Mechanisms of Resilience in Children of Mothers Who Self-Report with Depressive Symptoms in the First Postnatal Year

Background

Symptoms of maternal postnatal depression are associated with an increased risk of adverse effects on child development. However, some children exposed to postnatal depression have outcomes similar to unexposed children, and can be referred to as resilient. This study aimed to determine the mechanisms of resilience in children exposed to depressive symptoms postnatally.

Method

Data are from a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Self-report questionnaire data were collected during pregnancy and the child’s first 2 years regarding maternal views of parenting and her perception of the child. The Edinburgh Postnatal Depression Scale (EPDS) was completed postnatally at 8 months and the Strengths and Difficulties Questionnaire (SDQ) at age 11 years. Exposed children who scored above the median score of non-exposed children were defined as resilient. Structural equation modeling was used to investigate the development of resilience.

Results

From the core ALSPAC cohort, 1,009 children (6.9%) were exposed to maternal depression at 8 months postnatally. The SDQ total difficulties scores at 11 years of age indicated that 325 (32.2%) were resilient, 684 were non-resilient. Maternal positive feelings about parenting and child non-verbal communication at 15 months increased the likelihood of later resilience.

Conclusions

In this study, resilience was associated with two factors: the child’s nonverbal communication at 15 months and by maternal positive feelings about parenting. Early intervention to support mother-child interaction and foster child development in women identified with postnatal depressive symptoms may benefit later child resilience.     

Polygenic Analysis of Late-Onset Alzheimer’s Disease from Mainland China

Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD. Risk SNPs included rs9331888 (CLU), rs6691117 (CR1), rs4938933 (MS4A), rs9349407 (CD2AP), rs1160985 (TOMM40), rs4945261 (GAB2) and rs5984894 (PCDH11X); Protective SNPs consisted of rs744373 (BIN1), rs1562990 (MS4A), rs597668 (EXOC3L2), rs9271192 (HLA-DRB5/DRB1), rs157581 and rs11556505 (TOMM40). Among positive SNPs presented above, we found the interaction between rs4938933 (risk) and rs1562990 (protective) in MS4A weakened their each effect for LOAD; for three significant SNPs in TOMM40, their cumulative interaction induced the two protective SNPs effects lost and made the risk SNP effect aggravate for LOAD. Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk. In a word, our study indicates that SNP-SNP interaction existed in the same gene or cross different genes, which could weaken or aggravate their initial single effects for LOAD.     

SNAREs Interact with Retinal Degeneration Slow and Rod Outer Segment Membrane Protein-1 during Conventional and Unconventional Outer Segment Targeting

Mutations in the photoreceptor protein peripherin-2 (also known as RDS) cause severe retinal degeneration. RDS and its homolog ROM-1 (rod outer segment protein 1) are synthesized in the inner segment and then trafficked into the outer segment where they function in tetramers and covalently linked larger complexes. Our goal is to identify binding partners of RDS and ROM-1 that may be involved in their biosynthetic pathway or in their function in the photoreceptor outer segment (OS). Here we utilize several methods including mass spectrometry after affinity purification, in vitro co-expression followed by pull-down, in vivo pull-down from mouse retinas, and proximity ligation assay to identify and confirm the SNARE proteins Syntaxin 3B and SNAP-25 as novel binding partners of RDS and ROM-1. We show that both covalently linked and non-covalently linked RDS complexes interact with Syntaxin 3B. RDS in the mouse is trafficked from the inner segment to the outer segment by both conventional (i.e., Golgi dependent) and unconventional secretory pathways, and RDS from both pathways interacts with Syntaxin3B. Syntaxin 3B and SNAP-25 are enriched in the inner segment (compared to the outer segment) suggesting that the interaction with RDS/ROM-1 occurs in the inner segment. Syntaxin 3B and SNAP-25 are involved in mediating fusion of vesicles carrying other outer segment proteins during outer segment targeting, so could be involved in the trafficking of RDS/ROM-1.     

A global life cycle assessment for primary zinc production

Purpose

The purpose of this study was to update the average environmental impacts of global primary zinc production using a life cycle assessment (LCA) approach. This study represents the latest contribution from zinc producers, which historically established the first life cycle inventory for primary zinc production in 1998 (Western Europe) and the first global LCA-based cradle-to-gate study for zinc concentrate and special high-grade zinc (SHG; 99.99 %) in 2009. Improvements from the previous studies were realized through expanded geographical scope and range of production technologies.

Methods

The product system under study (SHG zinc) was characterized by collecting primary data for the relevant production processes, including zinc ore mining and concentration, transportation of the zinc concentrate, and zinc concentrate smelting. This data was modeled in GaBi 6 and complemented with background data from the GaBi 2013 databases to create the cradle-to-gate LCA model. Allocation was used to distribute the inputs and outputs among the various co-products produced during the production process, with mass of metal content being the preferred allocation approach, when applicable.

Results and discussion

In total, this global study includes primary data from 24 mines and 18 smelters, which cover 4.7?×?10⁶ MT of zinc concentrate and 3.4?×?10⁶ MT of SHG zinc, representing 36 and 27 % of global production, respectively. While the LCA model generated a full life cycle inventory, selected impact categories and indicators are reported in this article (global warming potential, acidification potential, eutrophication potential, photochemical ozone creation potential, ozone creation potential, and primary energy demand). The results show that SHG zinc has a primary energy demand of 37,500 MJ/t and a climate change impact of 2600 kg CO₂-eq./t. Across all impact categories and indicators reported here, around 65 % of the burden are associated with smelting, 30 % with mining and concentration, and 5 % with transportation of the concentrate. Sensitivity analyses were carried out for the allocation method (total mass versus mass of metal content) and transportation of zinc concentrate.

Conclusions

This study generated updated LCA information for the global production of SHG zinc, in line with the metal industry’s current harmonization efforts. Through the provision of unit process information for zinc concentrate and SHG zinc production, greater transparency is achieved. Technological and temporal representativeness was deemed to be high. Geographical representativeness, however, was found to be moderate to low. Future studies should focus on increasing company participation from underrepresented regions.

     

HUPO 2011: The new Cardiovascular Initiative - integrating proteomics and cardiovascular biology in health and disease

A newly reorganized HUPO Cardiovascular Initiative was announced at the HUPO 2011 Cardiovascular Initiative Workshop at Geneva. The new initiative is now part of the biology- and disease-driven component of the HUPO Human Proteome Project (B/D-HPP). Here we report the recent achievements and future directions of the initiative, and offer a perspective on the present challenges of cardiovascular proteomics and its integration with the cardiovascular biology community at large.     

EPR spectra and molecular dynamics agree that the nucleotide pocket of myosin V is closed and that it opens on binding actin

We have used EPR spectroscopy and computational modeling of nucleotide-analog spin probes to investigate conformational changes at the nucleotide site of myosin V. We find that, in the absence of actin, the mobility of a spin-labeled diphosphate analog [spin-labeled ADP (SLADP)] bound at the active site is strongly hindered, suggesting a closed nucleotide pocket. The mobility of the analog increases when the MV·SLADP complex (MV = myosin V) binds to actin, implying an opening of the active site in the A·MV·SLADP complex (A = actin). The probe mobilities are similar to those seen with myosin II, despite the fact that myosin V has dramatically altered kinetics. Molecular dynamics (MD) simulation was used to understand the EPR spectra in terms of the X-ray database. The X-ray structure of MV·ADP·BeFx shows a closed nucleotide site and has been proposed to be the detached state. The MV·ADP structure shows an open nucleotide site and has been proposed to be the A·MV·ADP state at the end of the working powerstroke. MD simulation of SLADP docked in the closed conformation gave a probe mobility comparable to that seen in the EPR spectrum of the MV·SLADP complex. The simulation of the open conformation gave a probe mobility that was 35-40° greater than that observed experimentally for the A·MV·SLADP state. Thus, EPR, X-ray diffraction, and computational analysis support the closed conformation as a myosin V state that is detached from actin. The MD results indicate that the MV·ADP crystal structure, which may correspond to the strained actin-bound post-powerstroke conformation resulting from head-head interaction in the dimeric processive motor, is superopened.