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IN THIS ISSUE N I in This Issue UE UE JUNE 4, 2013 THIS ISS N THIS ISS I IN THIS ISSUE N I In This Issue Nanoparticles against atherosclerotic cal southwestern Mexico. According to the authors, the reconstruc- tion reveals that the NAM remained active during the Last Glacial plaques Maximum but collapsed synchronously with cold periods such as Atherosclerosis is a leading cause of death in the United States, the Younger Dryas that are linked to a weakened Atlantic Meridi- in part because the disease can go undetected for years or until onal Overturning Circulation (AMOC). Based on this observation plaques composed of cholesterol and fat-laden immune cells de- and key climate tracers such as oxygen isotopic ratios, the authors tach from the artery wall and trigger blood clots or stroke. Because conclude that the NAM responded in concert with other global previous studies have tied the stability of atherosclerotic plaques monsoons, and that its strength was determined by AMOC-driven to the death of specialized immune cells known as macrophages, changes in the strength and location of the Intertropical Conver- Sean Marrache and Shanta Dhar (pp. 9445–9450) constructed a gence Zone—the band near the equator where the Northern and biodegradable nanoparticle that mimics high-density lipoprotein, Southern Hemisphere trade winds interact. Agriculture in south- or good cholesterol, and illuminates vulnerable plaques at risk of western Mexico may have flourished when the monsoon strength- detaching from the artery wall. The nanoparticle homed in on ened some 11,000 years ago, in the aftermath of Younger Dryas, apoptotic macrophages by detecting the collapse of mitochondrial according to the authors. — T.J. membrane potential that occurs as the cells die. In vitro experi- ments demonstrated that the nanoparticles were readily taken up Pathogenesis of a neonatal disease by cells, detected apoptosis, and bound to cholesterol. Additional studies in rats revealed that the nanoparticles were stable, biocom- Necrotizing enterocolitis causes devastating tissue death in the patible, nontoxic, and capable of reducing triglyceride levels. Ac- intestines of premature infants. The inflammation and necrosis cording to the authors, the nanoparticles hold promise as transla- underlying the disease are triggered by an immune protein called tional tools that could aid in early diagnosis and prevent vulnerable toll-like receptor 4 (TLR4), and breast milk is known to protect the plaque progression. — A.G. intestines from injury. To determine why blood supply to the intes- tines is reduced in the disease, Ibrahim Yazji et al. (pp. 9451–9456) engineered a mouse lacking TLR4 in the endothelium and found that TLR4 signaling within the blood vessels reduces the expression of a vasodilatory molecule called endothelial-nitric oxide synthase (eNOS), which restricts blood flow to the small intestine without affecting other organs. Further analysis revealed that mice lacking eNOS had more severe tissue damage compared with mice express- ing the vasodilator; treatment with the drug sildenafil enhanced the action of eNOS and reduced the severity of disease. Interestingly, human and mouse breast milk contain plentiful amounts of sodi- um nitrate, a precursor of nitric oxide in the intestines, the authors report. Formula supplemented with sodium nitrate/nitrite restored blood flow to the mouse intestines and decreased the severity of disease. According to the authors, the findings raise the possibil- ity that infant formulas that are supplemented with molecules like sodium nitrate/nitrite might help prevent necrotizing enterocolitis in premature infants. — A.G. Nanoparticles for atherosclerosis. Cave deposits reveal 22,000 years of North American Monsoon rainfall The North American Monsoon (NAM) influences summer rainfall throughout Mexico and the southwestern United States. An exten- sive feature of global atmospheric circulation, the NAM remains poorly understood due to the lack of detailed proxy records. Mat- thew Lachniet et al. (pp. 9255–9260) report a high-resolution and radiometrically dated history of NAM rainfall spanning the past 22,000 years and reconstructed from calcite cave deposits in tropi- Sodium-nitrate supplementation prevents necrotizing enterocolitis. www.pnas.org/cgi/doi/10.1073/iti2313110 PNAS | June 4, 2013 | vol. 110 | no. 23 | 9185–9186 Downloaded by guest on September 26, 2021 Self-propagating tau aggregates may tion, the authors observed steep declines in pertussis incidence in nearly every province of the country. Moreover, the authors found underlie neurodegenerative diseases that incidence declined among infants, who were not yet immu- A number of human neurological diseases have been linked to in- nized against the disease, suggesting that vaccination successfully soluble, filamentous aggregates of the protein tau in the brain. Flor- provided herd immunity. The analysis also revealed that pertussis ence Clavaguera et al. (pp. 9535–9540) previously injected brain immunity is long lasting, and indicated that repeat infections have extracts from transgenic mice carrying a mutated version of human contributed little to pertussis transmission in Thailand. Accord- tau into the brains of mice carrying the normal version of the pro- ing to the authors, the findings may aid the development of public tein, and observed the assembly of filamentous tau and its migra- health policies and vaccination campaigns to reduce the morbidity tion through the brains of the injected mice. The authors expanded and mortality associated with pertussis. — N.Z. those findings by injecting brain extracts from humans who died from various tau-related diseases into the hippocampus and cere- How dietary fiber content can affect bral cortices of transgenic mice carrying wild-type human tau. In each case, the injections induced the formation of tau aggregates mouse susceptibility to pathogenic E. coli in the mouse brain, and hallmark lesions of argyrophilic grain dis- Infection with the Shiga toxin (Stx)-producing pathogen Esch- ease, progressive supranuclear palsy, and corticobasal degeneration erichia coli O157:H7 generally causes severe diarrhea and colitis, developed. Similar tau aggregates were observed in nontransgenic but in some individuals this food-borne pathogen can produce the mice after injection with the human extracts. Once formed, the ag- potentially life-threatening hemolytic uremic syndrome. Steven gregates could be propagated between mouse brains, the authors Zumbrun et al. (pp. E2126–E2133) found that dietary fiber con- report. Interestingly, the study revealed that tau aggregates form tent affects susceptibility to Stx-producing E. coli O157:H7 in mice. and spread independently of amyloid beta, a major constituent of The authors found that mice fed a diet high in fiber had increased plaques in the brains of people with Alzheimer’s disease. According levels of butyric acid, which in turn increased the expression of to the authors, the finding suggest that tau aggregates can become the Stx receptor globotriaosylceramide (Gb3) in intestinal and re- self-propagating and spread in a prion-like manner. — A.G. nal tissues, leading to increased Stx-binding. Mice fed a high-fiber diet and then infected with E. coli O157:H7 exhibited a 10–100- Pertussis vaccination and immunity in fold increase in E. coli colonization, lost more body weight, and had greater morbidity and mortality relative to mice fed a low-fiber Thailand diet. Mice fed high-fiber diets contained reduced levels of native Despite widespread vaccination, several countries have recently re- Escherichia species in their guts compared with mice fed a low-fiber ported a resurgence in new cases of the highly contagious respira- diet, suggesting the potential creation of an available niche for E. tory disease, pertussis, also known as whooping cough. The reasons coli O157:H7 to colonize. Dietary fiber content affects butyric acid for this resurgence remain unclear, although some studies point to and Gb3 levels as well as microbiota composition, resulting in dif- waning immunity following childhood vaccination. To better un- ferences in susceptibility to E. coli O157:H7 infection, according to derstand the relationship between pertussis vaccination and im- the authors. — S.R. munity, Julie Blackwood et al. (pp. 9595–9600) developed a series of disease transmission models to explain records of pertussis in- cidence in Thailand between the years of 1981 and 2000, a time period during which Thailand greatly expanded its pertussis vac- cine usage. Coincident with the pronounced increase in vaccina- Mice fed a high fiber diet (HFD) lose more weight and are more Mean annual pertussis cases in Thailand per 100,000 (on a log likely to die after infection with E. coli O157:H7 than mice on a scale). low fiber diet (LFD). 9186 | www.pnas.org/cgi/doi/10.1073/iti2313110 Downloaded by guest on September 26, 2021.
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