On the extent and role of the small proteome in the parasitic eukaryote Trypanosoma brucei

Background: Although technical advances in genomics and proteomics research have yielded a better understanding of the coding capacity of a genome, one major challenge remaining is the identification of all expressed proteins, especially those less than 100 amino acids in length. Such information can be particularly relevant to human pathogens, such as Trypanosoma brucei, the causative agent of African trypanosomiasis, since it will provide further insight into the parasite biology and life cycle. Results: Starting with 993 T. brucei transcripts, previously shown by RNA-Sequencing not to coincide with annotated coding sequences (CDS), homology searches revealed that 173 predicted short open reading frames in these transcripts are conserved across kinetoplastids with 13 also conserved in representative eukaryotes. Mining mass spectrometry data sets revealed 42 transcripts encoding at least one matching peptide. RNAi-induced down-regulation of these 42 transcripts revealed seven to be essential in insect-form trypanosomes with two also required for the bloodstream life cycle stage. To validate the specificity of the RNAi results, each lethal phenotype was rescued by co-expressing an RNAi-resistant construct of each corresponding CDS. These previously non-annotated essential small proteins localized to a variety of cell compartments, including the cell surface, mitochondria, nucleus and cytoplasm, inferring the diverse biological roles they are likely to play in T. brucei. We also provide evidence that one of these small proteins is required for replicating the kinetoplast (mitochondrial) DNA. Conclusions: Our studies highlight the presence and significance of small proteins in a protist and expose potential new targets to block the survival of trypanosomes in the insect vector and/or the mammalian host

Phase and amplitude scintillations of microwave signals over an elevated atmospheric path

Phase and amplitude scintillations of microwave signals over elevated atmospheric path for obtaining atmospheric density profile

Salience and default mode network coupling predicts cognition in aging and Parkinson’s disease

OBJECTIVES: Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. METHODS: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. RESULTS: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. CONCLUSIONS: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease.Published versio

Low-dose Computed Tomography Screening: The (Other) Lung Cancer Revolution

The advent of immune checkpoint inhibitors for the treatment of metastatic non-small cell lung cancers has been a bright spot in the otherwise bleak landscape of the UK's deadliest cancer. In a disease where two-thirds of those who present with a new diagnosis will be dead within a year, and survival outcomes have changed little in the last four decades [1], the potential to extend progression-free and overall survival by, on average, 4 months [2] is noteworthy. Immunotherapy may play a starring role in the future of lung cancer treatment but there is a more revolutionary approach to improving lung cancer outcomes: low-dose computed tomography (LDCT) screening. Lung cancer screening (LCS) with LDCT demonstrates considerable lung cancer and all-cause mortality risk reduction [3], [4]. LCS and effective and embedded smoking cessation interventions show synergy, with the mortality reduction of screening essentially doubled by prolonged cessation [5]. However, when it comes to LDCT screening, there is still a hearts-and-minds battle to be won (see Table 1)

An Innovative Dynamic Test Method for Piles

The system described involves using solid propellant fuels to accelerate a reaction mass of the test pile. The force required to accelerate the reaction mass upwards acts equally downward on the pile. Very high forces be may applied to the pile in a controlled, linearly increasing manner. The duration of the applied load is approximately 100 milliseconds. This rate of loading is slow enough to allow the pile and soil to react together as a composite rigid body. The effects combine to produce pile and soil response no longer dominated by the transfer of force via stress pulse (as with impact). State of the art instrumentation systems are used to obtain test data. Displacement is monitored directly using a laser datum and integrated receiver located at the center axis of the pile. Force is also monitored directly using a calibrated load cell

Interstellar extinction towards open clusters and galactic structure

We study the distribution of interstellar matter near the galactic plane on the basis of open star clusters and reviewed the correlation of extinction with different physical parameters of the clusters to understand the galactic structure. It is seen from the extinction towards open clusters that about 90% of the absorbing material lie within -5<b<5 deg of the galactic plane. The mean thickness of the absorbing material, which is determined in terms of half-width value \beta, is estimated to be about 125+/-21 pc. We show that the interstellar absorption follows a sinusoidal variation with galactic longitude and maximum and minimum absorptions occur at l ~ 48+/-4 deg and l ~ 228+/-4 deg respectively. It is found that the galactic plane defined by the reddening material is inclined by an angle of 0.6+/-0.4 deg to the formal galactic plane and inclination is maximum at l ~ 54+/-6 deg. The reddening analysis has been used to constrain the Solar offset which is found to be about 22.8+/-3.3 pc above the reddening plane. We obtained a scale height of 53+/-5 pc for the distribution of open clusters while it is 186+/-25 pc for the distribution of reddening material from the reddening plane.Comment: 9 pages, 12 figures, accepted for the publication in MNRA

Role of the gerP Operon in Germination and Outgrowth of Bacillus anthracis Spores

Germination of Bacillus anthracis spores occurs when nutrients such as amino acids or purine nucleosides stimulate specific germinant receptors located in the spore inner membrane. The gerPABCDEF operon has been suggested to play a role in facilitating the interaction between germinants and their receptors in spores of Bacillus subtilis and Bacillus cereus. B. anthracis mutants containing deletions in each of the six genes belonging to the orthologue of the gerPABCDEF operon, or deletion of the entire operon, were tested for their ability to germinate. Deletion of the entire gerP operon resulted in a significant delay in germination in response to nutrient germinants. These spores eventually germinated to levels equivalent to wild-type, suggesting that an additional entry point for nutrient germinants may exist. Deletions of each individual gene resulted in a similar phenotype, with the exception of ΔgerPF, which showed no obvious defect. The removal of two additional gerPF-like orthologues was necessary to achieve the germination defect observed for the other mutants. Upon physical removal of the spore coat, the mutant lacking the full gerP operon no longer exhibited a germination defect, suggesting that the GerP proteins play a role in spore coat permeability. Additionally, each of the gerP mutants exhibited a severe defect in calcium-dipicolinic acid (Ca-DPA)–dependent germination, suggesting a role for the GerP proteins in this process. Collectively, these data implicate all GerP proteins in the early stages of spore germination

Aggregation of Lipid Rafts Accompanies Signaling via the T Cell Antigen Receptor

The role of lipid rafts in T cell antigen receptor (TCR) signaling was investigated using fluorescence microscopy. Lipid rafts labeled with cholera toxin B subunit (CT-B) and cross-linked into patches displayed characteristics of rafts isolated biochemically, including detergent resistance and colocalization with raft-associated proteins. LCK, LAT, and the TCR all colocalized with lipid patches, although TCR association was sensitive to nonionic detergent. Aggregation of the TCR by anti-CD3 mAb cross-linking also caused coaggregation of raft-associated proteins. However, the protein tyrosine phosphatase CD45 did not colocalize to either CT-B or CD3 patches. Cross-linking of either CD3 or CT-B strongly induced tyrosine phosphorylation and recruitment of a ZAP-70(SH2)2–green fluorescent protein (GFP) fusion protein to the lipid patches. Also, CT-B patching induced signaling events analagous to TCR stimulation, with the same dependence on expression of key TCR signaling molecules. Targeting of LCK to rafts was necessary for these events, as a nonraft- associated transmembrane LCK chimera, which did not colocalize with TCR patches, could not reconstitute CT-B–induced signaling. Thus, our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalization of LCK, LAT, and the TCR whilst excluding CD45, thereby triggering protein tyrosine phosphorylation

XO-5b: A Transiting Jupiter-sized Planet With A Four Day Period

The star XO-5 (GSC 02959-00729, V=12.1, G8V) hosts a Jupiter-sized, Rp=1.15+/-0.12 Rjup, transiting extrasolar planet, XO-5b, with an orbital period of P=4.187732+/-0.00002 days. The planet mass (Mp=1.15+/-0.08 Mjup) and surface gravity (gp=22+/-5 m/s^2) are significantly larger than expected by empirical Mp-P and Mp-P-[Fe/H] relationships. However, the deviation from the Mp-P relationship for XO-5b is not large enough to suggest a distinct type of planet as is suggested for GJ 436b, HAT-P-2b, and XO-3b. By coincidence XO-5 overlies the extreme H I plume that emanates from the interacting galaxy pair NGC 2444/NGC 2445 (Arp 143).Comment: 10 pages, 9 Figures, Submitted to Ap

A Transiting Planet of a Sun-like Star

A planet transits an 11th magnitude, G1V star in the constellation Corona Borealis. We designate the planet XO-1b, and the star, XO-1, also known as GSC 02041-01657. XO-1 lacks a trigonometric distance; we estimate it to be 200+-20 pc. Of the ten stars currently known to host extrasolar transiting planets, the star XO-1 is the most similar to the Sun in its physical characteristics: its radius is 1.0+-0.08 R_Sun, its mass is 1.0+-0.03 M_Sun, V sini < 3 km/s, and its metallicity [Fe/H] is 0.015+-0.04. The orbital period of the planet XO-1b is 3.941534+-0.000027 days, one of the longer ones known. The planetary mass is 0.90+-0.07 M_Jupiter, which is marginally larger than that of other transiting planets with periods between 3 and 4 days. Both the planetary radius and the inclination are functions of the spectroscopically determined stellar radius. If the stellar radius is 1.0+-0.08 R_Sun, then the planetary radius is 1.30+-0.11 R_Jupiter and the inclination of the orbit is 87.7+-1.2 degrees. We have demonstrated a productive international collaboration between professional and amateur astronomers that was important to distinguishing this planet from many other similar candidates.Comment: 31 pages, 9 figures, accepted for part 1 of Ap