CTH
Cystathionine gamma-lyase (EC 4.4.1.1) (Cysteine-protein sulfhydrase) (Gamma-cystathionase)
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The red-crowned crane ([i]Grus japonensis[/i]) is an endangered, large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is known to be positively correlated with body size and negatively correlated with metabolic rate, though the genetic mechanisms for the red-crowned crane's long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, including the long-lived common ostrich, we identified redcrowned crane candidate genes with known associations with longevity. Among these are positively selected genes in metabolism and immunity pathways ([i]NDUFA5, NDUFA8, NUDT12, SOD3, CTH , RPA1, PHAX, HNMT , HS2ST1 , PPCDC , PSTK CD8B, GP9, IL-9R,[/i] and [i]PTPRC[/i]). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and this genome should provide a useful genetic resource for future conservation studies of this rare and iconic species.
MeSH Terms
- Animals
- Avian Proteins
- Birds
- Endangered Species
- Immunity
- Longevity
- Polymorphism, Genetic
- Species Specificity
- Transcriptome
- Whole Genome Sequencing
Keywords
- genome
- longevity
- red-crowned crane
Evidence suggests the ɛ4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (ɛ4 , ɛ4-) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in ɛ4 , whereas these relationships were not evident in ɛ4-. In the rACC, higher CSF tau was associated with higher CTH for both ɛ4 and ɛ4-, and with lower CBF only in ɛ4 . Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer's disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in ɛ4 and a positive relationship in ɛ4-. Findings suggest the presence of an ɛ4-related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition.
Keywords
- APOE
- Aging
- Alzheimer’s disease
- cerebral blood flow
- cognition
- cognitive decline
- grey matter
- magnetic resonance imaging
- tau proteins
A 98-year-old man with 2 days of headache, nausea, malaise and unsteadiness was referred to the ED by his GP with a suspicion of an intracranial bleed. His medical history included atrial fibrillation (AF) (taking warfarin). Observations were SpO2 95% on air, RR24, HR88, BP210/104, GCS14, Temp 34.3. On examination he had bilateral creps and was sleepy but not confused. A septic screen was undertaken and intravenous ceftriaxone given. His CTH was essentially normal. His CXR is shown in figure 1 emermed;36/7/442/F1F1F1Figure 1Anteropsterior(AP) CXR at presentation. QUESTION: What is the diagnosis?Acute collapse and consolidation secondary to pneumonia.Spontaneous haemothorax.Acute consolidation with underlying old TB.Traumatic lung contusions.
MeSH Terms
- Aged, 80 and over
- Gait Disorders, Neurologic
- Headache
- Humans
- Male
- Nausea
- Pneumonia
- Radiography
- Treatment Outcome
Keywords
- bacterial
- chest
- geriatrics
- infectious diseases
- pneumonia/infections
- x-ray
Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source is demonstrated as a simple, facile and clean approach for the synthesis of substituted anilines and selected pharmaceutically relevant compounds. The scope of mechanochemical CTH is broad, as the reduction conditions tolerate various functionalities, for example nitro, amino, hydroxy, carbonyl, amide, urea, amino acid and heterocyclic. The presented methodology was also successfully integrated with other types of chemical reactions previously carried out mechanochemically, such as amide bond formation by coupling amines with acyl chlorides or anhydrides and click-type coupling reactions between amines and iso(thio)cyanates. In this way, we showed that active pharmaceutical ingredients Procainamide and Paracetamol could be synthesized from the respective nitro-precursors on milligram and gram scale in excellent isolated yields.
MeSH Terms
- Aniline Compounds
- Catalysis
- Hydrocarbons, Aromatic
- Hydrogenation
- Nitro Compounds
- Spectroscopy, Fourier Transform Infrared
Keywords
- aging
- ammonium formate
- aromatic nitro derivatives
- ball milling
- catalytic transfer hydrogenation
- mechanochemistry
- synthesis