SUMMARY Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and life-span observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration.

Population-based surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX) was conducted in four U.S. Emerging Infections Program sites (population 7.7 million) from May 1, 1995, to December 31, 1998, to define the incidence, epidemiologic features, and etiology of this syndrome. A case was defined as death or critical illness in a hospitalized, previously healthy person, 1 to 49 years of age, with infection hallmarks but no cause identified after routine testing. A total of 137 cases were identified (incidence rate 0.5 per 100,000 per year). Patients’ median age was 20 years, 72 (53%) were female, 112 (82%) were white, and 41 (30%) died. The most common clinical presentations were neurologic (29%), respiratory (27%), and cardiac (21%). Infectious causes were identified for 34 cases (28% of the 122 cases with clinical specimens); 23 (68%) were diagnosed by reference serologic tests, and 11 (32%) by polymerase chain reaction-based methods. The UNEX network model would improve U.S. diagnostic capacities and preparedness for emerging infections.

Recently killed cover crops often interfere with crop seedling growth. Controlled‐environment and field studies were conducted to characterize the nature and persistence of cover crop interference with sorghum [Sorghum bicolor (L.) Moench] seedling growth and to test several seed‐zone management practices that might alleviate detrimental effects. Germination, root and shoot length, and disease incidence of sorghum germinated at 25°C for 5 d in soil collected 2, 4, 7, 14, 23, and 32 d after killing cover crops indicated legume cover crops were more detrimental to seedling growth than were nonlegumes. Surface residues, subsurface residues, and residue leachates contributed to the deleterious effects. Seedling shoot disease incidence of 50% persisted through 32 d when legume residues were mixed into soil or placed on top of soil at planting, but disappeared by 7 to 14 d if residues were removed. Pathogenic organisms isolated from lesions on seedlings indicated legume cover crops increased damage due to Rhizoctonia solani Kühn. In a no‐till field study, stand density was reduced 15% and aboveground seedling dry weight was reduced 45%, from 85 to 45 mg plant−1 28 d after planting, when sorghum was planted 1 d after killing crimson clover (Trifolium incarnatum L.) compared with planting 21 d or longer after killing. Insecticide, activated charcoal, or CaO2 seed coating improved sorghum stand density 15%, but did not affect seedling size. In‐furrow fungicide drench had no effect on stand density, but phytotoxic effects of the fungicide reduced shoot and root growth rates in both field and controlled‐environment studies. Residue removal combined with selected in‐furrow treatments may allow the interval between cover‐crop killing and successful no‐till planting to be reduced to less than 7 d.

The lower portion of the Sacramento River, California, has been highly engineered to protect low‐lying surrounding communities from annual flood events. While engineered floodplains have provided adequate protection for the surrounding communities, there remain unintended consequences to migratory fish that become stranded during high flow events. In April 2011, we rescued 24 threatened Green Sturgeon Acipenser medirostris that were stranded in two flood diversions along the Sacramento River. We tagged these 24 Green Sturgeon with acoustic tags and analyzed their survival and migration success to their spawning grounds. Additionally, we provided a population viability analysis to show the potential impacts of stranding and the benefits of conducting rescues at the population level. We found that 17 of these 24 individuals continued their upstream migration to the spawning grounds. Modeling suggests that recurrent stranding of a similar magnitude without rescue could affect the long‐term viability of Green Sturgeon in the Sacramento River. Population viability analyses of rescue predicted a 7% decrease below the population baseline model over 50 years as opposed to 33% without rescue. Despite the mitigated impact to the population with rescue, fish passage improvements should be considered as a long‐term goal for preventing population risks at flood control diversions.Received May 4, 2012; accepted December 6, 2012