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Highlights from Early Edition

Selected articles appearing the week of November 27, 2017

New for November 28, 2017

Environmental Sciences; Sustainability Science


Genetics


Recent Highlights

Anthropology


Anthropology; Sustainability Science


Ecology


Ecology; Chemistry


Genetics


Immunology and Inflammation


Neuroscience


Neuroscience; Engineering



Anthropology; Sustainability Science

Human population, climate, and food production

Radiocarbon dating is increasingly used to reconstruct past dynamics of human population. In Britain and Ireland, archaeological sites have yielded a high density of radiocarbon samples from botanical and faunal material. Andrew Bevan et al. used more than 30,000 archaeological radiocarbon dates from databases and published reports to study human population dynamics in various regions of Britain and Ireland during the middle and later Holocene. The authors report at least three instances of human population decline that coincided with periodic changes in climate and subsequent societal responses in food use. For instance, after an increase in human population during the Early Neolithic around 4000–3850 BCE, a population decline occurred from around 3500–3000 BCE. The population decline was consistent with reduced solar activity and changing salt input to the Greenland ice sheet; the decline was also likely associated with cold winters and wet summers. Moreover, food use during the Middle–Late Neolithic, around 3500–2500 BCE, moved toward hardy cereals, gathered resources, and pastoralism, with wheat giving way to increased barley cultivation, and later, an emphasis on gathered hazelnuts and cattle herding. According to the authors, the findings offer insight into the long-term dynamics of human population, food production, and climate change. — C.S.

"Holocene fluctuations in human population demonstrate repeated links to food production and climate," by Andrew Bevan, et al.
[Abstract] OPEN ACCESS ARTICLE


Anthropology

Crocodile bites, ancient butchery, and human evolution

Linear marks and pits on a 2.5-million-year-old ungulate leg bone from Bouri, Ethiopia.

Linear marks and pits on a 2.5-million-year-old ungulate leg bone from Bouri, Ethiopia.

Traces and pits found on the surfaces of fossilized bones have been used to infer the use of stone tools by hominids for butchering carcasses. But whether the marks represent stone tool butchery or trampling and biting by carnivores remains unsettled, calling into question the inferred ages of hominid stone tool use. Yonatan Sahle et al. analyzed mammal bones from the Plio–Pleistocene fossil record in Ethiopia’s Middle Awash site that were dated to around 4.2 million years ago, 3.4 million years ago, and 2.5 million years ago. The authors suggest that when combined with contextual evidence, analysis of cuts, marks, grooves, and pits on dozens of fossil bones, which included a pair of Australopithecus humeral shafts and an equid femur recovered from water-deposited sands, suggests that several of the marks were likely the result of crocodile bites rather than stone tool use. Further, analysis of a bovid tibial midshaft specimen and a bovid mandible proved inconclusive, leaving open the possibility of one or both agents. Given that previous interpretations of hominid subsistence and tool use were based on the analysis of relatively small fossil assemblages from such sites as Tanzania’s Olduvai Gorge and Ethiopia’s Hadar village, where the Australopithecine fossil Lucy was discovered, the findings suggest the need for reassessment of assemblages used to infer early hominid behavior, according to the authors. — P.N.

"Hominid butchers and biting crocodiles in the African Plio–Pleistocene," by Yonatan Sahle, Sireen El Zaatari, and Tim D. White
[Abstract] OPEN ACCESS ARTICLE


Ecology

California bird nesting and climate change

California Scrub-Jay nestlings. Photograph by Joseph S. Dixon; ? 2007 Museum of Vertebrate Zoology.

California Scrub-Jay nestlings. Photograph by Joseph S. Dixon; ? 2007 Museum of Vertebrate Zoology.

Species respond to climate change by shifting their geographical ranges poleward or upward to remain in their preferred temperature zones, or by shifting the timing of life history events to mirror changes in resource availability. Jacob Socolar et al. examined the relationship between temperature and breeding dates for 150 bird species in California’s Coast Range and 160 bird species in California’s Sierra Nevada. Pairing bird data collected from 1911–1940 with 2003–2010 resurveys performed at the same sites, the authors found that breeding dates for California birds have advanced by approximately 5–12 days. The shift in nesting dates reduced average temperatures during nesting by more than 1 °C—approximately the same magnitude that average regional temperatures have warmed over the same period. Using national nest monitoring data, the authors found that in the early summer across North America, warm temperatures are associated with high nest success in the cold parts of the birds’ ranges and low nest success in the warm parts of the birds’ ranges. By nesting earlier, California birds are nesting at temperatures similar to those at which they nested a century ago, thus reducing the need for range shifts, according to the authors. — L.C.

"Phenological shifts conserve thermal niches in North American birds and reshape expectations for climate-driven range shifts," by Jacob B. Socolar, Peter N. Epanchin, Steven R. Beissinger, and Morgan W. Tingley
[Abstract]


Ecology; Chemistry

How alkali flies thrive in Mono Lake

Alkali fly.

Alkali fly.

To feed and lay their eggs, alkali flies (Ephydra hians) crawl down calcium carbonate rocks into California’s Mono Lake, where the water is both highly alkaline and three times as salty as the Pacific Ocean. The flies stay dry during their descent into this harsh environment within a protective air bubble that coalesces around their hydrophobic bodies, which are covered in waxy hairs. To explore the physical and chemical properties of this unique survival mechanism, Floris van Breugel and Michael Dickinson devised an optical force sensor to measure the work that flies perform when entering and exiting aqueous solutions with different salinities, pH, and charge densities. With a series of experiments, the authors demonstrate that high concentrations of sodium carbonate allow water to more easily penetrate and wet the flies’ hairy outer cuticles, making it difficult for the flies to escape the water’s surface. However, compared with other species, alkali flies are better able to resist this effect by virtue of possessing a dense hair layer and cuticular hydrocarbons that help resist wetting. The findings demonstrate that small-scale adaptations can allow species to occupy new ecological niches, according to the authors. — T.J.

"Superhydrophobic diving flies (Ephydra hians) and the hypersaline waters of Mono Lake," by Floris van Breugel and Michael H. Dickinson
[Abstract]


Environmental Sciences; Sustainability Science

Hydraulic fracturing and groundwater wells

Hydraulically fractured well in California’s San Joaquin Valley.

Hydraulically fractured well in California’s San Joaquin Valley.

Self-supply groundwater wells provide drinking water to around 45 million Americans. The number of self-supply or public-supply water wells that are in close proximity to hydraulic fracturing operations and at risk of potential contamination remains unestablished. Scott Jasechko and Debra Perrone determined the distances between domestic groundwater wells constructed between 2000 and 2014 and hydraulically fractured oil and gas wells stimulated in 2014 in 14 states. Out of the nearly 27,000 wells stimulated in 2014, 37% were within 2 km of at least one domestic groundwater well, and 60% were within 3 km of at least one domestic groundwater well. In 11 counties, a majority of domestic groundwater wells were within 2 km of a hydraulically fractured well, whereas a majority of domestic groundwater wells were within 2 km of a producing oil and gas well in 236 counties. The results suggest the importance of increased water quality monitoring efforts near hydraulic fracturing and conventional oil and gas wells to determine the risk of contamination and to protect well water quality. The results also identify hotspots of water wells in proximity to oil and gas wells where such efforts could be targeted, according to the authors. — B.D.

"Hydraulic fracturing near domestic groundwater wells," by Scott Jasechko and Debra Perrone.
[Abstract]


Genetics

Precision genome editing in mammalian cells

HEK293T cells glow after repair of a Cas9-induced DNA break with a PCR fragment encoding GFP and arms targeting the <em>Lamin A/C</em> locus.

HEK293T cells glow after repair of a Cas9-induced DNA break with a PCR fragment encoding GFP and arms targeting the Lamin A/C locus.

The discovery of CRISPR-Cas9 has provided researchers with a powerful technique for genome editing. Previous research has shown that linear DNAs can be used as templates for Cas9-mediated genome editing in roundworms. Alexandre Paix et al. (pp. xxx–xxx) investigated whether linear DNAs could also be used for precision genome editing in mammalian cells. The authors found that PCR fragments with only 35 base pairs of homology with the targeted locus can serve as efficient donors for genome editing in both mouse embryos and human cells, and could be used to introduce edits of up to 1,000 nucleotides. The authors used PCR fragments to introduce fluorescent protein tags in both human cells and mouse embryos. The linear DNAs initiated repair of Cas9-induced double-stranded breaks in a process that occurred locally, was sensitive to the polarity of the donor DNA, and was prone to template switching, which can combine sequences from overlapping donors in the same edit. This repair mechanism is consistent with gene conversion by synthesis-dependent strand-annealing. The authors conclude that single-stranded and double-stranded linear DNAs are efficient donors for genome editing in mouse embryos and human cells. The findings could be used to improve the efficiency of genome editing in a variety of cell types and organisms, according to the authors. — S.R.

"Precision genome editing using synthesis-dependent repair of Cas9-induced DNA breaks," by Alexandre Paix, et al.
[Abstract]


Genetics

Cas9-expressing mosquito strains pave the way toward gene drives

SEM image of genome-edited adult female mosquito. Left compound eye is split up, and there are three maxillary palps instead of the normal two. Image courtesy of Michelle Bui and Alexander Knyshov (University of California, Riverside, CA).

SEM image of genome-edited adult female mosquito. Left compound eye is split up, and there are three maxillary palps instead of the normal two. Image courtesy of Michelle Bui and Alexander Knyshov (University of California, Riverside, CA).

Previous efforts to use genome editing to thwart the ability of mosquito vectors to spread pathogens have been hampered by low mutation rates, poor survival of edited mosquitoes, and inefficient transmission of disrupted genes to offspring. Ming Li et al. developed transgenic strains of Aedes aegypti mosquitoes—major carriers of dengue, chikungunya, yellow fever, and zika viruses—that stably express a bacterial Cas9 enzyme in the germline, enabling highly efficient genome editing in the mosquito species. CRISPR-based gene disruption in the transgenic strains resulted in mosquitoes with an extra eye, an extra maxillary palp, a nonfunctional proboscis, malformed wings, and chromatic defects in the eyes and cuticle—traits that affect vision, flight, or blood feeding. Compared with coinjection of guide RNAs and recombinant Cas9 into wild-type mosquito embryos, genome editing using the transgenic strains resulted in increased mosquito survival rates, mutagenesis efficiency, and heritable mutation rates. Further, mutagenesis rates and efficiency of germline transmission of disrupted genes were boosted when multiple guide RNAs were coinjected into one of the transgenic strains. Double and triple mutants could be easily generated in a single step by coinjection of multiplexed RNAs targeting different genes into the transgenic strains. According to the authors, the study lays the groundwork for the development of efficient gene drives to control the mosquito population. — P.N.

"Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti," by Ming Li, et al.
[Abstract] OPEN ACCESS ARTICLE


Immunology and Inflammation

Enhancing neutrophil and macrophage antitumor activity

Overlay of the KWAR23/SIRPα and CD47/SIRPα crystal structure complexes.

Overlay of the KWAR23/SIRPα and CD47/SIRPα crystal structure complexes.

Immunotherapy has shown immense potential for treating cancers, but current immunotherapies fail to produce complete and durable responses in many cancer patients. Signal regulatory protein alpha (SIRPα) is a promising immunotherapy target that serves as a myeloid cell-specific immune checkpoint that engages the antiphagocytic signal CD47. Nan Guo Ring et al. developed the monoclonal antibody KWAR23, which binds SIRPα and disrupts its binding to CD47. The authors found that KWAR23 was inert when administered by itself, but when combined with tumor-opsonizing monoclonal antibodies, it greatly enhanced the killing of several human tumor-derived cell lines by inducing macrophage-dependent phagocytosis. KWAR23 enhanced the antitumor activity of neutrophils and macrophages both in vitro and in vivo. When the KWAR23 antibody was used to treat a mouse model with human SIRPα that had been knocked in, neutrophils and macrophages infiltrated a human Burkitt’s lymphoma xenograft and significantly reduced tumor growth. The authors created a bispecific anti-CD70/SIRPα antibody and found that it showed enhanced antitumor activity, compared with individually delivered antibodies in certain types of cancers. Using an antibody to block SIRPα led to increased antitumor activity by myeloid cell subsets that frequently infiltrate tumors, and KWAR23 might be a promising candidate for combination therapy, according to the authors. — S.R.

"Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity,”," by Nan Guo Ring, et al.
[Abstract]


Neuroscience

Molecular signatures across subtypes of Alzheimer’s disease patients

Amyloid plaques in brain tissue labeled by quadro-formyl thiophene acetic acid/ hepta-formyl thiophene acetic acid fluorescent dyes.

Amyloid plaques in brain tissue labeled by quadro-formyl thiophene acetic acid/ hepta-formyl thiophene acetic acid fluorescent dyes.

One major hallmark of Alzheimer’s disease (AD) is the accumulation of the amyloid-β peptide into plaque deposits in the brain. Despite the common molecular hallmark of the disease, clinical symptoms and pathologic changes in brain tissues vary significantly across patients. Jay Rasmussen et al. tested the hypothesis that the largely unexplained heterogeneity observed across patients may be influenced by diverse molecular structures of amyloid plaques in the brain. The authors analyzed postmortem tissue samples obtained from 40 clinically and pathologically diagnosed cases of AD. The authors labeled amyloid plaques in three brain regions—temporal, occipital, and frontal cortex—using a class of dyes called luminescent conjugated oligothiophenes, which bind to amyloid and emit variable fluorescence emission spectra that reflect the 3D structure of the protein aggregates. The spectral signatures of the amyloid plaque cores varied significantly across different patient subtypes, distinguishing carriers of certain types of mutations (e.g., APP V717I and PSEN1 A431E) from other groups. Within an individual brain, minor populations of amyloid-β aggregates had different molecular structures, even though the mean spectral properties of the amyloid plaques were similar across all three brain regions. According to the authors, the findings support the idea that the heterogeneous molecular structures of amyloid plaques in the brain might contribute to the diverse clinical and pathological disease manifestations observed across patients. — J.W.

"Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer’s disease," by Jay Rasmussen, et al.
[Abstract]


Neuroscience; Engineering

Measuring dopamine release over long timescales in monkeys

Dopamine is a brain chemical messenger implicated in a broad range of disorders, including depression, Parkinson’s disease, and other mood and movement disorders. Methods that enable accurate monitoring of dopamine over long timescales could improve diagnostic and therapeutic strategies. Helen Schwerdt et al. developed a neurochemical recording platform for long-term monitoring of dopamine release using sensors chronically implanted into the brains of nonhuman primates. The authors implanted chronic sensors into multiple sites in a deep brain structure called the striatum in two macaque monkeys. Over a period lasting more than 100 days, the chronically implanted sensors reliably detected increases in dopamine release that either occurred spontaneously or was triggered by electrical stimulation or administration of the dopamine-releasing drug raclopride. The chronic sensors also detected reproducible patterns of dopamine release elicited by food rewards delivered to monkeys engaged in an eye-movement task. Recordings made in separate sessions using sensors acutely implanted into the striatum confirmed the accuracy of measurements obtained from the chronic sensors. According to the authors, the findings demonstrate the feasibility of long-term, reproducible neurochemical measurements to explore the role of dopamine in complex behaviors and to improve diagnostic and treatment approaches for a wide range of neurological disorders. — J.W.

"Long-term dopamine neurochemical monitoring in primates," by Helen N. Schwerdt, et al.
[Abstract]


The articles in the Proceedings of the National Academy of Sciences report original research by independent authors and do not necessarily represent the view of the National Academies.

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