Determining Signalling Nodes for Apoptosis by a Genetic High-Throughput Screen

With the ever-increasing information emerging from the various sequencing and gene annotation projects, there is an urgent need to elucidate the cellular functions of the newly discovered genes. The genetically regulated cell suicide of apoptosis is especially suitable for such endeavours as it is governed by a vast number of factors.We have set up a high-throughput screen in 96-well microtiter plates for genes that induce apoptosis upon their individual transfection into human cells. Upon screening approximately 100,000 cDNA clones we determined 74 genes that initiate this cellular suicide programme. A thorough bioinformatics analysis of these genes revealed that 91% are novel apoptosis regulators. Careful sequence analysis and functional annotation showed that the apoptosis factors exhibit a distinct functional distribution that distinguishes the cell death process from other signalling pathways. While only a minority of classic signal transducers were determined, a substantial number of the genes fall into the transporter- and enzyme-category. The apoptosis factors are distributed throughout all cellular organelles and many signalling circuits, but one distinct signalling pathway connects at least some of the isolated genes. Comparisons with microarray data suggest that several genes are dysregulated in specific types of cancers and degenerative diseases.Many unknown genes for cell death were revealed through our screen, supporting the enormous complexity of cell death regulation. Our results will serve as a repository for other researchers working with genomics data related to apoptosis or for those seeking to reveal novel signalling pathways for cell suicide

Population statistics study of radio and gamma-ray pulsars in the Galactic plane

We present results of our pulsar population synthesis of ordinary isolated and millisecond pulsars in the Galactic plane. Over the past several years, a program has been developed to simulate pulsar birth, evolution and emission using Monte Carlo techniques. We have added to the program the capability to simulate millisecond pulsars, which are old, recycled pulsars with extremely short periods. We model the spatial distribution of the simulated pulsars by assuming that they start with a random kick velocity and then evolve through the Galactic potential. We use a polar cap/slot gap model for $\gamma$-ray emission from both millisecond and ordinary pulsars. From our studies of radio pulsars that have clearly identifiable core and cone components, in which we fit the polarization sweep as well as the pulse profiles in order to constrain the viewing geometry, we develop a model describing the ratio of radio core-to-cone peak fluxes. In this model, short period pulsars are more cone-dominated than in our previous studies. We present the preliminary results of our recent study and the implications for observing these pulsars with GLAST and AGILE.Comment: 6 pages, 3 figures, 1 table, accepted in Astrophysics and Space Scienc

How I report breast magnetic resonance imaging studies for breast cancer staging and screening

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes. This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates. In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study. The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a remarkable paradigm shift in the treatment of both early stage and locally advanced breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40644-016-0078-0) contains supplementary material, which is available to authorized users

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio (‘desaturation index’) – displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = −0.80; P = 0.0001) and the Boston Naming test (r = −0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD

Pollen, biomarker and stable isotope evidence of late Quaternary environmental change at Lake McKenzie, southeast Queensland

Unravelling links between climate change and vegetation response during the Quaternary is important if the climate–environment interactions of modern systems are to be fully understood. Using a sediment core from Lake McKenzie, Fraser Island, we reconstruct changes in the lake ecosystem and surrounding vegetation over the last ca. 36.9 cal kyr. Evidence is drawn from multiple sources, including pollen, micro-charcoal, biomarker and stable isotope (C and N) analyses, and is used to gain a better understanding of the nature and timing of past ecological changes that have occurred at the site. The glacial period of the record, from ca. 36.9 to 18.3 cal kyr BP, is characterised by an increased abundance of plants of the aquatic and littoral zone, indicating lower lake water levels. High abundance of biomarkers and microfossils of the colonial green alga Botryococcus occurred at this time and included large variation in individual botryococcene d13C values. A slowing or ceasing of sediment accumulation occurred during the time period from ca. 18.3 to 14.0 cal kyr BP. By around 14.0 cal kyr BP fire activity in the area was reduced, as was abundance of littoral plants and terrestrial herbs, suggesting wetter conditions from that time. The Lake McKenzie pollen record conforms to existing records from Fraser Island by containing evidence of a period of reduced effective precipitation that commenced in the mid-Holocene

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL