Environmental modulators of algae-bacteria interactions at scale.

Interactions between photosynthetic and heterotrophic microbes play a key role in global primary production. Understanding phototroph-heterotroph interactions remains challenging because these microbes reside in chemically complex environments. Here, we leverage a massively parallel droplet microfluidic platform that enables us to interrogate interactions between photosynthetic algae and heterotrophic bacteria in >100,000 communities across ∼525 environmental conditions with varying pH, carbon availability, and phosphorus availability. By developing a statistical framework to dissect interactions in this complex dataset, we reveal that the dependence of algae-bacteria interactions on nutrient availability is strongly modulated by pH and buffering capacity. Furthermore, we show that the chemical identity of the available organic carbon source controls how pH, buffering capacity, and nutrient availability modulate algae-bacteria interactions. Our study reveals the previously underappreciated role of pH in modulating phototroph-heterotroph interactions and provides a framework for thinking about interactions between phototrophs and heterotrophs in more natural contexts.

A MOFs/MIPs@GAs Ternary Composite Catalytic System with Graphene Oxide Aerogels as the Multifunctional Skeleton for High-Efficiency Detoxification of Organophosphate Nerve Agents in Pure Water.

Organophosphate nerve agents (OPs) are widely used as pesticides and chemical agents and pose a threat to human health and life. At present, most personal protective equipment usually only serves as physical protection and does not have an effect of chemical detoxification. In this work, ultra lightweight graphene oxide aerogels (GAs) have been used as a multifunctional skeleton to integrate the metal-organic frameworks (MOFs) and molecularly imprinted polymers (MIPs) together for obtaining a high-performance hybrid material (MOFs/MIPs@GAs) on hydrolysis detoxification of OPs. As a porous three-dimensional material full of carboxyl groups, GAs can not only support excellent mass transfer performance but also provide a proper pH self-buffering catalytic reaction external environment for hydrolyzing OPs. The obtained MOFs/MIPs@GAs can catalyze dimethyl-4-nitrophenyl phosphate (DMNP) hydrolysis detoxification rapidly in pure water (kobs = 0.2227 min-1, t1/2 = 3.11 min). This ternary hybrid material with exceptional performance and practical applicability has vast application prospects for the development of protective equipment.

An assessment on the effects of buffers on the productive, behavioral and metabolic parameters of Holstein dairy cows.

This study aimed to evaluate the impact of supplementing sodium bicarbonate or a commercial blend of buffering agents (BBA) comprising calcareous calcitic, magnesium oxide, calcareous algae, and sodium bicarbonate on the productive, behavioral and metabolic parameters of Holstein cows fed starchy diets. Over a 60-day trial period, thirty-six multiparous cows with an average milk yield of 38.84 ± 9.24 kg/day and 63.74 ± 18.63 days in milk (DIM), were randomly divided into two groups. The control group (n = 18) received a supplementation of 1.1% dry matter (DM) of sodium bicarbonate (Raudi®, Totalmix, Brazil), while the BBA group (n = 18) was administered with 0.5% DM of a blend of buffering agents (Equalizer®, Nutron/Cargill, Brazil). The mean values of ruminal pH (control 6.80 ± 0.06 and BBA 6.77 ± 0.06; P > 0.05) and volatile fatty acid (VFA) production (control: acetate 62.63 ± 1.29%, propionate 22.99 ± 1.07%, butyrate 14.30 ± 0.52%; BBA: acetate 63.07 ± 1.32%, propionate 23.47 ± 1.10%, butyrate 13.70 ± 0.57%), were similar (P > 0,05) between the two groups. The value of faecal pH was higher (P < 0.05) in the BBA group (6.25 ± 0.02) than the control group (6.12 ± 0.02). Animals treated with BBA exhibited lower (P < 0,05) dry matter intake (DMI) (24.75 ± 0.64 kg/day), higher feed efficiency (FE) (1.64 ± 0.03), and reduced feeding frequency (52.89 ± 3.73 n°/day) than the control group (DMI, 26.75 ± 0.62 kg/day; FE, 1.50 ± 0.03; feeding frequency, 66.07 ± 3.64 n°/day). Milk production remained similar across both groups (control, 39.11 ± 0.92 kg/day and BBA, 39.87 ± 0.92 kg/day; P > 0.05). Notably, the control group displayed a higher (P < 0,05) concentration of milk protein (1.21 ± 0.05 kg/day) than the BBA (1.18 ± 0.05 kg/day) group. The study concluded that both treatments effectively buffered the rumen and mitigated the risk of ruminal acidosis. Moreover, the higher faecal pH in the BBA-treated group suggests potential intestinal action attributable to the synergistic effects of diverse additives with buffering properties. Despite a reduced DMI, BBA-treated animals exhibited improved FE.

Rising Alkali-to-Acid Ratios in the Atmosphere May Correspond to Increased Aerosol Acidity.

Aerosol acidity (or pH) is one central parameter in determining the health, climate, and ecological effects of aerosols. While it is traditionally assumed that the long-term aerosol pH levels are determined by the relative abundances of atmospheric alkaline to acidic substances (referred to as RC/A hereinafter), we observed contrasting pH─RC/A trends at different sites globally, i.e., rising alkali-to-acid ratios in the atmosphere may unexpectedly lead to increased aerosol acidity. Here, we examined this apparently counterintuitive phenomenon using the multiphase buffer theory. We show that the aerosol water content (AWC) set a pH "baseline" as the peak buffer pH, while the RC/A and particle-phase chemical compositions determine the deviation of pH from this baseline within the buffer ranges. Therefore, contrasting long-term pH trends may emerge when RC/A increases while the AWC or nitrate fraction decreases, or vice versa. Our results provided a theoretical framework for a quantitative understanding of the response of aerosol pH to variations in SO2, NOx versus NH3, and dust emissions, offering broad applications in studies on aerosol pH and the associated environmental and health effects.

Addressing loneliness in older adults: predictors, protective factors, and implications for social work practice.

Loneliness significantly impacts the mental well-being of older adults, prompting an examination of psychological predictors and buffering factors associated with it in this demographic. A cross-sectional study involving 246 community-dwelling older adults was conducted. The UCLA Loneliness Scale identified predictors of loneliness, including negative mood, hopelessness (negative future expectations and loss of motivation), and despair. Buffering factors included ego-integrity, personal growth, and purpose in life. Regression analysis revealed that negative mood, negative future expectations, and despair increased loneliness, with negative mood showing a strong association. Conversely, ego-integrity, personal growth, and purpose in life reduced loneliness. The study underscores the complex interplay of psychological factors shaping loneliness in older adults, highlighting the importance of addressing both risk and protective factors. Social work practitioners in healthcare settings can play a pivotal role in addressing loneliness among older adults by leveraging these factors.

Comparison of Salivary Flow Rate, pH, Buffering Capacity, and Secretory Immunoglobulin A Levels between Children with Early Childhood Caries and Caries-free Children.

Background and objectives: Early childhood caries (ECC) is the most common chronic disease of childhood in many developing countries, which is associated with local, systemic, psychological, and social consequences. Multiple variables are shown to be associated with an increased risk of ECC. The knowledge regarding the role of saliva in the pathophysiological process of ECC still remains controversial and unexplored. Scanty studies focused on probing the role of salivary flow rate, pH, buffering capacity, and secretory immunoglobulin A (sIgA) in unstimulated whole saliva of children with ECC and children without ECC. Aim: To assess the salivary flow rate, pH, buffering capacity, and sIgA levels in children with ECC and caries-free children and to evaluate their role in caries risk assessment.Materials and Methods: The study was carried out among 64 children aged between 24 and 71 months. Clinical examinations were carried out according to the criteria by the World Health Organization, and carious status was recorded. Subjects were categorized as group I with ECC (dmfs-Decayed, Missing or Filled Surfaces (Deciduous dentition) of ≥5), and group II included children without ECC (dmfs = 0). Unstimulated whole salivary samples were collected in a sterile vial and stored at -70°C by draining. Estimations of salivary flow rate, pH, buffering capacity, and sIgA levels were done. Digital pH meters were used for the estimation of pH and buffering capacity. A human IgA enzyme-linked immunosorbent assay (ELISA) kit was used to estimate sIgA levels. Statistical software IBM Statistical Package for the Social Sciences (SPSS) statistics 20.0 (IBM Corporation, Armonk, New York, United States of America) was used to analyze the data. Results: The mean salivary flow rate decreased in group I children with ECC (0.15 ± 0.05) when compared to group II children without ECC (0.67 ± 0.14), which was statistically significant. In caries active children, no statistically significant correlation was found between salivary flow rate and the dmfs scores [r-value (-0.247)] and p-value (0.147). The mean level of salivary pH is decreased in group I children with ECC (4.65 ± 0.4) when compared to group II children without ECC (7.28 ± 0.18). In the caries active group, the levels of salivary pH decrease as the dmfs scores increase, and this correlation is found to be statistically significant (r-value of 0.547 and p-value of 0.002). The mean level of buffering capacity is decreased for caries-active children (5.45 ± 0.49) when compared to caries-free children (8.94 ± 0.42). In caries active children, as the dmfs scores increase, the salivary buffering capacity decreases, and this correlation is found to be not statistically significant (r-value of -0.334 and p-value of 0.161). The mean levels of sIgA in group I children with ECC were higher (10.61 ± 0.90) than that in group II children without ECC (6.11 ± 1.22). In the caries-active group, the salivary sIgA levels were comparatively higher than in the caries-free children. As the dmfs scores increase, the level of the sIgA increases in caries-active children, and this correlation is noted to be highly statistically significant (r-value of 0.769 and p-value 0.008). Conclusion: Children with ECC showed decreased salivary flow rate, pH, buffering capacity, and increased sIgA levels, while children without ECC showed increased salivary flow rate, pH, buffering capacity, and decreased sIgA levels. The salivary parameters, such as salivary flow rate and buffering capacity, showed no correlation with the dmfs score, while salivary pH and sIgA levels have a positive correlation in caries-active children. How to cite this article: Sivakumar A, Narayanan R. Comparison of Salivary Flow Rate, Ph, Buffering Capacity, and Secretory Immunoglobulin A Levels between Children with Early Childhood Caries and Caries-free Children. Int J Clin Pediatr Dent 2024;17(3):334-340.

Small Molecule Topical Ophthalmic Formulation Development-Data Driven Trends & Perspectives from Commercially Available Products in the US.

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems.

Three-Dimensional Carbon Nanotubes Buffering Interfacial Stress of the Silicon/Carbon Anodes for Long-Cycle Lithium Storage.

Silicon/graphite composites show a high specific capacity and improved cycling stability. However, the intrinsic difference between silicon and graphite, such as unequal volume expansion and lithium-ion diffusion kinetics, causes persistent stress at the silicon/graphite interface and the expansion of the electrical isolation region. Herein, carbon nanotubes (CNTs) were successfully introduced into silicon/carbon composites via ball milling and spray drying, which effectively relieved the stress concentration at the direct contact interface and formed a three-dimensional conductive structure. In addition, CNTs and amorphous carbon acting as "lubricants" further improved the inherent differences between silicon and graphite. As a result, the Si/CNTs/G@C-1 anode increased the cycling performance and rate capability, with a reversible capacity of up to 465 mAh g-1 after 500 cycles at 1 A g-1 and superior rate performance of 523 mAh g-1 at 2 A g-1. It is believed that this strategy may provide a feasible preparation of large-scale high-content silicon-based nanocomposite anodes in lithium-ion batteries.

From stress communication to depressive symptoms among couples facing vision impairment: The mediating role of dyadic coping.

Vision impairment is considered one of the most common disability worldwide, can induce considerable stress for both patients and their spouses and may subsequently affect couples' psychological functioning. This study examined whether dyadic coping (DC) mediated the association between stress communication (SC) and depressive symptoms among couples coping with one partner's vision impairment. A total of 99 Swiss couples completed questionnaires assessing SC, various types of DC, and depressive symptoms. An Actor-Partner Interdependence Mediation Model was performed. Results showed that (1) the more one partner communicated stress, the less the other partner perceived negative DC and, consequently, the less the partner perceiving negative DC reported depressive symptoms; (2) the more partners communicated stress, the more they and their partners engaged in common DC and, consequently, the less the partner engaging in common DC reported depressive symptoms; (3) the more partners communicated stress, the less they and their partners engaged in protective buffering and, consequently, the less the partner engaging in protective buffering reported depressive symptoms. This pattern of associations occurred similarly for patients and their spouses. Our findings underline the interpersonal experience of vision impairment within couples and the importance of fostering explicit SC and common DC in psychosocial rehabilitation interventions directed at couples facing one partner's vision impairment.

The effect of sodium bicarbonate mini-tablets ingested in a carbohydrate hydrogel system on 40 km cycling time trial performance and metabolism in trained male cyclists.

INTRODUCTION: Sodium bicarbonate (NaHCO3) ingestion has been found to be ergogenic in high-intensity exercise that ranges from 1 to 10 min; however, limited studies have investigated high-intensity exercise beyond this duration. PURPOSE: The present study aimed to determine the effect of NaHCO3 ingested using a carbohydrate hydrogel delivery system on 40 km time trial (TT) performance in trained male cyclists. METHODS: Fourteen trained male cyclists ingested 0.3 g kg-1 BM NaHCO3 (Maurten AB, Sweden) to determine individualised peak alkalosis, which established time of ingestion prior to exercise. Participants completed a 40 km familiarisation TT, and two 40 km experimental TTs after ingestion of either NaHCO3 or placebo in a randomised, double-blind, crossover design. RESULTS: NaHCO3 supplementation improved performance (mean improvement = 54.14 s ± 18.16 s; p = 0.002, g = 0.22) and increased blood buffering capacity prior to (HCO3- mean increase = 5.6 ± 0.2 mmol L-1, p < 0.001) and throughout exercise (f = 84.82, p < 0.001, pη2 = 0.87) compared to placebo. There were no differences in total gastrointestinal symptoms (GIS) between conditions either pre- (NaHCO3, 22 AU; Placebo, 44 AU; p = 0.088, r = 0.46) or post-exercise (NaHCO3, 76 AU; Placebo, 63 AU; p = 0.606, r = 0.14). CONCLUSION: The present study suggests that ingesting NaHCO3 mini-tablets in a carbohydrate hydrogel can enhance 40 km TT performance in trained male cyclists, with minimal GIS. This ingestion strategy could therefore be considered by cyclists looking for a performance enhancing ergogenic aid.

Shellfish CO2 excretion is modulated by seawater carbonate chemistry but largely independent of pCO2.

Four species of shellfish, blue mussel (Mytilus galloprovincialis), Pacific abalone (Haliotis discus hannai), zhikong scallops (Chlamys farreri), and Pacific oyster (Crassostrea gigas), were exposed to decoupled carbonate system variables to investigate the impacts of different seawater carbonate parameters on the CO2 excretion process of mariculture shellfish. Six experimental groups with two levels of seawater pH (pH 8.1 and pH 7.7) and three levels of total alkalinity (TA = 1000, 2300, and 3600 µmol/kg, respectively) were established, while pH 8.1 and TA = 2300 µmol/kg was taken as control. Results showed that the CO2 excretion rates of these tested shellfish were significantly affected by the change in carbonate chemistry (P < 0.05). At the same TA level, animals incubated in the acidified group (pH 7.7) had a lower CO2 excretion rate than those in the control group (pH 8.1). In comparison, at the same pH level, the CO2 excretion rate increased when seawater TA level was elevated. No significant correlation between the CO2 excretion rate and seawater pCO2 levels (P > 0.05) was found; however, a significant correlation (P < 0.05) between CO2 excretion rate and TA-DIC (the difference between total alkalinity and dissolved inorganic carbon) was observed. Blue mussel has a significantly higher CO2 excretion rate than the other three species in the CO2 excretions per unit mass of soft parts, with no significant difference observed among these three species. However, in terms of CO2 excretion rate per unit mass of gills, abalone has the highest CO2 excretion rate, while significant differences were found between each species. Our studies indicate that the CO2 buffering capacity impacts the CO2 excretion rate of four shellfish species largely independent of pCO2. Since CO2 excretion is related to acid-base balancing, the results imply that the effects of other carbonate parameters, particularly the CO2 buffering capacity, should be studied to fully understand the mechanism of how acidification affects shellfish. Besides, the species difference in gill to soft parts proportion may contribute to the species difference in responding to ocean acidification.

Sex, drugs, and zebrafish: Acute exposure to anxiety-modulating compounds in a modified novel tank dive test.

This study investigated the effects of anxiogenic and anxiolytic drugs on zebrafish (Danio rerio) behaviour using a modified novel tank dive test with higher walls and a narrower depth. Zebrafish were administered chondroitin sulfate, beta-carboline, delta-9-tetrahydrocannabinol (THC), ethanol, and beta-caryophyllene, and their behaviours were evaluated for geotaxis, swimming velocity, and immobility. Both anxiogenic and anxiolytic compounds generally increased bottom-dwelling behaviour, suggesting that the tank's modified dimensions significantly influence zebrafish responses. EC50 values for ethanol showed a lower threshold for velocity reduction compared to zone preference. Chondroitin sulfate uniquely caused a sex-specific increase in male swimming velocity, whereas no other sex-differences were observed with any compound. Interestingly, the presence of drug-treated fish did not alter the behaviour of observer fish, suggesting limited social buffering effects. The findings underscore the complexity of zebrafish behavioural phenotypes and highlight the need for considering tank dimensions and multiple behavioural parameters to accurately assess the effects of anxiety-modulating drugs. This study demonstrates the utility of the modified novel tank dive test in providing nuanced insights into the behavioural effects of different pharmacological agents in zebrafish.

"Why (Zebra)fish May Get Ulcers": Cognitive and Social Modulation of Stress in Fish.

BACKGROUND: In the bestseller book "Why Zebras Don't Get Ulcers", Robert Sapolsky argues that animals do not suffer from stress-related diseases like humans because for them, stress is episodic, while humans in contrast suffer from chronic psychological stress. In particular, the idea that fish cannot experience psychological stress is still prevalent, partly due to the lack of a homologous brain area to the neocortex. However, emerging evidence suggests that teleosts can undergo psychological stress, defined as a subjective and perceptual experience of the stressor, and in recent years, the underlying mechanisms started to be unveiled. SUMMARY: The occurrence of cognitive appraisal in the assessment of stressors has been demonstrated in fish, indicating that the subjective evaluation of stimulus valence and salience, rather than absolute intrinsic characteristics of the stimulus itself, play a key role in the activation of the stress response. Moreover, individual biases (i.e., cognitive bias) in the cognitive appraisal of stimuli have also been described in fish, with some individuals consistently evaluating ambiguous stimuli as positive (aka optimists) whereas other individuals (aka pessimists) appraise them as negative. As a result, optimists and pessimists show consistent differences in stress reactivity and susceptibility/resilience to disease. Finally, social context has also been shown to modulate the response to aversive stimuli with the behavior of conspecifics either buffering or enhancing the response (i.e., social buffering vs. social contagion). KEY MESSAGES: Cognitive appraisal of stressors occurs in fish, implying that the stress response is modulated by a subjective and perceptual experience of the stressor. Moreover, interindividual consistent cognitive biases in the appraisal of stressors are also present in fish making some individuals more susceptible to stress-related diseases. Therefore, psychological stress has a health toll in fish, and psychologically stressed fish can potentially have ulcers.

Status-dependent metabolic effects of social interactions in a group-living fish.

Social interactions can sometimes be a source of stress, but social companions can also ameliorate and buffer against stress. Stress and metabolism are closely linked, but the degree to which social companions modulate metabolic responses during stressful situations-and whether such effects differ depending on social rank-is poorly understood. To investigate this question, we studied Neolamprologus pulcher, a group-living cichlid fish endemic to Lake Tanganyika and measured the metabolic responses of dominant and subordinate individuals when they were either visible or concealed from one another. When individuals could see each other, subordinates had lower maximum metabolic rates and tended to take longer to recover following an exhaustive chase compared with dominants. In contrast, metabolic responses of dominants and subordinates did not differ when individuals could not see one another. These findings suggest that the presence of a dominant individual has negative metabolic consequences for subordinates, even in stable social groups with strong prosocial relationships.

The transgenerational consequences of paternal social isolation and predation exposure in threespined sticklebacks.

Parents routinely encounter stress in the ecological environment that can affect offspring development (transgenerational plasticity: TGP); however, parents' interactions with conspecifics may alter how parents respond to ecological stressors. During social buffering, the presence of conspecifics can reduce the response to or increase the speed of recovery from a stressor. This may have cascading effects on offspring if conspecifics can mitigate parental responses to ecological stress in ways that blunt the transmission of stress-induced transgenerational effects. Here, we simultaneously manipulated both paternal social isolation and experience with predation risk prior to fertilisation in threespined stickleback (Gasterosteus aculeatus). We generated offspring via in-vitro fertilisation to allow us to isolate paternal effects mediated via sperm alone (i.e. in the absence of paternal care). If social buffering mitigates TGP induced by paternal exposure to predation risk, then we expect the transgenerational effects of predation exposure to be weaker when a conspecific is present compared to when the father is isolated. Offspring of predator-exposed fathers showed reduced anxiety-like behaviour and tended to be captured faster by the predator. Fathers who were socially isolated also had offspring that were captured faster by a live predator, suggesting that paternal social isolation may have maladaptive effects on how offspring respond to ecological stressors. Despite additive effects of paternal social isolation and paternal predation risk, we found no evidence of an interaction between these paternal treatments, suggesting that the presence of a conspecific did not buffer fathers and/or offspring from the effects of predation risk. Our results suggest that socially induced stress is an important, yet underappreciated, mediator of TGP and can elicit transgenerational effects even in species that do not form permanent social groups. Future studies should therefore consider how the parental social environment can affect both within and trans-generational responses to ecological stressors.

The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation.

The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

Activity-dependent extracellular potassium changes in unmyelinated versus myelinated areas in olfactory regions of the isolated female guinea-pig brain.

The potassium released in the extracellular space during neuronal activity is rapidly removed by glia and neurons to maintain tissue homeostasis. Oligodendrocyte-derived myelin axonal coating contributes to potassium buffering and is therefore crucial to control brain excitability. We studied activity-dependent extracellular potassium ([K+]o) changes in the piriform cortex (PC), a region that features highly segregated bundles of myelinated and unmyelinated fibers. Four-aminopyridine (4AP; 50 µM) treatment or patterned high-frequency stimulations (hfST) were utilized to generate [K+]o changes measured with potassium-sensitive electrodes in the myelinated lateral olfactory tract (LOT), in the unmyelinated PC layer I and in the myelinated deep PC layers in the ex vivo isolated guinea-pig brain. Seizure-like events induced by 4AP are initiated by the abrupt [K+]o rise in the layer I formed by unmyelinated fibers (Uva et al., 2017). Larger [K+]o shifts occurred in unmyelinated layers compared to the myelinated LOT. LOT hfST that mimicks pre-seizure discharges also generated higher [K+]o changes in unmyelinated PC layer I than in LOT and deep PC layers. The treatment with the Kir4.1 potassium channel blocker BaCl2 (100 µM) enhanced the [K+]o changes generated by hfST in myelinated structures. Our data show that activity-dependent [K+]o changes are intrinsically different in myelinated vs unmyelinated cortical regions. The larger [K+]o shifts generated in unmyelinated structures may represent a vehicle for seizure generation.

Psychological distress and alcohol use disorder in college students of color: Social support's moderating properties.

Alcohol use is prevalent among college students. Research has found that psychological distress in the form of depression, anxiety, or loneliness has been consistently associated with greater alcohol use. Because Students of Color (SoC) disproportionately experience greater psychological distress than White students, it is critical to determine buffers against psychological distress and subsequent alcohol use consequences. Previous literature found that social support can protect against the effects of psychological distress and weaken its link with alcohol use. This study aimed to determine the moderating effect of social support in the relation between psychological distress and alcohol use among SoC. College Students of Color from across the U.S. (n = 211, Mage = 27.51, SD = 9.63) were recruited via Prolific to answer an online survey through Qualtrics. Linear regression analyses showed that psychological distress variables (i.e., depression, anxiety, and loneliness) were positively associated with alcohol use. However, moderation analysis did not find any form of social support to moderate the relation between psychological distress variables and alcohol use. Future research needs to identify other protective factors against alcohol use to support SoC in their academic journey.

Mitoferrin2 is a synthetic lethal target for chromosome 8p deleted cancers.

BACKGROUND: Somatic copy number alterations are a hallmark of cancer that offer unique opportunities for therapeutic exploitation. Here, we focused on the identification of specific vulnerabilities for tumors harboring chromosome 8p deletions. METHODS: We developed and applied an integrative analysis of The Cancer Genome Atlas (TCGA), the Cancer Dependency Map (DepMap), and the Cancer Cell Line Encyclopedia to identify chromosome 8p-specific vulnerabilities. We employ orthogonal gene targeting strategies, both in vitro and in vivo, including short hairpin RNA-mediated gene knockdown and CRISPR/Cas9-mediated gene knockout to validate vulnerabilities. RESULTS: We identified SLC25A28 (also known as MFRN2), as a specific vulnerability for tumors harboring chromosome 8p deletions. We demonstrate that vulnerability towards MFRN2 loss is dictated by the expression of its paralog, SLC25A37 (also known as MFRN1), which resides on chromosome 8p. In line with their function as mitochondrial iron transporters, MFRN1/2 paralog protein deficiency profoundly impaired mitochondrial respiration, induced global depletion of iron-sulfur cluster proteins, and resulted in DNA-damage and cell death. MFRN2 depletion in MFRN1-deficient tumors led to impaired growth and even tumor eradication in preclinical mouse xenograft experiments, highlighting its therapeutic potential. CONCLUSIONS: Our data reveal MFRN2 as a therapeutic target of chromosome 8p deleted cancers and nominate MFNR1 as the complimentary biomarker for MFRN2-directed therapies.