The “Unwelcome Obligation”: Why Neither State nor Federal Courts Should Draw District Lines

In recent years, the judiciary’s inability to hold state legislatures accountable for partisan gerrymanders has encouraged state governments to draw legislative and congressional district lines with high partisan advantage, thereby allowing a political party to acquire seats in numbers disproportionate to their popular support. In 2017, the U.S. Supreme Court granted certiorari on two partisan gerrymandering cases: Gill v. Whitford and Benisek v. Lamone. Although the Court might articulate a judicially manageable standard to determine when a districting plan is politically fair, other methods to prevent federal courts from creating district maps that perpetuate partisan bias exist. This Note examines and critiques current debates regarding the judiciary’s role in redistricting and adjudicating partisan gerrymandering claims. It argues that independent redistricting commissions—enacted through state voter initiatives or referendums—should replace federal courts’ authority to develop redistricting plans

Surface Plasmon Resonance kinetic analysis of the interaction between G-quadruplex nucleic acids and an anti-G-quadruplex monoclonal antibody

Background G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a highly sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody on the SPR sensor chip to optimize detection of binding antigens. Methods SPR was employed to characterize the anti-G4 antibody interaction with G4 and non-G4 oligonucleotides. Dextran-functionalized sensor chips were used both in covalent coupling and capturing procedures. Results The use of two leading molecule for orienting the antibody of interest allowed to improve its activity from completely non-functional to 65% active. The specificity of the anti-G4 antobody for G4 structures could thus be assessed with high sensitivity and reliability. Conclusions Optimization of the immobilization protocol for SPR biosensing, allowed us to determine the anti-G4 antibody affinity and specificity for G4 antigens with higher sensitivity with respect to other in vitro assays such as ELISA. Anti-G4 antibody specificity is a fundamental assumption for the future utilization of this kind of antibodies for monitoring G4s directly in cells. General significance The heterogeneous orientation of amine-coupling immobilized ligands is a general problem that often leads to partial or complete inactivation of the molecules. Here we describe a new strategy for improving ligand orientation: driving it from two sides. This principle can be virtually applied to every molecule that loses its activity or is poorly immobilized after standard coupling to the SPR chip surface

G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed

The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids

open5noBACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis.openLago, Sara; Tosoni, Elena; Nadai, Matteo; Palumbo, Manlio; Richter, Sara NLago, Sara; Tosoni, Elena; Nadai, Matteo; Palumbo, Manlio; Richter, Sar

Resource Mediated Competition of two South Texas Natives: _Acacia berlandieri_ and _Trichloris pluriflora_

*Background/Question/Methods* 
_Acacia berlandieri_, an early-successional C~3~ woody shrub legume, and _Trichloris pluriflora_, a late-successional/climax C~4~ mid-tall grass, reside in similar habitats and have both been documented in Texas for over 150 years. This study examines the resource mediated above and below ground competition within and between these species, which may illuminate some of the dynamics involved in the encroachment of woody shrub species into the former grasslands. These species, started from seed, were grown outdoors (5 replicates/treatment) using sandy clay loam soil in plastic lined 15×15 cm pots for 155 days and watered daily. Half of these pots received 12.5% Hoagland’s solution as a nutrient source. Growth measurements were taken 3 times, after a 72 day establishment period and prior to harvest. The plants were then harvested intact, dried at 60°C, and above and below ground dry mass for each individual plant was separated. The roots were ashed at 650°C and measurements were taken for the above and below ground biomass. 

*Results/Conclusions* 
The growth parameters of _Acacia berlandieri_, basal diameter, height, and number of leaves increased with density (P = 0.0024, P < 0.0001, and P < 0.0001), when grown in competition with _Trichloris pluriflora_, using the densities of 1/3, 2/2. 3/1, and 4/0 _Acacia/Trichloris_ plants/pot. None of these growth parameters for _A. berlandieri_ had an effect on the variables of density, nutrients or and their interaction (P > 0.0500), when grown alone with densities of 1, 2, and 4 plants/pot. The growth parameters of _T. pluriflora_, culms and height decreased with density (P = 0.0077 and P = 0.0006), when grown in competition with _A. berlandieri_, using densities of 1/3, 2/2. 3/1, and 4/0 _Trichloris/Acacia_ plants/pot. The culms, tillers, and height of _T. pluriflora_, when grown alone with densities of 1, 2, 4, and 8 plants/pot, decreased with density (P < 0.0001, P = 0.0312, and P < 0.0001). The measurement parameters of harvested _A. berlandieri_, above ground biomass and ash-free root biomass increased with density (P = 0.0463 and P = 0.0389), when grown in competition with _T. pluriflora_. The root biomass of harvested _A. berlandieri_, grown alone, decreased with the interaction of density and nutrients (P = 0.0068). The total plant dry mass, above ground biomass, root dry mass, and root dry mass of harvested _T. pluriflora_, grown in competition with _A. berlandieri_, decreased with density (P < 0.0001, P < 0.0001, P = 0.0235, and P = 0.0145). These same measurement parameters of harvested _T. pluriflora_, grown alone, increased with density (P < 0.0001 for all four). The addition of nutrients had no effect on the growth or harvest of _A. berlandieri_ and _T. pluriflora_ for either intra- or interspecific competition. Instead, density appeared to be the driving force for the competition between and among these two species for both growth and harvest. Although woody shrub and grassland interactions should be mediated by resource availability, that was not the case in this study. Clearly, density is an important variable involved in the disappearance of the grasslands

Highly Improved Electrospray Ionization-Mass Spectrometry Detection of G-Quadruplex-Folded Oligonucleotides and Their Complexes with Small Molecules

G-quadruplexes are nucleic acids structures stabilized by physiological concentration of potassium ions. Because low stability G-quadruplexes are hardly detectable by mass spectrometry, we optimized solvent conditions: isopropanol in a triethylamine/hexafluoroisopropanol mixture highly increased G-quadruplex sensitivity with no modification of the physiological G-quadruplex conformation. G-quadruplexes/G-quadruplex-ligand complexes were also correctly detected at concentration as low as 40 nM. Detection of the physiological conformation of G4s and their complexes opens up the possibility to perform high-throughput screening of G-quadruplex ligands for the development of drug molecules effective against critical human diseases

Comparing the cardiac autonomic activity profile of daytime naps and nighttime sleep.

Heart rate variability (HRV) is a reliable technique to evaluate autonomic activity and shows marked changes across a night of sleep. Previous nighttime sleep findings report changes in HRV during non-rapid eye movement sleep (NREM), which have been associated with cardiovascular health benefits. Daytime sleep, however, has been linked with both positive and negative cardiovascular outcomes. Yet, no studies have directly compared HRV profiles during an ecologically-valid daytime nap in healthy, well-rested adults to that of nighttime sleep. Using a within-subjects design, 32 people took a daytime nap and slept overnight in the lab at least one week apart; both sleep sessions had polysomnography, including electrocardiography (ECG), recorded. We measured inter-beat intervals (RR), total power (TP), low frequency power (LF; .04-.15 Hz), and high frequency power (HF; .15-.40 Hz) components of HRV during NREM and rapid eye movement (REM) sleep. Compared to the nap, we found longer RR intervals and decreased heart rate during the night for both Stage 2 and SWS and increased TP, LF and HF power during nighttime Stage 2 sleep only; however, no differences in the LFHF ratio or normalized HF power were found between the nap and the night. Also, no differences in REM sleep between the nap and night were detected. Similar relationships emerged when comparing the nap to one cycle of nighttime sleep. These findings suggest that longer daytime naps, with both SWS and REM, may provide similar cardiovascular benefits as nocturnal sleep. In light of the on-going debate surrounding the health benefits and/or risks associated with napping, these results suggest that longer daytime naps in young, healthy adults may support cardiac down-regulation similar to nighttime sleep. In addition, napping paradigms may serve as tools to explore sleep-related changes in autonomic activity in both healthy and at-risk populations

Uniplanar nystagmus associated with perceptual and cognitive visual dysfunction due to presumed focal ischemic occipital cortical atrophy: a missed diagnosis and new observation

Uniplanar nystagmus has been described in relation to pathology of the brain stem, retina, optic nerve, sensory visual deprivation, periventricular leucomalacia, and drug toxicity. This paper describes a case of uniplanar nystagmus associated with features of higher visual dysfunction and a presumed focal insult to the occipital lobes following an episode of neonatal apnea

Interventions targeted at primary care practitioners to improve the identification and referral of patients with co-morbid obesity: a realist review protocol

<b>Background </b>Obesity is one of the most significant public health challenges in the developed world. Recent policy has suggested that more can be done in primary care to support adults with obesity. In particular, general practitioners (GPs) and practice nurses (PNs) could improve the identification and referral of adults with obesity to appropriate weight management services. Previous interventions targeted at primary care practitioners in this area have had mixed results, suggesting a more complex interplay between patients, practitioners, and systems. The objectives of this review are (i) to identify the underlying ‘programme theory’ of interventions targeted at primary care practitioners to improve the identification and referral of adults with obesity and (ii) to explore how and why GPs and PNs identify and refer individuals with obesity, particularly in the context of weight-related co-morbidity. This protocol will explain the rationale for using a realist review approach and outline the key steps in this process. <p></p> <b>Methods</b> Realist review is a theory-led approach to knowledge synthesis that provides an explanatory analysis aimed at discerning what works, for whom, in what circumstances, how, and why. In this review, scoping interviews with key stakeholders involved in the planning and delivery of adult weight management services in Scotland helped to inform the identification of formal theories - from psychology, sociology, and implementation science - that will be tested as the review progresses. A comprehensive search strategy is described, including scope for iterative searching. Data analysis is outlined in three stages (describing context-mechanism-outcome configurations, exploring patterns in these configurations, and developing and testing middle-range theories, informed by the formal theories previously identified), culminating in the production of explanatory programme theory that considers individual, interpersonal, and institutional/systems-level components. <p></p> <b>Discussion </b>This is the first realist review that we are aware of looking at interventions targeted at primary care practitioners to improve the weight management of adults with obesity. Engagement with stakeholders at an early stage is a unique feature of realist review. This shapes the scope of the review, identification of candidate theories and dissemination strategies. The findings of this review will inform policy and future interventions. Systematic review registration PROSPERO CRD4201400939