Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters

Hookworms are one of the most prevalent and important parasites, infecting ~500 million people worldwide. Hookworm disease is among the leading causes of iron-deficiency anemia in the developing world and is associated with significant growth stunting and malnutrition. In humans, hookworms appear to impair memory and other forms of cognition, although definitive data are hard to come by. Here we study the impact of a human hookworm parasite, Ancylostoma ceylanicum, on cognition in hamsters in a controlled laboratory setting. We developed tests that measure long-term memory in hamsters. We find that hookworm-infected hamsters were fully capable of detecting a novel object. However, hookworm-infected hamsters were impaired in detecting a displaced object. Defects could be discerned at even at low levels of infection, whereas at higher levels of infection, hamsters were statistically unable to distinguish between displaced and non-displaced objects. These spatial memory deficiencies could not be attributed to defects in infected hamster mobility or to lack of interest. We also found that hookworm infection resulted in reproducible reductions in diversity and changes in specific taxanomic groups in the hamster gut microbiome. These data demonstrate that human hookworm infection in a laboratory mammal results in a specific, rapid, acute, and measurable deficit in spatial memory, and we speculate that gut alterations could play some role in these cognitive deficits. Our findings highlight the importance of hookworm elimination and suggest that finer tuned spatial memory studies be carried out in humans

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell

Unconditional teleportation of continuous-variable entanglement

We give a protocol and criteria for demonstrating unconditional teleportation of continuous-variable entanglement (i.e., entanglement swapping). The initial entangled states are produced with squeezed light and linear optics. We show that any nonzero entanglement (any nonzero squeezing) in both of two entanglement sources is sufficient for entanglement swapping to occur. In fact, realization of continuous-variable entanglement swapping is possible using only {\it two} single-mode squeezed states.Comment: 4 pages, 2 figures, published version, title change

Engineering design and economic analysis of offshore seaweed farm

As global demand for sustainable biomass and need to mitigate global warming begin to rise, cultivation of seaweed has gained significant attention in recent years due to its potential for carbon recycling. However, limited availability of suitable coastal areas for large-scale seaweed cultivation has led to exploration of offshore environments as a viable alternative. The nature of many offshore environments often exposes seaweed farming systems to harsh environmental conditions, including strong waves, currents, and wind. These factors can lead to structural failures, kelp losses, and significant financial losses for seaweed farmers. The main objective of this study is to present a robust design and numerical analysis of an economically viable floating offshore kelp farm facility, and evaluate its stability and mooring system performance. A numerical method of preliminary designs of the offshore aquaculture systems were developed using the OrcaFlex software. The models were subjected to a series of dynamic environmental loading scenarios representing extreme events. These simulations aimed to forecast the overall dynamic response of an offshore kelp farm at a depth of 50m and to determine the best possible farm design with structural integrity for a selected offshore environment. Furthermore, to assess the economic feasibility of establishing offshore seaweed farms, a comprehensive capital expenses analysis was conducted. The results revealed that, in terms of the kelp farms with the same number of the kelp cultivating lines, the cost of building kelp farms will be strongly affected by the cost of mooring lines. The present study may help to understand the dynamic response and economic feasibility of offshore kelp farms

Broadband teleportation

Quantum teleportation of an unknown broadband electromagnetic field is investigated. The continuous-variable teleportation protocol by Braunstein and Kimble [Phys. Rev. Lett. {\bf 80}, 869 (1998)] for teleporting the quantum state of a single mode of the electromagnetic field is generalized for the case of a multimode field with finite bandwith. We discuss criteria for continuous-variable teleportation with various sets of input states and apply them to the teleportation of broadband fields. We first consider as a set of input fields (from which an independent state preparer draws the inputs to be teleported) arbitrary pure Gaussian states with unknown coherent amplitude (squeezed or coherent states). This set of input states, further restricted to an alphabet of coherent states, was used in the experiment by Furusawa {\it et al.} [Science {\bf 282}, 706 (1998)]. It requires unit-gain teleportation for optimizing the teleportation fidelity. In our broadband scheme, the excess noise added through unit-gain teleportation due to the finite degree of the squeezed-state entanglement is just twice the (entanglement) source's squeezing spectrum for its ``quiet quadrature.'' The teleportation of one half of an entangled state (two-mode squeezed vacuum state), i.e., ``entanglement swapping,'' and its verification are optimized under a certain nonunit gain condition. We will also give a broadband description of this continuous-variable entanglement swapping based on the single-mode scheme by van Loock and Braunstein [Phys. Rev. A {\bf 61}, 10302 (2000)]Comment: 27 pages, 7 figures, revised version for publication, Physical Review A (August 2000); major changes, in parts rewritte

Photoacoustic Sentinel Lymph Node Imaging with Self-Assembled Copper Neodecanoate Nanoparticles

Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non-ionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for noninvasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that copper can be used as a contrast metal for near-infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipid-entrapped nanoparticle. The nanoparticles assumed a size of 80–90 nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least 6-fold higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in a rodent model. This work clearly demonstrates for the first time the potential use of copper as an optical contrast agent

Human Astrocytes Exhibit Tumor Microenvironment-, Age-, and Sex-Related Transcriptomic Signatures

: Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurological diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peri-tumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurological disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. This data provides powerful new insights into human astrocyte biology in several biologically relevant states, that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENTAstrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurological diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease

Knockdown of interferon-induced transmembrane protein 1 (IFITM1) inhibits proliferation, migration, and invasion of glioma cells

Interferon-induced transmembrane protein 1 (IFITM1) has recently been identified as a new molecular marker in human colorectal cancer. However, its role in glioma carcinogenesis is not known. In this study, we demonstrated that suppression of IFITM1 expression significantly inhibited proliferation of glioma cells in a time-dependent manner. The growth inhibitory effect was mediated by cell cycle arrest. Furthermore, IFITM1 knockdown significantly inhibited migration and invasion of glioma cells, which could be attributed to decreased expression and enzymatic activity of matrix metalloproteinase 9. Taken together, these results suggest that IFITM1 is a potential therapeutic target for gliomas

A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

SummaryGlioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma