Identification of a Likely Radio Counterpart of the Rapid Burster

We have identified a likely radio counterpart to the low-mass X-ray binary MXB 1730-335 (the Rapid Burster). The counterpart has shown 8.4 GHz radio on/off behavior correlated with the X-ray on/off behavior as observed by the RXTE/ASM during six VLA observations. The probability of an unrelated, randomly varying background source duplicating this behavior is 1-3% depending on the correlation time scale. The location of the radio source is RA 17h 33m 24.61s; Dec -33d 23' 19.8" (J2000), +/- 0.1". We do not detect 8.4 GHz radio emission coincident with type II (accretion-driven) X-ray bursts. The ratio of radio to X-ray emission during such bursts is constrained to be below the ratio observed during X-ray persistent emission at the 2.9-sigma level. Synchrotron bubble models of the radio emission can provide a reasonable fit to the full data set, collected over several outbursts, assuming that the radio evolution is the same from outburst to outburst, but given the physical constraints the emission is more likely to be due to ~hour-long radio flares such as have been observed from the X-ray binary GRS 1915+105.Comment: 28 pages, 4 figures; accepted for publication in ApJ (no changes

Use of Flow Cytometry and Stable Isotope Analysis to Determine Phytoplankton Uptake of Wastewater Derived Ammonium in a Nutrient-rich River

Anthropogenic alteration of the form and concentration of nitrogen (N) in aquatic ecosystems is widespread. Understanding availability and uptake of different N sources at the base of aquatic food webs is critical to establishment of effective nutrient management programs. Stable isotopes of N (14N,15N) are often used to trace the sources of N fuelling aquatic primary production, but effective use of this approach requires obtaining a reliable isotopic ratio for phytoplankton. In this study, we tested the use of flow cytometry to isolate phytoplankton from bulk particulate organic matter (POM) in a portion of the Sacramento River, California, during river-scale nutrient manipulation experiments that involved halting wastewater discharges high in ammonium (NH4 +). Field samples were collected using a Lagrangian approach, allowing us to measure changes in phytoplankton N source in the presence and absence of wastewater derived NH4 +. Comparison of δ15N-POM and δ15N-phytoplankton (δ15N-PHY) revealed that their δ15N values followed broadly similar trends. However, after 3 days of downstream travel in the presence of wastewater treatment plant (WWTP) effluent, δ15N-POM and δ15N-PHY in the Sacramento River differed by as much as 7‰. Using a stable isotope mixing model approach, we estimated that in the presence of effluent between 40 and 90% of phytoplankton-N was derived from NH4 + after 3 days of downstream transport. An apparent gradual increase over time in the proportion of NH4 + in the phytoplankton N pool suggests that either very low phytoplankton growth rates resulted in an N turnover time that exceeded the travel time sampled during this study, or a portion of the phytoplankton community continued to access nitrate even in the presence of elevated NH4 + concentrations

PfMFR3: A multidrug-resistant modulator in Plasmodium falciparum

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stag

Proposal of a water-quality index for high andean basins: application to the Chumbao river, Andahuaylas, Peru

Thewater fromthe high Andean rivers is peculiar due to its composition and the geomorphology of its sources, and naturally or anthropogenically contamination is not discarded along its course. This water is used for agriculture and human consumption, therefore knowing its quality is important. This research aimed to proposing and formulate a water-quality index for high Andean basins through the Delphimethod, and its application in the Chumbao River located in Andahuaylas-Peru. Forty-three water-quality parameters were evaluated through the Delphi method, and the water-quality index (WQIHA) was formulated with a weighted average of the weights of the selected parameters, it was compared with the WQI Dinius. For this purpose, ten sampling points were considered along the Chumbao River located between 4274 and 2572 m of altitude and theWQIHA was applied. In addition, field and laboratory analyses were carried out in 2018, 2019, and 2021, in dry and rainy seasons. Twenty parameters were grouped in the physicochemical sub-index (SIPC), heavy metals sub-index (SIHM), and organic matter sub-index (SIOM). Each group contributed with weights of 0.30, 0.30, and 0.40, respectively, for theWQIHA formulation. The SIPC and SIOM showed that the areas near the head of the basin presented excellent and good quality, while the urbanized areas were qualified as marginal to poor; SIHM reported good quality in all points and seasons. Regarding the WQIHA, the index shows good quality in the zones above 3184 m of altitude, contrasting with poor quality downstream, decreasing notably in both seasons, suggesting continuous degradation of the water body

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.United States. National Institutes of Health (HG002668)United States. National Institutes of Health (CA109901

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.United States. National Institutes of Health (HG002668)United States. National Institutes of Health (CA109901

Determinants at the N- and C-termini of G¿ 12 required for activation of Rho-mediated signaling

Abstract Background Heterotrimeric guanine nucleotide binding proteins of the G12/13 subfamily, which includes the α-subunits Gα12 and Gα13, stimulate the monomeric G protein RhoA through interaction with a distinct subset of Rho-specific guanine nucleotide exchange factors (RhoGEFs). The structural features that mediate interaction between Gα13 and RhoGEFs have been examined in crystallographic studies of the purified complex, whereas a Gα12:RhoGEF complex has not been reported. Several signaling responses and effector interactions appear unique to Gα12 or Gα13, despite their similarity in amino acid sequence. Methods To comprehensively examine Gα12 for regions involved in RhoGEF interaction, we screened a panel of Gα12 cassette substitution mutants for binding to leukemia-associated RhoGEF (LARG) and for activation of serum response element mediated transcription. Results We identified several cassette substitutions that disrupt Gα12 binding to LARG and the related p115RhoGEF. These Gα12 mutants also were impaired in activating serum response element mediated signaling, a Rho-dependent response. Most of these mutants matched corresponding regions of Gα13 reported to contact p115RhoGEF, but unexpectedly, several RhoGEF-uncoupling mutations were found within the N- and C-terminal regions of Gα12. Trypsin protection assays revealed several mutants in these regions as retaining conformational activation. In addition, charge substitutions near the Gα12 N-terminus selectively disrupted binding to LARG but not p115RhoGEF. Conclusions Several structural aspects of the Gα12:RhoGEF interface differ from the reported Gα13:RhoGEF complex, particularly determinants within the C-terminal α5 helix and structurally uncharacterized N-terminus of Gα12. Furthermore, key residues at the Gα12 N-terminus may confer selectivity for LARG as a downstream effector

Controlling Activity and Selectivity Using Water in the Au-Catalysed Preferential Oxidation of CO in H\u3csub\u3e2\u3c/sub\u3e

Industrial hydrogen production through methane steam reforming exceeds 50 million tons annually and accounts for 2–5% of global energy consumption. The hydrogen product, even after processing by the water–gas shift, still typically contains ∼1% CO, which must be removed for many applications. Methanation (CO + 3H2 → CH4 + H2O) is an effective solution to this problem, but consumes 5–15% of the generated hydrogen. The preferential oxidation (PROX) of CO with O2 in hydrogen represents a more-efficient solution. Supported gold nanoparticles, with their high CO-oxidation activity and notoriously low hydrogenation activity, have long been examined as PROX catalysts, but have shown disappointingly low activity and selectivity. Here we show that, under the proper conditions, a commercial Au/Al2O3 catalyst can remove CO to below 10 ppm and still maintain an O2-to-CO2 selectivity of 80–90%. The key to maximizing the catalyst activity and selectivity is to carefully control the feed-flow rate and maintain one to two monolayers of water (a key CO-oxidation co-catalyst) on the catalyst surface

The social relations of health care and household resource allocation in neoliberal Nicaragua

<p>Abstract</p> <p>Background</p> <p>With the transition to neoliberalism, Nicaragua's once-critically acclaimed health care services have substantially diminished. Local level social formations have been under pressure to try to bridge gaps as the state's role in the provision of health care and other vital social services has decreased. This paper presents a case study of how global and national health policies reverberated in the social relations of an extended network of female kin in a rural community during late 2002 - 2003.</p> <p>Methods</p> <p>The qualitative methods used in this ethnographic study included semi-structured interviews completed during bi-weekly visits to 51 households, background interviews with 20 lay and professional health practitioners working in the public and private sectors, and participant-observation conducted in the region's government health centers. Interviews and observational field notes were manually coded and iteratively reviewed to identify and conceptually organize emergent themes. Three households of extended kin were selected from the larger sample to examine as a case study.</p> <p>Results</p> <p>The ongoing erosion of vital services formerly provided by the public sector generated considerable frustration and tension among households, networks of extended kin, and neighbors. As resource allocations for health care seeking and other needs were negotiated within and across households, longstanding ideals of reciprocal exchange persisted, but in conditions of poverty, expectations were often unfulfilled, exposing the tension between the need for social support, versus the increasingly oppositional positioning of social network members as sources of competition for limited resources.</p> <p>Conclusions</p> <p>In compliance with neoliberal structural adjustment policies mandated by multilateral and bilateral agencies, government-provided health care services have been severely restricted in Nicaragua. As the national safety net for health care has been eroded, the viability of local level social formations and their ability to respond to struggles collectively has been put at risk as well. Bi-lateral and multilateral agencies need to take into account local needs and demands, and implement policies in a manner that respects national laws, and protects both the physical and social well-being of individuals.</p