Book Review: Red Scare! by Don E. Carleton.

Book review: Red Scare! By Don E. Carleton. Austin, Texas: Texas Monthly Press. 1985. Pp. xii, 390. Reviewed by: Harold M Hyman

Book Review: Red Scare! by Don E. Carleton.

Book review: Red Scare! By Don E. Carleton. Austin, Texas: Texas Monthly Press. 1985. Pp. xii, 390. Reviewed by: Harold M Hyman

Using a genetically informative design to examine the relationship between breastfeeding and childhood conduct problems

A number of public health interventions aimed at increasing the uptake of breastfeeding are in place in the United States and other Western countries. While the physical health and nutritional benefits of breastfeeding for the mother and child are relatively well established, the evidence for psychological effects is less clear. This study aimed to examine whether there is an association between breastfeeding and later conduct problems in children. It also considered the extent to which any relationship is attributable to maternally-provided inherited characteristics that influence both likelihood of breastfeeding and child conduct problems. A prenatal cross-fostering design with a sample of 870 families with a child aged 4–11 years was used. Mothers were genetically related or unrelated to their child as a result of assisted reproductive technologies. The relationship between breastfeeding and conduct problems was assessed while controlling for theorised measured confounders by multivariate regression (e.g. maternal smoking, education, and antisocial behaviour), and for unmeasured inherited factors by testing associations separately for related and unrelated mother-child pairs. Breastfeeding was associated with lower levels of conduct disorder symptoms in offspring in middle childhood. Breastfeeding was associated with lower levels of conduct problems even after controlling for observed confounders in the genetically related group, but not in the genetically unrelated group. In contrast, maternal antisocial behaviour showed robust associations with child conduct problems after controlling for measured and inherited confounders. These findings highlight the importance of using genetically sensitive designs in order to test causal environmental influences

Climate-Smart Crop-Livestock Systems for Smallholders in the Tropics: Integration of New Forage Hybrids to Intensify Agriculture and to Mitigate Climate Change through Regulation of Nitrification in Soil

It is widely recognized that less than 50% of applied nitrogen (N) fertilizer is recovered by crops, and based on current fertilizer prices the economic value of this “wasted N” globally is currently estimated as US$81 billion annually. Worse still, this wasted N has major effects on the environment (Subbarao et al. 2012). CIAT researchers and their collaborators in Japan reported a major breakthrough in managing N to benefit both agriculture and the environment (Subbarao et al. 2009). Termed Biological Nitrification Inhibition (BNI), this natural phenomenon has been the subject of long-term collaborative research that revealed the mechanism by which certain plants (and in particular the tropical pasture grass B. humidicola) naturally inhibit the conversion of N in the soil from a stable form to forms subject to leaching loss (NO3) or to the potent greenhouse gas N2O (Subbarao et al. 2012). Brachiaria humidicola which is well adapted to the low-nitrogen soils of South American savannas has shown high BNI-capacity among the tropical grasses tested (Subbarao et al. 2007). The major nitrification inhibitor in Brachiaria forage grasses is brachialactone, a cyclic diterpene (Subbarao et al. 2009). Reduction of N loss from the soil under a B. humidicola pasture has a direct and beneficial environmental effect. We hypothesize that this conservation of soil N will have an additional positive impact on a subsequent crop (e.g. maize). At present, recovery of fertilizer N and the impact on crop yield is not known. The main purpose of our inter-institutional and multi-disciplinary project, targeting small-scale farmers, is to develop the innovative approach of BNI using B. humidicola forage grass hybrids to realize sustainable economic and environmental benefits from integrated crop-livestock production systems

Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease

Abstract: Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may create opportunities for therapeutic interventions in AD

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele