Implications for fault locking south of Jakarta from an investigation of seismic activity along the Baribis fault, northwestern Java, Indonesia.

Recent borehole seismic deployments conducted along the Baribis Fault in northwestern Java reveal that it may be active. In this study, we exploit these data to locate proximal earthquakes using a relative relocation technique, estimate their moment magnitudes using a spectral fitting method and compute their focal mechanisms via waveform inversion. We observe that seismicity in the eastern part of the fault is significantly higher than in the west, where a previous GPS study of the region south of Jakarta demonstrated the existence of high compression rates. These observations imply that the western Baribis Fault is locked, and that neighbouring areas, including southern Jakarta and its surroundings, may be highly vulnerable to future sizeable earthquakes when accumulated elastic strain energy is eventually released during fault rupture. Significantly, the current generation of Indonesia's national hazard maps have not considered seismicity along the Baribis Fault. Our new results therefore call for an urgent reappraisal of the seismic hazard in northwestern Java that carefully takes into account the Baribis Fault and its earthquake potential, particularly in light of its proximity to Jakarta, a megacity that lies at the heart of one of the most densely populated islands in the world.

SAMPLE COMPOSITION: PARASITE ECOLOGY'S DIRTY LITTLE SECRET.

In comparative studies, the advantage of increased sample sizes might be outweighed by detrimental effects on sample homogeneity and comparability when small numbers of hosts from a different demographic of the same species are included in samples. A mixed sample of sunfishes (Lepomis spp.) was subdivided in different ways and examined using cumulative performance curves to determine whether the exclusion of larger hosts from a single-species sample and/or the inclusion of hosts of the same size demographic from closely related host species would produce more homogeneous samples. The exclusion of larger hosts from the single-species samples tended to reduce the aggregation of the infrapopulation samples, and mixed-species samples of smaller fishes tended to have lower degrees of aggregation for a given sample size relative to the single-species sample. Cumulative performance curves for diversity and richness, in concert with nonmetric multidimensional scaling of the infracommunities, demonstrated sunfish size to be a more reliable determinant of infracommunity similarity than sunfish species in this particular sample. The results demonstrate that cumulative aggregation curves can be an effective tool for delineating homogeneous and comparable subsamples and that, under some circumstances, it is possible to offset the smaller sample sizes that result from the exclusion of older/larger hosts by the addition of congeneric or confamilial hosts within the same size/age classes as the stratified sample.

Gene count from target sequence capture places three whole genome duplication events in Hibiscus L. (Malvaceae).

BACKGROUND: The great diversity in plant genome size and chromosome number is partly due to polyploidization (i.e. genome doubling events). The differences in genome size and chromosome number among diploid plant species can be a window into the intriguing phenomenon of past genome doubling that may be obscured through time by the process of diploidization. The genus Hibiscus L. (Malvaceae) has a wide diversity of chromosome numbers and a complex genomic history. Hibiscus is ideal for exploring past genomic events because although two ancient genome duplication events have been identified, more are likely to be found due to its diversity of chromosome numbers. To reappraise the history of whole-genome duplication events in Hibiscus, we tested three alternative scenarios describing different polyploidization events. RESULTS: Using target sequence capture, we designed a new probe set for Hibiscus and generated 87 orthologous genes from four diploid species. We detected paralogues in > 54% putative single-copy genes. 34 of these genes were selected for testing three different genome duplication scenarios using gene counting. All species of Hibiscus sampled shared one genome duplication with H. syriacus, and one whole genome duplication occurred along the branch leading to H. syriacus. CONCLUSIONS: Here, we corroborated the independent genome doubling previously found in the lineage leading to H. syriacus and a shared genome doubling of this lineage and the remainder of Hibiscus. Additionally, we found a previously undiscovered genome duplication shared by the /Pavonia and /Malvaviscus clades (both nested within Hibiscus) with the occurrences of two copies in what were otherwise single-copy genes. Our results highlight the complexity of genomic diversity in some plant groups, which makes orthology assessment and accurate phylogenomic inference difficult.

The effect of osteopathic manual therapy with breathing retraining on cardiac autonomic measures and breathing symptoms scores: A randomised wait-list controlled trial.

BACKGROUND: Breathing retraining and manual therapy (MT), delivered independently or together, influence autonomic activity, and improve symptoms in patients with chronic conditions. This study evaluated the effects of breathing retraining and osteopathic MT on cardiac autonomic measures and breathing symptoms during spontaneous breathing in healthy active adults. METHODS: Participants (n = 18) received breathing retraining and four, weekly manual therapy sessions, randomised to start immediately, or after 6-week delay. Heart-rate (HR) variability was assessed as a 7-day average of waking 6-min electrocardiograms, using time (logarithm of root-mean-square of successive differences; LnRMSSD) and frequency domain (logarithm of high-frequency; LnHF) measures. Recordings were taken before, one week following intervention or delay, and then following the later intervention for those with delayed starts. Changes were compared between those who received and had yet to receive the intervention, and before and after treatment for the whole cohort. RESULTS: Following the intervention, HR-variability measures increased 4% overall (Effect Sizes: 1.0-1.1) for the whole cohort. Between-group analyses showed that the immediate-start group increased more than the delayed start group: LnRMSSD 0.27 (0.02-0.52; 95%CI) ln.ms, and LnHF 0.41 (-0.01-0.84) ln.ms2 for immediate start; compared with LnRMSSD -0.09 (-0.29-0.11) ln.ms, and LnHF -0.19 (-0.59-0.22) ln.ms2 (P = 0.02-0.03 for interaction) for delayed start. Resting HR decreased following intervention in the whole cohort (Effect Size -0.8; P = 0.02). CONCLUSION: A 6-week osteopathic treatment consisting of breathing retraining and MT is beneficial in raising HR-variability compared to no treatment, and may induce favourable (parasympathetic over sympathetic) autonomic modulation. TRIAL REGISTRATION: ACTRN12614001119684.

Mass-zero constrained molecular dynamics for electrode charges in simulations of electrochemical systems.

Classical molecular dynamics simulations have recently become a standard tool for the study of electrochemical systems. State-of-the-art approaches represent the electrodes as perfect conductors, modeling their responses to the charge distribution of electrolytes via the so-called fluctuating charge model. These fluctuating charges are additional degrees of freedom that, in a Born-Oppenheimer spirit, adapt instantaneously to changes in the environment to keep each electrode at a constant potential. Here, we show that this model can be treated in the framework of constrained molecular dynamics, leading to a symplectic and time-reversible algorithm for the evolution of all the degrees of freedom of the system. The computational cost and the accuracy of the new method are similar to current alternative implementations of the model. The advantage lies in the accuracy and long term stability guaranteed by the formal properties of the algorithm and in the possibility to systematically introduce additional kinematic conditions of arbitrary number and form. We illustrate the performance of the constrained dynamics approach by enforcing the electroneutrality of the electrodes in a simple capacitor consisting of two graphite electrodes separated by a slab of liquid water.

Hairy Cell Leukemia Masquerading as Pancytopenia in Pregnancy.

Thrombocytopenia is one of the most common hematological abnormalities observed during pregnancy, and in rare cases, this may be the first indicator of an underlying hematological malignancy. Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder of which thrombocytopenia is a recurrent presenting feature. A case of pancytopenia presenting in pregnancy is described in which the thrombocytopenia persisted postpartum coincidental with a vesicular, pustular rash characterised as Sweet's syndrome. Hematological, histological, immunophenotypic, and molecular investigations confirmed the presence of HCL. The patient was treated with cladribine resulting in resolution of Sweet's syndrome, hematological remission from HCL, and achievement of a normal platelet count. This case highlights the need to maintain a wide differential diagnosis for presentations of pancytopenia or thrombocytopenia in pregnancy and the requirement for follow-up investigation of unusual cases with a lack of response to steroids or immunoglobulin.

Molecular Monitoring in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with the Variant e13a3 BCR-ABL1 Fusion.

Monitoring BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a widely adopted method to assess response to therapy. However, a small minority of Ph+ ALL patients express variant BCR-ABL1 transcript types, usually due to splicing of alternative BCR or ABL1 exons. Whether patients expressing these rare, variant BCR-ABL1 transcripts have a distinct phenotype or response to therapy is not known due to the limited number of reported cases. Here, we report the presenting features of Ph+ ALL in a young adult with a variant e13a3 BCR-ABL1 fusion. Molecular monitoring reflected the disease response from diagnosis through allogeneic stem cell transplantation which resulted in undetectable e13a3 BCR-ABL1 transcripts. This case highlights the value of molecular monitoring in Ph+ ALL patients with variant BCR-ABL1 transcripts and the requirement for standardization of such assays.

In situ ergot alkaloid detection in three Balansia epichloe-infected grass species.

AIMS: The objectives of this work were to characterize molecularly the morphologically described endophyte Balansia epichloe symbiotic on three grass species, and to determine the in situ production of ergot alkaloids on these three symbiota. METHODS AND RESULTS: Balansia epichloe symbiotic with smut grass (Sporobolus poiretii), love grass (Eragrostis hirsuta) and lace grass (Eragrostis capillaries, a new host) were characterized using DNA barcoding. Laser ablation electro spray ionization (LAESI)-mass spectrometry was used to detect ergot alkaloids in situ for each symbiotum. CONCLUSIONS: The three morphologically described symbionts on the three host grasses were indicated as belonging to the species B. epichloe, DNA barcoding suggested they were related although a cryptic species was suggested. LAESI-mass spectrometry showed that ergot alkaloids were produced in vivo in two hosts but not the third although this same symbiotum was related to one of the ergot alkaloid producing symbiota as revealed by the DNA-barcoding procedure. SIGNIFICANCE AND IMPACT OF THE STUDY: These results established the accumulation of ergot alkaloids in pot culture by a morpho species although there were variations with each species of grass. Barcoding described divergence among species, but considering its limitation, the suggested existence of cryptic species among this morphospecies requires substantiation by studies that are more rigorous.

Screening of Bacillus mojavensis biofilms and biosurfactants using laser ablation electrospray ionization mass spectroscopy.

AIMS: Biofilms are composed of micro-organisms within a matrix of chemically complex polymer compounds and from these structures many unknown competitive factors are suggested that many considered are important consequences for biological control. This research was undertaken to study further the endophyte, Bacillus mojavensis and its relationships to biofilm and two classes of lipopeptides considered relevant for biocontrol of plant pathogens. METHODS AND RESULTS: Laser ablation electrospray ionization mass spectrometry and conventional MS/MS were used to study in situ biofilm production and the production of lipopeptides fengycin and surfactin in different strains of B. mojavensis in plate and test tube culture on two media. All strains were capable of producing biofilm in vitro along with the accumulation of surfactin and fengycin although no concentration-dependent relationship between lipopeptide accumulation and biofilm was observed. CONCLUSION: All strains studied produce biofilms in culture with the accumulated surfactin and fengycin, demonstrating that endophytic bacteria also produced biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that this endophytic species produced biofilms along with two biocontrol compounds of which one, surfactin, considered by others as a quorum sensor, highlighting its ecological role as a signalling mechanism in planta.

The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eµ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eµ-Myc lymphoma cells but, counterintuitively, c-rel-/- Eµ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel-/- Eµ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eµ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel-/- TCL1-Tg mice and RelA Thr505Ala mutant Eµ-Myc mice. Analysis of wild-type Eµ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel-/- mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-κB/IκB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-κB signalling in cancer.

Reliability and Determinants of Self-Evaluation of Breathing Questionnaire (SEBQ) Score: A Symptoms-Based Measure of Dysfunctional Breathing.

Dysfunctional breathing is characterised by an abnormal breathing pattern leading to respiratory symptoms. The 25-item Self Evaluation of Breathing Questionnaire (SEBQ) has been developed to measure breathing-related symptoms and their severity but lacks thorough evaluation. To determine reproducibility, internal consistency and predictors of SEBQ score, 180 participants completed an online SEBQ with additional demographic and lifestyle questions. Two weeks later, 155 of those repeated SEBQ. Test-retest correlation of the SEBQ was high [intraclass correlation coefficient (3, 1) = 0.89; 95 % CI 0.85-0.92]. There was no difference in SEBQ score between test and retest (15.1 (11.6) [mean (SD)] versus 14.7 (12.4); P = 0.4) and the score showed a typical error (standard error of measurement) of 4.0. Internal consistency was high (Cronbach's α = 0.93), and a single factor structure for items was shown. Smoking status, reported respiratory disease, recent respiratory illness and female gender were positively-associated predictors of SEBQ score, and together explained 25.6 % of score variance (P ≤ 0.001). The SEBQ has high test-retest reproducibility and its score may be predicted by current smoking, chronic respiratory disease, recent respiratory illness and female gender, thus may be a useful clinical screening tool for dysfunctional breathing.

Bacillus mojavensis RRC101 Lipopeptides Provoke Physiological and Metabolic Changes During Antagonism Against Fusarium verticilliodes.

The mycotoxigenic pathogen Fusarium verticillioides threatens the quality and utility of maize across industrial and agricultural purposes. Chemical control is complicated by the intimate endophytic lifestyle of the pathogen with its host. Bacillus mojavensis RRC101, a maize-endophytic bacterium, has been observed to reduce F. verticillioides disease severity and fumonisin accumulation when coinoculated to maize. Genome sequencing and annotation identified a number of biocontrol-relevant pathways in RRC101. Biochemical assays confirmed the presence and activity of surfactin- and fengycin-type lipopeptides, with fengycins responsible for antifungal activity against F. verticillioides. This antagonism manifests as inhibition of filamentous growth, with microscopy revealing hyphal distortions, vacuolization, and lysis. F. verticillioides secondary metabolism also responds to antagonism, with lipopeptide challenge inducing greater fumonisin production and, in the case of fengycins, eliciting pigment accumulation at sites of inhibition. Together, these data suggest that antibiotic and toxin production are components of a complex biochemical interaction among maize endophytes, one pathogenic and one beneficial.

CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.

BACKGROUND: The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. METHODS: We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). RESULTS: 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. CONCLUSIONS: Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. CLINICAL TRIAL REGISTRATION: ID number NCT01193075.

Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.

Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.

c-MYC is a radiosensitive locus in human breast cells.

Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

Whole-Genome Shotgun Sequence of Bacillus mojavensis Strain RRC101, an Endophytic Bacterium Antagonistic to the Mycotoxigenic Endophytic Fungus Fusarium verticillioides.

Here, we report the whole-genome shotgun sequence of Bacillus mojavensis strain RRC101, isolated from a maize kernel. This strain is antagonistic to the mycotoxigenic plant pathogen Fusarium verticillioides and grows within maize tissue, suggesting potential as an endophytic biocontrol agent.