Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis.

Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development.

Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.

Octopamine is a well-established invertebrate neurotransmitter involved in fight or flight responses. In mammals, its function was replaced by epinephrine. Nevertheless, it is present at trace amounts and can modulate the release of monoamine neurotransmitters by a yet unidentified mechanism.

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD).

Reduced expression of mitochondrial complex I subunit Ndufs2 does not impact healthspan in mice.

Aging in mammals leads to reduction in genes encoding the 45-subunit mitochondrial electron transport chain complex I. It has been hypothesized that normal aging and age-related diseases such as Parkinson's disease are in part due to modest decrease in expression of mitochondrial complex I subunits. By contrast, diminishing expression of mitochondrial complex I genes in lower organisms increases lifespan.

A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice.

The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor.

Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species.

Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR-Cas9 genetic screen and uncovered that loss of genes encoding subunits of mitochondrial complex I was deleterious in the presence of the mitochondria-targeted antioxidant mito-vitamin E (MVE).

Mitochondrial ubiquinol oxidation is necessary for tumour growth.

The mitochondrial electron transport chain (ETC) is necessary for tumour growth and its inhibition has demonstrated anti-tumour efficacy in combination with targeted therapies. Furthermore, human brain and lung tumours display robust glucose oxidation by mitochondria. However, it is unclear why a functional ETC is necessary for tumour growth in vivo.

NAD+ Regeneration Rescues Lifespan, but Not Ataxia, in a Mouse Model of Brain Mitochondrial Complex I Dysfunction.

Mitochondrial complex I regenerates NAD+ and proton pumps for TCA cycle function and ATP production, respectively. Mitochondrial complex I dysfunction has been implicated in many brain pathologies including Leigh syndrome and Parkinson's disease. We sought to determine whether NAD+ regeneration or proton pumping, i.

Mitochondria control acute and chronic responses to hypoxia.

There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute increases in respiration triggered by the carotid body chemosensory cells, and chronic changes such as induction of red blood cell proliferation and angiogenesis by hypoxia inducible factor targets erythropoietin and vascular endothelial growth factor, respectively. Mitochondria account for the majority of oxygen consumption in the cell and have recently been appreciated to serve as signaling organelles required for the initiation or propagation of numerous homeostatic mechanisms.

Drowning deaths among anglers: Are waders a contributing factor?

Recreational fishing has been a popular activity for Australians over at least the past two centuries. While the use of waders for recreational fishing is widely adopted by participants, there is considerable speculation as to whether waders are contributing to fishing-related drowning deaths. This study involved a comprehensive search of peer-reviewed and grey literature to identify relevant information and a pilot investigation in a swimming pool to understand the accuracy of the currently available information.

Lentiviral delivery of RNAi for in vivo lineage-specific modulation of gene expression in mouse lung macrophages.

Although RNA interference (RNAi) has become a ubiquitous laboratory tool since its discovery 12 years ago, in vivo delivery to selected cell types remains a major technical challenge. Here, we report the use of lentiviral vectors for long-term in vivo delivery of RNAi selectively to resident alveolar macrophages (AMs), key immune effector cells in the lung. We demonstrate the therapeutic potential of this approach by RNAi-based downregulation of p65 (RelA), a component of the pro-inflammatory transcriptional regulator, nuclear factor κB (NF-κB) and a key participant in lung disease pathogenesis.

Long term retention of safe diving skills.

This short report describes a 20-month follow-up of safe diving skills, extending the 8-month retention period previously published in this journal. Thirty-four recreational swimmers with poor diving skills were evaluated before and immediately after a diving skills intervention program. Twenty-two returned for the eight-month follow-up evaluation and 16 returned 20 months post.

Retention of safe diving skills.

This study investigated diving skill maintenance over an eight-month retention period following an intervention program. Thirty-four recreational swimmers with poor diving skills were measured before and immediately after a diving skills intervention program. Twenty-two returned for follow-up evaluation.

Ambulatory paediatrics: does it work?

To determine whether a paediatric ambulatory assessment service is an effective and acceptable replacement for an inpatient unit. Analysis of hospital paediatric medical admissions. Postal questionnaire survey of local general practitioners.

Risk reduction in diving spinal cord injury: teaching safe diving skills.

Thirty-four recreational swimmers underwent an intervention program to improve diving skills. Participants with low diving skills completed seven 10-minute sessions which emphasised locking thumbs and holding arms extended beyond the head, and steering and gliding skills. Various dive entries were video-recorded and maximum depth reached was used as the criterion measure.

Characteristics of 'low risk' and 'high risk' dives by young adults: risk reduction in spinal cord injury.

Study Design: To establish benchmark normative data for dive entries performed by young adults of the age range most likely to sustain a diving spinal cord injury. Data acquired from analysis of the dives performed, along with survey information, were used to determine which factors make the most contribution to the level of risk in diving.

Objectives: To identify influential variables which could contribute to risk of spinal cord injury for each of four types of dives.

Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.

Objective: To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy.

Methods: Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy.

Establishment of consistent gait after fitting of new components.

Since the time required for a person with an amputation to become familiarized with a prosthesis after a change of a component is not known, the gait of a single subject, a man with a through-knee amputation, was examined with two different knee mechanisms interchanged in the same prosthesis. Several parameters were analyzed to determine when the subject's gait had stabilized sufficiently to permit confident assessment of the appropriateness of the knee mechanisms. At least one week of functional walking was required before a clinical decision could be made about the suitability of the component.

Benchmark data for elderly, vascular trans-tibial amputees after rehabilitation.

Benchmark data for lower limb amputees is often limited to young subjects who have had their amputations as the result of trauma. The majority of trans-tibial amputees rehabilitated are, however, elderly vascular amputees who may have different gait characteristics than their younger counterparts. Without biomechanical analyses to provide such benchmark data for this group it is not possible to compare the effects of different rehabilitation programmes, gait training regimens, or prosthetic devices.

The role of the general practitioner hospital in inpatient care.

The rationale of the general practitioner hospital continues to be questioned. A study of the services and case-mix of two of the four remaining general practitioner hospitals in Northern Ireland was undertaken to determine whether the nature and cost of inpatient care in these hospitals was comparable to the available alternatives. The case-notes of all non-maternity admissions (n = 509) were reviewed.

A community outbreak of echovirus infection associated with an outdoor swimming pool.

Forty-six people became ill with vomiting, diarrhoea and headache within days of an outdoor swimming pool opening for the summer season in a small seaside village. During the weekend of the outbreak, 185 tickets to the pool had been sold. It was found that 34 bathers were ill, and one subject had vomited into the pool.