Divergence in a Eukaryotic Transcription Factor's co-TF Dependence Involves Multiple Intrinsically Disordered Regions Affecting Activation and Autoinhibition.

Combinatorial control by multiple transcription factors (TFs) is a hallmark of eukaryotic gene regulation. Despite its prevalence and crucial roles in enhancing specificity and integrating information, the mechanisms behind why eukaryotic TFs depend on one another, and whether such interdependence evolves, are not well understood. We exploit natural variation in co-TF dependence in the yeast phosphate starvation (PHO) response to address this question.

Divergence of TORC1-mediated Stress Response Leads to Novel Acquired Stress Resistance in a Pathogenic Yeast.

Acquired stress resistance (ASR) enables organisms to prepare for environmental changes that occur after an initial stressor. However, the genetic basis for ASR and how the underlying network evolved remain poorly understood. In this study, we discovered that a short phosphate starvation induces oxidative stress response (OSR) genes in the pathogenic yeast and protects it against a severe HO stress; the same treatment, however, provides little benefit in the low pathogenic-potential relative, .

Parallel expansion and divergence of an adhesin family in pathogenic yeasts.

Opportunistic yeast pathogens arose multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistant (MDR) Candida auris. We show that homologs of a known yeast adhesin family in Candida albicans, the Hyr/Iff-like (Hil) family, are enriched in distinct clades of Candida species as a result of multiple, independent expansions. Following gene duplication, the tandem repeat-rich region in these proteins diverged extremely rapidly and generated large variations in length and β-aggregation potential, both of which are known to directly affect adhesion.

Predicting Postoperative Troponin in Patients Undergoing Elective Hip or Knee Arthroplasty: A Comparison of Five Cardiac Risk Prediction Tools.

Background: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty.

Methods: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty.

Transport features predict if a molecule is odorous.

In studies of vision and audition, stimuli can be chosen to span the visible or audible spectrum; in olfaction, the axes and boundaries defining the analogous odorous space are unknown. As a result, the population of olfactory space is likewise unknown, and anecdotal estimates of 10,000 odorants have endured. The journey a molecule must take to reach olfactory receptors (ORs) and produce an odor percept suggests some chemical criteria for odorants: a molecule must 1) be volatile enough to enter the air phase, 2) be nonvolatile and hydrophilic enough to sorb into the mucous layer coating the olfactory epithelium, 3) be hydrophobic enough to enter an OR binding pocket, and 4) activate at least one OR.

Lysozyme Resistance in Clostridioides difficile Is Dependent on Two Peptidoglycan Deacetylases.

() is a major cause of hospital-acquired infections leading to antibiotic-associated diarrhea. exhibits a very high level of resistance to lysozyme. Bacteria commonly resist lysozyme through modification of the cell wall.

Predicting postdischarge hospital-associated venous thromboembolism among medical patients using a validated mortality risk score derived from common biomarkers.

Background: Discharged medical patients are at risk for venous thromboembolism (VTE). It is difficult to identify which discharged patients would benefit from extended duration thromboprophylaxis. The Intermountain Risk Score is a prediction score derived from discrete components of the complete blood cell count and basic metabolic panel and is highly predictive of 1-year mortality.

Effects of acupuncture at Pericardium-6 and Stomach-36 on nausea, sedation and gastrointestinal motility in healthy dogs administered intravenous lidocaine infusions.

The objectives of this study were to assess gastrointestinal transit times, sedation, and signs of nausea associated with intravenous lidocaine infusions in dogs following targeted acupuncture at Pericardium-6 (PC6) and Stomach-36 (ST36). In a randomized, blind crossover design, 6 healthy, adult Beagles were fed thirty 1.5 mm barium-impregnated polyethylene spheres (BIPS), then were subject to 30 minutes of: 1) no acupuncture, 2) bilateral targeted acupuncture at PC6 and ST36, or 3) bilateral non-target acupuncture at Lung-5 (LU5) and Bladder-55 (BL55).

Consent process for US-based family reference DNA samples.

DNA collection from family members of the missing is a tenet for missing persons' and mass fatality investigations. Procedures for consenting family members are disparate, depending on the context supporting the reason for sample collection. While guidelines and best practices have been developed for handling mass fatalities and for identification of the missing, these guidelines do not address standard consent practices for living family members of potential victims.

Automated acoustic detection of mouse scratching.

Itch is an aversive somatic sense that elicits the desire to scratch. In animal models of itch, scratching behavior is frequently used as a proxy for itch, and this behavior is typically assessed through visual quantification. However, manual scoring of videos has numerous limitations, underscoring the need for an automated approach.

Semi-intact ex vivo approach to investigate spinal somatosensory circuits.

The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons.

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons.

Unlabelled: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers.

Generation of a NK1R-CreER knockin mouse strain to study cells involved in Neurokinin 1 Receptor signaling.

The Neurokinin 1 Receptor (NK1R), which binds Substance P, is expressed in discrete populations of neurons throughout the nervous system, where it has numerous roles including the modulation of pain and affective behaviors. Here, we report the generation of a NK1R-CreER knockin allele, in which CreER replaces the coding sequence of the TACR1 gene (encoding NK1R) in order to gain genetic access to these cells. We find that the NK1R-CreER allele mediates recombination in many regions of the nervous system that are important in pain and anxiety including the amygdala, hypothalamus, frontal cortex, raphe nucleus, and dorsal horn of the spinal cord.

Comparison of Dexmedetomidine-Ketamine with Isoflurane for Anesthesia of Chinchillas (Chinchilla lanigera).

The objective of this study was to compare isoflurane with a combination of dexmedetomidine and ketamine, administered intramuscularly, for anesthesia in chinchillas (Chinchilla lanigera). In a prospective, complete crossover study, adult chinchillas (n = 8; age, 2 to 5 y) were anesthetized with a combination of dexmedetomidine (0.015 mg/kg IM) and ketamine (4 mg/kg IM).

Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.

Auditory information is initially processed in the cochlear nuclei before being relayed to the brain. The cochlear nuclei are subdivided into dorsal, anterior ventral, and posterior ventral domains, each containing several subtypes of neurons that are thought to play discrete roles in the processing of sound. However, the ontogeny of these neurons is poorly understood, and this gap in knowledge hampers efforts to understand the basic neural circuitry of this nucleus.

An Unexpected Role for TRPV4 in Serotonin-Mediated Itch.

Previous studies have revealed that TRPV1 and TRPA1 function downstream of many itch receptors, where they mediate inward current to trigger action potentials in primary afferents. Although other TRP channels, such as TRPV4, are expressed in primary afferents, whether or not they play an analogous role in itch was previously unknown. Now, Akiyama et al.

Effects of Buprenorphine Added to Bupivacaine Infraorbital Nerve Blocks on Isoflurane Minimum Alveolar Concentration Using a Model for Acute Dental/Oral Surgical Pain in Dogs.

Bupivacaine appears to have a duration of action longer than previously reported. Results of this study demonstrate that the addition of buprenorphrine may enhance the analgesic duration of effect for bupivacaine regional nerve blocks. In addition, the use of bupivacaine alone may have analgesia that exceeds 24 hours in many cases.

Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling.

The kappa opioid receptor (KOR) has numerous important roles in the nervous system including the modulation of mood, reward, pain, and itch. In addition, KOR is expressed in many non-neuronal tissues. However, the specific cell types that express KOR are poorly characterized.

Comparison of anesthesia with a morphine-lidocaine-ketamine infusion or a morphine-lidocaine epidural on time to extubation in dogs.

Objective: To evaluate and compare the time to extubation in two commonly used methods of analgesia in dogs undergoing elective pelvic limb orthopedic procedures.

Study Design: Prospective, randomized, double-blinded clinical study.

Animals: Twenty-five adult, client-owned, healthy dogs aged 4.

Itch and its inhibition by counter stimuli.

Recent studies have made significant progress in the knowledge of how itch sensation is processed, especially the molecular identity of neurons involved in itch signaling, both in the dorsal root ganglion and spinal cord. Despite these advances, the organization of these neurons in dorsal spinal cord circuits and how they interact with other somatosensory modalities, such as pain or temperature, remain relatively unexplored. Recent work from our lab and others has begun to shed light on these questions and will be the focus of this chapter.

High-throughput analysis of mammalian olfactory receptors: measurement of receptor activation via luciferase activity.

Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors(1-11). This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems.

Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch.