TDP-43 condensation properties specify its RNA binding and regulation

Summary: Mutations causing amyotrophic lateral sclerosis (ALS) often affect the condensation properties of RNA-binding proteins (RBPs). However, the role of RBP condensation in the specificity and function of protein-RNA complexes remains unclear. We created a series of TDP-43 C-terminal domain (CTD) variants that exhibited a gradient of low to high condensation propensity, as observed in vitro and by nuclear mobility and foci formation. Notably, a capacity for condensation was required for efficient TDP-43 assembly on subsets of RNA-binding regions, which contain unusually long clusters of motifs of characteristic types and density. These “binding-region condensates” are promoted by homomeric CTD-driven interactions and required for efficient regulation of a subset of bound transcripts, including autoregulation of TDP-43 mRNA. We establish that RBP condensation can occur in a binding-region-specific manner to selectively modulate transcriptome-wide RNA regulation, which has implications for remodeling RNA networks in the context of signaling, disease, and evolution

Nyquist method for Wigner-Poisson quantum plasmas

By means of the Nyquist method, we investigate the linear stability of electrostatic waves in homogeneous equilibria of quantum plasmas described by the Wigner-Poisson system. We show that, unlike the classical Vlasov-Poisson system, the Wigner-Poisson case does not necessarily possess a Penrose functional determining its linear stability properties. The Nyquist method is then applied to a two-stream distribution, for which we obtain an exact, necessary and sufficient condition for linear stability, as well as to a bump-in-tail equilibrium.Comment: 6 figure

Long-term effects of a very low carbohydrate compared with a high carbohydrate diet on renal function in individuals with type 2 diabetes: a randomized trial

To compare the long-term effects of a very low carbohydrate, high-protein, low saturated fat (LC) diet with a traditional high unrefined carbohydrate, low-fat (HC) diet on markers of renal function in obese adults with type 2 diabetes (T2DM), but without overt kidney disease.One hundred fifteen adults (BMI 34.6 ± 4.3 kg/m, age 58 ± 7 years, HbA1c 7.3 ± 1.1%, 56 ± 12 mmol/mol, serum creatinine (SCr) 69 ± 15 μmol/L, glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR 94 ± 12 mL/min/1.73 m)) were randomized to consume either an LC (14% energy as carbohydrate [CHO < 50 g/day], 28% protein [PRO], 58% fat [<10% saturated fat]) or an HC (53% CHO, 17% PRO, 30% fat [<10% saturated fat]) energy-matched, weight-loss diet combined with supervised exercise training (60 min, 3 day/wk) for 12 months. Body weight, blood pressure, and renal function assessed by eGFR, estimated creatinine clearance (Cockcroft-Gault, Salazar-Corcoran) and albumin excretion rate (AER), were measured pre- and post-intervention.Both groups achieved similar completion rates (LC 71%, HC 65%) and reductions in weight (mean [95% CI]; -9.3 [-10.6, -8.0] kg) and blood pressure (-6 [-9, -4]/-6[-8, -5] mmHg), P ≥ 0.18. Protein intake calculated from 24 hours urinary urea was higher in the LC than HC group (LC 120.1 ± 38.2 g/day, 1.3 g/kg/day; HC 95.8 ± 27.8 g/day, 1 g/kg/day), P < 0.001 diet effect. Changes in SCr (LC 3 [1, 5], HC 1 [-1, 3] μmol/L) and eGFR (LC -4 [-6, -2], HC -2 [-3, 0] mL/min/1.73 m) did not differ between diets (P = 0.25). AER decreased independent of diet composition (LC --2.4 [-6, 1.2], HC -1.8 [-5.4, 1.8] mg/24 h, P = 0.24); 6 participants (LC 3, HC 3) had moderately elevated AER at baseline (30-300 mg/24 h), which normalized in 4 participants (LC 2, HC 2) after 52 weeks.Compared with a traditional HC weight loss diet, consumption of an LC high protein diet does not adversely affect clinical markers of renal function in obese adults with T2DM and no preexisting kidney disease.Jeannie Tay, Campbell H. Thompson, Natalie D. Luscombe-Marsh, Manny Noakes, Jonathan D. Buckley, Gary A. Wittert and Grant D. Brinkwort

Delocalization of states in two component superlattices with correlated disorder

Electron and phonon states in two different models of intentionally disordered superlattices are studied analytically as well as numerically. The localization length is calculated exactly and we found that it diverges for particular energies or frequencies, suggesting the existence of delocalized states for both electrons and phonons. Numerical calculations for the transmission coefficient support the existence of these delocalized states.Comment: RevTeX, 12 pages, 2 PS figures adde

Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli

The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with less changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: 1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation, and 2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog

Transcription levels of a noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast

Transcription through noncoding regions of the genome is pervasive. How these transcription events regulate gene expression remains poorly understood. Here, we report that, in S. cerevisiae, the levels of transcription through a noncoding region, IRT2, located upstream in the promoter of the inducer of meiosis, IME1, regulate opposing chromatin and transcription states. At low levels, the act of IRT2 transcription promotes histone exchange, delivering acetylated histone H3 lysine 56 to chromatin locally. The subsequent open chromatin state directs transcription factor recruitment and induces downstream transcription to repress the IME1 promoter and meiotic entry. Conversely, increasing transcription turns IRT2 into a repressor by promoting transcription-coupled chromatin assembly. The two opposing functions of IRT2 transcription shape a regulatory circuit, which ensures a robust cell-type-specific control of IME1 expression and yeast meiosis. Our data illustrate how intergenic transcription levels are key to controlling local chromatin state, gene expression, and cell fate outcomes

Anomalous self-diffusion in the ferromagnetic Ising chain with Kawasaki dynamics

We investigate the motion of a tagged spin in a ferromagnetic Ising chain evolving under Kawasaki dynamics. At equilibrium, the displacement is Gaussian, with a variance growing as $A t^{1/2}$. The temperature dependence of the prefactor $A$ is derived exactly. At low temperature, where the static correlation length $\xi$ is large, the mean square displacement grows as $(t/\xi^2)^{2/3}$ in the coarsening regime, i.e., as a finite fraction of the mean square domain length. The case of totally asymmetric dynamics, where $(+)$ (resp. $(-)$) spins move only to the right (resp. to the left), is also considered. In the steady state, the displacement variance grows as $B t^{2/3}$. The temperature dependence of the prefactor $B$ is derived exactly, using the Kardar-Parisi-Zhang theory. At low temperature, the displacement variance grows as $t/\xi^2$ in the coarsening regime, again proportionally to the mean square domain length.Comment: 22 pages, 8 figures. A few minor changes and update

Food services using energy- and protein-fortified meals to assist vulnerable community-residing older adults meet their dietary requirements and maintain good health and quality of life: findings from a pilot study

The effects of "standard (STD)" vs. "protein- and energy-enriched (HEHP)" food-service meals on the nutrient intake, nutritional status, functional capacity, and wellbeing of older adults was investigated using a 12 week, double-blinded, parallel group design. All participants received dietetics counseling and either an STD (2.3 MJ and 30 g protein per meal) or a HEHP (4.6 MJ and 60 g protein) hot lunchtime meal for at least 3 days/week; those who did not want food-service meals were included in the control group (CON). Twenty-nine participants completed the study (STD = 7; HEHP = 12; CON = 10). From baseline to week 12, the HEHP subjects increased their mean daily energy intake from 6151 ± 376 kJ to 8228 ± 642 kJ (p = 0.002 for effect of time) and protein intake from 67 ± 4 g to 86 ± 8 g (p = 0.014 for effect of time). The MNA (Mini Nutritional Assessment) score was increased significantly in HEHP by 4.0 ± 1.1 points (p = 0.001), but not in the STD and CON groups (2.8 ± 2.1 points and 1.8 ± 1.1 points, p > 0.05). No difference was found for other clinical outcomes between the groups. The findings indicate that provision of HEHP-fortified food-service meals can increase energy and protein intake and improve the nutritional status of nutritionally at-risk older people.Tony Arjuna, Michelle Miller, Tomoko Ueno, Renuka Visvanathan, Kylie Lange, Stijn Soenen, Ian Chapman and Natalie Luscombe-Mars