of lyophilized açaí fruit pulp added to the diet may result from its ability to influence antioxidant and anti-inflammatory signaling.

Capital breeding and allocation to life-history demands are highly plastic in lizards.

The use of stored resources to fuel reproduction, growth, and self-maintenance in the face of uncertain nutrient availability is a tactic common to many organisms. The degree to which organisms rely on stored resources in response to varied nutrients, however, is not well quantified. In this study, we used stable isotope methods to quantify the use of stored versus incoming nutrients to fuel growth and egg and fat body development in lizards under differing nutrient regimes. We found that the degree of capital breeding is a function of an individual's body condition. Furthermore, given sufficient income, lizards in poor condition can allocate simultaneously to storage, growth, and reproduction and "catch up" in body size and reproductive allocation to better-conditioned animals. Using natural variation in the δ(13)C of environmental nutrient pulses, we also found a high degree of variation in capital breeding in a lizard community. These findings demonstrate that capital breeding in lizards is not simply a one-way flow of endogenous stores to eggs but is a function of the condition state of individuals and seasonal nutrient availability. We use our findings to comment on capital breeding in lizards and the utility of the capital-income concept in general.

Total recoil: perch compliance alters jumping performance and kinematics in green anole lizards (Anolis carolinensis).

Jumping is a common form of locomotion for many arboreal animals. Many species of the arboreal lizard genus Anolis occupy habitats in which they must jump to and from unsteady perches, e.g. narrow branches, vines, grass and leaves. Anoles therefore often use compliant perches that could alter jump performance. In this study we conducted a small survey of the compliance of perches used by the arboreal green anole Anolis carolinensis in the wild (N=54 perches) and then, using perches within the range of compliances used by this species, investigated how perch compliance (flexibility) affects the key jumping variables jump distance, takeoff duration, takeoff angle, takeoff speed and landing angle in A. carolinensis in the laboratory (N=11). We observed that lizards lost contact with compliant horizontal perches prior to perch recoil, and increased perch compliance resulted in decreased jump distance and takeoff speed, likely because of the loss of kinetic energy to the flexion of the perch. However, the most striking effect of perch compliance was an unexpected one; perch recoil following takeoff resulted in the lizards being struck on the tail by the perch, even on the narrowest perches. This interaction between the perch and the tail significantly altered body positioning during flight and landing. These results suggest that although the use of compliant perches in the wild is common for this species, jumping from these perches is potentially costly and may affect survival and behavior, particularly in the largest individuals.

Epidemiologic trends of multiple sclerosis in Puerto Rico (2013-2020).

BACKGROUND: Previous studies have demonstrated higher multiple sclerosis (MS) incidence and prevalence in Puerto Rico (PR) than in other Caribbean and Latin American countries. Our objectives are to update the epidemiologic trends in MS incidence and prevalence rates for PR from 2017 through 2020 and compare them to prior rate data from 2013 to 2016. METHODS: We used the Puerto Rico MS Foundation's registry (PRMS Registry) data to identify all newly diagnosed MS cases between January 2017 and December 2020. The study population included 568 MS patients, 406 women and 162 men living in PR. All individuals were 18 years and older and met the 2017 revised McDonald criteria for MS diagnosis. In addition, age- and sex-standardized incidence rates were estimated. RESULTS: A total of 568 new MS cases were diagnosed in Puerto Rico between 2017 and 2020. The 2020 MS cumulative prevalence for Puerto Rico was 95.3/100,000 (95% CI: 91.6, 99.1), higher than previously reported. The age- and sex-standardized MS incidence rate for Puerto Rico decreased from 6.5/100,000 (2017) to 6.3/100,000 (2020). The annual age-standardized MS incidence rates declined for females: from 9.5/100,000 (2017) to 8.2/100,000 (2020) but increased for males from 3.6/100,000 to 4.6/100,000 during the same period. CONCLUSION: These incidence and prevalence rates are among the highest reported among Caribbean and Latin American countries. A peak in the age- and sex-standardized MS incidence rate was observed after hurricane María (2018) and a decline during the first year of the COVID-19 pandemic (2020). Further investigation is needed to determine whether there was a causal relationship between the fluctuations observed and those natural events.

Maternal immune activation in mice disrupts proteostasis in the fetal brain.

Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.

Genital morphology associated with mating strategy in the polymorphic lizard, Uta stansburiana.

Sexual selection can lead to rapid evolution of sexual traits and striking morphological diversity across taxa. In populations where competition for mates is intense, males sometimes evolve distinct behavioral strategies along with morphological differences that help them secure mating opportunities. Strong postcopulatory selection and differential resource allocation across male strategy type can result in strategy-specific differences in sexual traits, such as sperm morphology, ejaculate components, and testis size. Some polymorphic species also have strategy-specific genital morphology. Thus far, among vertebrates, this has only been observed in fish. Here, we present the first morphological description of the intromittant copulatory organ, the hemipenis, of the three mating types of the side-blotched lizard, Uta stansburiana, from a population that exhibits alternative mating strategies. We found that the isometrically scaling hemipenis was shortest in the nonterritorial (yellow) morph that sneaks copulations with other males' mates. Although the hemipenes were generally the same shape across morphs, the usurping territorial (orange) morph had a significantly wider apical horn than the nonterritorial sneaker morph. Sneaker males also had smaller relative body masses than both the mate-guarding (blue) morph and the usurper morph, and shorter tibia than the usurper morph. This study using a small sample of males suggests that strong sexual selection may drive genital trait differentiation across morphs within populations of terrestrial vertebrates.

Geckos as Springs: Mechanics Explain Across-Species Scaling of Adhesion.

One of the central controversies regarding the evolution of adhesion concerns how adhesive force scales as animals change in size, either among or within species. A widely held view is that as animals become larger, the primary mechanism that enables them to climb is increasing pad area. However, prior studies show that much of the variation in maximum adhesive force remains unexplained, even when area is accounted for. We tested the hypothesis that maximum adhesive force among pad-bearing gecko species is not solely dictated by toepad area, but also depends on the ratio of toepad area to gecko adhesive system compliance in the loading direction, where compliance (C) is the change in extension (Δ) relative to a change in force (F) while loading a gecko's adhesive system (C = dΔ/dF). Geckos are well-known for their ability to climb on a range of vertical and overhanging surfaces, and range in mass from several grams to over 300 grams, yet little is understood of the factors that enable adhesion to scale with body size. We examined the maximum adhesive force of six gecko species that vary in body size (~2-100 g). We also examined changes between juveniles and adults within a single species (Phelsuma grandis). We found that maximum adhesive force and toepad area increased with increasing gecko size, and that as gecko species become larger, their adhesive systems become significantly less compliant. Additionally, our hypothesis was supported, as the best predictor of maximum adhesive force was not toepad area or compliance alone, but the ratio of toepad area to compliance. We verified this result using a synthetic "model gecko" system comprised of synthetic adhesive pads attached to a glass substrate and a synthetic tendon (mechanical spring) of finite stiffness. Our data indicate that increases in toepad area as geckos become larger cannot fully account for increased adhesive abilities, and decreased compliance must be included to explain the scaling of adhesion in animals with dry adhesion systems.

Tissue-carbon incorporation rates in lizards: implications for ecological studies using stable isotopes in terrestrial ectotherms.

Carbon stable isotope (delta(13)C) analysis can be used to infer the origin and to estimate the flow of nutrient resources through animals and across ecological compartments. These applications require knowledge of the rates at which carbon is incorporated into animal tissues and diet-to-tissue discrimination factors (Delta(13)C). Studies of carbon dynamics in terrestrial vertebrates to date have focused almost solely on endothermic animals; ectotherms such as reptiles have received little attention. Here we determined carbon incorporation rates and Delta(13)C in tissues of prairie lizards (Sceloporus undulatus consobrinus) and collared lizards (Crotaphytus collaris). The smaller lizard, S. undulatus, had carbon retention times of 25 and 61 d in plasma and red blood cells (RBC), respectively, compared with 44 and 311 d for the larger C. collaris. Liver, muscle, and skin carbon retention times for S. undulatus were 21, 81, and 94 d. Growth contributed 9%-19% of the carbon incorporated into these tissues. This contribution is similar to endotherms measured at comparable developmental stages. Mean Delta(13)C for plasma (-0.2 per thousand +/- 0.4 per thousand Vienna Pee Dee Belemnite Standard) and RBCs (-1.3 per thousand +/- 0.8 per thousand) were similar to values reported for other vertebrates. Carbon incorporation rates for these ectotherms, however, are seven times slower than in similarly sized adult endotherms. Although a limited comparison with data for warm-water fishes suggests comparable incorporation rates between aquatic and terrestrial ectotherms, this study highlights the lack of experimental data for isotope dynamics in ectotherms across a range of temperatures, body sizes, and developmental stages.

Use of portable ultrasonography as a nondestructive method for estimating reproductive effort in lizards.

Obtaining population-level life history data such as egg and clutch size in reptiles has most often required that individuals be sacrificed. This prevents a reexamination of individuals over intra-annual and inter-annual time scales, limiting insight into the effects of varying environmental conditions on reproductive output. Here, we test the use of a laptop-sized portable ultrasound imaging system as a nondestructive means for quantifying reproductive investment in five species of lizards with a range of body sizes, forms and life histories. Ultrasound scans produced egg counts that were accurate for clutch sizes of two to seven eggs, and provided good estimates (within 5.5+/-1.69 eggs, mean +/- s.e.m., relative error 21%) for clutch sizes of between 18 and 41 eggs. Egg measurements using virtual calipers produced average egg volumes that deviated from actual volumes by 0.09+/-0.01 cm(3) (relative error 25.9%), and estimated clutch volumes that differed from actual volumes by 1.03+/-0.26 cm(3) (relative error 29.5%). We also monitored development in five lizard species and found that changes in follicle and egg size and degree of embryonic development can be measured over periods of just a few days.