Miracle-dz/UniFAR-FTUs huggingface dataset:
Contributions of Environmental Signals and Conserved Residues to the Functions of Carbon Storage Regulator A of Borrelia burgdorferi

ABSTRACT Carbon storage regulator A of Borrelia burgdorferi (CsrABb) contributes to vertebrate host-specific adaptation by modulating activation of the Rrp2-RpoN-RpoS pathway and is critical for infectivity. We hypothesized that the functions of CsrABb are dependent on environmental signals and on select residues. We analyzed the phenotype of csrABb deletion and site-specific mutants to determine the conserved and pathogen-specific attributes of CsrABb. Levels of phosphate acetyltransferase (Pta) involved in conversion of acetyl phosphate to acetyl-coenzyme A (acetyl-CoA) and posttranscriptionally regulated by CsrABb in the csrABb mutant were reduced from or similar to those in the control strains under unfed- or fed-tick conditions, respectively. Increased levels of supplemental acetate restored vertebrate host-responsive determinants in the csrABb mutant to parental levels, indicating that both the levels of CsrABb and the acetyl phosphate and acetyl-CoA balance contribute to the activation of the Rrp2-RpoN-RpoS pathway. Site-specific replacement of 8 key residues of CsrABb (8S) with alanines resulted in increased levels of CsrABb and reduced levels of Pta and acetyl-CoA, while levels of RpoS, BosR, and other members of rpoS regulon were elevated. Truncation of 7 amino acids at the C terminus of CsrABb (7D) resulted in reduced csrABb transcripts and posttranscriptionally reduced levels of FliW located upstream of CsrABb. Electrophoretic mobility shift assays revealed increased binding of 8S mutant protein to the CsrA binding box upstream of pta compared to the parental and 7D truncated protein. Two CsrABb binding sites were also identified upstream of fliW within the flgK coding sequence. These observations reveal conserved and unique functions of CsrABb that regulate adaptive gene expression in B. burgdorferi.
TGMD: A trajectory-based group message delivery protocol for Vehicular Ad Hoc Networks

Infrastructure-to-vehicle (I2V) group message delivery is a common operation required by a wide variety of vehicular ad hoc network (VANET) applications. However, due to the highly dynamic mobility in VANETs, it remains a difficult problem to deliver messages to a group of moving vehicles scattering over the whole network. The contribution of this paper is to propose the first trajectory-based I2V group message delivery protocol, TGMD, that exploits vehicle trajectories to improve the group-message delivery performance. TGMD contains two phases. The first phase determines a few rendezvous points from which the member vehicles can receive the message. Then the second phase transmits the group message over multiple hops to these selected rendezvous points using a multicast-like forwarding scheme to avoid redundant packet transmissions over the overlapped road segments. TGMD aims to minimize the required number of network-layer packet transmissions under a relatively loose delay constraint. Our extensive simulation results indicate that in comparison with the trajectory-based single-destination I2V message delivery scheme (through N-unicasting), TGMD significantly reduces the required number of packet transmissions (and thus bandwidth consumption) while achieving a high delivery ratio around 90%.
Game Theoretic Resource Allocation in Media Cloud With Mobile Social Users

Due to the rapid increases in both the population of mobile social users and the demand for quality of experience (QoE), providing mobile social users with satisfied multimedia services has become an important issue. Media cloud has been shown to be an efficient solution to resolve the above issue, by allowing mobile social users to connect to it through a group of distributed brokers. However, as the resource in media cloud is limited, how to allocate resource among media cloud, brokers, and mobile social users becomes a new challenge. Therefore, in this paper, we propose a game theoretic resource allocation scheme for media cloud to allocate resource to mobile social users though brokers. First, a framework of resource allocation among media cloud, brokers, and mobile social users is presented. Media cloud can dynamically determine the price of the resource and allocate its resource to brokers. A mobile social user can select his broker to connect to the media cloud by adjusting the strategy to achieve the maximum revenue, based on the social features in the community. Next, we formulate the interactions among media cloud, brokers, and mobile social users by a four-stage Stackelberg game. In addition, through the backward induction method, we propose an iterative algorithm to implement the proposed scheme and obtain the Stackelberg equilibrium. Finally, simulation results show that each player in the game can obtain the optimal strategy where the Stackelberg equilibrium exists stably.
Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+ IL-10+ CD4+ T Cell Responses and Suppress Pathology in a Mouse Model of Colitis

ABSTRACT Evidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we and others have shown that some of the suppressive effects of hookworms reside in their excretory/secretory (ES) products. Here, we demonstrate that ES products of the hookworm Ancylostoma caninum (AcES) suppress intestinal pathology in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterized by coexpression of interleukin-4 (IL-4) and IL-10 by CD4+ T cells, downregulation of proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Protease digestion and heat denaturation of AcES resulted in impaired induction of CD4+ IL-4+ IL-10+ cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. Identification of the specific parasite-derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human inflammatory bowel disease.
Modular Arrangement of Allelic Variants Explains the Divergence in Moraxella catarrhalis UspA Protein Function

ABSTRACT Ubiquitous surface protein A molecules (UspAs) of Moraxella catarrhalis are large, nonfimbrial, autotransporter proteins that can be visualized as a “fuzzy” layer on the bacterial surface by transmission electron microscopy. Previous studies attributed a wide array of functions and binding activities to the closely related UspA1, UspA2, and/or UspA2H protein, yet the molecular and phylogenetic relationships among these activities remain largely unexplored. To address this issue, we determined the nucleotide sequence of the uspA1 genes from a variety of independent M. catarrhalis isolates and compared the deduced amino acid sequences to those of the previously characterized UspA1, UspA2, and UspA2H proteins. Rather than being conserved proteins, we observed a striking divergence of individual UspA1, UspA2, and UspA2H proteins resulting from the modular assortment of unrelated “cassettes” of peptide sequence. The exchange of certain variant cassettes correlates with strain-specific differences in UspA protein function and confers differing phenotypes upon these mucosal surface pathogens.
Traitement adjuvant du cancer du côlon : vers une banalisation du XELOX ?

depuis la publication initiale de Moertel en 1990, le traitement adjuvant des cancers du côlon (CC) a bien évolué. dès 2003 et la communication à l’ASCO d’Aimery de Gramont des résultats de l’essai MOSAIC, publiés l’année suivante dans le New England [1], le standard thérapeutique est devenu le FOLFOX 4 administré pendant six mois. Toutes les tentatives récentes pour améliorer ce standard ont échoué mais parallèlement un schéma différent d’association du 5Fu et de l’oxaliplatine a été validé en utilisant la capécitabine : le schéma XELOX [2]. Avec cet état des lieux rapide des différents protocoles en évaluation dans le traitement adjuvant du CC, nous essaierons de voir comment le XELOX peut devenir une véritable alternative au FOLFOX et à qui le proposer en particulier. ❚ L’échec des thérapeutiques ciblées
Kinetics of Innate Immune Response to Yersinia pestis after Intradermal Infection in a Mouse Model

ABSTRACT A hallmark of Yersinia pestis infection is a delayed inflammatory response early in infection. In this study, we use an intradermal model of infection to study early innate immune cell recruitment. Mice were injected intradermally in the ear with wild-type (WT) or attenuated Y. pestis lacking the pYV virulence plasmid (pYV−). The inflammatory responses in ear and draining lymph node samples were evaluated by flow cytometry and immunohistochemistry. As measured by flow cytometry, total neutrophil and macrophage recruitment to the ear in WT-infected mice did not differ from phosphate-buffered saline (PBS) controls or mice infected with pYV−, except for a transient increase in macrophages at 6 h compared to the PBS control. Limited inflammation was apparent even in animals with high bacterial loads (105 to 106 CFU). In addition, activation of inflammatory cells was significantly reduced in WT-infected mice as measured by CD11b and major histocompatibility complex class II (MHC-II) expression. When mice infected with WT were injected 12 h later at the same intradermal site with purified LPS, Y. pestis did not prevent recruitment of neutrophils. However, significant reduction in neutrophil activation remained compared to that of PBS and pYV− controls. Immunohistochemistry revealed qualitative differences in neutrophil recruitment to the skin and draining lymph node, with WT-infected mice producing a diffuse inflammatory response. In contrast, focal sites of neutrophil recruitment were sustained through 48 h postinfection in pYV−-infected mice. Thus, an important feature of Y. pestis infection is reduced activation and organization of inflammatory cells that is at least partially dependent on the pYV virulence plasmid.
Effects of Perinatal Depression and Anxiety on Labor and Delivery Outcomes

INTRODUCTION: The purpose of this study was to determine how perinatal depression and anxiety effect obstetric outcomes and perceptions of labor and delivery experiences. METHODS: This prospective observational study examined the labor and delivery experiences of 25 high-risk and 25 low-risk women. The high-risk group was defined by symptoms during pregnancy as determined by the Edinburgh Postnatal Depression Scale, whereas the low-risk group reported no symptoms. Women in both groups were monitored with the Hamilton Rating Scales for depression and anxiety and filled out a questionnaire about their labor and delivery. RESULTS: The high-risk cohort had significantly more depressive symptoms than the low-risk cohort throughout pregnancy and into the postpartum period (P<.001). Similarly, the high-risk cohort had significantly more anxiety symptoms than the low-risk cohort (P<.001). The high-risk cohort was significantly more likely to report their labor and delivery was a traumatic experience (P=.046) and to have their labor induced (P=.018) as compared with the low-risk cohort. There was no significant difference in the rates of preterm labor (P=.149) or method of delivery (P=1.00) between both groups. CONCLUSIONS: Factors such as preterm labor, labor induction, and cesarean deliveries can cause women to report having traumatic deliveries. It is not known whether labor induction alone caused traumatic birth experiences or whether mood was a predisposing factor to a traumatic delivery. More research must be done to identify the mechanisms by which mood can influence labor and delivery outcomes.
Original Research: Analysis of hepatic microRNA alterations in response to hepatitis B virus infection and pegylated interferon alpha-2a treatment

Interferons play important roles in defense mechanisms against viral infection, and thus interferon therapy has been a standard treatment in chronic hepatitis B patients. Interferons signaling pathways promote interferon-inducible genes including microRNAs. In this research, we aimed to determine microRNAs expression profiles in vitro and in vivo. For in vitro model, Huh7 cells were transfected with or without hepatitis B virus plasmid for 6 h, and then treated with 100 ng of pegylated-interferon alpha-2a for 24 h. In vivo, we defined microRNAs expression profiles in pair-liver tissues of chronic hepatitis B patients in comparison between before and after treatment of pegylated-interferon alpha-2a for 48 weeks. Cellular small RNAs were extracted followed by library preparation. To determine microRNAs expression profiles, the next-generation sequencing was carried out on MiSeq platform (Illumina®). In vitro analysis demonstrated that microRNAs can be classified into up-regulated and down-regulated microRNAs in response to hepatitis B virus, interferon, and combination of hepatitis B virus and interferon. Moreover, in vivo analysis revealed microRNAs profiles in non-responders, responders without hepatitis B surface antigen clearance, and responders with hepatitis B surface antigen clearance. The target genes of the candidate microRNAs were determined in terms of roles in cellular pathways and immune response, which might be related to treatment in chronic hepatitis B patients. Results revealed that two down-regulated microRNAs including miR-185-5p and miR-186-5p were correlated in both in vitro and in vivo studies. These two microRNAs might be represented as specific hepatic microRNAs responding to hepatitis B virus and pegylated-interferon alpha-2a treatment, which may remarkable and attractive for further study involving in the association of their target genes and prediction of pegylated-interferon alpha-2a response. Interestingly, microRNAs expression patterns might be useful for understanding the response mechanism and serve as biomarkers for prediction of pegylated-interferon alpha-2a treatment response in patients with chronic hepatitis B.
Social Attribute Aware Incentive Mechanism for Device-to-Device Video Distribution

To offload and alleviate the heavy base station (BS) traffic load caused by the rapidly growing video services, device-to-device (D2D) communication, as one of the most indispensable technologies of the future cellular networks, can be potentially exploited by mobile users to distribute videos for a BS. In this paper, an effective pricing-based multicast video distribution system and a grid-based clustering method are proposed to support the distribution. Moreover, with the consideration of users’ mobility and social characteristics, we classify them into multicast and core types by studying the user stay probability and familiarity. In particular, core users can cooperate with the BS to distribute videos to the multicast users through intracluster D2D multicast. However, core users cannot selflessly help the BS to distribute videos; instead, they will evaluate their personal benefits before distributing the videos to the multicast users. Further, a Stackelberg game-based pricing mechanism is proposed to inspire the core users to distribute videos. Simulation results demonstrate that the proposed mechanism can not only effectively alleviate the BS traffic load, but also significantly improve the effectiveness and reliability of video transmission.
COMPUTER USE AMONG ELDERLY PERSONS IN LONG-TERM CARE FACILITIES

Computers play an important role in modern society by allowing people to communicate and be connected with sources of activities whether social, political, recreational, and so forth. However, elderly persons residing in long-term care facilities are often removed from these ubiquitous and virtually omnipotent sources of interface. This project included 24 elderly persons in a long-term care setting who participated in the activities of a computer-class designed specifically to teach them to become independent in operating a computer. After 15 months, only five residents remained in the class, and they used computers several times a week for a variety of reasons (e.g., access e-mail, write letters, work on special projects, search the Web for special issues/items, and play games). The article discusses the five categories of obstacles that may have caused the discontinuation of participation: physical and cognitive, personal, hardware/software/technological, organizational, and environmental.
Surto de mastite bovina causada por Arcanobacterium pyogenes

An uncommon outbreak of mastitis caused by Arcanobacterium pyogenes in 26 cows is reported. The epidemiological findings, clinical signs, microbiological exams, somatic cell count, in vitro susceptibility profile of strains, efficacy of intramammary treatment and control measures were discussed. Florfenicol (96.2%), cefoperazona (92.3%), cefaloxin (84.6%) and ceftiofur (84.6%) were the most effective antimicrobials, and neomicin (27.0%) and enrofloxacin (17.4%) the least effective antimicrobials.
Adhesion, Invasion, and Agglutination Mediated by Two Trimeric Autotransporters in the Human Uropathogen Proteus mirabilis

ABSTRACT Fimbriae of the human uropathogen Proteus mirabilis are the only characterized surface proteins that contribute to its virulence by mediating adhesion and invasion of the uroepithelia. PMI2122 (AipA) and PMI2575 (TaaP) are annotated in the genome of strain HI4320 as trimeric autotransporters with “adhesin-like” and “agglutinating adhesin-like” properties, respectively. The C-terminal 62 amino acids (aa) in AipA and 76 aa in TaaP are homologous to the translocator domains of YadA from Yersinia enterocolitica and Hia from Haemophilus influenzae. Comparative protein modeling using the Hia three-dimensional structure as a template predicted that each of these domains would contain four antiparallel beta sheets and that they formed homotrimers. Recombinant AipA and TaaP were seen as ∼28 kDa and ∼78 kDa, respectively, in Escherichia coli, and each also formed high-molecular-weight homotrimers, thus supporting this model. E. coli synthesizing AipA or TaaP bound to extracellular matrix proteins with a 10- to 60-fold-higher level of affinity than the control strain. Inactivation of aipA in P. mirabilis strains significantly (P < 0.01) reduced the mutants' ability to adhere to or invade HEK293 cell monolayers, and the functions were restored upon complementation. A 51-aa-long invasin region in the AipA passenger domain was required for this function. E. coli expressing TaaP mediated autoagglutination, and a taaP mutant of P. mirabilis showed significantly (P < 0.05) more reduced aggregation than HI4320. Gly-247 in AipA and Gly-708 in TaaP were indispensable for trimerization and activity. AipA and TaaP individually offered advantages to P. mirabilis in a murine model. This is the first report characterizing trimeric autotransporters in P. mirabilis as afimbrial surface adhesins and autoagglutinins.
Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives

Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials. ILE 4-HPR administered as five-day continuous infusion achieved over 50 µmol/L at MTD with minimal systemic toxicities; multiple complete and partial responses were observed in peripheral T cell lymphomas. The LXS oral powder 4-HPR formulation increased plasma levels approximately two-fold at MTD in children without dose-limiting toxicities and demonstrated multiple complete responses in recurrent neuroblastoma. The clinical activity observed with new 4-HPR formulations is attributed to increased bioavailability. Phase I and II clinical trials of both LXS 4-HPR and ILE 4-HPR are in progress as a single agent or in combination with other drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.
Hypertension: pathophysiology and perioperative implications

### Key points Raised blood pressure (BP) is common and predisposes to cardiovascular events, renal impairment, cognitive impairment, and premature death. The burden of morbidity and mortality associated with BP elevation makes it a major public health concern. It accounts for ∼12% of primary care consultations: the remuneration of general practitioners in the UK is linked to quality standards including one on BP control, and BP measurement is a component of routine NHS health checks. In this review, we will examine the epidemiology and management of hypertension, the implications of raised BP for anaesthesia and surgery, the pathophysiology of the condition, and its perioperative management. In 2011, the UK National Institute for Health and Clinical Excellence (NICE), working in collaboration with the British Hypertension Society, released updated guidance on the management of hypertension.1 This guideline introduced a number of significant changes. Essential hypertension, so-called to reflect the understanding that the elevated pressure was essential to perfuse diseased arteries, was renamed primary hypertension. Ambulatory monitoring was introduced as the preferred method of obtaining serial BP readings to diagnose hypertension, with home BP monitoring by the patient if ambulatory monitoring is not feasible and BP readings in the clinic as the least favoured option. Pressures obtained on ambulatory monitoring reflect the patient's BP during everyday activity …
Eine neue Infektionskrankheit

In den letzten Wochen hatte ich Gelegenheit, etwa 20 Krankheitsfälle zu beobachten, deren Symptomenbild sich nicht in die uns bekannten Krankheiten einreihen läßt. Unter hohem Fieber (bis über 400) erkrankt der Befallene plötzlich aus voller Gesundheit, manchma' mit Schüttelfrost. Der Puls zeigt bei Erwachsenen meist nicht über 100 Schläge in der Minute. Die Kranken klagen über Kopfschmerzen und Abgeschlagenheit. Objektiv sind außer dem Fieber und der geringen Pulobeschleunigung keinerlei