Symbiosis modulates gene expression of symbionts, but not coral hosts, under thermal challenge.

Increasing ocean temperatures are causing dysbiosis between coral hosts and their symbionts. Previous work suggests that coral host gene expression responds more strongly to environmental stress compared to their intracellular symbionts; however, the causes and consequences of this phenomenon remain untested. We hypothesized that symbionts are less responsive because hosts modulate symbiont environments to buffer stress. To test this hypothesis, we leveraged the facultative symbiosis between the scleractinian coral Oculina arbuscula and its symbiont Breviolum psygmophilum to characterize gene expression responses of both symbiotic partners in and ex hospite under thermal challenges. To characterize host and in hospite symbiont responses, symbiotic and aposymbiotic O. arbuscula were exposed to three treatments: (1) control (18°C), (2) heat (32°C), and (3) cold (6°C). This experiment was replicated with B. psygmophilum cultured from O. arbuscula to characterize ex hospite symbiont responses. Both thermal challenges elicited classic environmental stress responses (ESRs) in O. arbuscula regardless of symbiotic state, with hosts responding more strongly to cold challenge. Hosts also exhibited stronger responses than in hospite symbionts. In and ex hospite B. psygmophilum both down-regulated gene ontology pathways associated with photosynthesis under thermal challenge; however, ex hospite symbionts exhibited greater gene expression plasticity and differential expression of genes associated with ESRs. Taken together, these findings suggest that O. arbuscula hosts may buffer environments of B. psygmophilum symbionts; however, we outline the future work needed to confirm this hypothesis.

Urbanization and edge effects interact to drive mutualism breakdown and the rise of unstable pathogenic communities in forest soil.

Temperate forests are threatened by urbanization and fragmentation, with over 20% (118,300 km2) of U.S. forest land projected to be subsumed by urban land development. We leveraged a unique, well-characterized urban-to-rural and forest edge-to-interior gradient to identify the combined impact of these two land use changes-urbanization and forest edge creation-on the soil microbial community in native remnant forests. We found evidence of mutualism breakdown between trees and their fungal root mutualists [ectomycorrhizal (ECM) fungi] with urbanization, where ECM fungi colonized fewer tree roots and had less connectivity in soil microbiome networks in urban forests compared to rural forests. However, urbanization did not reduce the relative abundance of ECM fungi in forest soils; instead, forest edges alone led to strong reductions in ECM fungal abundance. At forest edges, ECM fungi were replaced by plant and animal pathogens, as well as copiotrophic, xenobiotic-degrading, and nitrogen-cycling bacteria, including nitrifiers and denitrifiers. Urbanization and forest edges interacted to generate new "suites" of microbes, with urban interior forests harboring highly homogenized microbiomes, while edge forest microbiomes were more heterogeneous and less stable, showing increased vulnerability to low soil moisture. When scaled to the regional level, we found that forest soils are projected to harbor high abundances of fungal pathogens and denitrifying bacteria, even in rural areas, due to the widespread existence of forest edges. Our results highlight the potential for soil microbiome dysfunction-including increased greenhouse gas production-in temperate forest regions that are subsumed by urban expansion, both now and in the future.

10 Simple Rules for a Supportive Lab Environment.

The transition to principal investigator (PI), or lab leader, can be challenging, partially due to the need to fulfil new managerial and leadership responsibilities. One key aspect of this role, which is often not explicitly discussed, is creating a supportive lab environment. Here, we present ten simple rules to guide the new PI in the development of their own positive and thriving lab atmosphere. These rules were written and voted on collaboratively, by the students and mentees of Professor Mark Stokes, who inspired this piece.

Association of APOE Genotypes and Chronic Traumatic Encephalopathy.

Importance: Repetitive head impact (RHI) exposure is the chief risk factor for chronic traumatic encephalopathy (CTE). However, the occurrence and severity of CTE varies widely among those with similar RHI exposure. Limited evidence suggests that the APOEε4 allele may confer risk for CTE, but previous studies were small with limited scope. Objective: To test the association between APOE genotype and CTE neuropathology and related endophenotypes. Design, Setting, and Participants: This cross-sectional genetic association study analyzed brain donors from February 2008 to August 2019 from the Veterans Affairs-Boston University-Concussion Legacy Foundation Brain Bank. All donors had exposure to RHI from contact sports or military service. All eligible donors were included. Analysis took place between June 2020 and April 2022. Exposures: One or more APOEε4 or APOEε2 alleles. Main Outcomes and Measures: CTE neuropathological status, CTE stage (0-IV), semiquantitative phosphorylated tau (p-tau) burden in 11 brain regions (0-3), quantitative p-tau burden in the dorsolateral frontal lobe (log-transformed AT8+ pixel count per mm2), and dementia. Results: Of 364 consecutive brain donors (100% male; 53 [14.6%] self-identified as Black and 311 [85.4%] as White; median [IQR] age, 65 [47-77] years) 20 years or older, there were 294 individuals with CTE and 70 controls. Among donors older than 65 years, APOEε4 status was significantly associated with CTE stage (odds ratio [OR], 2.34 [95% CI, 1.30-4.20]; false discovery rate [FDR]-corrected P = .01) and quantitative p-tau burden in the dorsolateral frontal lobe (ß, 1.39 [95% CI, 0.83-1.94]; FDR-corrected P = 2.37 × 10-5). There was a nonsignificant association between APOEε4 status and dementia (OR, 2.64 [95% CI, 1.06-6.61]; FDR-corrected P = .08). Across 11 brain regions, significant associations were observed for semiquantitative p-tau burden in the frontal and parietal cortices, amygdala, and entorhinal cortex (OR range, 2.45-3.26). Among football players, the APOEε4 association size for CTE stage was similar to playing more than 7 years of football. Associations were significantly larger in the older half of the sample. There was no significant association for CTE status. Association sizes were similar when donors with an Alzheimer disease neuropathological diagnosis were excluded and were reduced but remained significant after adjusting for neuritic and diffuse amyloid plaques. No associations were observed for APOEε2 status. Models were adjusted for age at death and race. Conclusions and Relevance: APOEε4 may confer increased risk for CTE-related neuropathological and clinical outcomes among older individuals with RHI exposure. Further work is required to validate these findings in an independent sample.

Soil microbiome predictability increases with spatial and taxonomic scale.

Soil microorganisms shape ecosystem function, yet it remains an open question whether we can predict the composition of the soil microbiome in places before observing it. Furthermore, it is unclear whether the predictability of microbial life exhibits taxonomic- and spatial-scale dependence, as it does for macrobiological communities. Here, we leverage multiple large-scale soil microbiome surveys to develop predictive models of bacterial and fungal community composition in soil, then test these models against independent soil microbial community surveys from across the continental United States. We find remarkable scale dependence in community predictability. The predictability of bacterial and fungal communities increases with the spatial scale of observation, and fungal predictability increases with taxonomic scale. These patterns suggest that there is an increasing importance of deterministic versus stochastic processes with scale, consistent with findings in plant and animal communities, suggesting a general scaling relationship across biology. Biogeochemical functional groups and high-level taxonomic groups of microorganisms were equally predictable, indicating that traits and taxonomy are both powerful lenses for understanding soil communities. By focusing on out-of-sample prediction, these findings suggest an emerging generality in our understanding of the soil microbiome, and that this understanding is fundamentally scale dependent.

Encoding-related brain activity and accelerated forgetting in transient epileptic amnesia.

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems.

Slow wave sleep and accelerated forgetting.

We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF.

Sleep-dependent memory consolidation and accelerated forgetting.

Accelerated long-term forgetting (ALF) is a form of memory impairment in which learning and initial retention of information appear normal but subsequent forgetting is excessively rapid. ALF is most commonly associated with epilepsy and, in particular, a form of late-onset epilepsy called transient epileptic amnesia (TEA). ALF provides a novel opportunity to investigate post-encoding memory processes, such as consolidation. Sleep is implicated in the consolidation of memory in healthy people and a deficit in sleep-dependent memory consolidation has been proposed as an explanation for ALF. If this proposal were correct, then sleep would not benefit memory retention in people with ALF as much as in healthy people, and ALF might only be apparent when the retention interval contains sleep. To test this theory, we compared performance on a sleep-sensitive memory task over a night of sleep and a day of wakefulness. We found, contrary to the hypothesis, that sleep benefits memory retention in TEA patients with ALF and that this benefit is no smaller in magnitude than that seen in healthy controls. Indeed, the patients performed significantly more poorly than the controls only in the wake condition and not the sleep condition. Patients were matched to controls on learning rate, initial retention, and the effect of time of day on cognitive performance. These results indicate that ALF is not caused by a disruption of sleep-dependent memory consolidation. Instead, ALF may be due to an encoding abnormality that goes undetected on behavioural assessments of learning, or by a deficit in memory consolidation processes that are not sleep-dependent.

Long-term memory prepares neural activity for perception.

Past experience provides a rich source of predictive information about the world that could be used to guide and optimize ongoing perception. However, the neural mechanisms that integrate information coded in long-term memory (LTM) with ongoing perceptual processing remain unknown. Here, we explore how the contents of LTM optimize perception by modulating anticipatory brain states. By using a paradigm that integrates LTM and attentional orienting, we first demonstrate that the contents of LTM sharpen perceptual sensitivity for targets presented at memory-predicted spatial locations. Next, we examine oscillations in EEG to show that memory-guided attention is associated with spatially specific desynchronization of alpha-band activity over visual cortex. Additionally, we use functional MRI to confirm that target-predictive spatial information stored in LTM triggers spatiotopic modulation of preparatory activity in extrastriate visual cortex. Finally, functional MRI results also implicate an integrated cortical network, including the hippocampus and a dorsal frontoparietal circuit, as a likely candidate for organizing preparatory states in visual cortex according to the contents of LTM.

DNA damage in horticultural farmers: a pilot study showing an association with organophosphate pesticide exposure.

A study of horticultural farmers exposed to organophosphate pesticides (OPs) and controls investigated the relationships between OP exposure, DNA damage and oxidative stress. Blood acetylcholinesterase (AChE) and urinary dialkylphosphate (DAP) levels determined exposure and 8-hydroxy-29- deoxyguanosine (8OHdG) indicated oxidative stress status. The farmers had approximately 30% lower AChE activity and increased DAP levels compared with the controls, reflecting moderate OP exposure. They had higher DNA damage than the controls and there was a significant positive relationship between DAP and DNA damage with greater than 95% power. The farmers also had a significant positive relationship between urinary DAP and 8OHdG levels.

Glucuronidation of the soyabean isoflavones genistein and daidzein by human liver is related to levels of UGT1A1 and UGT1A9 activity and alters isoflavone response in the MCF-7 human breast cancer cell line.

The soyabean isoflavones genistein and daidzein, which may protect against some cancers, cardiovascular disease and bone mineral loss, undergo substantial Phase 2 metabolism, predominantly glucuronidation. We observed a correlation between rates of metabolism of marker substrates of specific UGTs and rates of glucuronidation of genistein and daidzein in vitro by a panel of human liver microsomes, demonstrating that UGT1A1 and UGT1A9, but not UGT1A4, make a major contribution to the metabolism of these isoflavones by human liver. These findings were substantiated by observations that recombinant human UGT1A1 and UGT1A9, but not UGT1A4, catalysed the production of the major glucuronides of both genistein and daidzein in vitro. Recombinant human UGT1A8 also metabolised both genistein and daidzein, whereas UGT1A6 was specific to genistein and UGTs 2B7 and 2B15 were inactive, or only marginally active, with either isoflavone as substrate. The intestinal isoform UGT1A10 metabolised either both isoflavones or genistein only, depending on the commercial supplier of the recombinant enzyme, possibly as a result of a difference in amino acid sequence, which we were unable to confirm. Daidzein (16 microM) increased cell death in the MCF-7 human breast cancer cell line and this effect was reversed by glucuronidation. In view of a well-characterised functional polymorphism in UGT1A1, these observations may have implications for inter-individual variability in the potential health-beneficial effects of isoflavone consumption.

Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic CYPs 1A1 and 1B1 affects biological activity.

Metabolism of the isoflavones daidzein and genistein, which may protect against some cancers, was studied using human liver microsomes and recombinant CYP isoforms. The detection of three, more polar metabolites of each isoflavone by RP-HPLC required NADPH, consistent with CYP-mediated metabolism. For different liver preparations, metabolite generation from daidzein showed a significant linear correlation with metabolite generation from genistein, indicating metabolism by the same CYP(s). The lowest rate of metabolism of both isoflavones was by the preparation with the lowest CYP1A2 activity. Metabolite peak areas were substantially and significantly reduced by the CYP1A2 inhibitor furafylline and to a lesser extent by the CYP2E1 inhibitor 4-methylpyrazole. Recombinant CYP1A2, but not CYP2E1, generated the metabolites of daidzein and genistein and recombinant CYP1A1 and CYP1B1, expressed at sites including the breast and prostate, were also active. The effects of two CYP-derived metabolites of daidzein, 6,7,4'-trihydroxyisoflavone and 7,3',4'-trihydroxyisoflavone, were studied in the MCF-7 human breast cancer cell line at a concentration (50 microM) at which daidzein induces an antiproliferative response. 7,3',4'-Trihydroxyisoflavone reduced total cell numbers to a greater extent than 6,7,4'-trihydroxyisoflavone or daidzein and increased cell death. Together, these data demonstrate proof of principle that CYP-mediated metabolism of daidzein can be an activation pathway. We conclude that CYP1A2 makes the major contribution to the hepatic metabolism of both daidzein and genistein and along with metabolism at sites of hormone-dependent tumours may enhance a cancer-protective effect of daidzein if sufficiently high concentrations are reached in target tissues.

Cavity-enhanced spectroscopy in fiber cavities.

We discuss the relative merits of passive and active fiber cavities for ring-down. Ring-down times of approximately 2 micros were recently demonstrated in passive cavities, but operation is restricted to weak evanescent wave interaction. We report on active cavities with amplifiers used for loss compensation, permitting the use of open-path micro-optic cells. Ring-down times of tens of microseconds can readily be achieved and extended to several hundred microseconds in gain-clamped cavities, but relaxation oscillations and system drift impose limits on accuracy and repeatability. A cavity enhancement of 2 orders of magnitude is realistically possible, and sensitivity may be further enhanced if ring-down is combined with established spectroscopic methods.