Melanoma central nervous system metastases: An update to approaches,challenges, and opportunities

In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.     

The Structural Basis of the Farnesylated and Methylated KRas4B Interaction with Calmodulin

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Phytoplankton decline in the eastern North Pacific transition zone associated with atmospheric blocking

Global climate change can significantly influence oceanic phytoplankton dynamics, and thus biogeochemical cycles and marine food webs. However, associative explanations based on the correlation between chlorophyll‐a concentration (Chl‐a) and climatic indices is inadequate to describe the mechanism of the connection between climate change, large‐scale atmospheric dynamics, and phytoplankton variability. Here, by analyzing multiple satellite observations of Chl‐a and atmospheric conditions from National Center for Environmental Prediction/National Center for Atmospheric Research reanalysis datasets, we show that high‐latitude atmospheric blocking events over Alaska are the primary drivers of the recent decline of Chl‐a in the eastern North Pacific transition zone. These blocking events were associated with the persistence of large‐scale atmosphere pressure fields that decreased westerly winds and southward Ekman transport over the subarctic ocean gyre. Reduced southward Ekman transport leads to reductions in nutrient availability to phytoplankton in the transition zone. The findings describe a previously unidentified climatic factor that contributed to the recent decline of phytoplankton in this region and propose a mechanism of the top‐down teleconnection between the high‐latitude atmospheric circulation anomalies and the subtropical oceanic primary productivity. The results also highlight the importance of understanding teleconnection among atmosphere–ocean interactions as a means to anticipate future climate change impacts on oceanic primary production.     

Prospects for seascape repair: Three case studies from eastern Australia

Three case studies spanning tropical, subtropical and temperate environments highlight the minimum potential benefits of investing in repair of coastal seascapes. Fisheries, a market benefit indicator readily understood by a range of stakeholders from policymakers to community advocates, were used as a surrogate for ecosystem services generated through seascape habitat restoration. For each case study, while recognising that biological information will always remain imperfect, the prospects for seascape repair are compelling.     

Genomic analysis and lactose transporter expression in Kluyveromyces marxianus CCT 7735

Kluyveromyces marxianus CCT 7735 has been used to produce ethanol, aromatic compounds, enzymes and heterologous proteins besides assimilates lactose as carbon source. Its genome has 10.7 Mb and encodes 4787 genes distributed in 8 nuclear chromosomes and one mitochondrial. Contrary to Kluyveromyces lactis, which has a unique LAC12 gene (encodes lactose permease), K. marxianus possesses four. The presence of degenerated copies and Solo-LTRs related to retrotransposon TKM close to the LAC12 genes in K. marxianus indicates ectopic recombinations. The Lac12 permeases of K. marxianus and K. lactis are conserved, however the conservation is higher between the copy of the left side of the chromosome three and the unique copy of K. lactis, indicating that this copy is the ancestor. The expression of the four LAC12 genes occurred in aerobiosis and hypoxia. Notably, the high lactose consumption in hypoxia seems to be related to the high expression of the LAC12 genes.     

Resolving the genetic basis of invasiveness and predicting invasions

Considerable effort has been invested in determining traits underlying invasiveness. Yet, identifying a set of traits that commonly confers invasiveness in a range of species has proven elusive, and almost nothing is known about genetic loci affecting invasive success. Incorporating genetic model organisms into ecologically relevant studies is one promising avenue to begin dissecting the genetic underpinnings of invasiveness. Molecular biologists are rapidly characterizing genes mediating developmental responses to diverse environmental cues, i.e., genes for plasticity, as well as to environmental factors likely to impose strong selection on invading species, e.g., resistance to herbivores and competitors, coordination of life-history events with seasonal changes, and physiological tolerance of heat, drought, or cold. Here, we give an overview of molecular genetic tools increasingly used to characterize the genetic basis of adaptation and that may be used to begin identifying genetic mechanisms of invasiveness. Given the divergent traits that affect invasiveness, “invasiveness genes” common to many clades are unlikely, but the combination of developmental genetic advances with further evolutionary studies and modeling may provide a framework for identifying genes that account for invasiveness in related species.     

Weight gain prevention among women

Objective: Women 25 to 45 years old are at risk for weight gain and future obesity. This trial was designed to evaluate the efficacy of two interventions relative to a control group in preventing weight gain among normal or overweight women and to identify demographic, behavioral, and psychosocial factors related to weight gain prevention. Research Methods and Procedures: Healthy women (N = 284), ages 25 to 44, with BMI < 30 were randomized to one of three intervention conditions: a clinic‐based group, a correspondence course, or an information‐only control. Intervention was provided over 2 years, with a follow‐up at Year 3. BMI and factors related to eating and weight were assessed yearly. Results: Over the 3‐year study period, 40% (n = 114) of the women remained at or below baseline body weight (±2 lbs), and 60% gained weight (>2 lbs). Intervention had no effect on weight over time. Independently of intervention, women who were older, not actively dieting to lose weight, and who reported less perceived hunger at baseline were more likely to be successful at weight maintenance. Weight maintenance also was associated with increasing dietary restraint (conscious thoughts and purposeful behaviors to control calorie intake) and decreasing dietary disinhibition (the tendency to lose control over eating) over time. Discussion: This study raises concern about the feasibility and efficacy of weight gain prevention interventions because most women were interested in weight loss, rather than weight gain prevention, and the interventions had no effect on weight stability. Novel approaches to the prevention of weight gain are needed.     

Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the alpha- and beta-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium.