The Mediator complex subunit MED25 interacts with HDA9 and PIF4 to regulate thermomorphogenesis.

Thermomorphogenesis is, among other traits, characterized by enhanced hypocotyl elongation due to the induction of auxin biosynthesis genes like YUCCA8 by transcription factors, most notably PHYTOCHROME INTERACTING FACTOR 4 (PIF4). Efficient binding of PIF4 to the YUCCA8 locus under warmth depends on HISTONE DEACETYLASE 9 (HDA9) activity, which mediates histone H2A.Z depletion at the YUCCA8 locus. However, HDA9 lacks intrinsic DNA-binding capacity, and how HDA9 is recruited to YUCCA8, and possibly other PIF4-target sites, is currently not well understood. The Mediator complex functions as a bridge between transcription factors bound to specific promoter sequences and the basal transcription machinery containing RNA polymerase II. Mutants of Mediator component Mediator25 (MED25) exhibit reduced hypocotyl elongation and reduced expression of YUCCA8 at 27°C. In line with a proposed role for MED25 in thermomorphogenesis in Arabidopsis (Arabidopsis thaliana), we demonstrated an enhanced association of MED25 to the YUCCA8 locus under warmth and interaction of MED25 with both PIF4 and HDA9. Genetic analysis confirmed that MED25 and HDA9 operate in the same pathway. Intriguingly, we also showed that MED25 destabilizes HDA9 protein. Based on our findings, we propose that MED25 recruits HDA9 to the YUCCA8 locus by binding to both PIF4 and HDA9.

GNAT toxins evolve toward narrow tRNA target specificities.

Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.

Root canal re-treatment with gutta percha - which techniques influence success?

OBJECTIVE: A systematic review and meta-analysis of the literature was carried out assessing the success rate of root canal retreatment using gutta percha. DATA SOURCES: Four of the largest databases were used to identify existing literature with no date or language restrictions. PubMed, Cochrane, ScienceDirect, Scopus and other additional sources were searched. Grey literature was also reviewed. STUDY SELECTION: Two authors, with Master's degrees in endodontics and with extensive university teaching experience, were selected to screen the databases to identify suitable studies. In case the authors were not able to agree during the study selection process, a third investigator was consulted. Specific inclusion and exclusion criteria were outlined and adhered to in the study selection. Two randomised controlled trials, seven single arm prospective studies and one single arm ambispective study published before the 10th of December 2022 were included. These studies evaluated the success of root canal re-treatment, obturated with gutta percha with at least a 1-year follow-up. Nine of the studies were published between 1998 and 2022. Seven studies were conducted in Europe, one in North America and one in Asia. DATA EXTRACTION AND SYNTHESIS: Standard Cochrane methods to assess interval validity were used. Risk of bias in individual studies was assessed using The Newcastle-Ottawa quality assessment scale (NOS) for single-arm studies, and the Cochrane risk of bias tool (RoB2) was used for randomised controlled trials. Outcome measures were standardised as either success or failure of root canal retreatment. Success was classified into 2 different criteria: Strict criteria = absence of clinical signs and symptoms and radiographically normal periodontal ligament space; and Loose criteria = absence of clinical signs and symptoms and absence or reduction of apical radiolucency in the control radiograph. Statistical analysis was undertaken using R software and the Freeman-Turkey transformation was performed. Results were visualised using forest plots. Heterogeneity between studies was measured using the Cochrane Q test and I2 values. RESULTS: Whilst following strict criteria, the success rate of non-surgical root canal retreatment obturated with gutta percha was 71% for 1-3 years follow-up (95% CI, 0.66-0.77) and 77% for 4-5 years follow-up (95% CI, 0.67-0.86). Heterogeneity was moderate (I2 = 61.4) and low (I2 = 0.0), respectively. Factors reducing the success rate of root canal re-retreatment under the strict criteria were older patients, mandibular teeth, molar teeth, the presence of a peri-apical radiolucency, teeth with a previous radiolucency, large peri-apical radiolucency's, higher initial periapical index scores and multiple visit-retreatments. Following the loose criteria, the success rate of non-surgical root canal re-treatment obturated with gutta percha was 87% for 1-3 years follow-up (95% CI, 0.79-0.93) with significant heterogeneity across the studies (I2 = 88.5%). Factors influencing the success rate under the loose criteria were large periapical lesions >5 mm and higher initial periapical index (PAI) scores. CONCLUSIONS: Non-surgical root canal retreatment results in favourable outcomes. However, there are several factors which can result in a lower success rate: the presence and size of a periapical radiolucency, a higher initial PAI score, multiple-visit retreatments, and the size and position of the tooth.

Auxiliary interfaces support the evolution of specific toxin-antitoxin pairing.

Toxin-antitoxin (TA) systems are a large family of genes implicated in the regulation of bacterial growth and its arrest in response to attacks. These systems encode nonsecreted toxins and antitoxins that specifically pair, even when present in several paralogous copies per genome. Salmonella enterica serovar Typhimurium contains three paralogous TacAT systems that block bacterial translation. We determined the crystal structures of the three TacAT complexes to understand the structural basis of specific TA neutralization and the evolution of such specific pairing. In the present study, we show that alteration of a discrete structural add-on element on the toxin drives specific recognition by their cognate antitoxin underpinning insulation of the three pairs. Similar to other TA families, the region supporting TA-specific pairing is key to neutralization. Our work reveals that additional TA interfaces beside the main neutralization interface increase the safe space for evolution of pairing specificity.

Warming increased bark beetle-induced tree mortality by 30% during an extreme drought in California.

Quantifying the responses of forest disturbances to climate warming is critical to our understanding of carbon cycles and energy balances of the Earth system. The impact of warming on bark beetle outbreaks is complex as multiple drivers of these events may respond differently to warming. Using a novel model of bark beetle biology and host tree interactions, we assessed how contemporary warming affected western pine beetle (Dendroctonus brevicomis) populations and mortality of its host, ponderosa pine (Pinus ponderosa), during an extreme drought in the Sierra Nevada, California, United States. When compared with the field data, our model captured the western pine beetle flight timing and rates of ponderosa pine mortality observed during the drought. In assessing the influence of temperature on western pine beetles, we found that contemporary warming increased the development rate of the western pine beetle and decreased the overwinter mortality rate of western pine beetle larvae leading to increased population growth during periods of lowered tree defense. We attribute a 29.9% (95% CI: 29.4%-30.2%) increase in ponderosa pine mortality during drought directly to increases in western pine beetle voltinism (i.e., associated with increased development rates of western pine beetle) and, to a much lesser extent, reductions in overwintering mortality. These findings, along with other studies, suggest each degree (°C) increase in temperature may have increased the number of ponderosa pine killed by upwards of 35%-40% °C-1 if the effects of compromised tree defenses (15%-20%) and increased western pine beetle populations (20%) are additive. Due to the warming ability to considerably increase mortality through the mechanism of bark beetle populations, models need to consider climate's influence on both host tree stress and the bark beetle population dynamics when determining future levels of tree mortality.

Methods for Estimating Locations of Housing Units Served by Private Domestic Wells in the United States Applied to 2010.

In 1990, the last time the decennial census included a question on domestic drinking water source, it was estimated that private domestic water wells (PDWs) supplied household water to about 15.1 million housing units (15% of the population) in the United States (U.S.). PDWs are not regulated by the Safe Drinking Water Act, and with few exceptions, are not subject to the water quality testing required of public water suppliers. We expanded two methods in estimating housing units reliant on PDWs from an Oklahoma pilot study (Weaver et al. 2017), nationally. Both use 1990 census data on drinking water sources as a baseline. The first method uses housing unit change and private well drilling logs for 20 states. This allows for the rate of well use to change between 1990 and 2010 in these states. The second, based solely on housing unit change, assumes a constant rate of well use. Ordinary least squares regression demonstrated (R 2 = 0.78) that the methods yield similar estimates for nationwide well use. Using the housing unit change method, it is estimated that in 2010, 23 million housing units were reliant on PDWs (17% of the population). We provide these estimates at the census block group and census block resolution. This dataset will assist in a better understanding of the reliance on PDWs in the U.S., and position local, tribal, state, and national groups to better protect this water resource from contaminant sources. RESEARCH IMPACT STATEMENT: The work provides improved estimates of the spatial distribution of housing units reliant on private domestic wells in the United States and a foundation to protect this water supply at all levels of government.

Global biochemical and structural analysis of the type IV pilus from the Gram-positive bacterium Streptococcus sanguinis.

Type IV pili (Tfp) are functionally versatile filaments, widespread in prokaryotes, that belong to a large class of filamentous nanomachines known as type IV filaments (Tff). Although Tfp have been extensively studied in several Gram-negative pathogens where they function as key virulence factors, many aspects of their biology remain poorly understood. Here, we performed a global biochemical and structural analysis of Tfp in a recently emerged Gram-positive model, Streptococcus sanguinis In particular, we focused on the five pilins and pilin-like proteins involved in Tfp biology in S. sanguinis We found that the two major pilins, PilE1 and PilE2, (i) follow widely conserved principles for processing by the prepilin peptidase PilD and for assembly into filaments; (ii) display only one of the post-translational modifications frequently found in pilins, i.e. a methylated N terminus; (iii) are found in the same heteropolymeric filaments; and (iv) are not functionally equivalent. The 3D structure of PilE1, solved by NMR, revealed a classical pilin-fold with a highly unusual flexible C terminus. Intriguingly, PilE1 more closely resembles pseudopilins forming shorter Tff than bona fide Tfp-forming major pilins, underlining the evolutionary relatedness among different Tff. Finally, we show that S. sanguinis Tfp contain a low abundance of three additional proteins processed by PilD, the minor pilins PilA, PilB, and PilC. These findings provide the first global biochemical and structural picture of a Gram-positive Tfp and have fundamental implications for our understanding of a widespread class of filamentous nanomachines.

Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.

BACKGROUND: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated. METHODS: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI. RESULTS: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate. CONCLUSIONS: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.

Ecological light pollution affects anuran calling season, daily calling period, and sensitivity to light in natural Brazilian wetlands.

Ecological light pollution alters an environment's light cycle, potentially affecting photoperiod-controlled behavior. Anurans, for example, generally breed nocturnally, and the influence of light pollution on their natural history may therefore be especially strong. In this study, we tested this hypothesis by measuring male calling behavior of anuran communities in natural wetlands in southern Brazil exposed or not exposed to street lights. We recorded seasonal and diel calling activity and calling response to a light pulse. The peak calling season differed between continuously lit and unlit locations with most species in illuminated wetlands shortening their calling season and calling earlier in the year. In unlit breeding sites, Boana pulchella, Pseudis minuta, and Pseudopaludicola falcipes confined their calling activity to well-defined hours of the night, but in continuously lit areas, these species called more continuously through the night. A 2-minute light pulse inhibited calling, but only in unlit wetlands. After a light pulse, frogs quickly resumed calling-suggesting acclimatization to brief artificial light exposure. Our field experiment presents a convincing example of ecological light pollution showing that artificial light alters the seasonal and diel calling time of some South American wetland anurans. It also documents their acclimatization to brief lighting when being continuously exposed to light.

Cloning-independent markerless gene editing in Streptococcus sanguinis: novel insights in type IV pilus biology.

Streptococcus sanguinis, a naturally competent opportunistic human pathogen, is a Gram-positive workhorse for genomics. It has recently emerged as a model for the study of type IV pili (Tfp)-exceptionally widespread and important prokaryotic filaments. To enhance genetic manipulation of Streptococcus sanguinis, we have developed a cloning-independent methodology, which uses a counterselectable marker and allows sophisticated markerless gene editing in situ. We illustrate the utility of this methodology by answering several questions regarding Tfp biology by (i) deleting single or mutiple genes, (ii) altering specific bases in genes of interest, and (iii) engineering genes to encode proteins with appended affinity tags. We show that (i) the last six genes in the pil locus harbouring all the genes dedicated to Tfp biology play no role in piliation or Tfp-mediated motility, (ii) two highly conserved Asp residues are crucial for enzymatic activity of the prepilin peptidase PilD and (iii) that pilin subunits with a C-terminally appended hexa-histidine (6His) tag are still assembled into functional Tfp. The methodology for genetic manipulation we describe here should be broadly applicable.

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema.

PURPOSE: Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. METHODS: Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometer arm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. RESULTS: Median follow-up was 34.7 months over 4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurement techniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207 mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170 mL [+ 105, + 237 mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. CONCLUSIONS: This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.

Structural and functional changes in the somatosensory cortex in euthymic females with bipolar disorder.

OBJECTIVE: Current evidence from neuroimaging data suggests possible dysfunction of the fronto-striatal-limbic circuits in individuals with bipolar disorder. Somatosensory cortical function has been implicated in emotional recognition, risk-taking and affective responses through sensory modalities. This study investigates anatomy and function of the somatosensory cortex in euthymic bipolar women. METHODS: In total, 68 right-handed euthymic women (bipolar disorder = 32 and healthy controls = 36) between 16 and 45 years of age underwent high-resolution anatomical and functional magnetic resonance imaging during the mid-follicular menstrual phase. The somatosensory cortex was used as a seed region for resting-state functional connectivity analysis. Voxel-based morphometry was used to evaluate somatosensory cortical gray matter volume between groups. RESULTS: We found increased resting-state functional connectivity between the somatosensory cortex and insular cortex, inferior prefrontal gyrus and frontal orbital cortex in euthymic bipolar disorder subjects compared to healthy controls. Voxel-based morphometry analysis showed decreased gray matter in the left somatosensory cortex in the bipolar disorder group. Whole-brain voxel-based morphometry analysis controlled by age did not reveal any additional significant difference between groups. CONCLUSION: This study is the first to date to evaluate anatomy and function of the somatosensory cortex in a well-characterized sample of euthymic bipolar disorder females. Anatomical and functional changes in the somatosensory cortex in this population might contribute to the pathophysiology of bipolar disorder.

Therapist-Driven Telephone Call Outreach to Improve Depression Remission in a Federally Qualified Health Center.

The authors examined the feasibility and impact of a therapist-driven outreach program on depression outcomes in a primary care clinic. Patients with a diagnosis of depression but missing a 1-year follow-up Patient Health Questionnaire-9 (PHQ-9) screening were rescreened via telephone. Eligible patients (N=241) were contacted, and implementation rates and outcomes, along with feasibility, were assessed. Of the patients contacted, 47% indicated a depression response (reduction in PHQ-9 score of ≥50%), and 33% met remission criteria (PHQ-9 score <5). PHQ-9 scores decreased by approximately 7 points (p<0.001). This project may have helped to improve depression symptoms and remission rates for patients of the clinic and to facilitate patient reengagement with treatment.

Long-Term Survival Rates and Treatment Trends of Burkitt Lymphoma in Patients with HIV-A National Cancer Database (NCDB) Study.

BACKGROUND: Burkitt lymphoma (BL) accounts for 10-35% of AIDS-defining lymphoma in people with HIV (PWH). Previous research consisting of smaller cohorts has shown decreased survival for HIV-associated BL. This study aims to compare overall mortality in BL patients with and without HIV, while investigating impact of treatment modalities in HIV-associated BL. METHODS: Using the 2004-2019 NCDB, we identified 4312 patients with stage 3 or 4 BL who had a known HIV status and received either chemotherapy alone or chemotherapy and immunotherapy. Time to death was evaluated using Kaplan-Meier survival estimates. Risk of death was evaluated using an extended multivariable Cox model adjusted for multiple factors and with a Heaviside function for HIV status by time period (0-3 month vs. 3-60 month). RESULTS: Of the 4312 patients included, 1514 (35%) had HIV. For months 0-3 from time of diagnosis, HIV status was not associated with a statistically significant increase in risk of death (HR = 1.04, 95% CI: 0.86, 1.26, p = 0.6648). From month 3to 60, positive HIV status was associated with a 55% increase in risk of death compared to those without HIV (95% CI: 1.38, 1.75, p < 0.0001). Further, this difference in hazard rates (0-3 vs. 3-60) was statistically significant (HR = 1.49, 95% CI: 1.22-1.82, p < 0.001). CONCLUSIONS: There is an increased mortality rate from months 3 to 60 in BL patients with HIV compared to patients without HIV. Additionally, risk of death in the first 3 months is significantly decreased by 45% in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV receiving combination chemotherapy and immunotherapy, providing valuable clinical insight into treatment decision making in the care of HIV-associated BL.

The Transcriptomic Signature of Cyclical Parthenogenesis.

Cyclical parthenogenesis, where females can engage in sexual or asexual reproduction depending on environmental conditions, represents a novel reproductive phenotype that emerged during eukaryotic evolution. The fact that environmental conditions can trigger cyclical parthenogens to engage in distinct reproductive modes strongly suggests that gene expression plays a key role in the origin of cyclical parthenogenesis. However, the genetic basis underlying cyclical parthenogenesis remains understudied. In this study, we characterize the female transcriptomic signature of sexual versus asexual reproduction in the cyclically parthenogenetic microcrustacean Daphnia pulex and Daphnia pulicaria. Our analyses of differentially expressed genes (DEGs), pathway enrichment, and gene ontology (GO) term enrichment clearly show that compared with sexual reproduction, the asexual reproductive stage is characterized by both the underregulation of meiosis and cell cycle genes and the upregulation of metabolic genes. The consensus set of DEGs that this study identifies within the meiotic, cell cycle, and metabolic pathways serves as candidate genes for future studies investigating how the two reproductive cycles in cyclical parthenogenesis are mediated at a molecular level. Furthermore, our analyses identify some cases of divergent expression among gene family members (e.g., doublesex and NOTCH2) associated with asexual or sexual reproductive stage, suggesting potential functional divergence among gene family members.

Mycophenolate Mofetil for Systemic Lupus Erythematosus: Our 20-Year Experience.

OBJECTIVES: Mycophenolate mofetil (MMF) has been long used in the treatment of systemic lupus erythematosus (SLE). Further studies are warranted to investigate its long-term use in maintenance treatment of lupus nephritis (LN). The purpose of this study was to describe our practice experience using MMF with regard to its indications, safety, tolerability, and treatment efficacy. We sought to identify rates of renal remission, flare and progression to end-stage renal disease (ESRD). METHODS: In this retrospective chart review, we identified all patients treated with MMF between 1999 and 2019. Descriptive statistics were used to identify occurrence of remission, occurrence of flares, progression to ESRD, and occurrence of adverse effects. RESULTS: One hundred and one patients were treated with MMF for a mean duration of 69 months. The most common indication was LN (90%). Among patients with LN, 60% achieved complete remission and 16% achieved partial remission at one-year follow-up. Ten patients flared while on maintenance therapy and seven patients flared after treatment was discontinued. Of the 40 patients who were treated for at least five years, one patient developed a flare. Of the 13 patients who were treated for at least 10 years, none developed a flare. One patient on maintenance therapy progressed to ESRD. The most common adverse effects were leukopenia (9%), nausea (7%) and diarrhea (6%). CONCLUSION: Maintenance treatment with MMF constitutes an effective long-term treatment for lupus nephritis. Our practice demonstrates its tolerability over many years with few adverse effects, prevention of renal flares, and a low progression rate to ESRD.

Anesthetic Management for Cesarean Delivery in a Patient With a Difficult Airway and Risks for Postpartum Hemorrhage: A Case Report.

Neuraxial anesthesia is the preferred anesthesia technique for cesarean delivery, however, conversion to general anesthesia may be required for a variety of clinical scenarios, including massive post-partum hemorrhage. Obstetric patients are known to have otherwise more difficult airways and emergent situations can increase the likelihood of failed intubation with potentially disastrous consequences. We describe a novel anesthesia technique for cesarean delivery using neuraxial anesthesia as the primary anesthetic technique and electively securing the airway for a patient with multiple risk factors for post-partum hemorrhage and features concerning difficult intubation.

Serotonin transporter (5-HTT) gene network moderates the impact of prenatal maternal adversity on orbitofrontal cortical thickness in middle childhood.

In utero, the developing brain is highly susceptible to the environment. For example, adverse maternal experiences during the prenatal period are associated with outcomes such as altered neurodevelopment and emotion dysregulation. Yet, the underlying biological mechanisms remain unclear. Here, we investigate whether the function of a network of genes co-expressed with the serotonin transporter in the amygdala moderates the impact of prenatal maternal adversity on the structure of the orbitofrontal cortex (OFC) in middle childhood and/or the degree of temperamental inhibition exhibited in toddlerhood. T1-weighted structural MRI scans were acquired from children aged 6-12 years. A cumulative maternal adversity score was used to conceptualize prenatal adversity and a co-expression based polygenic risk score (ePRS) was generated. Behavioural inhibition at 18 months was assessed using the Early Childhood Behaviour Questionnaire (ECBQ). Our results indicate that in the presence of a low functioning serotonin transporter gene network in the amygdala, higher levels of prenatal adversity are associated with greater right OFC thickness at 6-12 years old. The interaction also predicts temperamental inhibition at 18 months. Ultimately, we identified important biological processes and structural modifications that may underlie the link between early adversity and future deviations in cognitive, behavioural, and emotional development.

Examining resting-state network connectivity in children exposed to perinatal maternal adversity using anatomically weighted functional connectivity (awFC) analyses; A preliminary report.

Introduction: Environmental perturbations during critical periods can have pervasive, organizational effects on neurodevelopment. To date, the literature examining the long-term impact of early life adversity has largely investigated structural and functional imaging data outcomes independently. However, emerging research points to a relationship between functional connectivity and the brain's underlying structural architecture. For instance, functional connectivity can be mediated by the presence of direct or indirect anatomical pathways. Such evidence warrants the use of structural and functional imaging in tandem to study network maturation. Accordingly, this study examines the impact of poor maternal mental health and socioeconomic context during the perinatal period on network connectivity in middle childhood using an anatomically weighted functional connectivity (awFC) approach. awFC is a statistical model that identifies neural networks by incorporating information from both structural and functional imaging data. Methods: Resting-state fMRI and DTI scans were acquired from children aged 7-9 years old. Results: Our results indicate that maternal adversity during the perinatal period can affect offspring's resting-state network connectivity during middle childhood. Specifically, in comparison to controls, children of mothers who had poor perinatal maternal mental health and/or low socioeconomic status exhibited greater awFC in the ventral attention network. Discussion: These group differences were discussed in terms of the role this network plays in attention processing and maturational changes that may accompany the consolidation of a more adult-like functional cortical organization. Furthermore, our results suggest that there is value in using an awFC approach as it may be more sensitive in highlighting connectivity differences in developmental networks associated with higher-order cognitive and emotional processing, as compared to stand-alone FC or SC analyses.