Investigating the consequences of asymmetric endoplasmic reticulum inheritance in Saccharomyces cerevisiae under stress using a combination of single cell measurements and mathematical modelling.

Adaptation allows organisms to maintain a constant internal environment, which is optimised for growth. The unfolded protein response (UPR) is an example of a feedback loop that maintains endoplasmic reticulum (ER) homeostasis, and is characteristic of how adaptation is often mediated by transcriptional networks. The more recent discovery of asymmetric division in maintaining ER homeostasis, however, is an example of how alternative non-transcriptional pathways can exist, but are overlooked by gold standard transcriptomic or proteomic population-based assays. In this study, we have used a combination of fluorescent reporters, flow cytometry and mathematical modelling to explore the relative roles of asymmetric cell division and the UPR in maintaining ER homeostasis. Under low ER stress, asymmetric division leaves daughter cells with an ER deficiency, necessitating activation of the UPR and prolonged cell cycle during which they can recover ER functionality before growth. Mathematical analysis of and simulation results from our mathematical model reinforce the experimental observations that low ER stress primarily impacts the growth rate of the daughter cells. These results demonstrate the interplay between homeostatic pathways and the importance of exploring sub-population dynamics to understand population adaptation to quantitatively different stresses.

Clinical characteristics of Guillain-Barré syndrome in a tropical country: a Brazilian experience.

OBJECTIVE: To analyze the clinical variants, outcomes, and prognosis of Guillain-Barré syndrome (GBS) in a Brazilian population. MATERIALS AND METHODS: Clinical and laboratory data of 149 cases of GBS diagnosed from 1994 to 2007 were analyzed. RESULTS: Acute inflammatory demyelinating polyneuropathy (AIDP) was the most frequent variant (81.8%) of GBS, followed by acute motor axonal neuropathy (AMAN) (14.7%) and acute motor and sensory axonal neuropathy (AMSAN) (3.3%). The incidence of GBS was 0.3/100,000 for the state of Rio Grande do Norte and cases occurred at a younger age. GBS was preceded by infections, with the axonal variant associated with episodes of diarrheas (P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP (P < 0.0001), 84.6% of cases with the axonal variant had nadir in <10 days. Individuals with the axonal variant took longer to recover deambulation (P < 0.0001). The mortality of GBS was 5.3%. CONCLUSION: A predominance of the AIDP variant was seen, and the incidence of the disease decreased with age. As expected, the distribution of weakness correlated with the clinical variants, and individuals with the axonal variant had a poorer prognosis.

The successful treatment of lupus pernio with the flashlamp pulsed dye laser.

Lupus pernio of the nose is the most characteristic cutaneous lesion of sarcoidosis. It is cosmetically disfiguring and can be the cause of significant morbidity. In particular, the affected skin is often red or purple due to increased vasculature. It is particularly resistant to both surgical and medical therapy. We describe a patient with lupus pernio affecting her nose, which showed a dramatic improvement following treatment with the pulse dye laser (PDL). A biopsy taken after treatment showed the continued presence of sarcoidal granulomas. We therefore feel that treatment with the PDL is an effective tool in improving the cosmetic appearance of lupus pernio, but does not influence the underlying disease process.

Topically applied niacinamide in isoniazid-induced pellagra.

A patient with tuberculous meningitis developed a pellagra-like skin eruption after treatment with isoniazid. Administration of the drug was continued, and a topical preparation of niacinamide (nico-tinamide) was applied to one half of the face and the back of one hand. The areas treated responded rapidly, and subsequently all affected areas of the patient were treated, with almost complete resolution of the rash. At the same time, there was noticeable improvement in the patient's depression and apathy. We suggest that all of these changes could be due to percutaneous absorption of niacinamide.

Cutaneous and ocular reactions to practolol.

A total of 21 patients suffering from drug-induced rashes from practolol have been seen over the past two years. The clinical manifestations varied, with the morphological appearances of the rash resembling those of eczema, lupus erythematosus, lichen planus, and a highly characteristic toxic erythematous psoriasiform eruption. Persistent ocular damage was a feature in three cases.