Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention

Damned if they do, damned if they don't: negotiating the tricky context of anti-social behaviour and keeping safe in disadvantaged urban neighbourhoods

Young people's relationship with anti-social behaviour (ASB) is complicated. While their behaviours are often stereotyped as anti-social (e.g. ‘hanging about’), they also experience ASB in their neighbourhood. In this study, we explore young people's own perspectives on ASB, comparing results from ‘go-along’ interviews and focus groups conducted in disadvantaged neighbourhoods in Glasgow, Scotland. This article discusses how young people's everyday experience of ASB was contextualised by social factors such as cultural stereotyping of marginalised groups, poor social connectivity and spatial marginalisation within their neighbourhood. Furthermore, we found that these social factors were mutually reinforcing and interacted in a way that appeared to leave young people in a ‘no-win’ situation regarding their association with ASB. Participation in ASB and attempts to avoid such involvement were seen to involve negative consequences: participation could entail violence and spatial restrictions linked to territoriality, but avoidance could lead to being ostracised from their peer group. Regardless of involvement, young people felt that adults stereotyped them as anti-social. Our findings therefore provide support for policies and interventions aimed at reducing ASB (perpetrated by residents of all ages); in part by better ensuring that young people have a clear incentive for avoiding such behaviours

Near real-time detection of low-frequency baleen whale calls from an autonomous surface vehicle: implementation, evaluation, and remaining challenges

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Baumgartner, M. F., Ball, K., Partan, J., Pelletier, L., Bonnell, J., Hotchkin, C., Corkeron, P. J., & Van Parijs, S. M. Near real-time detection of low-frequency baleen whale calls from an autonomous surface vehicle: implementation, evaluation, and remaining challenges. Journal of the Acoustical Society of America, 149(5), (2021): 2950-2962, https://doi.org/10.1121/10.0004817.Mitigation of threats posed to marine mammals by human activities can be greatly improved with a better understanding of animal occurrence in real time. Recent advancements have enabled low-power passive acoustic systems to be integrated into long-endurance autonomous platforms for persistent near real-time monitoring of marine mammals via the sounds they produce. Here, the integration of a passive acoustic instrument capable of real-time detection and classification of low-frequency (LF) tonal sounds with a Liquid Robotics wave glider is reported. The goal of the integration was to enable monitoring of LF calls produced by baleen whales over periods of several months. Mechanical noises produced by the platform were significantly reduced by lubricating moving parts with polytetrafluoroethylene, incorporating rubber and springs to decelerate moving parts and shock mounting hydrophones. Flow noise was reduced with the development of a 21-element hydrophone array. Surface noise produced by breaking waves was not mitigated despite experimentation with baffles. Compared to a well-characterized moored passive acoustic monitoring buoy, the system greatly underestimated the occurrence of sei, fin, and North Atlantic right whales during a 37-d deployment, and therefore is not suitable in its current configuration for use in scientific or management applications for these species at this time.Funding for this project was provided by the Environmental Security Technology Certification Program of the U.S. Department of Defense and the U.S. Navy's Living Marine Resources Program

Sex differences in visuospatial abilities persist during induced hypogonadism

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates

Unilateral thoracoscopic surgical approach for diffuse emphysema

AbstractWe evaluated the use of a lateral thoracoscopic approach for lung reduction surgery in patients with diffuse emphysema. Sixty-seven patients with a mean age of 61.9 years underwent operation. Operative side was determined by preoperative imaging. The procedures were laser ablation in 10 patients and stapler resection in 57 patients. Ten patients, including six of the 10 patients in the laser-only group had poor outcome (death or hospitalization longer than 30 days), leading us to abandon the laser technique. Of the remaining 57 patients undergoing primary stapled resection, duration of chest tube placement averaged 13 days (range 3 to 53 days) with a mean hospital stay of 17 days (range 6 to 99 days). Seven patients required ventilation for longer than 72 hours, six patients underwent conversion of the procedure to open thoracotomy, four patients acquired arrhythmias, and three patients were treated for empyema. There was one early death (1.7%), from cardiopulmonary failure. Forty patients returned for 3-month evaluation. Significant ( p < 0.0001) improvements were seen in forced vital capacity (2.69 L after vs 2.26 L before) and forced expiration volume in 1 second (1.04 L after vs 0.82 L before), with 25 of 40 patients (63%) showing an improvement of more than 20%. Lung volume measures, in particular residual volume, fell significantly. Arterial blood gas analysis revealed that carbon dioxide tension fell significantly in patients with preoperative hypercapnia (carbon dioxide tension >45 mm Hg, p = 0.018). Six-minute walk test results improved (894 feet after vs 784 feet before, p = 0.002), and symptomatic benefit was confirmed by significant improvement in the dyspnea index. The combination of both hypercapnia and reduced single-breath diffusing capacity for carbon monoxide was significantly more frequent ( p = 0.0026) and was 86% specific (5 of 6 patients) in predicting serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse emphysema offers significant improvement in pulmonary mechanics and functional impairment. Patients with a combination of hypercapnia and reduced single-breath diffusing capacity for carbon monoxide should not be considered for this procedure because of significant perioperative risk. (J THORAC CARDIOVASC SURG 1996;111:308-16

Long-term change in calcareous grassland vegetation and drivers over three time periods between 1970 and 2016

Analysis of long-term vegetation change is limited. Furthermore most studies evaluating change only examine two snapshots in time, which makes it difficult to define rates of change and accurately assess potential drivers. To assess long-term change in calcareous grassland over multiple time periods, we re-surveyed a transect study undertaken at Parsonage Down National Nature Reserve, Wiltshire, southern England in 1970 and 1990 by T. Wells. We examined differences in soil properties and species traits in each of the survey years to understand potential drivers of vegetation change, including nitrogen deposition and grazing management. There was a clear shift in species composition, combined with significant declines in species richness and diversity between 1970 and 2016, with the greater rate of change occurring between 1990 and 2016. A significant increase in soil total nitrogen was found, which was significantly associated with the decline in species diversity between 1970 and 1990. Significant changes in community-weighted mean traits were identified for plant height (increasing), specific leaf area (decreasing), grazing tolerance (decreasing) and Ellenberg N (decreasing) between 1970 and 2016. By using survey data from multiple time periods, we suggest that N deposition may have contributed towards community changes between 1970 and 1990, as indicated by the change in soil properties and the associated decline in species diversity. Vegetation change between 1990 and 2016 is likely to be largely attributable to a decline in grazing pressure, indicated by the increase in taller species and a decrease in grazing tolerance

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

Energy Levels and Transition Probabilities for Nitrogen-Like Fe xx

Energies of the 700 lowest levels in Fexx have been obtained using the multiconfiguration Dirac-Fock method. Configuration interaction method on the basis set of transformed radial orbitals with variable parameters taking into account relativistic corrections in the Breit-Pauli approximation was used to crosscheck our presented results. Transition probabilities, oscillator and line strengths are presented for electric dipole (E1), electric quadrupole (E2) and magnetic dipole (M1) transitions among these levels. The total radiative transition probabilities from each level are also provided. Results are compared with data compiled by NIST and with other theoretical work

Radiocarbon data reveal contrasting sources for carbon fractions in thermokarst lakes and rivers of Eastern Canada (Nunavik, Quebec)

Greenhouse gas (GHG) emissions from permafrost organic carbon decomposition in lakes and rivers can accelerate global warming. We used radiocarbon (14C) measurements to determine the predominant sources of dissolved organic carbon (DOC), particulate organic carbon (POC), dissolved inorganic carbon (DIC), and methane (CH4) in five thermokarst lakes and three rivers in an area of widespread permafrost degradation in Northern Quebec to assess contributions from thawing permafrost and other old carbon (fixed before CE 1950) reservoirs. We compared emission pathways (dissolved gas and ebullition), seasons (summer and winter), and surface soil type (mineral and peat soils). Modern carbon (fixed after CE 1950) was the dominant source of DOC, DIC, and CH4 of non‐peatland aquatic systems, while POC and sediment carbon were predominantly fixed in the last millennia. In the peatland systems, modern and permafrost carbon were important sources of DOC, lake DIC, lake ebullition CO2, and lake dissolved CH4. In contrast, POC, lake ebullition CH4, and river DIC were dominated by millennial‐old carbon. In winter, the 14C age of DOC, DIC, and POC in the peatland lakes increased, but the 14C age of dissolved CH4 did not change. Our results point to a clearly older overall carbon source for ebullition CH4 relative to dissolved CH4 in the peatland lakes, but not the non‐peatland lakes. The younger ages of diffusive CH4 and DIC relative to DOC and POC in all lakes suggest that recent primary productivity strongly influences the large total lake CH4 emissions in this area, as diffusion fluxes greatly exceed ebullition fluxes