Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates.Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented.Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = −0.32; 95% CI: −0.59, −0.06; p = 0.014) and NT-3 (SMD = −0.31; 95% CI: −0.52, −0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes.Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.

Background-There is growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of addictive disorders. MicroRNAs (miRNAs) are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level. However, the role of miRNAs as potential biomarkers for addiction is still underexplored. Based on translational and clinical findings, we compared the expression levels of microRNA-124 (miR-124), microRNA-181 (miR-181), and microRNA-212 (miR-212) between a group of females with cocaine use disorder (CUD; n = 30) and a group of healthy female controls (HC; n = 20). Methods-Blood expression levels of miR-124, miR-181, and miR-212 in the HC and CUD group were determined by qPCR, using two miRNAs as endogenous controls (miR-24 and miR-126). Substance use behavior was assessed by self-report using the Addiction Severity Index (ASI-6) and depressive symptoms severity was measured using the Beck Depressive Inventory (BDI-II). Urine screen test was performed to detect cocaine metabolites.

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.

No abstract

BackgroundRNA‐seq experiments have traditionally been done with short‐read sequencing technologies that, by nature, collapse all RNA isoforms for a given gene into a single expression measurement—a major oversimplification of the underlying biology. Collapsing all RNA isoforms for a single gene severely limits our ability to characterize all RNA isoforms and determine their individual downstream functions. While computational approaches for assembling short reads into full transcripts exist, these methods are inherently structurally inaccurate, especially when compared to full‐length sequencing possible with long‐read sequencing technologies. In contrast, long‐read sequencing technologies can sequence entire RNA molecules, allowing researchers to accurately quantify expression for the complete set of RNA isoform species, including de novo RNA isoforms. Long‐read sequencing is especially well suited for discovering novel isoforms in the recently released telomere‐to‐telomere (T2T) human reference genome (CHM13). The new CHM13 genome assembly resolved highly homologous regions that are challenging to study with short‐reads. Here we sequenced post‐mortem human brain tissue with long‐reads and aligned them to CHM13 to explore novel gene bodies and transcript isoforms.MethodsWe sequenced pre‐frontal cortex tissue from four post‐mortem human brain samples using Oxford Nanopore Technologies long‐read sequencing for PCR amplified cDNA. Data were basecalled using Guppy, reads were aligned to the CHM13 human reference genome using minimap2, and transcripts were assembled and quantified with the Bambu package in R.ResultsAmong other findings, we discovered 84 new, high‐confidence gene bodies expressed in all four samples with at least 5 reads in each sample. We also found 223 novel RNA isoforms in previously annotated gene bodies. Of these 223 novel isoforms, 29 aligned to medically relevant genes such as MAOB, HLA‐DRB1, and ABO.ConclusionsOur results suggest long‐reads aligned to the CHM13 reference genome have the potential to reveal novel gene bodies and transcript isoforms that were missed in previous studies. These methods can provide a more complete picture of the transcriptomic landscape of diseases, including Alzheimer’s disease—hopefully generating information with potential to help inform future treatment and/or early diagnostic efforts.

No abstract

No abstract

BackgroundFor many regions of the genome, genetic variants are completely overlooked when using standard short‐read sequencing approaches because of either; (1) lack of coverage (i.e., ‘dark‐by‐depth'), or (2) reads aligning to multiple regions (i.e., ‘dark‐by‐MAPQ', a.k.a. ‘camouflaged’ genes). Multiple alignments occur because of genomic duplication events that contribute to molecular evolution, but present major analytical challenges for aligning short‐read sequencing data to the genome. We previously presented a method to identify and differentiate dark and camouflaged regions by analyzing the read depth and reads with multiple alignments. Here we present data demonstrating that not only do camouflaged regions conceal essential genetic variants, but they further conceal results from other short‐read sequencing assays, including ATAC‐Seq and Hi‐C. Our results have important implications for all disease research, including Alzheimer’s disease.MethodsWe identified and validated genome‐wide camouflaged regions using an updated version of our algorithm to identify camouflaged genomic regions, and then applied it to publicly available ATAC‐Seq and Hi‐C sequencing data sets.ResultsWe identified 148,197 camouflaged regions of greater than 20 bases. Of these regions 23.23% overlap at least one Ensembl transcript. Additionally, we found that results for camouflaged regions, including CR1 (a top Alzheimer’s disease gene), are also non‐existent in ATAC‐Seq and Hi‐C data. As previously described, we can rescue variants that fall within these regions such as the frameshift we described in CR1. Thereby, we show that including a rescuing step in your alignment pipeline may provide important insights into disease etiology.ConclusionWhile short‐read sequencing has been a major boon to research, there are many systematic flaws to using short‐read sequencing, including camouflaged regions. Rescuing variants or peaks in these camouflaged regions could elucidate important findings related to Alzheimer’s Disease etiology that are missed by standard short‐read sequencing methods.