Rare variants analyses suggest novel cleft genes in the African population

Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E−04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.</p

Neoadjuvant Therapy in Early Breast Cancer:Treatment Considerations and Common Debates in Practice

Neoadjuvant treatment offers a number of benefits for patients with early breast cancer, and is an important option for consideration by multidisciplinary teams. Despite literature showing its efficacy, the use of neoadjuvant therapy varies widely. Here we discuss the clinical evidence supporting the use of neoadjuvant therapy in early stage breast cancer, including patient selection, monitoring response, surgery and radiotherapy considerations, with the aim of assisting multidisciplinary teams to determine patient suitability for neoadjuvant treatment

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives

Background Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies

Fatty acid profiles of phyllosoma larvae of western rock lobster (Panulirus cygnus) in cyclonic and anticyclonic eddies of the Leeuwin Current off Western Australia

The recent dramatic decline in settlement in the population of the spiny lobster, Panulirus cygnus, may be due to changes in the oceanographic processes that operate offshore of Western Australia. It has been suggested that this decline could be related to poor nutritional condition of the post-larvae, especially lipid which is accumulated in large quantities during the preceding extensive pelagic larval stage. The current study focused on investigations into the lipid content and fatty acid (FA) profiles of lobster phyllosoma larvae from three mid to late stages of larval development (stages VI, VII, VIII) sampled from two cyclonic and two anticyclonic eddies of the Leeuwin Current off Western Australia. The results showed significant accumulation of lipid and energy storage FAs with larval development regardless of location of capture, however, larvae from cyclonic eddies had more lipid and FAs associated with energy storage than larvae from anticyclonic eddies. FA food chain markers from the larvae indicated significant differences in the food webs operating in the two types of eddy, with a higher level of FA markers for production from flagellates and a lower level from copepod grazing in cyclonic versus anticyclonic eddies. The results indicate that the microbial food web operating in cyclonic eddies provides better feeding conditions for lobster larvae despite anticyclonic eddies being generally more productive and containing greater abundances of zooplankton as potential prey for lobster larvae. Gelatinous zooplankton, such as siphonophores, may play an important role in cyclonic eddies by accumulating dispersed microbial nutrients and making them available as larger prey for phyllosoma. The markedly superior nutritional condition of lobster larvae feeding in the microbial food web found in cyclonic eddies, could greatly influence their subsequent settlement and recruitment to the coastal fishery

Multi-locus DNA metabarcoding of zooplankton communities and scat reveal trophic interactions of a generalist predator

To understand the ecosystem dynamics that underpin the year-round presence of a large generalist consumer, the Bryde’s whale (Balaenoptera edeni brydei), we use a DNA metabarcoding approach and systematic zooplankton surveys to investigate seasonal and regional changes in zooplankton communities and if whale diet reflects such changes. Twenty-four zooplankton community samples were collected from three regions throughout the Hauraki Gulf, New Zealand, over two temperature regimes (warm and cool seasons), as well as 20 samples of opportunistically collected Bryde’s whale scat. Multi-locus DNA barcode libraries were constructed from 18S and COI gene fragments, representing a trade-of between identifcation and resolution of metazoan taxa. Zooplankton community OTU occurrence and relative read abundance showed regional and seasonal diferences based on permutational analyses of variance in both DNA barcodes, with signifcant changes in biodiversity indices linked to season in COI only. In contrast, we did not fnd evidence that Bryde’s whale diet shows seasonal or regional trends, but instead indicated clear prey preferences for krill-like crustaceans, copepods, salps and ray-fnned fshes independent of prey availability. The year-round presence of Bryde’s whales in the Hauraki Gulf is likely associated with the patterns of distribution and abundance of these key prey items.Te research was supported by a University of Auckland FRDF Post-Doctoral Grant, Te Hauraki Gulf Marine Mammal Fund administered by the Department of Conservation, and NZGL. Tanks to Andrew Dopheide for technical advice, the crew of Dolphin Explorer and RV Hawere for sample collection, Asela Dassanayake and Emma Scheltema for support with this research