Slx5/Slx8-dependent ubiquitin hotspots on chromatin contribute to stress tolerance

Chromatin is a highly regulated environment, and protein association with chromatin is often controlled by post-translational modifications and the corresponding enzymatic machinery. Specifically, SUMO-targeted ubiquitin ligases (STUbLs) have emerged as key players in nuclear quality control, genome maintenance, and transcription. However, how STUbLs select specific substrates among myriads of SUMOylated proteins on chromatin remains unclear. Here, we reveal a remarkable co-localization of the budding yeast STUbL Slx5/Slx8 and ubiquitin at seven genomic loci that we term "ubiquitin hotspots". Ubiquitylation at these sites depends on Slx5/Slx8 and protein turnover on the Cdc48 segregase. We identify the transcription factor-like Ymr111c/Euc1 to associate with these sites and to be a critical determinant of ubiquitylation. Euc1 specifically targets Slx5/Slx8 to ubiquitin hotspots via bipartite binding of Slx5 that involves the Slx5 SUMO-interacting motifs and an additional, novel substrate recognition domain. Interestingly, the Euc1-ubiquitin hotspot pathway acts redundantly with chromatin modifiers of the H2A.Z and Rpd3L pathways in specific stress responses. Thus, our data suggest that STUbL-dependent ubiquitin hotspots shape chromatin during stress adaptation

Accuracy of computerized tomography in determining hepatic tumor size in patients receiving liver transplantation or resection

Computerized tomography (CT) of liver is used in oncologic practice for staging tumors, evaluating response to treatment, and screening patients for hepatic resection. Because of the impact of CT liver scan on major treatment decisions, it is important to assess its accuracy. Patients undergoing liver transplantation or resection provide a unique opportunity to test the accuracy of hepatic-imaging techniques by comparison of finding of preoperative CT scan with those at gross pathologic examination of resected specimens. Forty-one patients who had partial hepatic resection (34 patients) or liver transplantation (eight patients) for malignant (30 patients) or benign (11 patients) tumors were evaluable. Eight (47%) of 17 patients with primary malignant liver tumors, four (31%) of 13 patients with metastatic liver tumors, and two (20%) of 10 patients with benign liver tumors had tumor nodules in resected specimens that were not apparent on preoperative CT studies. These nodules varied in size from 0.1 to 1.6 cm. While 11 of 14 of these nodules were 1.0 cm. These results suggest that conventional CT alone may be insufficient to accurately determine the presence or absence of liver metastases, extent of liver involvement, or response of hepatic metastases to treatment

Shoulder-and Back-Muscle Activation During Shoulder Abduction and Flexion Using a Bodyblade Pro Versus Dumbbells

Context: The Bodyblade Pro is used for shoulder rehabilitation after injury. Resistance is provided by blade oscillations—faster oscillations or higher speeds correspond to greater resistance. However, research supporting the Bodyblade Pro’s use is scarce, particularly in comparison with dumbbell training. Objective: To compare muscle activity, using electromyography (EMG), in the back and shoulder regions during shoulder exercises with the Bodyblade Pro vs dumbbells. Design: Randomized crossover study. Setting: San Diego State University biomechanics laboratory. Participants: 11 healthy male subjects age 19–32 y. Intervention: Subjects performed shoulder-flexion and -abduction exercises using a Bodyblade Pro and dumbbells (5, 8, and 10 lb) while EMG recorded activity of the deltoid, pectoralis major, infraspinatus, serratus anterior, and erector spinae. Main Outcome Measures: Average peak muscle activity (% maximum voluntary isometric contraction) was separately measured for shoulder abduction and flexion in the range of 85° to 95°. Differences among exercise devices were separately analyzed for the flexed and abducted positions using 1-way repeated-measures ANOVA. Results: The Bodyblade Pro produced greater muscle activity than all the dumbbell trials. Differences were significant for all muscles measured (all P \u3c .01) except for the erector spinae during shoulder flexion with a 10-lb dumbbell. EMG activity for the Bodyblade Pro exceeded 50% of the MVIC during both shoulder flexion and abduction. For the dumbbell conditions, only the 10-lb trials approached this effect. Conclusions: Using a Bodyblade during shoulder exercises results in greater shoulder- and back-muscle recruitment than dumbbells. The Bodyblade Pro can activate multiple muscles in a single exercise and thereby minimize the need for multiple dumbbell exercises. The Bodyblade Pro is an effective device for shoulder- and back-muscle activation that warrants further use by clinicians interested in its use for rehabilitation

Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell. Keywords: cryo-EM; isothermal titration calorimetry; magnesium transport; molecular biophysics; structural biology; transport assays; x-ray crystallogrpah

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Reply to discussion by G. Carosi and H. Chanson on "Turbulence characteristics in skimming flows on stepped spillways"

A main technical issue seems to be associated with the structure of the two-phase air–water flow skimming over the pseudo-bottom formed by the step edges. This is a difficult topic. In the air–water skimming flow, the microscopic structure of the gas–liquid mixture is closely linked with the interactions between turbulent vortices and air–water entities (bubbles, droplets, packets) (e.g., Chanson and Toombes 2002; Carosi and Chanson 2008; Gonzalez and Chanson 2008). In the high-velocity free-surface flow, the strong interactions between the turbulent waters and the atmosphere lead to a complete deformation at the interface. Through the free-surface, air is continuously trapped, and the resulting air–water mixture extends through the entire flow (Rao and Kobus 1971; Wood 1991; Chanson 1997). The air–water flow is characterized a complicated two-phase turbulent motion with void fractions ranging from some small, often nonzero values close to the invert to 100% above a pseudo "free-surface" that is usually defined as the location where the void fraction equals 90% (Cain and Wood 1981; Wood 1991; Chanson 1997; Matos 2000). The notion of "effective homogenous flow" contradicts detailed measurements conducted with accurate instrumentations in large-size facilities with well-controlled flow conditions and it is obsolete. Recent findings (Carosi and Chanson 2008) demonstrated in fact a marked changed in flow properties for C ~ 0.95 to 0.97, that is consistent with earlier studies suggesting the use of Y95 or even Y98 as the characteristic air–water flow thickness (Jevdjevich and Levin 1953; Aivazyan 1986)

Image resonance in the many-body density of states at a metal surface

The electronic properties of a semi-infinite metal surface without a bulk gap are studied by a formalism that is able to account for the continuous spectrum of the system. The density of states at the surface is calculated within the GW approximation of many-body perturbation theory. We demonstrate the presence of an unoccupied surface resonance peaked at the position of the first image state. The resonance encompasses the whole Rydberg series of image states and cannot be resolved into individual peaks. Its origin is the shift in spectral weight when many-body correlation effects are taken into account