The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Midcontinental Native American population dynamics and late Holocene hydroclimate extremes

Climate’s influence on late Pre-Columbian (pre-1492 CE), maize-dependent Native American populations in the midcontinental United States (US) is poorly understood as regional paleoclimate records are sparse and/or provide conflicting perspectives. Here, we reconstruct regional changes in precipitation source and seasonality and local changes in warm-season duration and rainstorm events related to the Pacific North American pattern (PNA) using a 2100-year-long multi-proxy lake-sediment record from the midcontinental US. Wet midcontinental climate reflecting negative PNA-like conditions occurred during the Medieval Climate Anomaly (950–1250 CE) as Native American populations adopted intensive maize agriculture, facilitating population aggregation and the development of urban centers between 1000–1200 CE. Intensifying midcontinental socio-political instability and warfare between 1250–1350 CE corresponded with drier positive PNA-like conditions, culminating in the staggered abandonment of many major Native American river valley settlements and large urban centers between 1350–1450 CE during an especially severe warm-season drought. We hypothesize that this sustained drought interval rendered it difficult to support dense populations and large urban centers in the midcontinental US by destabilizing regional agricultural systems, thereby contributing to the host of socio-political factors that led to population reorganization and migration in the midcontinent and neighboring regions shortly before European contact

A 2000 year varve-based climate record from the central Brooks Range, Alaska

Varved minerogenic sediments from glacial-fed Blue Lake, northern Alaska, are used to investigate late Holocene climate variability. Varve-thickness measurements track summer temperature recorded at Atigun Pass, located 41 km east at a similar elevation (r2 = 0.31, P = 0.08). Results indicate that climate in the Brooks Range from 10 to 730 AD (varve year) was warm with precipitation inferred to be higher than during the twentieth century. The varve-temperature relationship for this period was likely compromised and not used in our temperature reconstruction because the glacier was greatly reduced, or absent, exposing sub-glacial sediments to erosion from enhanced precipitation. Varve-inferred summer temperatures and precipitation decreased after 730 AD, averaging 0.4°C above the last millennial average (LMA = 4.2°C) from 730 to 850 AD, and 0.1°C above the LMA from 850 to 980 AD. Cooling culminated between 980 and 1030 AD with temperatures 0.7°C below the LMA. Varve-inferred summer temperatures increased between 1030 and 1620 AD to the LMA, though the period between 1260 and 1350 AD was 0.2°C below the LMA. Although there is no equivalent to the European Medieval Warm Period in the Blue Lake record, two warm intervals occurred from 1350 to 1450 AD and 1500 to 1620 AD (0.4 and 0.3°C above the LMA, respectively). During the Little Ice Age (LIA; 1620 to 1880 AD), inferred summer temperature averaged 0.2°C below the LMA. After 1880 AD, inferred summer temperature increased to 0.8°C above the LMA, glaciers retreated, but aridity persisted based on a number of regional paleoclimate records. Despite warming and glacial retreat, varve thicknesses have not achieved pre-730 AD levels. This reflects limited sediment availability and transport due to a less extensive retreat compared to the first millennium, and continued relative aridity. Overall, the Blue Lake record is similar to varve records from the eastern Canadian Arctic that document a cool LIA and twentieth century warming. However, the occurrence and timing of events, such as the LIA and Medieval Warm Period, varies considerably among records, suggesting heterogeneous climatic patterns across the North American Arctic

Late-Holocene floodplain development, land-use, and hydroclimate–flood relationships on the lower Ohio River, US

Floodplain development, land-use, and flooding on the lower Ohio River are investigated with a 3100-year-long sediment archive from Avery Lake, a swale lake on the Black Bottom floodplain in southern Illinois, US. In all, 12 radiocarbon dates show that Avery Lake formed at 1130 BCE (3100 cal. yr BP), almost 3000 years later than previously thought, indicating that the Black Bottom floodplain is younger and more dynamic than previously estimated. Three subsequent periods of extensive land clearance were identified by changes in pollen composition, corresponding to Native American occupations before 1500 CE and the current Euro-American occupation beginning in the 18th century. Sedimentation rates prior to 1820 CE changed independently of land clearance events, suggesting natural as opposed to land-use controls. Comparison with high-resolution paleoclimate data from Martin Lake, IN, indicates that lower Ohio River flooding was frequent when cold-season precipitation originating from the Pacific/Arctic predominated when atmospheric circulation resembled positive Pacific North American (PNA) conditions and the Pacific Decadal Oscillation (PDO) was in a positive mean state (1130 BCE to 350 CE and 1150–1820 CE). Conversely, Ohio River flooding was less frequent when warm-season precipitation from the Gulf of Mexico prevailed during negative PDO- and PNA-like mean states (350 and 1150 CE). This flood dynamic appears to have been fundamentally altered after 1820 CE. We suggest that extensive land clearance in the Ohio River watershed increased runoff and landscape erosion by reducing interception, infiltration, and evapotranspiration, thereby increasing flooding despite a shift to negative PDO- and PNA-like mean states. Predicted increases in average precipitation and extreme rainfall events across the mid-continental US are likely to perpetuate current trends toward more frequent flood events, because anthropogenic modifications have made the landscape less resilient to changing hydroclimatic conditions

Estimating Nuisance Parameters in Inverse Problems

Many inverse problems include nuisance parameters which, while not of direct interest, are required to recover primary parameters. Structure present in these problems allows efficient optimization strategies - a well known example is variable projection, where nonlinear least squares problems which are linear in some parameters can be very efficiently optimized. In this paper, we extend the idea of projecting out a subset over the variables to a broad class of maximum likelihood (ML) and maximum a posteriori likelihood (MAP) problems with nuisance parameters, such as variance or degrees of freedom. As a result, we are able to incorporate nuisance parameter estimation into large-scale constrained and unconstrained inverse problem formulations. We apply the approach to a variety of problems, including estimation of unknown variance parameters in the Gaussian model, degree of freedom (d.o.f.) parameter estimation in the context of robust inverse problems, automatic calibration, and optimal experimental design. Using numerical examples, we demonstrate improvement in recovery of primary parameters for several large- scale inverse problems. The proposed approach is compatible with a wide variety of algorithms and formulations, and its implementation requires only minor modifications to existing algorithms.Comment: 16 pages, 5 figure

Severe Little Ice Age drought in the midcontinental United States during the Mississippian abandonment of Cahokia

Drought has long been suspected as playing an important role in the abandonment of pre-Columbian Native American settlements across the midcontinental United States between 1350 and 1450 CE. However, high-resolution paleoclimatic reconstructions reflecting local effective moisture (the ratio of precipitation to evaporation) that are located in proximity to Mississippi period (1050–1450 CE) population centers are lacking. Here, we present a 1600-year-long decadally resolved oxygen isotope (δ18O) record from Horseshoe Lake (Collinsville, IL), an evaporatively influenced oxbow lake that is centrally located within the largest and mostly densely populated series of Mississippian settlements known as Greater Cahokia. A shift to higher δ18O in the Horseshoe Lake sediment record from 1200 to 1400 CE indicates that strongly evaporative conditions (i.e., low effective moisture) were persistent during the leadup to Cahokia’s abandonment. These results support the hypothesis that climate, and drought specifically, strongly impacted agriculturally based pre-Columbian Native American cultures in the midcontinental US and highlights the susceptibility of this region, presently a global food production center, to hydroclimate extremes

Modeling the isotopic evolution of snowpack and snowmelt : Testing a spatially distributed parsimonious approach

This work was funded by the NERC/JPI SIWA project (NE/M019896/1) and the European Research Council ERC (project GA 335910 VeWa). The Krycklan part of this study was supported by grants from the Knut and Alice Wallenberg Foundation (Branch-points), Swedish Research Council (SITES), SKB and Kempe foundation. The data and model code is available upon request. Authors declare that they have no conflict of interest. We would like to thank the three anonymous reviewers for their constructive comments that improved the manuscript.Peer reviewedPublisher PD

Paleoclimate support for a persistent dry island effect in the Colombian Andes during the last 4700 years

We investigated middle- and late-Holocene hydroclimate patterns in the Colombian Andes using indicators of watershed erosion (lithic abundance), precipitation intensity (% silt), lake-level variability (organic carbon and nitrogen, % sand, and diatoms), and fire frequency (fossil charcoal) from a ~4700-year-long sediment archive from Laguna de Ubaque, a small sub-alpine lake on the eastern flank of the eastern Colombian Andes. Our results indicate reduced precipitation, low lake levels, and increased fire occurrence at Ubaque between 4700 and 3500 cal. yr BP (hereafter BP). Precipitation and lake levels increased abruptly while fire occurrence decreased between 3500 and 2100 BP, with the exception of a 300-year dry phase between 2800 and 2500 BP. Although wetter than the 4700–3500 BP interval, precipitation decreased, lake levels fell, and fire occurrence increased after 2100 BP, but with high-frequency variability. Comparison of the Ubaque results with other Colombian paleoclimate records (e.g. Lakes Fúquene and La Cocha) supports an antiphase pattern of precipitation between the high/interior Andes and frontal slope sites. This spatial pattern of variability is consistent with modern responses to the changes in terrestrial atmospheric convection associated with the so-called ‘dry island’ effect. Further comparison with paleoclimate records from Venezuela suggests that the millennial trend toward increasing frontal slope precipitation is consistent with orbitally induced increases in Andean atmospheric convection. Sub-orbital dry island–like hydroclimate variability suggests that other mechanisms that affect Northern Hemisphere convection may act to enhance or diminish this effect on centennial and shorter timescales

Ocean-atmosphere forcing of centennial hydroclimate variability in the Pacific Northwest

Reconstructing centennial timescale hydroclimate variability during the late Holocene is critically important for understanding large-scale patterns of drought and their relationship with climate dynamics. We present sediment oxygen isotope records spanning the last two millennia from 10 lakes, as well as climate model simulations, indicating that the Little Ice Age was dry relative to the Medieval Climate Anomaly in much of the Pacific Northwest of North America. This pattern is consistent with observed associations between the El Niño–Southern Oscillation (ENSO), the Northern Annular Mode, and drought as well as with proxy-based reconstructions of Pacific and Atlantic ocean-atmosphere variations over the past 1000 years. The large amplitude of centennial variability indicated by the lake data suggests that regional hydroclimate is characterized by longer-term shifts in ENSO-like dynamics and that an improved understanding of the centennial timescale relationship between external forcing and drought is necessary for projecting future hydroclimatic conditions in western North America.U.S. National Science Foundation. Grant Numbers: AGS-1137750 (B.A.S.), EAR-0902200 (M.B.A.), ATM-0902133 (M.E.M.), EAR-0902753 (J.D.O.), AGS-1103316 (S.F.