Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure.

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS.

Model biological systems demonstrate the inducibility of pathways that strongly reduce cryoprotectant toxicity.

Cryoprotectant toxicity is a limiting factor for the cryopreservation of many living systems. We were moved to address this problem by the potential of organ vitrification to relieve the severe shortage of viable donor organs available for human transplantation. The M22 vitrification solution is presently the only solution that has enabled the vitrification and subsequent transplantation with survival of large mammalian organs, but its toxicity remains an obstacle to organ stockpiling for transplantation. We therefore undertook a series of exploratory studies to identify potential pretreatment interventions that might reduce the toxic effects of M22. Hormesis, in which a living system becomes more resistant to toxic stress after prior subtoxic exposure to a related stress, was investigated as a potential remedy for M22 toxicity in yeast, in the nematode worm C. elegans, and in mouse kidney slices. In yeast, heat shock pretreatment increased survival by 18-fold after exposure to formamide and by over 9-fold after exposure to M22 at 30 °C; at 0 °C and with two-step addition, treatment with 90% M22 resulted in 100% yeast survival. In nematodes, surveying a panel of pretreatment interventions revealed 3 that conferred nearly total protection from acute whole-worm M22-induced damage. One of these protective pretreatments (exposure to hydrogen peroxide) was applied to mouse kidney slices in vitro and was found to strongly protect nuclear and plasma membrane integrity in both cortical and medullary renal cells exposed to 75-100% M22 at room temperature for 40 min. These studies demonstrate for the first time that endogenous cellular defenses, conserved from yeast to mammals, can be marshalled to substantially ameliorate the toxic effects of one of the most toxic single cryoprotectants and the toxicity of the most concentrated vitrification solution so far described for whole organs.

Association of Depression, Comorbidities, and Sociodemographic Factors among Home Healthcare Recipients.

OBJECTIVES: More than 15 million individuals receive home health care (HHC) for chronic conditions, which allows them to maintain a level of independence and self-sufficiency. Although poor mental health can negatively impact health outcomes, little research has been done on the mental health of these individuals. METHODS: Utilizing National Health Interview Survey years 2019-2022, we ran a cross-sectional analysis to determine rates of depression among individuals who indicated that they utilized HHC services, based on their sociodemographic statuses and diagnosis, as well as their rate of depression by condition whether they utilized HHC services. RESULTS: HHC recipients were significantly more likely to be depressed if they reported being female, age 55-64, low income, low educational attainment, American Indian/Alaskan Native, Hispanic, or lived in a rural area. HHC recipients were more likely to be depressed than their non-HHC recipient counterparts. CONCLUSIONS: These results underscore the need for integrated mental health care in home health. Further, the financial burden of HHC, which may have an additional impact on stress, emphasizes the need for expanded accessibility of these services. CLINICAL IMPLICATIONS: General practitioners and home health professionals should inquire about mental health concerns of these care recipients, and treat or refer accordingly.

Association between steroid use and concussions among high school athletes: a cross-sectional analysis of the Youth Risk Behavior Surveillance System.

CONTEXT: In 2017, there were almost 2.5 million high school students who experienced a concussion while playing a sport, raising concern for the neurologic problems that they could face. Some of these athletes may seek to gain a competitive advantage in their sport by utilizing substances like steroids. However, steroid use can cause increased aggression and body mass index (BMI), which might lead to heightened risk for concussions. Despite extensive research, we found no previous evidence linking these two factors. OBJECTIVES: This analysis aims to investigate steroid use trends in high school athletes and to determine whether there is an association between steroid use and concussions in these athletes. METHODS: We conducted a cross-sectional analysis of the cumulative Youth Risk Behavior Surveillance System (YRBSS). Respondents were added if they participated in sports and answered the steroid and concussion prompts. Demographic variables were assessed including age, grade, BMI, gender, and race/ethnicity. RESULTS: We found that 3.7 % (n=2991) of high school athletes reported previous steroid use and that 20.7 % (n=2273) reported having sustained a concussion. There was a statistically significant difference in steroid use by race/ethnicity (p<0.001), with the highest rate of use (7.2 %) among American Indian/Alaska Natives (AI/AN). A significantly higher prevalence of steroid use occurred in athletes who were males (4.7 %) than females (2.5 %) and in athletes with a BMI>95 % (5.2 %) compared with those with a BMI between 85 and 95 % (3.9 %) and <85 % (3.5 %) (χ2=135.1, p<0.001 and χ2=16.3, p<0.001, respectively). Further, our results showed that the prevalence of steroid use among high school athletes decreased from 3.4 % in 1999 to 1.9 % in 2019, with the most drastic drop occurring between 2015 and 2019-declining 1.9 %. Whereas 19.6 % of athletes reported a concussion without steroid use, 54.6 % of steroid-utilizing athletes reported having experienced a concussion-a statistically significant finding (adjusted odds ratio [AOR]=4.3; 95 % CI: 3.2-5.9). Finally, compared with White athletes, we found that AI/AN athletes were significantly more likely to have sustained a concussion (AOR=2.3; 95 % CI=1.2-4.3). CONCLUSIONS: Although our study found decreasing rates of steroid use among high school athletes from 1999 through 2019, our results also show that steroid use is significantly associated with sustaining a concussion. Additionally, the data from YRBSS also demonstrates that AI/AN high school athletes are more likely to utilize steroids and sustain a concussion. Given the long-term consequences of traumatic brain injuries, we recommend that coaches should be aware of potential steroid use among players, and that coaches, athletic trainers, and physicians should all be aware of concussion protocols and remove players from games for evaluation when a concussion is suspected.

ER-dependent membrane repair of mycobacteria-induced vacuole damage.

IMPORTANCE: Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. Mycobacterium tuberculosis, the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the endoplasmic reticulum (ER)-Golgi lipid transfer protein OSBP8 in the Dictyostelium discoideum/Mycobacterium marinum system. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defense mechanism against intracellular pathogens such as M. tuberculosis.

Under peroxisome proliferation acyl-CoA oxidase coordinates with catalase to enhance ethanol metabolism.

In peroxisomes, acyl-CoA oxidase (ACOX) oxidizes fatty acids and produces H2O2, and the latter is decomposed by catalase. If ethanol is present, ethanol will be oxidized by catalase coupling with decomposition of H2O2. Peroxisome proliferator-activated receptor α (PPARα) agonist WY-14,643 escalated ethanol clearance, which was not observed in catalase knockout (Cat-/-) mice or partially blocked by an ACOX1 inhibitor. WY-14,643 induced peroxisome proliferation via peroxin 16 (PEX16). PEX16 liver-specific knockout (Pex16Alb-Cre) mice lack intact peroxisomes in liver, but catalase and ACOX1 were upregulated. Due to lacking intact peroxisomes, the upregulated catalase and ACOX1 in the Pex16Alb-Cre mice were mislocated in cytosol and microsomes, and the escalated ethanol clearance was not observed in the Pex16Alb-Cre mice, implicating that the intact functional peroxisomes are essential for ACOX1/catalase to metabolize ethanol. Alcohol-associated liver disease (ALD) is a spectrum of liver disorders ranging from alcoholic steatosis to steatohepatitis. WY-14,643 ameliorated alcoholic steatosis but tended to enhance alcoholic steatohepatitis. In mice lacking nuclear factor erythroid 2-related factor 2 (Nrf2-/-), WY-14,643 still induced PEX16, ACOX1 and catalase to escalate ethanol clearance and blunt alcoholic steatosis, which was not observed in the PPARα-absent Nrf2-/- mice (Pparα-/-/Nrf2-/-) mice, suggesting that WY-14,643 escalates ethanol clearance through PPARα but not through Nrf2.

SnRK2.10 kinase differentially modulates expression of hub WRKY transcription factors genes under salinity and oxidative stress in Arabidopsis thaliana.

In nature, all living organisms must continuously sense their surroundings and react to the occurring changes. In the cell, the information about these changes is transmitted to all cellular compartments, including the nucleus, by multiple phosphorylation cascades. Sucrose Non-Fermenting 1 Related Protein Kinases (SnRK2s) are plant-specific enzymes widely distributed across the plant kingdom and key players controlling abscisic acid (ABA)-dependent and ABA-independent signaling pathways in the plant response to osmotic stress and salinity. The main deleterious effects of salinity comprise water deficiency stress, disturbances in ion balance, and the accompanying appearance of oxidative stress. The reactive oxygen species (ROS) generated at the early stages of salt stress are involved in triggering intracellular signaling required for the fast stress response and modulation of gene expression. Here we established in Arabidopsis thaliana that salt stress or induction of ROS accumulation by treatment of plants with H2O2 or methyl viologen (MV) induces the expression of several genes encoding transcription factors (TFs) from the WRKY DNA-Binding Protein (WRKY) family. Their induction by salinity was dependent on SnRK2.10, an ABA non-activated kinase, as it was strongly reduced in snrk2.10 mutants. The effect of ROS was clearly dependent on their source. Following the H2O2 treatment, SnRK2.10 was activated in wild-type (wt) plants and the induction of the WRKY TFs expression was only moderate and was enhanced in snrk2.10 lines. In contrast, MV did not activate SnRK2.10 and the WRKY induction was very strong and was similar in wt and snrk2.10 plants. A bioinformatic analysis indicated that the WRKY33, WRKY40, WRKY46, and WRKY75 transcription factors have a similar target range comprising numerous stress-responsive protein kinases. Our results indicate that the stress-related functioning of SnRK2.10 is fine-tuned by the source and intracellular distribution of ROS and the co-occurrence of other stress factors.

Non-Small Cell Lung Cancer Treatment with Molecularly Targeted Therapy and Concurrent Radiotherapy-A Review.

Lung cancer is the leading cause of death worldwide for both men and women. Surgery can be offered as a radical treatment at stages I and II and selected cases of stage III (III A). Whereas at more advanced stages, combined modalities of treatment are applied: radiochemotherapy (IIIB) and molecularly targeted treatment (small molecule tyrosine kinase inhibitors, VEGF receptor inhibitors, monoclonal antibodies, and immunological treatment with monoclonal antibodies). Combination treatment, composed of radiotherapy and molecular therapy, is increasingly employed in locally advanced and metastatic lung cancer management. Recent studies have indicated a synergistic effect of such treatment and modification of immune response. The combination of immunotherapy and radiotherapy may result in the enhancement of the abscopal effect. Anti-angiogenic therapy, in combination with RT, is associated with high toxicity and should be not recommended. In this paper, the authors discuss the role of molecular treatment and the possibility of its concurrent use with radiotherapy in non-small cell lung cancer (NSCLC).

Discontinuation and nonpublication of clinical trials for the pharmacologic treatment of posttraumatic stress disorder among military veterans.

Failures by researchers and clinicians to overcome barriers in veteran health-related research may result in clinical trial (CT) discontinuation and nonpublication. Such outcomes are a waste of limited academic resources. To determine rates of discontinuation and nonpublication among CTs for posttraumatic stress disorder (PTSD) with pharmaceutical interventions specific to the veteran population, we performed a systematic search of registered trials in ClinicalTrials.gov for pharmaceutical interventions for the treatment of PTSD. Extracted study characteristics included sample size, study design, trial status, phase, and funding source. Studies were classified as completed or discontinued based on the status listed in ClinicalTrials.gov. Descriptive statistics of trials were reported, and associations of trial termination and nonpublication were assessed using logistic regression. The final sample included 54 CTs, 15 of which (27.8%) had not been published within the FDA's required timeframe, and 11 (20.4%) were discontinued. The total number of trial participants was 3,463, with a median of 37 (interquartile range: 15-92). Of the 54 trials, 12 (22.2%) were nonrandomized, and 42 (77.8%) were randomized. There were 25 (46.3%) trials that were in either Phase 3 or Phase 4, and 39 (72.2%) were government-funded. We found high rates of CT discontinuation and nonpublication among PTSD pharmaceutical intervention studies in veterans, as has been shown in other fields of research.

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.

The Structure of the Relationship between Physical Activity and Psychosocial Functioning of Women and Men during the COVID-19 Epidemic in Poland.

Since the coronavirus disease (COVID-19) pandemic is a serious crisis in many countries around the world, it is important to conduct empirical research aimed at identifying risks and factors protecting the functioning of people affected by it. For this reason, the goals of the present research were to determine the level of physical activity and the severity of symptoms characteristic of mental disorders, cognitive disorders and the quality of social functioning, as well as the structure of the relationship between physical activity and psychosocial functioning of 226 women and 226 men during the COVID-19 epidemic in Eastern Poland. The research was conducted using the IPAQ-SF Questionnaire, GHQ-28 Questionnaires, TUS Test-6/9 version, the original SFS Scale and a self-developed sociodemographic survey. The collected data indicate that women as compared to men show lower levels of weekly physical activity, walking, moderate activity, vigorous activity and quality of functioning in family relationships, but higher severity of mental health disorders, somatic symptoms, functional disorders, depressive symptoms, cognitive disorders, perceptual work disorders, attention deficits and higher quality of functioning in work relationships. On the other hand, the structural model indicates that physical activity, interacting with mental health disorders and cognitive disorders, is positively associated with the social functioning of the respondents, and gender is the moderator of the occurring dependencies. This suggests that physical activity adapted to the condition of health may be an important component of gender-individualized psychopreventive interventions.

Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review.

Photodynamic therapy is an unconventional yet increasingly common method of treating dermatological diseases and cancer that is implemented more often in adults than in children. Current clinical uses include treatment of actinic keratosis, superficial basal cell carcinomas, and acne. Despite its high efficiency, photodynamic therapy support supplements have recently been reported in the literature, including calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, and vitamin D3 cholecalciferol. In clinical trials, photodynamic therapy enhanced with vitamin D or D3 supplementation has been reported for treatment of squamous cell skin cancers, actinic keratosis, and psoriasis. Experimental research on the effect of photodynamic therapy with vitamin D or D3 has also been carried out in breast cancer cell lines and in animal models. The aim of this review is to evaluate the usefulness and effectiveness of vitamin D and D3 as supports for photodynamic therapy. For this purpose, the Pubmed and Scopus literature databases were searched. The search keyword was: "vitamin D in photodynamic therapy". In the analyzed articles (1979-2022), the authors found experimental evidence of a positive effect of vitamin D and D3 when used in conjunction with photodynamic therapy. An average of 6-30% (in one case, up to 10 times) increased response to photodynamic therapy was reported in combination with vitamin D and D3 as compared to photodynamic therapy alone. Implementing vitamin D and D3 as a supplement to photodynamic therapy is promising and may lead to further clinical trials and new clinical methodologies.

Photodynamic Therapy for Treatment of Disease in Children-A Review of the Literature.

Photodynamic therapy is a mode of treatment whereby local irradiation of an administered photosensitizer with light of a specific wavelength generates cytotoxic reactive oxygen species. Despite the upward trend in the popularity of this method in adults, it is not yet commonly used in the treatment of children. Due to certain limitations, underdeveloped treatment regimens and potential side effects, the use of photodynamic therapy in the pediatric population is still in the initial phases of evaluation in clinical trials. METHOD: This study is a review of articles in English from the databases PubMed and Web of Science retrieved by applying the search term "photodynamic therapy in children" from 2000-2020. RESULTS: Based on the literature review, we analyze selected pediatric clinical cases in which photodynamic therapy was used for treatment in children. Examples of photodynamic therapy for treatment of dermatological diseases, diseases of the mucosa of the upper respiratory tract, halitosis, eye diseases and brain tumors are described. The paper describes the effectiveness of anti-cancer photodynamic therapy, including its use in antibacterial therapy. CONCLUSIONS: The results of the analysis suggest the potential of photodynamic therapy for the treatment of various diseases in children.

Some Natural Photosensitizers and Their Medicinal Properties for Use in Photodynamic Therapy.

Despite significant advances in early diagnosis and treatment, cancer is one of the leading causes of death. Photodynamic therapy (PDT) is a therapy for the treatment of many diseases, including cancer. This therapy uses a combination of a photosensitizer (PS), light irradiation of appropriate length and molecular oxygen. The photodynamic effect kills cancer cells through apoptosis, necrosis, or autophagy of tumor cells. PDT is a promising approach for eliminating various cancers but is not yet as widely applied in therapy as conventional chemotherapy. Currently, natural compounds with photosensitizing properties are being discovered and identified. A reduced toxicity to healthy tissues and a lower incidence of side effects inspires scientists to seek natural PS for PDT. In this review, several groups of compounds with photoactive properties are presented. The use of natural products has been shown to be a fruitful approach in the discovery of novel pharmaceuticals. This review focused on the anticancer activity of furanocoumarins, polyacetylenes, thiophenes, tolyporphins, curcumins, alkaloid and anthraquinones in relation to the light-absorbing properties. Attention will be paid to their phototoxic and anti-cancer effects on various types of cancer.

Radiation Effects on Methamphetamine Pharmacokinetics and Pharmacodynamics in Rats.

BACKGROUND AND OBJECTIVES: Whole-body radiation exposure has been shown to alter the pharmacokinetics of certain drugs in both animal models and humans, but little is known about the effect of radiation on psychoactive medications. These drugs may have altered pharmacokinetics when administered during or after space travel or therapeutic or accidental radiation exposure, resulting in reduced efficacy or increased toxicity. METHODS: Methamphetamine was used to determine the effects of acutely administered 1, 3, and 6 Gy radiation on drug pharmacokinetics and pharmacodynamics. Male Wistar rats were exposed to 0, 1, 3, or 6 Gy X-ray radiation on day 0. The serum pharmacokinetics of subcutaneously administered 1 mg/kg methamphetamine was determined on day 3. Methamphetamine-induced (1 mg/kg) locomotor activity was measured on day 5. Brain methamphetamine concentrations were determined 2 h after methamphetamine administration (1 mg/kg) on day 6. Renal and hepatic serum biomarkers were assessed on days 3 and 6, with liver histology performed on day 6. RESULTS: While serum half-life and unchanged methamphetamine urine clearance were unaffected by any radiation dose, maximum methamphetamine concentrations and methamphetamine and amphetamine metabolite area under the serum concentration-time curve values from 0 to 300 min were significantly reduced after 6 Gy radiation exposure. Additionally, methamphetamine-induced locomotor activity and the brain to serum methamphetamine concentration ratio were significantly elevated after 6 Gy radiation. CONCLUSIONS: While 1-6 Gy radiation exposure did not affect methamphetamine elimination, 6 Gy exposure had effects on both subcutaneous absorption and brain distribution. These effects should be considered when administering drugs during or after radiation exposure.

Coping with pain: Polish versions of the Pain Coping Questionnaire for both children and parents.

Aim: This article presents the cultural adaptation and evaluation of the psychometric properties of the Polish versions of the Pain Coping Questionnaire for both children and parents. Materials & methods: The study involved children aged 12-17 years (n = 220), who experienced trauma-related pain, and their parents (n = 220). Results: In the questionnaire for children and parents, the Kaisera-Mayera-Olkina (KMO) measure of sample adequacy was 0.457 and 0.455, whereas Bartlett's test of sphericity: Chi-square = 1523.93, p < 0.001 and Chi-square = 1325.31, p < 0.001, returned a statistically significant result. Cronbach's alpha for the factors identified in both groups was between 0.833 and 0.904. Conclusion: The linguistic adaptation has shown that the Polish version of the Pain Coping Questionnaire meets the psychometric criteria for reliability and accuracy of the tool.

This study aimed to find out whether the Pain Coping Questionnaire (PCQ) in Poland, which was translated from an English version of the same questionnaire, was useful for the study of coping with pain by children and their parents. It is important that translated questionnaires be tested to make sure they are still effective in the new language. The PCQ was completed by children experiencing pain, and by their parents, and the results were evaluated. The results show that the PCQ is a questionnaire that can be effectively used in nursing care. The study also shows that children cope with pain most poorly when they rely on their emotions; the same is true also for parents. This research will make possible the use of an appropriate style of coping with pain for children and adolescents and will help in planning and implementing nursing care before the pain can become worse.

Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure.

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca+2 channel subunit α2δ-1, known to be involved in key developmental synaptogenic pathways, in mediating these effects. Pregnant mouse dams were treated orally with either the opioid drug buprenorphine (commonly used in medication-assisted treatment for substance use patients), gabapentin (neuropathic pain drug that binds to α2δ-1 and has been increasingly co-abused with opioids), a combination of both drugs, or vehicle daily from gestational day 6 until postnatal day 11. Confocal fluorescence immunohistochemistry (IHC) imaging of the brains of the resulting wild-type (WT) pups at postnatal day 21 revealed a number of significant alterations in excitatory and inhibitory synaptic populations within the anterior cingulate cortex (ACC), nucleus accumbens (NAC), and medial prefrontal cortex (PFC), particularly in the buprenorphine or combinatorial buprenorphine/gabapentin groups. Furthermore, we observed several drug- and region-specific differences in synaptic connectivity between WT and α2δ-1 haploinsufficient mice, indicating that critical α2δ-1-associated synaptogenic pathways are disrupted with early life drug exposure.

Rapid test to assess the escape of SARS-CoV-2 variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are concerning in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a rapid test, termed CoVariant-SCAN, that detects neutralizing antibodies (nAbs) capable of blocking interactions between the angiotensin-converting enzyme 2 receptor and the spike protein of wild-type (WT) SARS-CoV-2 and three other variants: B.1.1.7, B.1.351, and P.1. Using CoVariant-SCAN, we assessed neutralization/blocking of monoclonal antibodies and plasma from COVID-19­positive and vaccinated individuals. For several monoclonal antibodies and most plasma samples, neutralization against B.1.351 and P.1 variants is diminished relative to WT, while B.1.1.7 is largely cross-neutralized. We also showed that we can rapidly adapt the platform to detect nAbs against an additional variant­B.1.617.2 (Delta)­without reengineering or reoptimizing the assay. Results using CoVariant-SCAN are consistent with live virus neutralization assays and demonstrate that this easy-to-deploy test could be used to rapidly assess nAb response against multiple SARS-CoV-2 variants.

The SnRK2.10 kinase mitigates the adverse effects of salinity by protecting photosynthetic machinery.

SNF1-Related protein kinases Type 2 (SnRK2) are plant-specific enzymes widely distributed across the plant kingdom. They are key players controlling abscisic acid (ABA)-dependent and ABA-independent signaling pathways in the plant response to osmotic stress. Here we established that SnRK2.4 and SnRK2.10, ABA-nonactivated kinases, are activated in Arabidopsis thaliana rosettes during the early response to salt stress and contribute to leaf growth retardation under prolonged salinity but act by maintaining different salt-triggered mechanisms. Under salinity, snrk2.10 insertion mutants were impaired in the reconstruction and rearrangement of damaged core and antenna protein complexes in photosystem II (PSII), which led to stronger non-photochemical quenching, lower maximal quantum yield of PSII, and lower adaptation of the photosynthetic apparatus to high light intensity. The observed effects were likely caused by disturbed accumulation and phosphorylation status of the main PSII core and antenna proteins. Finally, we found a higher accumulation of reactive oxygen species (ROS) in the snrk2.10 mutant leaves under a few-day-long exposure to salinity which also could contribute to the stronger damage of the photosynthetic apparatus and cause other deleterious effects affecting plant growth. We found that the snrk2.4 mutant plants did not display substantial changes in photosynthesis. Overall, our results indicate that SnRK2.10 is activated in leaves shortly after plant exposure to salinity and contributes to salt stress tolerance by maintaining efficient photosynthesis and preventing oxidative damage.

Astrocyte-Derived Thrombospondin Induces Cortical Synaptogenesis in a Sex-Specific Manner.

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the CNS. Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared with female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to TSP2, which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17ß-estradiol (E2) production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that male and female neurons show a divergent response to TSP synaptogenic signaling, contributing to sex differences in astrocyte-mediated synaptic connectivity.