Rapid-Onset, Short-Duration Induction of Colorectal Contractions in Anesthetized, Adult, Male Rats.

Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal chemoreceptors and mechanoreceptors and are involved in various rectal hypersensitivity disorders with common features of colorectal overactivity. These stimulatory properties of TRPV1 receptors on colorectal function suggested that brief stimulation of TRPV1 might provide a means of pharmacologically activating the colorectum to induce defecation in patients with an "unresponsive" colorectum. The current studies explored the basic features of TRPV1 receptor-induced contractions of the colorectum in anesthetized rats with and without acute spinal cord injury (aSCI).

Recent Developments in On-Demand Voiding Therapies.

One cannot survive without regularly urinating and defecating. People with neurologic injury (spinal cord injury, traumatic brain injury, stroke) or disease (multiple sclerosis, Parkinson's disease, spina bifida) and many elderly are unable to voluntarily initiate voiding. The great majority of them require bladder catheters to void urine and "manual bowel programs" with digital rectal stimulation and manual extraction to void stool.

Effect of GR205171 on autonomic dysreflexia induced by colorectal distension in spinal cord injured rats.

Study Design: Preclinical pharmacology.

Objectives: To determine whether blocking substance P signaling attenuates the hypertension and bradycardia evoked by colorectal distension (CRD) in spinal cord injured (SCI) rats.

Setting: University laboratory in Pennsylvania, U.

Colorectal and bladder prokinetic activity of [Lys, MeLeu, Nle]-NKA after intranasal or sublingual delivery in dogs.

The feasibility of eliciting defecation and urination after intranasal (IN) or sublingual (SL) delivery of a small peptide NK2 receptor agonist, [Lys, MeLeu, Nle]-NKA, was examined using prototype formulations in dogs. In anesthetized animals, administration of 100 or 300 µg/kg IN or 2.0-6.

The Small Ras Superfamily GTPase Rho4 of the Maize Anthracnose Fungus Is Required for β-1,3-glucan Synthesis, Cell Wall Integrity, and Full Virulence.

Small Ras superfamily GTPases are highly conserved regulatory factors of fungal cell wall biosynthesis and morphogenesis. Previous experiments have shown that the Rho4-like protein of the maize anthracnose fungus , formerly erroneously annotated as a Rho1 protein, physically interacts with the β-1,3-glucan synthase Gls1 (Lange et al., 2014; Curr.

The Genetic Characterization of the First Detected Bat Coronaviruses in Poland Revealed SARS-Related Types and Alphacoronaviruses.

Bats are a major global reservoir of alphacoronaviruses (alphaCoVs) and betaCoVs. Attempts to discover the causative agents of COVID-19 and SARS have revealed horseshoe bats (Rhinolophidae) to be the most probable source of the virus. We report the first detection of bat coronaviruses (BtCoVs) in insectivorous bats in Poland and highlight SARS-related coronaviruses found in Rhinolophidae bats.

Neurokinin 2 receptor-mediated bladder and colorectal responses in aged spinal cord injured rats.

Study Design: Animal proof of principle study.

Objectives: Bladder and bowel dysfunction are common after spinal cord injury (SCI) and in the elderly. Neurokinin 2 receptor agonists are known to produce on-demand urination and defecation in adult SCI rats.

A novel allele of the Arabidopsis thaliana MACPF protein CAD1 results in deregulated immune signaling.

Immune recognition in plants is governed by two major classes of receptors: pattern recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat receptors (NLRs). Located at the cell surface, PRRs bind extracellular ligands originating from microbes (indicative of "non-self") or damaged plant cells (indicative of "infected-self"), and trigger signaling cascades to protect against infection. Located intracellularly, NLRs sense pathogen-induced physiological changes and trigger localized cell death and systemic resistance.

Publisher Correction: The calcium-permeable channel OSCA1.3 regulates plant stomatal immunity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Needs, priorities, and attitudes of individuals with spinal cord injury toward nerve stimulation devices for bladder and bowel function: a survey.

Study Design: Survey.

Objectives: To investigate the needs and priorities of people with spinal cord injury for managing neurogenic bladder and bowel function and to determine their willingness to adopt neuromodulation interventions for these functions.

Methods: Anonymous online survey.

Chronic, Twice-Daily Dosing of an NK2 Receptor Agonist [Lys,MeLeu,Nle]-NKA(4-10), Produces Consistent Drug-Induced Micturition and Defecation in Chronic Spinal Rats.

Acute administration of [Lys5,Me,Leu9,Nle10]-NKA(4-10) (LMN-NKA) produces contractions of the detrusor and rectum with voiding in intact and acutely spinal cord injured (SCI) rats. In the current study, the ability of LMN-NKA (10 μg/kg or 100 μg/kg, subcutaneous [SC], twice a day [bid]) or vehicle to induce voiding and defecation in chronic SCI rats was examined across 30 days. After the last day of administration, voiding response rates and bladder pressure (BP) responses to LMN-NKA (intravenous [IV] and SC) were evaluated under anesthesia.

Potency, efficacy, and selectivity of GR64349 at human recombinant neurokinin NK2 and NK1 receptors.

The affinity, potency, efficacy, and selectivity of the NK2 receptor agonist GR64349 ([Lys,Gly,-R-γ-lactam-Leu]NKA(3-10)) at human recombinant NK2 and NK1 receptors was examined. In radioligand binding studies, GR64349 displaced [I]-NKA binding to NK2 receptors with high affinity (pKi 7.77 + 0.

Prokinetic effects of the neurokinin NK2 receptor agonist [Lys,MeLeu,Nle]-NKA on bladder and colorectal activity in minipigs.

The effects of the neurokinin NK2 receptor agonist [Lys,MeLeu,Nle]-NKA (LMN-NKA) on bladder and colorectal function were examined in minipigs. In anesthetized animals, subcutaneous (SC) administration of 30-100 μg/kg increased peak bladder and colorectal pressures. Increases in bladder and colorectal pressure were inhibited by a 15 min pretreatment with the NK2 receptor antagonist GR 159897 (1 mg/kg intravenously (IV)).

Calcium-Nutrient and Messenger.

Calcium is an essential element needed for growth and development of plants under both non-stressed and stress conditions. It thereby fulfills a dual function, being not only an important factor for cell wall and membrane stability, but also serving as a second messenger in many developmental and physiological processes, including the response of plants to biotic stress. The perception of non-self hereby induces an influx of calcium ions (Ca) into the cytosol, which is decoded into downstream responses ultimately leading to defense.

Affinity, potency, efficacy, and selectivity of neurokinin A analogs at human recombinant NK2 and NK1 receptors.

A series of peptide NK2 receptor agonists was evaluated for affinity, potency, efficacy, and selectivity at human recombinant NK2 and NK1 receptors expressed in CHO cells to identify compounds with the greatest separation between NK2 and NK1 receptor agonist activity. Binding studies were performed using displacement of [125I]-NKA binding to NK2 receptors and displacement of [3H]-Septide binding to NK1 receptors expressed in CHO cells. Functional studies examining the increase in intracellular calcium levels and cyclic AMP stimulation were performed using the same cell lines.

New technology assessment and current and upcoming therapies for underactive bladder.

Background And Aims: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder.

Methods: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB.

Results: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria.

Colorectal and cardiovascular effects of [Lys,MeLeu,Nle]-NKA in anesthetized macaques.

The effects of the tachykinin NK2 receptor agonist LMN-NKA ([Lys,MeLeu,Nle]-NKA) on colorectal and arterial blood pressure were examined in anesthetized macaques. Intravenous (IV) administration of 1-100 μg/kg caused dose-related increases in colorectal pressure up to 120 mmHg above baseline, and area under the curve (AUC) up to 24,987 mmHg*s. This was accompanied at all doses by transient hypotension, with up to 26% reduction in mean arterial pressure (MAP) from baseline.

[Lys,MeLeu,Nle]-NKA Elicits NK2 Receptor-Mediated Micturition and Defecation, and NK1 Receptor-Mediated Emesis and Hypotension, in Conscious Dogs.

Tachykinin neurokinin 2 (NK2) receptor agonists may have potential to alleviate clinical conditions associated with bladder and gastrointestinal underactivity by stimulating contraction of visceral smooth muscle. The ability of [Lys,MeLeu,Nle]-neurokinin A (LMN-NKA) to elicit micturition and defecation was examined after repeated administration in groups of 2-10 conscious dogs. Administration of 10-100 g/kg, i.

NK2 and NK1 receptor-mediated effects of NKA and analogs on colon, bladder, and arterial pressure in anesthetized dogs.

Tachykinin NK2 receptor (NK2R) agonists have potential to alleviate clinical conditions associated with bladder and gastrointestinal under activity. The effects of agonists with differing selectivity for NK2R over NK1Rs on colorectal, bladder, and cardiovascular function were examined in anesthetized dogs. Intravenous (IV) administration of NKA, LMN-NKA ([Lys,MeLeu,Nle]-NKA), and [β-Ala]-NKA caused a dose-related increase in colorectal pressure (up to 98 mmHg) that was blocked by pretreatment with the NK2R antagonist GR 159897 (1 mg/kg), and hypotension (decrease in mean arterial pressure of ~40 mmHg) that was blocked by the NK1R antagonist CP-99,994 (1 mg/kg).

Prokinetic effects of neurokinin-2 receptor agonists on the bladder and rectum of rats with acute spinal cord transection.

The suitability of various neurokinin-2 (NK2) receptor agonists and routes of administration to elicit on-demand voiding of the bladder and bowel, as future therapy for individuals with spinal cord injury, was examined using a rat model. The current study examined the feasibility of alternative routes of administration, which are more practical for clinical use than intravenous (IV) administration. Voiding and isovolumetric cystometry were recorded in anesthetized, acutely spinalized, female rats after IV, subcutaneous (SC), intramuscular (IM), intranasal (IN), or sublingual (SL) administration of [Lys,MeLeu,Nle]-NKA (LMN-NKA).

Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues.

No Silver Bullet - Canonical Poly(ADP-Ribose) Polymerases (PARPs) Are No Universal Factors of Abiotic and Biotic Stress Resistance of .

Abiotic and biotic stress can have a detrimental impact on plant growth and productivity. Hence, there is a substantial demand for key factors of stress responses to improve yield stability of crops. Members of the poly(ADP-ribose)polymerase (PARP) protein family, which post-translationally modify (PARylate) nuclear proteins, have been suggested as such universal determinants of plant stress responses.