Miracle-dz/UniFAR-FTUs huggingface dataset:
Entometabolomics: applications of modern analytical techniques to insect studies

Metabolomic analyses can reveal associations between an organism's metabolome and further aspects of its phenotypic state, an attractive prospect for many life‐sciences researchers. The metabolomic approach has been employed in some, but not many, insect study systems, starting in 1990 with the evaluation of the metabolic effects of parasitism on moth larvae. Metabolomics has now been applied to a variety of aspects of insect biology, including behaviour, infection, temperature stress responses, CO2 sedation, and bacteria–insect symbiosis. From a technical and reporting standpoint, these studies have adopted a range of approaches utilising established experimental methodologies. Here, we review current literature and evaluate the metabolomic approaches typically utilised by entomologists. We suggest that improvements can be made in several areas, including sampling procedures, the reduction in sampling and equipment variation, the use of sample extracts, statistical analyses, confirmation, and metabolite identification. Overall, it is clear that metabolomics can identify correlations between phenotypic states and underlying cellular metabolism that previous, more targeted, approaches are incapable of measuring. The unique combination of untargeted global analyses with high‐resolution quantitative analyses results in a tool with great potential for future entomological investigations.
Emerging Therapies for Acute Coronary Syndromes

In the majority of cases acute coronary syndromes (ACS) are caused by activation and aggregation of platelets and subsequent thrombus formation leading to a decrease in coronary artery blood flow. Recent focus on the treatment of ACS has centered on reducing the response of platelets to vascular injury as well as inhibiting fibrin deposition. Novel therapies include more effective P2Y12 receptor blockers thereby reducing inter-individual variability, targeting the platelet thrombin receptor (protease activated receptor 1) as well as directly inhibiting factor Xa or thrombin activity. In this review we discuss the clinical data evaluating the effectiveness of these various new ACS treatment options.
Nash equilibria of packet forwarding strategies in wireless ad hoc networks

In self-organizing ad hoc networks, all the networking functions rely on the contribution of the participants. As a basic example, nodes have to forward packets for each other in order to enable multihop communication. In recent years, incentive mechanisms have been proposed to give nodes incentive to cooperate, especially in packet forwarding. However, the need for these mechanisms was not formally justified. In this paper, we address the problem of whether cooperation can exist without incentive mechanisms. We propose a model,based on game theory and graph theory to investigate equilibrium conditions of packet forwarding strategies. We prove theorems about the equilibrium conditions for both cooperative and noncooperative strategies. We perform simulations to estimate the probability that the conditions for a cooperative equilibrium hold in randomly generated network scenarios. As the problem is involved, we deliberately restrict ourselves to a static configuration. We conclude that in static ad hoc networks where the relationships between the nodes are likely to be stab le-cooperation needs to be encouraged.
Coronavirus Replication Does Not Require the Autophagy Gene ATG5

Macroautophagy (herein autophagy) is a cellular process, requiring ATG5, by which cells deliver double membrane-bound packets containing cytoplasm or cytoplasmic organelles to the lysosome. This process has been reported in some cases to be antiviral, while in other cases it has been reported to be required for efficient viral replication or release. A role for autophagy in RNA virus replication has been an attractive hypothesis because of the association of RNA virus replication with complex membrane rearrangements in the cytoplasm that can generate opposed double membranes. In this study we demonstrate that ATG5 is not required for murine hepatitis virus (MHV) replication in either bone marrow derived macrophages (BMMφ) lacking ATG5 by virtue of Cre-recombinase mediated gene deletion or primary low passage murine ATG5-/- embryonic fibroblasts (pMEFs). We conclude that neither ATG5 nor an intact autophagic pathway are required for MHV replication or release.
Specific Pathogen Recognition by Multiple Innate Immune Sensors in an Invertebrate

Detection of pathogens by all living organisms is the primary step needed to implement a coherent and efficient immune response. This implies a mediation by different soluble and/or membrane-anchored proteins related to innate immune receptors called PRRs (pattern-recognition receptors) to trigger immune signaling pathways. In most invertebrates, their roles have been inferred by analogy to those already characterized in vertebrate homologs. Despite the induction of their gene expression upon challenge and the presence of structural domains associated with the detection of pathogen-associated molecular patterns in their sequence, their exact role in the induction of immune response and their binding capacity still remain to be demonstrated. To this purpose, we developed a fast interactome approach, usable on any host–pathogen couple, to identify soluble proteins capable of directly or indirectly detecting the presence of pathogens. To investigate the molecular basis of immune recognition specificity, different pathogens (Gram-positive bacterium, Micrococcus luteus; Gram-negative, Escherichia coli; yeast, Saccharomyces cerevisiae; and metazoan parasites, Echinostoma caproni or Schistosoma mansoni) were exposed to hemocyte-free hemolymph from the gastropod Biomphalaria glabrata. Twenty-three different proteins bound to pathogens were identified and grouped into three different categories based on their primary function. Each pathogen was recognized by a specific but overlapping set of circulating proteins in mollusk’s hemolymph. While known PRRs such as C-type lectins were identified, other proteins not known to be primarily involved in pathogen recognition were found, including actin, tubulin, collagen, and hemoglobin. Confocal microscopy and specific fluorescent labeling revealed that extracellular actin present in snail hemolymph was able to bind to yeasts and induce their clotting, a preliminary step for their elimination by the snail immune system. Aerolysin-like proteins (named biomphalysins) were the only ones involved in the recognition of all the five pathogens tested, suggesting a sentinel role of these horizontally acquired toxins. These findings highlight the diversity and complexity of a highly specific innate immune sensing system. It paves the way for the use of such approach on a wide range of host–pathogen systems to provide new insights into the specificity and diversity of immune recognition by innate immune systems.
Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA

Autosomal dominant dyskeratosis congenita (DKC), as well as aplastic anemia, has been linked to mutations in the RNA component of telomerase, the ribonucleoprotein responsible for telomere maintenance. Here we examine the effect of the DKC mutations on the structure and stability of human telomerase RNA pseudoknot and CR7 domains by using NMR and thermal melting. The CR7 domain point mutation decreases stability and alters a conserved secondary structure thought to be involved in human telomerase RNA accumulation in vivo. We find that pseudoknot constructs containing the conserved elements of the pseudoknot domain are in equilibrium with a hairpin conformation. The solution structure of the wild-type hairpin reveals that it forms a continuous helix containing a novel run of three consecutive U⋅U and a U⋅C base pairs closed by a pentaloop. The six base pairs unique to the hairpin conformation are phylogenetically conserved in mammals, suggesting that this conformation is also functionally important. The DKC mutation in the pseudoknot domain results in a shift in the equilibrium toward the hairpin form, primarily due to destabilization of the pseudoknot. Our results provide insight into the effect of these mutations on telomerase structure and suggest that the catalytic cycle of telomerase involves a delicate interplay between RNA conformational states, alteration of which leads to the disease state.
Joint Power Control and Time Allocation for Wireless Powered Underlay Cognitive Radio Networks

This letter considers a wireless powered underlay cognitive radio network where secondary users (SUs) first harvest energy in the downlink wireless power transfer (WPT) phase and then use the energy for data transmission in the uplink wireless information transmission phase adopting the time-division multiple access. Our aim is to maximize the sum rate of the SUs under the interference power constraint enforced by the primary user and the transmit power constraints. The optimal joint power control for the WPT phase and time allocation among the SUs is obtained. Simulation results show that the obtained optimal scheme outperforms the scheme that employs only the optimal time allocation or the optimal power control.
Cooperative diversity in wireless networks: algorithms and architectures

To effectively combat multipath fading across multiple protocol layers in wireless networks, this dissertation develops energy-efficient algorithms that employ certain kinds of cooperation among terminals, and illustrates how one might incorporate these algorithms into various network architectures. In these techniques, sets of terminals relay signals for each other to create a virtual antenna array, trading off the costs-in power, bandwidth, and complexity-for the greater benefits gained by exploiting spatial diversity in the channel. By contrast, classical network architectures only employ point-to-point transmission and thus forego these benefits. After summarizing a model for the wireless channel, we present various practical cooperative diversity algorithms based upon different types of relay processing and re-encoding, both with and without limited feedback from the ultimate receivers. Using informationtheoretic tools, we show that all these algorithms can achieve full spatial diversity, as if each terminal had as many transmit antennas as the entire set of cooperating terminals. Such diversity gains translate into greatly improved robustness to fading for the same transmit power, or substantially reduced transmit power for the same level of performance. For example, with two cooperating terminals, power savings as much as 12 dB (a factor of sixteen) are possible for outage probabilities around one in a thousand. Finally, we discuss how the required level of complexity in the terminals makes different algorithms suitable for particular network architectures that arise in, for example, current cellular and ad-hoc networks. Thesis Supervisor: Gregory W. Wornell Title: Professor
ATP-binding Cassette Transporter A1 Contains an NH2-terminal Signal Anchor Sequence That Translocates the Protein's First Hydrophilic Domain to the Exoplasmic Space*

Mutations in the ATP-binding cassette transporter A1 (ABCA1) transporter are associated with Tangier disease and a defect in cellular cholesterol efflux. The amino terminus of the ABCA1 transporter has two putative in-frame translation initiation sites, 60 amino acids apart. A cluster of hydrophobic amino acids form a potentially cleavable signal sequence in this 60-residue extension. We investigated the functional role of this extension and found that it was required for stable protein expression of transporter constructs containing any downstream transmembrane domains. The extension directed transporter translocation across the ER membrane with an orientation that resulted in glycosylation of amino acids immediately distal to the signal sequence. Neither the native signal sequence nor a green fluorescent protein tag, fused at the amino terminus, was cleaved from ABCA1. The green fluorescent protein fusion protein had efflux activity comparable with wild type ABCA1 and demonstrated a predominantly plasma membrane distribution in transfected cells. These data establish a requirement for the upstream 60 amino acids of ABCA1. This region contains an uncleaved signal anchor sequence that positions the amino terminus in a type II orientation leading to the extracellular presentation of an ∼600-amino acid loop in which loss-of-function mutations cluster in Tangier disease patients.
Colony Genetic Structure of Reticulitermes flavipes (Kollar) from Natural Populations in Nebraska

Abstract Genetic markers are a powerful tool to investigate the breeding structure and population genetics of subterranean termites. In this study, 10 - 20 subterranean termite workers, Reticulitermes flavipes (Kollar) were collected from colonies at 8 sites, separated by at least 200 m. Ten workers from each site were genotyped at 7 microsatellite loci. The data revealed that all 7 microsatellites were polymorphic with up to 6 alleles per locus. The frequency of most the common allele ranged from 0.11 - 0.60. Observed patterns of genetic variation within colonies revealed that most were the result of fusions of multiple colonies. Few colonies exhibited genetic variation consistent with a simple family headed by a single pair of reproductives. The analyses of F-statistics and relatedness coefficients indicated that the colonies were often inbred, suggesting they contained neotenic reproductives.
Insulin Therapy and Body Weight, Body Composition and Muscular Strength in Patients with Type 2 Diabetes Mellitus

Aims. To determine the progression of body weight (BW) and body composition (BC) in patients with type 2 diabetes mellitus (T2D) on insulin therapy and the consequences on muscle strength (MS) as a reflect of free fat mass increases. Research design and methods. We analysed BC using air displacement plethysmography and MS by hand grip dynamometry in 40 T2D before and after three (M3) and six months (M6) of insulin therapy. Results. at baseline HbA1c was 9.76 ±1.6% and BW was stable with fat mass (FM) 28 ± 10.7 kg; and fat free mass (FFM) 52.4 ± 11 kg; at M6, HbA1c improved to 7.56 ± 0.8%; insulin doses tended to increase. BW gain at M6 was + 3.2 ± 4.2 kg and with an increase of only 25% by M3; it was composed of FM, whereas FFM was unchanged. MS did not increase on insulin therapy. Conclusions. In T2D, BW gain was composed exclusively of FM with no improvement in MS.
Causality assessment in drug-induced hepatotoxicity

Drugs are currently an important cause of liver disease, ranked as the most frequent reason for acute liver failure. Despite recent advances in knowledge of the mechanisms implicated in drug-induced hepatocellular damage and cholestasis, as well as the identification of several risk factors, the diagnosis of hepatotoxicity remains a difficult task because specific tests are not available. In a step-by-step approach, the incrimination of a drug in liver symptoms requires a high degree of suspicion on the part of the physician, temporal eligibility, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Ultimately, the use of diagnostic algorithms may add consistency to the diagnostic process either by translating the suspicion into a quantitative score or by providing a framework that emphasises the features that merit attention in cases of suspected hepatic adverse reactions.
Inflammation‐mediated genomic instability: roles of activation‐induced cytidine deaminase in carcinogenesis

Chronic inflammation is a strong risk factor for the development of cancer. Many previous studies have demonstrated that a transcriptional factor, nuclear factor (NF)‐κB, plays an important role in the association between inflammation and cancer development, particularly tumor promotion and tumor progression. Although it is well recognized that cancer develops via stepwise accumulation of genetic aberrations, the mechanisms underlying the generation of these genetic alterations in normal epithelial cells under inflammatory conditions are not known. We recently demonstrated that pathogenic bacterial or viral factors and the subsequent inflammatory reactions lead to the aberrant expression of a DNA mutator enzyme, activation‐induced cytidine deaminase (AID), in various epithelial cells via NF‐κB activation, which causes the accumulation of genetic alterations in tumor‐related genes. AID activation is widely observed in gastrointestinal tissues with cancer‐associated inflammation, such as chronic viral hepatitis, Helicobacter pylori‐related gastritis, Barrett's esophagus and inflammatory bowel disease. Furthermore, a deficiency of endogenous AID expression reduces both accumulation of somatic mutations in tumor‐related genes and tumor incidence in a mouse model of inflammation‐associated cancer development. These findings strongly suggest that AID plays an integral role in inflammation‐associated carcinogenesis and is therefore a potential target molecule for the prevention and treatment of cancers. (Cancer Sci 2012; 103: 1201–1206)
Impact of Laminitis on the Canonical Wnt Signaling Pathway in Basal Epithelial Cells of the Equine Digital Laminae

The digital laminae is a two layer tissue that attaches the distal phalanx to the inner hoof wall, thus suspending the horse's axial skeleton in the hoof capsule. This tissue fails at the epidermal:dermal junction in laminitic horses, causing crippling disease. Basal epithelial cells line the laminar epidermal:dermal junction, undergo physiological change in laminitic horses, and lose versican gene expression. Versican gene expression is purportedly under control of the canonical Wnt signaling pathway and is a trigger for mesenchymal-to-epithelial transition; thus, its repression in laminar epithelial cells of laminitic horses may be associated with suppression of the canonical Wnt signaling pathway and loss of the epithelial cell phenotype. In support of the former contention, we show, using laminae from healthy horses and horses with carbohydrate overload-induced laminitis, quantitative real-time polymerase chain reaction, Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis, and immunofluorescent tissue staining, that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in laminar basal epithelial cells of healthy horses. Furthermore, expression of positive regulators is suppressed and negative regulators elevated in laminae of laminitic compared to healthy horses. We also show that versican gene expression in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, consistent with regulation by the canonical Wnt signaling pathway. In addition, gene and protein expression of β-catenin correlates positively with that of integrin β4 and both are strongly suppressed in laminar basal epithelial cells of laminitic horses, which remain E-cadherin+/vimentin−, excluding mesenchymal transition as contributing to loss of the adherens junction and hemidesmosome components. We propose that suppression of the canonical Wnt signaling pathway, and accompanying reduced expression of β catenin and integrin β4 in laminar basal epithelial cells reduces cell:cell and cell:basement membrane attachment, thus, destabilizing the laminar epidermal:dermal junction.
Genetic Alterations in Signaling Pathways in Melanoma

Alterations in the RAS signaling cascade are almost uniformly present in melanoma. RAS itself is only infrequently mutated in melanoma although downstream of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the protein kinase B/Akt pathway. These genes are often altered in melanomas; indeed, the most frequent target of mutation in melanomas is BRAF, which is mutated in ∼60% to 70% of superficial spreading melanomas. These mutations occur in a background that is not normal, with the CDKN2A locus also typically being mutated. We review herein the data that suggest that the distribution of the signaling mutations is important. In general, melanomas carry a mutated NRAS, a mutated BRAF, or concurrent BRAF and PTEN mutations. These data support the hypothesis that the biochemical functions of RAS are portioned by mutations in the pathways lying downstream. Moreover, these mutations have no apparent relationship to the patterns of alteration of CDKN2A and its downstream effectors. Thus, the data also suggest that successful exploitation of mutations in melanoma will be dependent on understanding not only mutations and their frequency but their genetic context as well.
The meanings of and attitudes about cancer pain among African Americans.

PURPOSE/OBJECTIVES To describe the meaning of cancer pain and attitudes in dealing with cancer pain among a group of African Americans with cancer. RESEARCH APPROACH Qualitative descriptive design. SETTING Three outpatient medical oncology clinics in the mid-Atlantic region. PARTICIPANTS Purposive sample of 35 self-identified African Americans older than age 18 and diagnosed with solid tumors, with self-reported cancer-related pain lasting at least one month in duration and no major surgery in the previous three months. METHODOLOGIC APPROACH In-depth, semistructured, taped-recorded interviews were transcribed verbatim and analyzed. Initial codes were categorized into meaningful themes, and the data were analyzed until no new themes emerged. FINDINGS Cancer pain was articulated by participants in terms of its physical, emotional, and existential dimensions. Themes related to cancer and pain remained intertwined. Some participants viewed pain as a signal of underlying disease progression and described it as a monitoring strategy for staying ahead of their cancer. Stoicism, faith, and finding meaning in the cancer pain experience emerged as main themes in participants dealing with cancer pain. CONCLUSIONS The findings suggest that perceived meanings and interpretations of the nature of cancer pain, its causes, and consequences may be important in shaping participants' pain treatment negotiations with providers. Understanding patient-level factors is crucial to fully comprehend pain treatment disparities. INTERPRETATION Providers must assume a more proactive role in assessing physical, emotional, and existential dimensions of cancer pain, improving trust and communication, and identifying educational and behavioral interventions for African American patients and families to optimize pain treatment outcomes.
Human resource management and performance: lessons from the Netherlands

The relationship between HRM and firm performance has been a hotly debated topic over the last decade, with the great bulk of the primary scientific research coming from the USA and, to a lesser extent, the UK. We start with an overview of this research to give a frame of reference to compare the findings from the Netherlands. By comparing the results of research in the Netherlands with those in the USA and the UK we hope to reveal the secret of achieving 'competitive advantage through people' (Pfeffer, 1994) in the Netherlands. The comparison may further allow us to supplement resource-based approaches with a more institutional perspective.
An achievable error exponent for the mismatched multiple-access channel

This paper considers channel coding for the discrete memoryless multiple-access channel with a given (possibly suboptimal) decoding rule. Using constant-composition random coding, an achievable error exponent is obtained which is tight with respect to the ensemble average, and positive for all rate pairs in the interior of Lapidoth's achievable rate region.