Explore the vast range of titles available.

Recent observations of dynamic water systems beneath the Greenland and Antarctic ice sheets have sparked renewed interest in modelling subglacial drainage. The foundations of today's models were laid decades ago, inspired by measurements from mountain glaciers, discovery of the modern ice streams and the study of landscapes evacuated by former ice sheets. Models have progressed from strict adherence to the principles of groundwater flow, to the incorporation of flow 'elements' specific to the subglacial environment, to sophisticated two-dimensional representations of interacting distributed and channelized drainage. Although presently in a state of rapid development, subglacial drainage models, when coupled to models of ice flow, are now able to reproduce many of the canonical phenomena that characterize this coupled system. Model calibration remains generally out of reach, whereas widespread application of these models to large problems and real geometries awaits the next level of development.

It is now well documented that over 400 subglacial lakes exist across the bed of the Antarctic Ice Sheet. They comprise a variety of sizes and volumes (from the approx. 250 km long Lake Vostok to bodies of water less than 1 km in length), relate to a number of discrete topographic settings (from those contained within valleys to lakes that reside in broad flat terrain) and exhibit a range of dynamic behaviours (from ‘active’ lakes that periodically outburst some or all of their water to those isolated hydrologically for millions of years). Here we critique recent advances in our understanding of subglacial lakes, in particular since the last inventory in 2012. We show that within 3 years our knowledge of the hydrological processes at the ice-sheet base has advanced considerably. We describe evidence for further ‘active’ subglacial lakes, based on satellite observation of ice-surface changes, and discuss why detection of many ‘active’ lakes is not resolved in traditional radio-echo sounding methods. We go on to review evidence for large-scale subglacial water flow in Antarctica, including the discovery of ancient channels developed by former hydrological processes. We end by predicting areas where future discoveries may be possible, including the detection, measurement and significance of groundwater (i.e. water held beneath the ice-bed interface).

During development, the decision of stem and progenitor cells to switch from proliferation to differentiation is of critical importance for the overall size of an organ. Too early a switch will deplete the stem/progenitor cell pool, and too late a switch will not generate the required differentiated cell types. With a focus on the developing neocortex, a six-layered structure constituting the major part of the cerebral cortex in mammals, we discuss here the cell biological features that are crucial to ensure the appropriate proliferation vs. differentiation decision in the neural progenitor cells. In the last two decades, the neural progenitor cells giving rise to the diverse types of neurons that function in the neocortex have been intensely investigated for their role in cortical expansion and gyrification. In this review, we will first describe these different progenitor types and their diversity. We will then review the various cell biological features associated with the cell fate decisions of these progenitor cells, with emphasis on the role of the radial processes emanating from these progenitor cells. We will also discuss the species-specific differences in these cell biological features that have allowed for the evolutionary expansion of the neocortex in humans. Finally, we will discuss the emerging role of cell cycle parameters in neocortical expansion.

PurposeTo evaluate the effects of percutaneous vertebroplasty (PVP) with conventional transpedicle approach (CTA) or basal transverse process-pedicle approach (BTPA) on the treatment of thoracolumbar osteoporotic vertebral compression fractures (TL-OVCFs) with narrow pedicles.MethodsA retrospective study of TL-OVCFs with narrow pedicles was performed, including 78 cases of CTA and 84 cases of BTPA. The surgical outcomes, radiographic parameters [the width and height of the pedicle (PW, PH), the inclination angle of puncture (PIA)] and clinical indicators [visual analog scale (VAS) score, Oswestry Disability Index (ODI)] of two groups were compared.ResultsIn terms of surgical outcomes of them, there was no difference in operation time (P > 0.05), while the volume of bone cement, the incidence of bone cement leakage and rate of good bone cement distribution were significantly worse in the CTA group (4.4 ± 0.6 ml vs. 5.5 ± 0.5 ml, 37.2% vs. 20.2%, 52.6% vs. 79.8%, P < 0.05). As for radiographic parameters and clinical indicators of them, the differences were not observed in the PH, PW, preoperative VAS score and ODI (P > 0.05), whereas the PIA, VAS score and ODI at 1 day postoperatively were significantly better in the BTPA group (17.3 ± 2.1° vs. 29.6 ± 2.8°, 2.7 ± 0.7 vs. 2.1 ± 0.8, 32.8 ± 4.6 vs. 26.7 ± 4.0, P < 0.05).ConclusionThe study provided solid evidence that PVP with BTPA had more advantages in the treatment of TL-OVCFs with narrow pedicles, which can better relieve postoperative pain.

The spittlebug genus Anyllis Kirkaldy (Hemiptera: Aphrophoridae), endemic to Australia, is redefined and new autapomorphies are proposed to support the monophyly of the genus. A new sensillum found on the expanded flagellar base of antennae of Anyllis species, named as ‘conical sensillum’, and a new male genitalic structure, named as ‘basal anal processes,’ are named. Anyllis is moved from the tribe Locrisini Lallemand of Cercopidae to the tribe Aphrophorini of Aphrophoridae. A new species, Anyllis spinostylus Liang sp. nov., is described and illustrated from Tasmania, Australia.

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo . Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS , in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4 . This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.

Significance Although forest succession has been approached as a predictable process, successional trajectories vary widely, even among nearby stands with similar environmental conditions and disturbance histories. We quantified predictability and uncertainty during tropical forest succession using dynamical models describing the interactions among stem density, basal area, and species density over time. We showed that the trajectories of these forest attributes were poorly predicted by stand age and varied significantly within and among sites. Our models reproduced the general successional trends observed, but high levels of noise were needed to increase model predictability. These levels of uncertainty call into question the premise that successional processes are consistent over space and time, and challenge the way ecologists view tropical forest regeneration. Although forest succession has traditionally been approached as a deterministic process, successional trajectories of vegetation change vary widely, even among nearby stands with similar environmental conditions and disturbance histories. Here, we provide the first attempt, to our knowledge, to quantify predictability and uncertainty during succession based on the most extensive long-term datasets ever assembled for Neotropical forests. We develop a novel approach that integrates deterministic and stochastic components into different candidate models describing the dynamical interactions among three widely used and interrelated forest attributes—stem density, basal area, and species density. Within each of the seven study sites, successional trajectories were highly idiosyncratic, even when controlling for prior land use, environment, and initial conditions in these attributes. Plot factors were far more important than stand age in explaining successional trajectories. For each site, the best-fit model was able to capture the complete set of time series in certain attributes only when both the deterministic and stochastic components were set to similar magnitudes. Surprisingly, predictability of stem density, basal area, and species density did not show consistent trends across attributes, study sites, or land use history, and was independent of plot size and time series length. The model developed here represents the best approach, to date, for characterizing autogenic successional dynamics and demonstrates the low predictability of successional trajectories. These high levels of uncertainty suggest that the impacts of allogenic factors on rates of change during tropical forest succession are far more pervasive than previously thought, challenging the way ecologists view and investigate forest regeneration.

Background The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily. Methods This phase 2, double-blind study randomized patients 1:2 to sonidegib 200:800 mg daily, respectively. Key endpoints included objective response rate (ORR), duration of response (DOR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). laBCC tumors were assessed by both mRECIST and ERIVANCE-like criteria. Per mRECIST, an overall response of CR was based on negative histology; photographic assessment of CR, PR (scar/fibrosis only), SD (scar/fibrosis only), or not available (NA); and a magnetic resonance imaging response of CR or NA. An overall response of CR was primarily based on negative histology using ERIVANCE-like criteria. Results Per mRECIST criteria, ORR (95% confidence interval [CI]) by central and investigator review for patients with laBCC ( n  = 66) was 56.1% (43.3–68.3%) and 71.2% (58.7–81.7%), respectively. CR per central review was achieved in 3 (4.5%) patients and PR, SD, and PD occurred in 34 (51.5%), 23 (34.8%), and 1 (1.5%) patient, respectively. Median (95% CI) DOR was 26.1 months (not estimable [NE]). Using ERIVANCE-like criteria, efficacy outcomes per central and investigator review were higher, with an ORR (95% CI) of 60.6% (47.8–72.4%) and 74.2% (62.0–84.2%), respectively. CR per central review was reached in 14 (21.2%) patients and PR, SD, and PD occurred in 26 (39.4%), 20 (30.3%), and 1 (1.5%) patient, respectively. DOR was unchanged with a median (95% CI) of 26.1 months (NE). Conclusions Overall, applying ERIVANCE-like criteria to patients with laBCC receiving sonidegib 200 mg daily yielded higher response rates vs mRECIST criteria. Trial registration BOLT registration: ClinicalTrials.gov ( NCT01327053 ) on March 30, 2011.

Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Active subglacial lakes provide a rare glimpse of the subglacial environment and hydrological processes at play. Several studies contributed to establishing active subglacial lake inventories and document lake drainage and connection, but few focused on the period between lake drainage when the melt production and transport contribute to the refilling of these lakes. In this study, we employ high-resolution CryoSat-2 altimetry data from 2010 to 2021 to compile an inventory of recharging lakes across Antarctica. We extract recharge rates from these lakes, which serve as a lower limit on subglacial melt production. These recharge rates are compared against predictions obtained by routing modelled subglacial meltwater at the ice-sheet's base. Our findings indicate that modelled recharge rates are consistent with observations in all but one of the investigated lakes, providing a lower bound on geothermal heat fluxes. Lake Cook E2 displays recharge rates far exceeding predictions, indicating that processes are taking place that are currently unaccounted for. Considering recharge in hydrologically connected lake networks instead of individually provides a stricter constraint on melt production. Recharge rates extracted from the Thwaites Lake system suggest that subglacial melt production has been underestimated.