The streptococcal coaggregation regulator (ScaR) of Streptococcus gordonii is a manganese-dependent transcriptional regulator. When intracellular manganese concentrations become elevated, ScaR represses transcription of the scaCBA operon, which encodes a manganese uptake transporter. A member of the DtxR/MntR family of metalloregulators, ScaR shares sequence similarity with other family members, and many metal-binding residues are conserved. Here, we show that ScaR is an active dimer, with two dimers binding the 46-bp scaC operator. Each ScaR subunit binds two manganese ions, and the protein is activated by a variety of other metal ions, including Cd2+, Co2+ and Ni2+, but not Zn2+. The crystal structure of apo-ScaR reveals a tertiary and quaternary structure similar to its homolog, the iron-responsive regulator DtxR. While each DtxR subunit binds a metal ion in two sites, labeled primary and ancillary, crystal structures of ScaR determined in the presence of Cd2+ and Zn2+ show only a single occupied metal binding site that is novel to ScaR. The site analogous to the primary site in DtxR is unoccupied, and the ancillary site is absent from ScaR. Instead, metal ions bind to ScaR at a site labeled “secondary”, which is composed of Glu80, Cys123, His125 and Asp160 and lies roughly 5 Å away from where the ancillary site would be predicted to exist. This difference suggests that ScaR and its closely related homologs are activated by a mechanism distinct from that of either DtxR or MntR.

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Low-level laser therapy in combination with surgery decreases the time to ambulation in dogs with T3-L3 myelopathy secondary to intervertebral disk herniation.

A 14-year-old male castrated domestic shorthair cat was examined because of an acute onset of vomiting, inappetence, and ataxia in all 4 limbs of 2 days duration. There was no history of any exposure to known toxins or trauma and the cat had no medical problems before this examination. The cat was fed a diet of commercially available but unbalanced canned cat food (beef, turkey, or chicken based) mixed with a dry cat food formulated for feline maintenance (chicken based) for the previous 9 months. The CBC and serum biochemistry profile did not reveal important abnormalities. The cat was 5% dehydrated, in poor body condition score (BCS 2/9), and the rectal temperature was 97.01F (36.11C). The cat was moderately obtunded, weakly ambulatory, tetraparetic with ataxia in all 4 limbs, and had a wide-based stance. Proprioceptive positioning was absent in all 4 limbs. Menace response was inconsistent in both eyes. Fundic examination, thoracic radiographs, and abdominal ultrasound did not reveal abnormalities. The neuroanatomical localization was multifocal intracranial disease.The cat had a generalized seizure the day after initial examination and was treated with diazepam a (1.6 mg/kg IV once) followed by phenobarbital b (5 mg/kg IV q12h). The cat became severely obtunded, had an absent menace in both eyes, and was nonambulatory; the phenobarbital dosage was reduced to 3 mg/kg IV q12h and dexamethasone sodium phosphate c was administered at 0.1 mg/kg IV q24h. Magnetic resonance (MR) imaging d of the brain followed by cisternal cerebrospinal fluid (CSF) collection and analysis was done on the 3rd day of hospitalization. MR imaging revealed bilaterally symmetrical well-demarcated hyperintense lesions on T2-weighted (T2W), T2 Ã , and fluid-attenuated inversion recovery (FLAIR) images involving the cerebral cortex (parietal, occipital, hippocampal lobe), the subcortical white matter, thalamus, tectum, dorsal, and ventral medulla. There was enhancement of the cerebral cortical lesions as well as faint enhancement of the thalamic and dorsal medullary lesions after IV administration of contrast e (Fig 1). Analysis of CSF collected from the cisterna magna revealed a mildly increased protein concentration (29 mg/dL; N o 25 mg/dL). The MR and CSF findings were most consistent with a metabolic or toxic encephalopathy. Another potential but much less likely differential for the bilateral symmetrical lesions on MRI involving the cerebrum and brain stem was a neurodegenerative disorder such as a mitochondrial encephalopathy.Approximately 3 mL of whole blood was collected in sodium heparin tubes and then immediately transferred to an amber transport tube to protect the sample from light for thiamine analysis. The specimen was frozen at À201 overnight and then dispatched by courier on ice packs to keep the specimens frozen.Whole blood thiamine concentration f determined via high-performance liquid chromatography (HPLC) was 1.0 mg/dL, whereas thiamine concentrations in 3 healthy control cats on a complete and balanced diet were 4.2, 4....