High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of ??-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38???kDa)

Historical Reconstruction Reveals Recovery in Hawaiian Coral Reefs

Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (∼AD 1400–1820) and an ongoing recovery in the NWHI (∼AD 1950–2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>103 km2). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts

A Role for the Chemokine RANTES in Regulating CD8 T Cell Responses during Chronic Viral Infection

RANTES (CCL5) is a chemokine expressed by many hematopoietic and non-hematopoietic cell types that plays an important role in homing and migration of effector and memory T cells during acute infections. The RANTES receptor, CCR5, is a major target of anti-HIV drugs based on blocking viral entry. However, defects in RANTES or RANTES receptors including CCR5 can compromise immunity to acute infections in animal models and lead to more severe disease in humans infected with west Nile virus (WNV). In contrast, the role of the RANTES pathway in regulating T cell responses and immunity during chronic infection remains unclear. In this study, we demonstrate a crucial role for RANTES in the control of systemic chronic LCMV infection. In RANTES−/− mice, virus-specific CD8 T cells had poor cytokine production. These RANTES−/− CD8 T cells also expressed higher amounts of inhibitory receptors consistent with more severe exhaustion. Moreover, the cytotoxic ability of CD8 T cells from RANTES−/− mice was reduced. Consequently, viral load was higher in the absence of RANTES. The dysfunction of T cells in the absence of RANTES was as severe as CD8 T cell responses generated in the absence of CD4 T cell help. Our results demonstrate an important role for RANTES in sustaining CD8 T cell responses during a systemic chronic viral infection

Noise-Driven Stem Cell and Progenitor Population Dynamics

BACKGROUND: The balance between maintenance of the stem cell state and terminal differentiation is influenced by the cellular environment. The switching between these states has long been understood as a transition between attractor states of a molecular network. Herein, stochastic fluctuations are either suppressed or can trigger the transition, but they do not actually determine the attractor states. METHODOLOGY/PRINCIPAL FINDINGS: We present a novel mathematical concept in which stem cell and progenitor population dynamics are described as a probabilistic process that arises from cell proliferation and small fluctuations in the state of differentiation. These state fluctuations reflect random transitions between different activation patterns of the underlying regulatory network. Importantly, the associated noise amplitudes are state-dependent and set by the environment. Their variability determines the attractor states, and thus actually governs population dynamics. This model quantitatively reproduces the observed dynamics of differentiation and dedifferentiation in promyelocytic precursor cells. CONCLUSIONS/SIGNIFICANCE: Consequently, state-specific noise modulation by external signals can be instrumental in controlling stem cell and progenitor population dynamics. We propose follow-up experiments for quantifying the imprinting influence of the environment on cellular noise regulation.Engineering and Applied SciencesOther Research Uni

Primary Human mDC1, mDC2, and pDC Dendritic Cells Are Differentially Infected and Activated by Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) causes recurrent infections throughout life. Vaccine development may depend upon understanding the molecular basis for induction of ineffective immunity. Because dendritic cells (DCs) are critically involved in early responses to infection, their interaction with RSV may determine the immunological outcome of RSV infection. Therefore, we investigated the ability of RSV to infect and activate primary mDCs and pDCs using recombinant RSV expressing green fluorescent protein (GFP). At a multiplicity of infection of 5, initial studies demonstrated ∼6.8% of mDC1 and ∼0.9% pDCs were infected. We extended these studies to include CD1c−CD141+ mDC2, finding mDC2 infected at similar frequencies as mDC1. Both infected and uninfected cells upregulated phenotypic markers of maturation. Divalent cations were required for infection and maturation, but maturation did not require viral replication. There is evidence that attachment and entry/replication processes exert distinct effects on DC activation. Cell-specific patterns of RSV-induced maturation and cytokine production were detected in mDC1, mDC2, and pDC. We also demonstrate for the first time that RSV induces significant TIMP-2 production in all DC subsets. Defining the influence of RSV on the function of selected DC subsets may improve the likelihood of achieving protective vaccine-induced immunity

The impact of co-infections on fish: a review

International audienceAbstractCo-infections are very common in nature and occur when hosts are infected by two or more different pathogens either by simultaneous or secondary infections so that two or more infectious agents are active together in the same host. Co-infections have a fundamental effect and can alter the course and the severity of different fish diseases. However, co-infection effect has still received limited scrutiny in aquatic animals like fish and available data on this subject is still scarce. The susceptibility of fish to different pathogens could be changed during mixed infections causing the appearance of sudden fish outbreaks. In this review, we focus on the synergistic and antagonistic interactions occurring during co-infections by homologous or heterologous pathogens. We present a concise summary about the present knowledge regarding co-infections in fish. More research is needed to better understand the immune response of fish during mixed infections as these could have an important impact on the development of new strategies for disease control programs and vaccination in fish

ICAR: endoscopic skull‐base surgery

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