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Regeneration requires cellular proliferation, differentiation, and other processes that are regulated by secreted cues originating from cells in the local environment. Recent studies suggest that signaling by extracellular vesicles (EVs), another mode of paracrine communication, may also play a significant role in coordinating cellular behaviors during regeneration. EVs are nanoparticles composed of a lipid bilayer enclosing proteins, nucleic acids, lipids, and other metabolites, and are secreted by most cell types. Upon EV uptake by target cells, EV cargo can influence diverse cellular behaviors during regeneration, including cell survival, immune responses, extracellular matrix remodeling, proliferation, migration, and differentiation. In this review, we briefly introduce the history of EV research and EV biogenesis. Then, we review current understanding of how EVs regulate cellular behaviors during regeneration derived from numerous studies of stem cell-derived EVs in mammalian injury models. Finally, we discuss the potential of other established and emerging research organisms to expand our mechanistic knowledge of basic EV biology, how injury modulates EV biogenesis, cellular sources of EVs in vivo , and the roles of EVs in organisms with greater regenerative capacity.

Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT−) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may aid in diagnosis of CT-occult TBI. The current manuscript aimed to evaluate the diagnostic, therapeutic and risk-stratification utility of known biomarkers and intracranial MRI pathology. Materials and Methods: The PubMed database was queried with keywords (plasma OR serum) AND (biomarker OR marker OR protein) AND (brain injury/trauma OR head injury/trauma OR concussion) AND (magnetic resonance imaging/MRI) (title/abstract) in English. Seventeen articles on TBI biomarkers and MRI were included: S100 calcium-binding protein B (S100B; N = 6), glial fibrillary acidic protein (GFAP; N = 3), GFAP/ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1; N = 2), Tau (N = 2), neurofilament-light (NF-L; N = 2), alpha-synuclein (N = 1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor peptide (AMPAR; N = 1). Results: Acute GFAP distinguished CT−/MRI+ from CT−/MRI− (AUC = 0.777, 0.852 at 9–16 h). GFAP discriminated CT−/diffuse axonal injury (DAI+) from controls (AUC = 0.903). Tau correlated directly with number of head strikes and inversely with white matter fractional anisotropy (FA), and a cutoff > 1.5 pg/mL discriminated between DAI+ and DAI− (sensitivity = 74%/specificity = 69%). NF-L had 100% discrimination of DAI in severe TBI and correlated with FA. Low alpha-synuclein was associated with poorer functional connectivity. AMPAR cutoff > 0.4 ng/mL had a sensitivity of 91% and a specificity of 92% for concussion and was associated with minor MRI findings. Low/undetectable S100B had a high negative predictive value for CT/MRI pathology. UCH-L1 showed no notable correlations with MRI. Conclusions: An acute circulating biomarker capable of discriminating intracranial MRI abnormalities is critical to establishing diagnosis for CT-occult TBI and can triage patients who may benefit from outpatient MRI, surveillance and/or follow up with TBI specialists. GFAP has shown diagnostic potential for MRI findings such as DAI and awaits further validation. Tau shows promise in detecting DAI and disrupted functional connectivity. Candidate biomarkers should be evaluated within the context of analytical performance of the assays used, as well as the post-injury timeframe for blood collection relative to MRI abnormalities.

Introduction: Traumatic brain injury (TBI) remains a primary cause of pediatric morbidity. The improved characterization of healthcare disparities for pediatric TBI in United States (U.S.) rural communities is needed to advance care. Methods: The PubMed database was queried using keywords ((“brain/head trauma” OR “brain/head injury”) AND “rural/underserved” AND “pediatric/child”). All qualifying articles focusing on rural pediatric TBI, including the subtopics epidemiology (N = 3), intervention/healthcare cost (N = 6), and prevention (N = 1), were reviewed. Results: Rural pediatric TBIs were more likely to have increased trauma and head injury severity, with higher-velocity mechanisms (e.g., motor vehicle collisions). Rural patients were at risk of delays in care due to protracted transport times, inclement weather, and mis-triage to non-trauma centers. They were also more likely than urban patients to be unnecessarily transferred to another hospital, incurring greater costs. In general, rural centers had decreased access to mental health and/or specialist care, while the average healthcare costs were greater. Prevention efforts, such as mandating bicycle helmet use through education by the police department, showed improved compliance in children aged 5–12 years. Conclusions: U.S. rural pediatric patients are at higher risk of dangerous injury mechanisms, trauma severity, and TBI severity compared to urban. The barriers to care include protracted transport times, transfer to less-resourced centers, increased healthcare costs, missing data, and decreased access to mental health and/or specialty care during hospitalization and follow-up. Preventative efforts can be successful and will require an improved multidisciplinary awareness and education.

The most widely used attractant to capture adult female mosquitoes is CO 2 . However, there are also baits available on the market that emit a scent resembling human skin. These baits were specifically designed to attract highly anthropophilic species such as Aedes albopictus and Aedes aegypti . In this study, we compare the effectiveness of CDC traps baited either with CO 2 or with a commercial blend simulating skin odor, BG-Sweetscent, for trapping female mosquitoes during daylight hours in an urban reserve in the City of Buenos Aires. We employed a hurdle generalized linear mixed model to analyze trap capture probability and the number of mosquitoes captured per hour, considering the effects of attractant, mosquito species, and their interaction. Traps baited with CO 2 captured ten mosquito species, while those baited with BG-Sweetscent captured six in overall significantly lower abundance. The odds of capturing mosquitoes were 292% higher for the CO 2 -baited traps than for those baited with BG-Sweetscent. No evidence of a combined effect of attractant type and species on female mosquito captures per hour was found. Results indicated that CDC traps baited with CO 2 were more effective than those baited with BG-Sweetscent in capturing more mosquito species and a higher number of mosquitoes within each species, even if the species captured with CO 2 exhibited a certain level of anthropophilia. This result has practical implications for mosquito surveillance and control in urban natural reserves.

Extracellular vesicles (EVs) are secreted nanoparticles composed of a lipid bilayer that carry lipid, protein, and nucleic acid cargo between cells as a mode of intercellular communication. Although EVs can promote tissue repair in mammals, their roles in animals with greater regenerative capacity are not well understood. Planarian flatworms are capable of whole‐body regeneration due to pluripotent somatic stem cells called neoblasts that proliferate in response to injury. Here, using transmission electron microscopy, nanoparticle tracking analysis, and protein content examination, we showed that EVs enriched from the tissues of the planarian Schmidtea mediterranea had similar morphology and size as other eukaryotic EVs, and that these EVs carried orthologs of the conserved EV biogenesis regulators ALIX and TSG101. PKH67‐labeled EVs were taken up efficiently by planarian cells, including S/G2 neoblasts, G1 neoblasts/early progeny, and differentiated cells. When injected into living planarians, EVs from regenerating tissue fragments enhanced the upregulation of neoblast‐enriched and proliferation‐related transcripts. In addition, EV injection increased the number of F‐ara‐EdU‐labelled cells by 49% as compared to buffer injection only. Our findings demonstrate that regenerating planarians produce EVs that promote stem cell proliferation, and suggest the planarian as an amenable in vivo model for the study of EV function during regeneration. We enriched EVs from the tissue of the planarian flatworm Schmidtea mediterranea, which is capable of whole‐body regeneration. We characterized these EVs using NTA, TEM and Capillary Western Blot, and demonstrated that planarian cells take up EVs. Then, we used RNA‐Seq, F‐ara‐EdU labelling and flow cytometry to show that microinjection of EVs stimulates proliferation of planarian pluripotent stem cells in vivo.

Experimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis. EAU spontaneously resolves and is marked by ocular autoantigen-specific regulatory immunity in the spleen. Kallikrein binding protein (KBP) or kallistatin is a serine proteinase inhibitor that inhibits angiogenesis and inflammation, but its role in autoimmune uveitis has not been explored. We report that T cells activation is inhibited and EAU is attenuated in human KBP (HKBP) mice with no significant difference in the Treg population that we previously identified both before and after recovery from EAU. Moreover, following EAU immunization HKBP mice have potent ocular autoantigen specific regulatory immunity that is functionally suppressive.

The Dark Matter Daily Modulation experiment (DMSQUARE) seeks for dark matter interactions with a Skipper CCD. It is currently running at surface level in Bariloche, Argentina, and will be moved to a shallow underground site at Sierra Grande, Argentina in November 2021. The low threshold achieved by Skipper CCDs allows to search for electron recoil events with an ionization energy down to 1.2 eV. In order to extract a potential dark matter signal from noise at the single electron level, we propose to search for a diurnal modulation of events, resulting from the potential interaction of the dark matter wind with the particles in the Earth. Depending on the model, mass and cross-section, this modulation can be maximum at 40deg of latitude in the Southern Hemisphere, where DMSQUARE is operated. In this article we present the experiment, report preliminary results with a prototype Skipper CCD taking data at surface level and comment on future prospects.

Understanding the underlying genetic bases of yield‐related selection and distinguishing these changes from genetic drift are critical for both improved understanding and future success of plant breeding. Soybean [Glycine max (L.) Merr.] is a key species for world food security, yet knowledge of the mechanism of selective breeding in soybean, such as the century‐long program of artificial selection in U.S. soybean germplasm, is currently limited to certain genes and loci. Here, we identify genome‐wide signatures of selection in separate populations of soybean subjected to artificial selection for increased yield by multiple breeding programs in the United States. We compared the alternative soybean breeding population (AGP) created by USDA‐ARS to the conventional public soybean lines (CGP) developed at three different stages of breeding (ancestral, intermediate, and elite) to identify shared signatures of selection and differentiate these from drift. The results showed a strong selection for specific haplotypes identified by single site frequency and haplotype homozygosity methods. A set of common selection signatures was identified in both AGP and CGP that supports the hypothesis that separate breeding programs within similar environments coalesce on the fixation of the same key haplotypes. Signatures unique to each breeding program were observed. These results raise the possibility that selection analysis can allow the identification of favorable alleles to enhance directed breeding approaches. Core Ideas Specific loci are under selection for key traits during soybean breeding. These loci can be detected and mapped by analysis of signatures of selection in the population. Signatures of drift versus selection can be differentiated by the use of parallel, separate populations that are under selection for the same traits in the same environment. Identification of desirable traits from different populations can add to the overall diversity of the elite soybean gene pool. Plain Language Summary Understanding how plants achieve higher yields through selective breeding and distinguishing these changes from random genetic variations is crucial for advancing plant breeding. Soybeans play a vital role in global food security, but our knowledge of how selective breeding actually works is currently limited to just a few genes. In this study, we investigated the genome‐wide signs of selection in soybean populations that underwent artificial selection for increased yield in multiple U.S. breeding programs. By comparing the USDA‐ARS‐created alternative soybean breeding population to conventional public soybean lines at different breeding stages, we aimed to identify common selection patterns and distinguish them from random genetic drift. Our findings revealed a strong preference for specific genetic variations in higher yielding soybeans derived from both the AGP and CGP, indicating that breeding programs favor the same key genetic variations even when starting from different plants.

Extracellular vesicles (EVs) are secreted nanoparticles composed of a lipid bilayer that carry lipid, protein, and nucleic acid cargo between cells as a mode of intercellular communication. Although EVs can promote tissue repair in mammals, their roles in animals with greater regenerative capacity are not well understood. Planarian flatworms are capable of whole body regeneration due to pluripotent somatic stem cells called neoblasts that proliferate in response to injury. Here, using transmission electron microscopy, nanoparticle tracking analysis, and protein content examination, we showed that EVs enriched from the tissues of the planarian had similar morphology and size as other eukaryotic EVs, and that these EVs carried orthologs of the conserved EV biogenesis regulators ALIX and TSG101. PKH67-labeled EVs were taken up more quickly by S/G2 neoblasts than G1 neoblasts/early progeny and differentiated cells. When injected into living planarians, EVs from regenerating tissue fragments enhanced upregulation of neoblast-associated transcripts. In addition, EV injection increased the number of -EdU-labelled cells by 49% as compared to buffer injection only. Our findings demonstrate that regenerating planarians produce EVs that promote stem cell proliferation, and suggest the planarian as an amenable model for the study of EV function during regeneration.

Rationale: Pregnancy, especially for first-time parents, can be filled with a lot of anxiety and stress. Women often experience hormonal changes as well as adapting to physical bodily changes, which can impact the pregnancy, and the mother-coparent relationship. Pregnancy during the Covid-19 pandemic likely further contributes to expectant couples’ experience. However, little is known about the impact of Covid-19 related stressors on pregnant women and partners, and the existing literature has largely focused solely on challenges.Objective: The aim of the current study is to describe the nature of expectant parents’ experiences with pregnancy and childbirth during the Covid-19 pandemic, with a particular focus on identifying individual and couple stressors and coping strategies.Methods: 11 participants, 6 mothers and 5 co-parenting partners, completed questionnaires and participated in a qualitative interview querying them about their experience being pregnancy during the Covid-19 pandemic, pandemic related stressors, coping strategies, and navigating the transition to parenthood as a couple.Results: Qualitative themes emerging through the data analysis indicated not only common challenges (i.e., stress related to uncertainty, not being able to attend prenatal visits as a couple and fears about the impact of covid-19 on the pregnancy or baby), but also coping strategies. Coping strategies included couple outdoor walks, drawing on spousal and family support, faith/religiosity, focusing on adaptation rather than challenges, and viewing increased time together due to working from home during the pandemic as an opportunity to grow closer as a couple.Implications: Coping strategies identified by couples who were pregnant during the Covid-19 pandemic may help couples undergoing diverse stressors, as well as having the potential to help couples who are pregnant during the current context of ongoing Covid-19 changes. Research findings also have implications for public policy.