Emergence of an Orphan Nitrogenase Protein Following Atmospheric Oxygenation.

Molecular innovations within key metabolisms can have profound impacts on element cycling and ecological distribution. Yet, much of the molecular foundations of early evolved enzymes and metabolisms are unknown. Here, we bring one such mystery to relief by probing the birth and evolution of the G-subunit protein, an integral component of certain members of the nitrogenase family, the only enzymes capable of biological nitrogen fixation.

Enhancing Partnerships of Institutions and Journals to Address Concerns About Research Misconduct: Recommendations From a Working Group of Institutional Research Integrity Officers and Journal Editors and Publishers.

Importance: Institutions and journals strive to promote and protect the integrity of the research record, and both groups are equally committed to ensuring the reliability of all published data.

Observations: Three US universities coordinated a series of virtual meetings from June 2021 to March 2022 for a working group composed of senior, experienced US research integrity officers (RIOs), journal editors, and publishing staff who are familiar with managing issues of research integrity and publication ethics. The goal of the working group was to improve the collaboration and transparency between institutions and journals to ensure that research misconduct and publication ethics are managed properly and efficiently.

Nitrogenase resurrection and the evolution of a singular enzymatic mechanism.

The planetary biosphere is powered by a suite of key metabolic innovations that emerged early in the history of life. However, it is unknown whether life has always followed the same set of strategies for performing these critical tasks. Today, microbes access atmospheric sources of bioessential nitrogen through the activities of just one family of enzymes, nitrogenases.

Automated Laboratory Growth Assessment and Maintenance of Azotobacter vinelandii.

Azotobacter vinelandii (A. vinelandii) is a commonly used model organism for the study of aerobic respiration, the bacterial production of several industrially relevant compounds, and, perhaps most significantly, the genetics and biochemistry of biological nitrogen fixation. Laboratory growth assessments of A.

Blood RNA signatures predict recent tuberculosis exposure in mice, macaques and humans.

Tuberculosis (TB) is the leading cause of death due to a single infectious disease. Knowing when a person was infected with Mycobacterium tuberculosis (M.tb) is critical as recent infection is the strongest clinical risk factor for progression to TB disease in immunocompetent individuals.

Characterization of lung inflammation and its impact on macrophage function in aging.

Systemic inflammation that occurs with increasing age (inflammaging) is thought to contribute to the increased susceptibility of the elderly to several disease states. The elderly are at significant risk for developing pulmonary disorders and infectious diseases, but the contribution of inflammation in the pulmonary environment has received little attention. In this study, we demonstrate that the lungs of old mice have elevated levels of proinflammatory cytokines and a resident population of highly activated pulmonary macrophages that are refractory to further activation by IFN-γ.

Clonal expansions of CD8+ T cells with IL-10 secreting capacity occur during chronic Mycobacterium tuberculosis infection.

The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)). CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden.

IL-10 inhibits mature fibrotic granuloma formation during Mycobacterium tuberculosis infection.

Protective immunity and latent Mycobacterium tuberculosis infection in humans are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small-animal models that can develop mature granulomas. In this article, we describe for the first time, to our knowledge, the formation of mature, fibrotic M.

Killer cell lectin-like receptor G1 deficiency significantly enhances survival after Mycobacterium tuberculosis infection.

The expression of T cell differentiation markers is known to increase during Mycobacterium tuberculosis infection, and yet the biological role of such markers remains unclear. We examined the requirement of the T cell differentiation marker killer cell lectin-like receptor G1 (KLRG1) during M. tuberculosis infection using mice deficient in KLRG1.

Breathing Retraining for Individuals Who Fear Respiratory Sensations: Examination of Safety Behavior and Coping Aid Hypotheses.

Cognitive behavioral theorists have suggested that breathing retraining may be used as a safety behavior. Safety behaviors are acts aimed at preventing or minimizing feared catastrophe and may maintain pathologic anxiety by hindering resolution of maladaptive cognitive processes. An opposing position is that breathing retraining is an effective coping aid.

CBA/J mice generate protective immunity to soluble Ag85 but fail to respond efficiently to Ag85 during natural Mycobacterium tuberculosis infection.

In CBA/J mice, susceptibility to Mycobacterium tuberculosis (M.tb) is associated with low interferon-gamma (IFN-γ) responses to antigens (Antigen 85 (Ag85) and early secreted antigenic target-6 (ESAT-6)) that have been defined as immunodominant. Here, we asked whether the failure of CBA/J mice to recognize Ag85 is a consequence of M.

Validation of increased blood storage times with the T-SPOT.TB assay with T-Cell Xtend reagent in individuals with different tuberculosis risk factors.

We compared the performance of the T-SPOT.TB assay with blood used within 0 to 3.5 h after collection (control) to its performance with blood stored for 0 to 3.

Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.

H-2 alleles contribute to antigen 85-specific interferon-gamma responses during Mycobacterium tuberculosis infection.

The in vitro immune responses to mycobacterial antigens have been linked to the H-2 loci in mice. We evaluated in vitro and in vivo immune responses during early Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2(b)), C57BL/6 (H-2(k)), CBA/J (H-2(k)), and C3H/HeJ (H-2(k)) mice to determine H-2(k)-dependent and -independent effects.

Definitions and aetiology of myalgic encephalomyelitis: how the Canadian consensus clinical definition of myalgic encephalomyelitis works.

A perspective on the various definitions of myalgic encephalomyelitis and the process of discovering its aetiology is presented. The importance of clinical guidelines is emphasised to encourage clinicians to provide clear descriptions of their individual patients required for proper clinical activity; diagnosis, estimation of severity of effect, prognosis, treatment and rehabilitation. This individual knowledge is informed by general and (hopefully) publicly confirmed knowledge resulting from scientific research during the second-person interaction which lies at the core of the clinical encounter.

Dosimetric characteristics of a low-kV intra-operative x-ray source: implications for use in a clinical trial for treatment of low-risk breast cancer.

The dosimetric characteristics of a low-kV x-ray device for performing intra-operative irradiations, the Intrabeam (Photoelectron Corporation, Lexington, MA), are examined. Two dosimetric models are considered--an analytical model considering only the primary x-ray beam, and a Monte Carlo model utilizing the EGSnrc code and a spherical simulation geometry. Both models prove reliable for verifying measured dose distributions for the device.

Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein.

The TTX-sensitive Na(v)1.7 (PN1) Na(+) channel alpha subunit protein is expressed mainly in small dorsal root ganglion (DRG) neurones. This study examines immunocytochemically whether it is expressed exclusively or preferentially in nociceptive primary afferent DRG neurones, and determines the electrophysiological properties of neurones that express it.

Dosimetry of a low-kV intra-operative X-ray source using basic analytical beam models.

The low energy (30-50 kVp) beams from an intra-operative X-ray source are modelled using a basic analytical model considering just primary beam attenuation and absorption. Spatial dosimetry at such low energies is difficult due to the rapid changes in dose-rate from the radiation source. The purpose of the model was to determine the variation with distance in water of coefficients required for beam dosimetry and to validate beam measurements performed in water of high-gradient dose distributions.

Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat.

Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin.

Changes in partial pressure of carbon dioxide with time in carotid arterial blood in cats.

1. A rapidly responding CO2 sensor and cuvette were placed in the carotid artery of anaesthetized cats and changes of PCO2 in post-pulmonary capillary blood were recorded when flow through the cuvette was suddenly stopped. 2.

Preservation of the hypoxic pulmonary vasoconstrictor mechanism during methoxyflurane anaesthesia in the dog.

The effect of methoxyflurane on the hypoxic pulmonary vasoconstrictor response in the dog lung was assessed by measuring the redistribution of pulmonary blood flow in response to two levels of unilateral alveolar hypoxia. Methoxyflurane 0.5% had no significant effect on the redistribution of blood flow resulting from the unilateral administration of oxygen 7% or nitrogen and there were no significant differences in PaO2 between the measurements made during unilateral hypoxia with methoxyflurane and those made during unilateral hypoxia in the control periods.

Effect of orciprenaline on hypoxic pulmonary vasoconstriction in dogs.

The effect of orciprenaline on hypoxic pulmonary vasoconstriction and arterial oxygen tension (PaO2) was studied in 8 dogs by measuring the redistribution of blood flow in response to unilateral alveolar hypoxia. The distribution of blood flow was recorded continuously by measuring the radioactivity of the mixed expired gas from each lung during the continuous intravenous infusion of xenon-133. The hypoxic vasoconstrictor response was significantly depressed by an infusion of 1.

A comparison of the cardiorespiratory effects of continuous positive airway pressure breathing and continuous positive pressure ventilation in dogs.

Five patterns of ventilation have been compared in dogs: (1) spontaneous ventilation at ambient pressure (SV); (2) intermittent positive pressure ventilation (IPPV); (3) spontaneous ventilation at 0.98 kPa positive airway pressure, delivered from a non-rebreathing circuit incorporating a 5-litre reservoir bag and fresh-gas flow of twice the minute volume (CPAP (bag)); (4) spontaneous ventilation at 0.98 kPa positive airway pressure, with the reservoir bag replaced by a weighted bellows (CPAP (bellows)) and (5) IPPV with 0.