Microbial residents of the human oral cavity have long been a major focus of microbiology due to their influence on host health and intriguing patterns of site specificity amidst the lack of ...dispersal limitation. However, the determinants of niche partitioning in this habitat are yet to be fully understood, especially among taxa that belong to recently discovered branches of microbial life.
Here, we assemble metagenomes from tongue and dental plaque samples from multiple individuals and reconstruct 790 non-redundant genomes, 43 of which resolve to TM7, a member of the Candidate Phyla Radiation, forming six monophyletic clades that distinctly associate with either plaque or tongue. Both pangenomic and phylogenomic analyses group tongue-specific clades with other host-associated TM7 genomes. In contrast, plaque-specific TM7 group with environmental TM7 genomes. Besides offering deeper insights into the ecology, evolution, and mobilome of cryptic members of the oral microbiome, our study reveals an intriguing resemblance between dental plaque and non-host environments indicated by the TM7 evolution, suggesting that plaque may have served as a stepping stone for environmental microbes to adapt to host environments for some clades of microbes. Additionally, we report that prophages are widespread among oral-associated TM7, while absent from environmental TM7, suggesting that prophages may have played a role in adaptation of TM7 to the host environment.
Our data illuminate niche partitioning of enigmatic members of the oral cavity, including TM7, SR1, and GN02, and provide genomes for poorly characterized yet prevalent members of this biome, such as uncultivated Flavobacteriaceae.
Climate change could pose a major challenge to efforts towards strongly increase food production over the coming decades. However, model simulations of future climate-impacts on crop yields differ ...substantially in the magnitude and even direction of the projected change. Combining observations of current maximum-attainable yield with climate analogues, we provide a complementary method of assessing the effect of climate change on crop yields. Strong reductions in attainable yields of major cereal crops are found across a large fraction of current cropland by 2050. These areas are vulnerable to climate change and have greatly reduced opportunity for agricultural intensification. However, the total land area, including regions not currently used for crops, climatically suitable for high attainable yields of maize, wheat and rice is similar by 2050 to the present-day. Large shifts in land-use patterns and crop choice will likely be necessary to sustain production growth rates and keep pace with demand.
To understand how Toll signaling controls the activation of a cellular immune response in Drosophila blood cells (hemocytes), we carried out a genetic modifier screen, looking for deletions that ...suppress or enhance the mobilization of sessile hemocytes by the gain-of-function mutation Toll10b (Tl10b). Here we describe the results from chromosome arm 3R, where five regions strongly suppressed this phenotype. We identified the specific genes immune response deficient 1 (ird1), headcase (hdc) and possibly Rab23 as suppressors, and we studied the role of ird1 in more detail. An ird1 null mutant and a mutant that truncates the N-terminal kinase domain of the encoded Ird1 protein affected the Tl10b phenotype, unlike mutations that affect the C-terminal part of the protein. The ird1 null mutant suppressed mobilization of sessile hemocytes, but enhanced other Tl10b hemocyte phenotypes, like the formation of melanotic nodules and the increased number of circulating hemocytes. ird1 mutants also had blood cell phenotypes on their own. They lacked crystal cells and showed aberrant formation of lamellocytes. ird1 mutant plasmatocytes had a reduced ability to spread on an artificial substrate by forming protrusions, which may explain why they did not go into circulation in response to Toll signaling. The effect of the ird1 mutation depended mainly on ird1 expression in hemocytes, but ird1-dependent effects in other tissues may contribute. Specifically, the Toll receptor was translocated from the cell membrane to intracellular vesicles in the fat body of the ird1 mutant, and Toll signaling was activated in that tissue, partially explaining the Tl10b-like phenotype. As ird1 is otherwise known to control vesicular transport, we conclude that the vesicular transport system may be of particular importance during an immune response.
Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone ...marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.
We present Magnetospheric Multiscale observations of an electron‐scale reconnecting current sheet in the mixing region along the trailing edge of a Kelvin‐Helmholtz vortex during southward ...interplanetary magnetic field conditions. Within this region, we observe intense electrostatic wave activity, consistent with lower‐hybrid waves. These waves lead to the transport of high‐density magnetosheath plasma across the boundary layer into the magnetosphere and generate a mixing region with highly compressed magnetic field lines, leading to the formation of a thin current sheet associated with electron‐scale reconnection signatures. Consistencies between these reconnection signatures and a realistic, local, fully‐kinetic simulation modeling this current sheet indicate a temporal evolution of the observed electron‐scale reconnection current sheet. The multi‐scale and inter‐process character of this event can help us understand plasma mixing connected to the Kelvin‐Helmholtz instability and the temporal evolution of electron‐scale reconnection.
Plain Language Summary
Like wind blowing over water, the stream of ionized gas released from the Sun, called the solar wind, can lead to waves and rolled‐up vortex structures at the boundary of Earth's magnetosphere, called the magnetopause. These so‐called Kelvin‐Helmholtz waves have been shown to be connected to various different plasma processes on different scales. This multi‐scale and multi‐process character makes them an ideal candidate to study the relation between these processes from both spacecraft observations and simulations. By using spacecraft data from the Magnetospheric Multiscale mission, which was designed for the study of small‐scale plasma processes in Earth's magnetosphere, we show observations of electron‐scale magnetic reconnection, an explosive energy conversion process in plasmas, in a region along the trailing edge of these waves. These observations shed new light on the multi‐scale and multi‐process character of the Kelvin‐Helmholtz instability and the energy conversion processes along its boundary.
Key Points
A reconnecting electron‐scale current sheet is observed by Magnetospheric Multiscale (MMS) in mixing plasma along the trailing edge of a Kelvin‐Helmholtz vortex
Realistic 2.5D fully‐kinetic simulation shows reasonable agreement with MMS data
Consistencies between the simulation and MMS indicate a temporal evolution of the reconnecting current sheet
In this letter, we present vertical InAs-Si nanowire heterojunction tunnel FETs (TFETs). The devices consist of an InAs source on a Si channel and drain, with a wraparound gate stack. The Si-InAs ...combination allows achieving high I on / I off ratios above 10 6 , with an I on of 2.4 μA/μm and an inverse subthreshold slope of 150 mV/dec measured over three decades of current. Ni alloying of the InAs top contact is shown to improve performance of both diodes and TFETs significantly. The combination of higher doping at the contact and the alloying also leads to an enhanced performance compared with previously published devices.
Objectives
We investigated the effect of different dietary substances on deciduous and permanent enamel.
Materials and methods
Enamel specimens were prepared from human teeth (
n
= 108 ...deciduous molars and
n
= 108 permanent premolars). We measured the chemical parameters (pH, titratable acidity, viscosity, calcium, phosphate, fluoride concentration and degree of saturation) of nine dietary substances. The teeth were immersed in the respective substance (2 × 2 min; 30 °C; shaking), and we measured the baseline surface hardness (SH) in Vickers hardness numbers (VHN), and the changes in SH after 2 min (ΔSH
2–0
) and the 4 min (ΔSH
4–0
) immersion. We analysed the differences between deciduous and permanent teeth using the Wilcoxon test and correlated ΔSH to the different chemical parameters.
Results
Deciduous teeth were significantly softer (549.53 ± 59.41 VHN) than permanent teeth (590.15 ± 55.31 VHN;
p
< 0.001) at baseline, but they were not more vulnerable to erosive demineralization. Only orange juice, which presented milder erosive potential, caused significantly more demineralisation in deciduous teeth at ΔSH
4–0
. Practically all chemical parameters significantly correlated with ΔSH (
p
< 0.05). Substances with lower pH, higher titratable acidity, lower Ca, higher P
i
and lower F concentrations, higher viscosity and more undersaturated solutions presented more erosive demineralisation.
Conclusion
Different parameters in dietary substances affect erosive demineralisation in deciduous and permanent teeth, but we generally observed no differences in susceptibility to erosion between both types of teeth; only orange juice (less severe acid conditions) caused perceptible differences.
Clinical relevance
We observe that permanent teeth are harder than deciduous teeth, but most substances cause no perceptible difference in erosive demineralisation in both types of teeth.
Introduction:
Treatment for differentiated thyroid carcinoma (DTC) in pediatric patients is based mainly on evidence from adult series due to lack of data from pediatric cohorts. Our objective was to ...evaluate presentation, treatment-related complications, and long-term outcome in patients with pediatric DTC in The Netherlands.
Patients and Methods:
In this nationwide study, presentation, complications, and outcome of patients with pediatric DTC (age at diagnosis ≤18 y) treated in The Netherlands between 1970 and 2013 were assessed using medical records.
Results:
We identified 170 patients. Overall survival was 99.4% after a median follow-up of 13.5 years (range 0.3–44.7 y). Extensive follow-up data were available for 105 patients (83.8% women), treated in 39 hospitals. Median age at diagnosis was 15.6 years (range 5.8–18.9 y). At initial diagnosis, 43.8% of the patients had cervical lymph node metastases; 13.3% had distant metastases. All patients underwent total thyroidectomy. Radioiodine was administered to 97.1%, with a median cumulative activity of 5.66 GBq (range 0.74–35.15 GBq). Life-long postoperative complications (permanent hypoparathyroidism and/or recurrent laryngeal nerve injury) were present in 32.4% of the patients. At last known follow-up, 8.6% of the patients had persistent disease and 7.6% experienced a recurrence. TSH suppression was not associated with recurrences (odds ratio 2.00, 95% confidence interval 0.78–5.17, P = .152).
Conclusions:
Survival of pediatric DTC is excellent. Therefore, minimizing treatment-related morbidity takes major priority. Our study shows a frequent occurrence of life-long postoperative complications. Adverse effects may be reduced by the centralization of care, which is crucial for children with DTC.
This Dutch nationwide study on pediatric differentiated thyroid carcinoma reports an excellent survival. However, life-long surgical complications occur frequently.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. ...However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown.
We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed.
The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT.
The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).
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