Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy, which is positively regulated by the JNK/c-Jun pathway and is defective in the injured central nervous system.

Objectives Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. Methods We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with lifethreatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction. Results A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. Conclusions The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.

A critical evolutionary step during rice domestication was the elimination of seed shattering. Wild rice disperses seeds freely at maturity to guarantee the propagation, while cultivated rice retains seeds on the straws to make easy harvest and decrease the loss of production. The molecular basis for this key event during rice domestication remains to be elucidated. Here we show that the seed shattering is controlled by a single dominant gene, Shattering1 (SHA1), encoding a member of the trihelix family of plant-specific transcription factors. SHA1 was mapped to a 5.5 kb genomic fragment, which contains a single open reading frame, using a backcrossed population between cultivated rice Teqing and an introgression line IL105 with the seed shattering habit derived from perennial common wild rice, YJCWR. The predicted amino acid sequence of SHA1 in YJCWR and IL105 is distinguished from that in eight domesticated rice cultivars, including Teqing, by only a single amino acid substitution (K79N) caused by a single nucleotide change (g237t). Further sequence verification on the g237t mutation site revealed that the g237t mutation is present in all the domesticated rice cultivars, including 92 indica and 108 japonica cultivars, but not in any of the 24 wild rice accessions examined. Our results demonstrate that the g237t mutation in SHA1 accounts for the elimination of seed shattering, and that all the domesticated rice cultivars harbor the mutant sha1 gene and therefore have lost the ability to shed their seeds at maturity. In addition, our data support the theory that the non-shattering trait selection during rice domestication occurred prior to the indica-japonica differentiation in rice evolutionary history.

Abstract. Tumor necrosis factor ␣ (TNF␣) plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. TNF␣ blockade is a potential therapy for these disorders. Methods: An open-label, multi-center, prospective clinical trial in two subgroups was performed. Study I examined acute disease, either first presentation or relapse (Birmingham Vasculitis Activity Score [BVAS] Ն 10; n ϭ 16); study II examined persistent disease (BVAS Ն 4; n ϭ 16). Patients received infliximab (5 mg/kg) at 0, 2, 6, and 10 wk. Concomitant therapy in study I included prednisolone and cyclophosphamide. Study II patients continued their existing treatment regimens, with prednisolone tapered according to clinical status. Results: Mean age was 52.4 yr, 53% of the patients were female, and follow-up was 16.8 mo. Twenty-eight patients (88%) achieved remission (14 per study group). BVAS decreased from 12.3 (confidence interval [CI] ϭ 10.5 to 14.0) at entry to 0.3 (CI ϭ 0.2 to 0.9) at wk 14 (P Ͻ 0.001). C-reactive protein (mg/L) decreased from 29.4 (CI ϭ 16.8 to 42.0) at entry to 7.0 (CI ϭ 3.3 to 10.9) by wk 14 (P ϭ 0.001). Mean prednisolone dose (mg/d) in study II decreased from 23.8 (CI ϭ 15.0 to 32.5) at entry to 8.8 (CI ϭ 5.9 to 11.7) at wk 14 (P ϭ 0.002). There were two deaths and seven serious infections. Relapse occurred in five patients (three in study II) after a mean of 27 wk. Conclusion: TNF␣ blockade with infliximab was effective at inducing remission in 88% of patients with antibody-associated systemic vasculitis and permitted reduction in steroid doses. Severe infections were seen in 21% of patients, and despite continued infliximab, 20% of initial responders experienced disease flares. Infliximab is a promising new therapy for vasculitis both as a component of initial therapy and in the management of refractory disease. These results need confirmation in larger randomized trials.The primary systemic necrotizing vasculitides are a group of life-threatening diseases that, untreated, have an 85% 2-yr mortality. The best defined and most studied subgroup of these diseases are the anti-neutrophil cytoplasmic antibody (ANCA)-related small vessel vasculitides (AASV), which are characterized by a pauci-immune microscopic vasculitis and focal, necrotizing glomerulonephritis (1).The introduction of steroids and cyclophosphamide results in disease remission in 80% of patients by 3 mo and in 95% by 6 mo (15). However, there is considerable morbidity related to current regimens, on which at least 25% of patients experience severe drug-related adverse effects. Furthermore, 50% of patients experience disease relapse, resulting in accumulating damage from disease scars and treatment (2,3,16). The addition of plasma exchange or pulsed methylprednisolone improves rates of renal recovery but increases the risk of side effects. There is a clear need to achieve more effective remission induction and to reduce therapy-related toxicity in AASV.Evidence suggests that tumor necrosis factor ␣ (TNF␣) plays...