A short guide to hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is the only known predisposition syndrome dominated by carcinoma of the stomach and with a recognised genetic cause. Germline mutations in the E-cadherin gene (CDH1) co-segregate with the disease in about half of the families with multiple diffuse gastric cancer. In these families, identification of the CDH1 mutation allows for clinical measures to be taken. Importantly, clinical intervention is likely to be therapeutic and associated with tolerable morbidity. This review is thus aimed at providing a current overview of the clinical management and the underlying biology of HDGC

The role of the testa during development and in establishment of dormancy of the legume seed

Timing of seed germination is one of the key steps in plant life cycles. It determines the beginning of plant growth in natural or agricultural ecosystems. In the wild, many seeds exhibit dormancy and will only germinate after exposure to certain environmental conditions. In contrast, crop seeds germinate as soon as they are imbibed usually at planting time. These domestication-triggered changes represent adaptations to cultivation and human harvesting. Germination is one of the common sets of traits recorded in different crops and termed the “domestication syndrome.” Moreover, legume seed imbibition has a crucial role in cooking properties. Different seed dormancy classes exist among plant species. Physical dormancy (often called hardseededness), as found in legumes, involves the development of a water-impermeable seed coat, caused by the presence of phenolics- and suberin-impregnated layers of palisade cells. The dormancy release mechanism primarily involves seed responses to temperature changes in the habitat, resulting in testa permeability to water. The underlying genetic controls in legumes have not been identified yet. However, positive correlation was shown between phenolics content (e.g., pigmentation), the requirement for oxidation and the activity of catechol oxidase in relation to pea seed dormancy, while epicatechin levels showed a significant positive correlation with soybean hardseededness. myeloblastosis family of transcription factors, WD40 proteins and enzymes of the anthocyanin biosynthesis pathway were involved in seed testa color in soybean, pea and Medicago, but were not tested directly in relation to seed dormancy. These phenolic compounds play important roles in defense against pathogens, as well as affecting the nutritional quality of products, and because of their health benefits, they are of industrial and medicinal interest. In this review, we discuss the role of the testa in mediating legume seed germination, with a focus on structural and chemical aspects

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study

Background: Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS. Methods: In this small cohort observation study, we examined the efficacy of bilateral sequential theta-burst stimulation (bsTBS) in 8 treatment resistant depression (TRD) military veterans with PTSD comorbidity stemming from military service experience. Results: bsTBS was generally well tolerated and resulted in 25% and 38% remission and response rates on Depression scores respectively; 25% remission and response rate on PTSD scores. Discussion: This study demonstrates preliminary feasibility and safety of bsTBS in TRD with comorbid military service related PTSD. We concluded that this paradigm might hold promise as a therapeutic tool to help patients with TRD co-morbid with military service related PTSD. Further adequately powered studies to compare rTMS treatment paradigms in this patient group are warranted

The Parallel Roads of Glen Roy, Scotland : geoconservation history and challenges

Glen Roy is a classic geosite for ice-dammed lake shorelines, the Parallel Roads, and associated features formed during the Loch Lomond (Younger Dryas) Stade (12.9–11.7 ka). The area played a key part in the development of the glacial theory in the early 19th century and continues today to have outstanding scientific value for understanding the processes and timing of events at the end of the last glaciation. Glen Roy has also been long-appreciated as an awe-inspiring visitor attraction, and is now a flagship site for geotourism within Lochaber Geopark. Statutory geoconservation in Glen Roy, beginning in the second half of the 20th century, was founded on the exceptional scientific value of the area. The history and practice of geoconservation in Glen Roy illustrate the contested values of geoheritage and the evolving approaches adopted. Important lessons include the need for open dialogue and partnership working among the local community, land owners and managers, the statutory conservation agency (Scottish Natural Heritage), Lochaber Geopark and the scientific community.PostprintPeer reviewe

Australian climate warming: observed change from 1850 and global temperature targets

Mean annual temperature is often used as a benchmark for monitoring climate change and as an indicator of its potential impacts. The Paris Agreement of 2015 aims to keep the global average temperature well below 2°C above pre-industrial levels, with a preferred limit of 1.5°C. Therefore, there is interest in understanding and examining regional temperature change using this framework of ‘global warming levels’, as well as through emissions pathways and time horizons. To apply the global warming level framework regionally, we need to quantify regional warming from the late 19th century to today, and to future periods where the warming levels are reached. Here we supplement reliable observations from 1910 with early historical datasets currently available back to 1860 and the latest set of global climate model simulations from CMIP5/CMIP6 to examine the past and future warming of Australia from the 1850–1900 baseline commonly used as a proxy for pre-industrial conditions. We find that Australia warmed by ~1.6°C between 1850–1900 and 2011–2020 (with uncertainty unlikely to substantially exceed ±0.3°C). This warming is a ratio of ~1.4 times the ~1.1°C global warming over that time, and in line with observed global land average warming. Projections for global warming levels are also quantified and suggest future warming of slightly less than the observed ratio to date, at ~1.0–1.3 for all future global warming levels. We also find that to reliably examine regional warming under the emissions pathway framework using the latest climate models from CMIP6, appropriate weights to the ensemble members are required. Once these weights are applied, results are similar to CMIP5

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation

Evaluation of diversity among common beans (Phaseolus vulgaris L.) from two centers of domestication using 'omics' technologies

<p>Abstract</p> <p>Background</p> <p>Genetic diversity among wild accessions and cultivars of common bean (<it>Phaseolus vulgaris </it>L.) has been characterized using plant morphology, seed protein allozymes, random amplified polymorphic DNA, restriction fragment length polymorphisms, DNA sequence analysis, chloroplast DNA, and microsatellite markers. Yet, little is known about whether these traits, which distinguish among genetically distinct types of common bean, can be evaluated using omics technologies.</p> <p>Results</p> <p>Three 'omics' approaches: transcriptomics, proteomics, and metabolomics were used to qualitatively evaluate the diversity of common bean from two Centers of Domestication (COD). All three approaches were able to classify common bean according to their COD using unsupervised analyses; these findings are consistent with the hypothesis that differences exist in gene transcription, protein expression, and synthesis and metabolism of small molecules among common bean cultivars representative of different COD. Metabolomic analyses of multiple cultivars within two common bean gene pools revealed cultivar differences in small molecules that were of sufficient magnitude to allow identification of unique cultivar fingerprints.</p> <p>Conclusions</p> <p>Given the high-throughput and low cost of each of these 'omics' platforms, significant opportunities exist for their use in the rapid identification of traits of agronomic and nutritional importance as well as to characterize genetic diversity.</p

Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.Peer reviewe