Nanoparticles against atherosclerotic plaques
Nanoparticles for atherosclerosis.
Atherosclerosis is a leading cause of death in the United States, in part because the disease can go undetected for years or until plaques composed of cholesterol and fat-laden immune cells detach from the artery wall and trigger blood clots or stroke. Because previous studies have tied the stability of atherosclerotic plaques to the death of specialized immune cells known as macrophages, Sean Marrache and Shanta Dhar (pp. 9445–9450) constructed a biodegradable nanoparticle that mimics high-density lipoprotein, or good cholesterol, and illuminates vulnerable plaques at risk of detaching from the artery wall. The nanoparticle homed in on apoptotic macrophages by detecting the collapse of mitochondrial membrane potential that occurs as the cells die. In vitro experiments demonstrated that the nanoparticles were readily taken up by cells, detected apoptosis, and bound to cholesterol. Additional studies in rats revealed that the nanoparticles were stable, biocompatible, nontoxic, and capable of reducing triglyceride levels. According to the authors, the nanoparticles hold promise as translational tools that could aid in early diagnosis and prevent vulnerable plaque progression. — A.G.
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 extensive feature of global atmospheric circulation, the NAM remains poorly understood due to the lack of detailed proxy records. Matthew 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 tropical southwestern Mexico. According to the authors, the reconstruction reveals that the NAM remained active during the Last Glacial Maximum but collapsed synchronously with cold periods such as the Younger Dryas that are linked to a weakened Atlantic Meridional Overturning Circulation (AMOC). Based on this observation and key climate tracers such as oxygen isotopic ratios, the authors conclude that the NAM responded in concert with other global monsoons, and that its strength was determined by AMOC-driven changes in the strength and location of the Intertropical Convergence Zone—the band near the equator where the Northern and Southern Hemisphere trade winds interact. Agriculture in southwestern Mexico may have flourished when the monsoon strengthened some 11,000 years ago, in the aftermath of Younger Dryas, according to the authors. — T.J.
Pathogenesis of a neonatal disease
Sodium-nitrate supplementation prevents necrotizing enterocolitis.
Necrotizing enterocolitis causes devastating tissue death in the intestines of premature infants. The inflammation and necrosis underlying the disease are triggered by an immune protein called toll-like receptor 4 (TLR4), and breast milk is known to protect the intestines from injury. To determine why blood supply to the intestines 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 expressing 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 sodium 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 possibility that infant formulas that are supplemented with molecules like sodium nitrate/nitrite might help prevent necrotizing enterocolitis in premature infants. — A.G.
Self-propagating tau aggregates may underlie neurodegenerative diseases
A number of human neurological diseases have been linked to insoluble, filamentous aggregates of the protein tau in the brain. Florence Clavaguera et al. (pp. 9535–9540) previously injected brain extracts from transgenic mice carrying a mutated version of human tau into the brains of mice carrying the normal version of the protein, and observed the assembly of filamentous tau and its migration through the brains of the injected mice. The authors expanded those findings by injecting brain extracts from humans who died from various tau-related diseases into the hippocampus and cerebral cortices of transgenic mice carrying wild-type human tau. In each case, the injections induced the formation of tau aggregates in the mouse brain, and hallmark lesions of argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration developed. Similar tau aggregates were observed in nontransgenic mice after injection with the human extracts. Once formed, the aggregates could be propagated between mouse brains, the authors report. Interestingly, the study revealed that tau aggregates form and spread independently of amyloid beta, a major constituent of plaques in the brains of people with Alzheimer’s disease. According to the authors, the finding suggest that tau aggregates can become self-propagating and spread in a prion-like manner. — A.G.
Pertussis vaccination and immunity in Thailand
Mean annual pertussis cases in Thailand per 100,000 (on a log scale).
Despite widespread vaccination, several countries have recently reported a resurgence in new cases of the highly contagious respiratory disease, pertussis, also known as whooping cough. The reasons for this resurgence remain unclear, although some studies point to waning immunity following childhood vaccination. To better understand the relationship between pertussis vaccination and immunity, Julie Blackwood et al. (pp. 9595–9600) developed a series of disease transmission models to explain records of pertussis incidence in Thailand between the years of 1981 and 2000, a time period during which Thailand greatly expanded its pertussis vaccine usage. Coincident with the pronounced increase in vaccination, the authors observed steep declines in pertussis incidence in nearly every province of the country. Moreover, the authors found that incidence declined among infants, who were not yet immunized against the disease, suggesting that vaccination successfully provided herd immunity. The analysis also revealed that pertussis immunity is long lasting, and indicated that repeat infections have contributed little to pertussis transmission in Thailand. According to the authors, the findings may aid the development of public health policies and vaccination campaigns to reduce the morbidity and mortality associated with pertussis. — N.Z.
How dietary fiber content can affect mouse susceptibility to pathogenic E. coli
Mice fed a high fiber diet (HFD) lose more weight and are more likely to die after infection with E. coli O157:H7 than mice on a low fiber diet (LFD).
Infection with the Shiga toxin (Stx)-producing pathogen Escherichia coli O157:H7 generally causes severe diarrhea and colitis, but in some individuals this food-borne pathogen can produce the potentially life-threatening hemolytic uremic syndrome. Steven Zumbrun et al. (pp. E2126–E2133) found that dietary fiber content affects susceptibility to Stx-producing E. coli O157:H7 in mice. The authors found that mice fed a diet high in fiber had increased levels of butyric acid, which in turn increased the expression of the Stx receptor globotriaosylceramide (Gb3) in intestinal and renal tissues, leading to increased Stx-binding. Mice fed a high-fiber diet and then infected with E. coli O157:H7 exhibited a 10–100-fold increase in E. coli colonization, lost more body weight, and had greater morbidity and mortality relative to mice fed a low-fiber diet. Mice fed high-fiber diets contained reduced levels of native Escherichia species in their guts compared with mice fed a low-fiber diet, suggesting the potential creation of an available niche for E. coli O157:H7 to colonize. Dietary fiber content affects butyric acid and Gb3 levels as well as microbiota composition, resulting in differences in susceptibility to E. coli O157:H7 infection, according to the authors. — S.R.