Pushing Back Against Deficit Narratives: Mentoring as Scholars of Color

In this article we share our lived experiences with mentoring. As tenured women professors of color, we push back against the assumption that institutions of higher education are neutral sites, that we have to change to belong, and that we do not belong. Each of us underscores the importance and value of our realities and the knowledge we generate to address inequality and to counteract negative stereotyping. We argue that rejecting deficit narratives and privileging the narratives of those we mentor and of those who have mentored us is vital to increasing faculty of color diversity, inclusion and belonging in higher education.Educatio

Cutaneous Angiosarcoma of the Scalp: A Case Report of Sustained Complete Response Following Liposomal Doxorubicin and Radiation Therapy

Cutaneous angiosarcomas of the head and neck are aggressive cancers with a mean overall survival of 30 months. We add to the literature a case report of a 65-year-old man with a large, >10 cm, unresectable, angiosarcoma of the scalp who was treated with two cycles of liposomal doxorubicin (Caelyx®) followed by electron beam radiation therapy (30 Gy in 10 fractions over 2 weeks) who has sustained a complete response with a 4-year follow-up. The dose and fractionation of the radiation therapy in this case was palliative and was not expected to give lasting local control of this lesion. It is therefore possible that either the genetic profile of the tumour conferred radiosensitivity or that the radiation therapy induced a recall phenomenon of the liposomal doxorubicin

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs.

OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter

Combined linkage and association analysis of classical Hodgkin lymphoma

Peer reviewedPublisher PD

Evolution of Antarctic Sea Ice Ahead of the Record Low Annual Maximum Extent in September 2023

The 2023 Antarctic sea ice extent (SIE) maximum on 7 September was the lowest annual maximum in the satellite era (16.98 × 106 km2), with the largest contributions to the anomaly coming from the Ross (37.7%, −0.57 × 106 km2) and Weddell (32.9%, −0.49 × 106 km2) Seas. The SIE was low due to anomalously warm (>0.3°C) upper-ocean temperatures combined with anomalously strong northerly winds impeding the ice advance during the fall and winter. Northerly winds of >12 ms−1 in the Weddell Sea occurred because of negative pressure anomalies over the Antarctic Peninsula, while those in the Ross Sea were associated with extreme blocking episodes off the Ross Ice Shelf. The Ross Sea experienced an unprecedented SIE decrease of −1.08 × 103 km2 d−1 from 1 June till the annual maximum. The passage of quasi-stationary and explosive polar cyclones contributed to periods of southward ice-edge shift in both sectors

The TcEG1 beetle (Tribolium castaneum) cellulase produced in transgenic switchgrass is active at alkaline pH and auto-hydrolyzes biomass for increased cellobiose release

Background Genetically engineered biofuel crops, such as switchgrass (Panicum virgatum L.), that produce their own cell wall-digesting cellulase enzymes would reduce costs of cellulosic biofuel production. To date, non-bioenergy plant models have been used in nearly all studies assessing the synthesis and activity of plant-produced fungal and bacterial cellulases. One potential source for cellulolytic enzyme genes is herbivorous insects adapted to digest plant cell walls. Here we examine the potential of transgenic switchgrass-produced TcEG1 cellulase from Tribolium castaneum (red flour beetle). This enzyme, when overproduced in Escherichia coliand Saccharomyces cerevisiae, efficiently digests cellulose at optima of 50 °C and pH 12.0. Results TcEG1 that was produced in green transgenic switchgrass tissue had a range of endoglucanase activity of 0.16–0.05 units (µM glucose release/min/mg) at 50 °C and pH 12.0. TcEG1 activity from air-dried leaves was unchanged from that from green tissue, but when tissue was dried in a desiccant oven (46 °C), specific enzyme activity decreased by 60%. When transgenic biomass was “dropped-in” into an alkaline buffer (pH 12.0) and allowed to incubate at 50 °C, cellobiose release was increased up to 77% over non-transgenic biomass. Saccharification was increased in one transgenic event by 28%, which had a concurrent decrease in lignin content of 9%. Histological analysis revealed an increase in cell wall thickness with no change to cell area or perimeter. Transgenic plants produced more, albeit narrower, tillers with equivalent dry biomass as the control. Conclusions This work describes the first study in which an insect cellulase has been produced in transgenic plants; in this case, the dedicated bioenergy crop switchgrass. Switchgrass overexpressing the TcEG1 gene appeared to be morphologically similar to its non-transgenic control and produced equivalent dry biomass. Therefore, we propose TcEG1 transgenics could be bred with other transgenic germplasm (e.g., low-lignin lines) to yield new switchgrass with synergistically reduced recalcitrance to biofuel production. In addition, transgenes for other cell wall degrading enzymes may be stacked with TcEG1 in switchgrass to yield complementary cell wall digestion features and complete auto-hydrolysis

Understanding Heterogeneity in the Impact of National Neglected Tropical Disease Control Programmes: Evidence from School-Based Deworming in Kenya.

BACKGROUND: The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya. MATERIALS AND METHODS: Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels. PRINCIPAL FINDINGS: The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores. CONCLUSIONS: The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes

Characterizing the Near-infrared Spectra of Flares from TRAPPIST-1 During JWST Transit Spectroscopy Observations

We present the first analysis of JWST near-infrared spectroscopy of stellar flares from TRAPPIST-1 during transits of rocky exoplanets. Four flares were observed from 0.6--2.8 $\mu$m with NIRISS and 0.6--3.5 $\mu$m with NIRSpec during transits of TRAPPIST-1b, f, and g. We discover P$\alpha$ and Br$\beta$ line emission and characterize flare continuum at wavelengths from 1--3.5 $\mu$m for the first time. Observed lines include H$\alpha$, P$\alpha$-P$\epsilon$, Br$\beta$, He I $\lambda$0.7062$\mu$m, two Ca II infrared triplet (IRT) lines, and the He I IRT. We observe a reversed Paschen decrement from P$\alpha$-P$\gamma$ alongside changes in the light curve shapes of these lines. The continuum of all four flares is well-described by blackbody emission with an effective temperature below 5300 K, lower than temperatures typically observed at optical wavelengths. The 0.6--1 $\mu$m spectra were convolved with the TESS response, enabling us to measure the flare rate of TRAPPIST-1 in the TESS bandpass. We find flares of 10$^{30}$ erg large enough to impact transit spectra occur at a rate of 3.6$\substack{+2.1 \\ -1.3}$ flare d$^{-1}$, $\sim$10$\times$ higher than previous predictions from K2. We measure the amount of flare contamination at 2 $\mu$m for the TRAPPIST-1b and f transits to be 500$\pm$450 and 2100$\pm$400 ppm, respectively. We find up to 80% of flare contamination can be removed, with mitigation most effective from 1.0--2.4 $\mu$m. These results suggest transits affected by flares may still be useful for atmospheric characterization efforts.Comment: 29 pages, 17 figures, 3 tables, accepted to The Astrophysical Journa

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs

Objectives Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. Methods The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. Results All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. Conclusions TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporte