Miracle-dz/UniFAR-FTUs huggingface dataset:
The Human Papillomavirus Type 16 E5 Oncoprotein Translocates Calpactin I to the Perinuclear Region

ABSTRACT The human papillomavirus type 16 (HPV-16) E5 oncoprotein is embedded in membranes of the endoplasmic reticulum and nuclear envelope with its C terminus exposed to the cytoplasm. Among other activities, E5 cooperates with the HPV E6 oncoprotein to induce koilocytosis in human cervical cells and keratinocytes in vitro. The effect of E5 on infected cells may rely on its interactions with various cellular proteins. In this study we identify calpactin I, a heterotetrameric, Ca2+- and phospholipid-binding protein complex that regulates membrane fusion, as a new cellular target for E5. Both the annexin A2 and p11 subunits of calpactin I coimmunoprecipitate with E5 in COS cells and in human epithelial cell lines, and an intact E5 C terminus is required for binding. Moreover, E5-expressing cells exhibit a perinuclear redistribution of annexin A2 and p11 and show increased fusion of perinuclear membrane vesicles. The C terminus of E5 is required for both the perinuclear redistribution of calpactin I and increased formation of perinuclear vacuoles. These results support the hypothesis that the E5-induced relocalization of calpactin I to the perinuclear region promotes perinuclear membrane fusion, which may underlie the development of koilocytotic vacuoles.
Respiratory Syncytial Virus Nonstructural Proteins Decrease Levels of Multiple Members of the Cellular Interferon Pathways

ABSTRACT Viruses of the Paramyxoviridae family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique nonstructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both of the NS proteins affect the steady-state levels of key members of the IFN pathway. We found that both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing signals, although NS1 was more efficient. Only NS1 reduced IKKε, a key protein kinase that specifically phosphorylates and activates IFN regulatory factor 3. Loss of the TRAF3 and IKKε proteins appeared to involve a nonproteasomal mechanism. Interestingly, NS2 modestly increased IKKε levels. In the IFN response pathway, NS2 decreased the levels of STAT2, the essential transcription factor for IFN-inducible antiviral genes. Preliminary mapping revealed that the C-terminal 10 residues of NS1 were essential for reducing IKKε levels and the C-terminal 10 residues of NS2 were essential for increasing and reducing IKKε and STAT2, respectively. In contrast, deletion of up to 20 residues of the C termini of NS1 and NS2 did not diminish their TRAF3-reducing activity. Coimmunoprecipitation studies revealed that NS1 and NS2 form a heterodimer. Clearly, the NS proteins of RSV, working individually and together, regulate key signaling molecules of both the IFN activation and response pathways.
Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments

ABSTRACT Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase δ was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.
Active-Site Mutations in the South African Human Immunodeficiency Virus Type 1 Subtype C Protease Have a Significant Impact on Clinical Inhibitor Binding: Kinetic and Thermodynamic Study

ABSTRACT Human immunodeficiency virus (HIV) infections in sub-Saharan Africa represent about 56% of global infections. Study of active-site mutations (the V82A single mutation and the V82F I84V double mutation) in the less-studied South African HIV type 1 subtype C (C-SA) protease indicated that neither mutation had a significant impact on the proteolytic functioning of the protease. However, the binding affinities of, and inhibition by, saquinavir, ritonavir, indinavir, and nelfinavir were weaker for each variant than for the wild-type protease, with the double mutant exhibiting the most dramatic change. Therefore, our results show that the C-SA V82F I84V double mutation decreased the binding affinities of protease inhibitors to levels significantly lower than that required for effective inhibition.
Human Resources Information Systems (HRIS) for military domain - a conceptual framework

Human Resources Information Systems (HRIS) plays an important role for any organisation to effectively manage its human assets. In military domain, HRIS is particularly crucial as the organisation comprises a huge number of personnel who not only possess various skill sets but also are physically scattered at remote locations. Military operations in essence require the selection of right personnel for right tasks during troop deployment in the battlefield. Right selection is very critical as in war there is no second prize for the runner up. As the selection is normally based on the information in HRIS, the system must incorporate the necessary elements of military operations in order to suit the needs and goals of the organisation. This paper discusses the factors that contribute to the success of HRIS implementation for military domain. The factors form a HRIS framework that integrates three important elements in military, namely people, process, product. The framework was proposed based on literature review as well as field study that used interviews and observations techniques as the instruments. The sampling frame consisted of fifteen members of HRIS users from military domain. The data were analysed by using qualitative method. The framework can guide future military HRIS implementation that support armed forces' work processes and needs.
Fast Approximate Joint Diagonalization Incorporating Weight Matrices

We propose a new low-complexity approximate joint diagonalization (AJD) algorithm, which incorporates nontrivial block-diagonal weight matrices into a weighted least-squares (WLS) AJD criterion. Often in blind source separation (BSS), when the sources are nearly separated, the optimal weight matrix for WLS-based AJD takes a (nearly) block-diagonal form. Based on this observation, we show how the new algorithm can be utilized in an iteratively reweighted separation scheme, thereby giving rise to fast implementation of asymptotically optimal BSS algorithms in various scenarios. In particular, we consider three specific (yet common) scenarios, involving stationary or block-stationary Gaussian sources, for which the optimal weight matrices can be readily estimated from the sample covariance matrices (which are also the target-matrices for the AJD). Comparative simulation results demonstrate the advantages in both speed and accuracy, as well as compliance with the theoretically predicted asymptotic optimality of the resulting BSS algorithms based on the weighted AJD, both on large scale problems with matrices of the size 100times100.
Rehabilitation following rotator cuff repair: a systematic review

Background The aim of this systematic review was to evaluate the effectiveness of rehabilitation programmes following surgical repair of the rotator cuff with emphasis upon length of immobilisation and timing of introduction of load. Methods An electronic search of CENTRAL, MEDLINE and PEDro was undertaken to August 2014 and supplemented by hand searching. Randomised controlled trials were included, quality appraised using the PEDro scale and synthesised via meta-analysis or narrative synthesis, based upon levels of evidence, where appropriate. Results Twelve studies were included. There is strong evidence that early initiation of rehabilitation does not adversely affect clinical outcome but there is a marginally higher, statistically non-significant, incidence of tendon re-tear (OR 1.3; 95% CI 0.72 to 2.2). There is strong evidence that initiation of functional loading early in the rehabilitation programme does not adversely affect clinical outcome. Discussion Concern about early initiation of rehabilitation and introduction of gradual functional load does not appear warranted but this should be considered in a context of potential for Type II error. There is further need to evaluate approaches that foster early initiation of rehabilitation and gradual introduction of functional load as well as considering key outcomes such as return to work.
The caring partnership: Staff and families of persons institutionalized with Alzheimer's disease

This article has set forth a strategy to increase family/staff cooperation in the care of persons institutionalized with AD. The FIC program was developed as an outgrowth of research that demonstrated family member dissatisfaction with their roles. It is specifically designed to provide a partnership role with staff for families whose relatives with AD are institutionalized. Hypothesized outcomes include the reduction of stress in caregiving, increased satisfaction in role and improved patient cognitive and functional outcomes. Testing of the FIC is currently underway.
rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming

ABSTRACT Primary infection of a plant with a pathogen that causes high accumulation of salicylic acid in the plant typically via a hypersensitive response confers enhanced resistance against secondary infection with a broad spectrum of pathogens, including viruses. This phenomenon is called systemic acquired resistance (SAR), which is a plant priming for adaption to repeated biotic stress. However, the molecular mechanisms of SAR-mediated enhanced inhibition, especially of virus infection, remain unclear. Here, we show that SAR against cucumber mosaic virus (CMV) in tobacco plants (Nicotiana tabacum) involves a calmodulin-like protein, rgs-CaM. We previously reported the antiviral function of rgs-CaM, which binds to and directs degradation of viral RNA silencing suppressors (RSSs), including CMV 2b, via autophagy. We found that rgs-CaM-mediated immunity is ineffective against CMV infection in normally growing tobacco plants but is activated as a result of SAR induction via salicylic acid signaling. We then analyzed the effect of overexpression of rgs-CaM on salicylic acid signaling. Overexpressed and ectopically expressed rgs-CaM induced defense reactions, including cell death, generation of reactive oxygen species, and salicylic acid signaling. Further analysis using a combination of the salicylic acid analogue benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and the Ca2+ ionophore A23187 revealed that rgs-CaM functions as an immune receptor that induces salicylic acid signaling by simultaneously perceiving both viral RSS and Ca2+ influx as infection cues, implying its autoactivation. Thus, secondary infection of SAR-induced tobacco plants with CMV seems to be effectively inhibited through 2b recognition and degradation by rgs-CaM, leading to reinforcement of antiviral RNA silencing and other salicylic acid-mediated antiviral responses. IMPORTANCE Even without an acquired immune system like that in vertebrates, plants show enhanced whole-plant resistance against secondary infection with pathogens; this so-called systemic acquired resistance (SAR) has been known for more than half a century and continues to be extensively studied. SAR-induced plants strongly and rapidly express a number of antibiotics and pathogenesis-related proteins targeted against secondary infection, which can account for enhanced resistance against bacterial and fungal pathogens but are not thought to control viral infection. This study showed that enhanced resistance against cucumber mosaic virus is caused by a tobacco calmodulin-like protein, rgs-CaM, which detects and counteracts the major viral virulence factor (RNA silencing suppressor) after SAR induction. rgs-CaM-mediated SAR illustrates the growth versus defense trade-off in plants, as it targets the major virulence factor only under specific biotic stress conditions, thus avoiding the cost of constitutive activation while reducing the damage from virus infection.
Review: Beyond KRAS: perspectives on new potential markers of intrinsic and acquired resistance to epidermal growth factor receptor inhibitors in metastatic colorectal cancer

The monoclonal antibodies cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), are licensed for the treatment of KRAS wild-type metastatic colorectal cancer (mCRC). Such ‘molecular restriction’ derived from post-hoc analyses of randomized trials and from other retrospective series all indicate how tumors bearing KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations are resistant to EGFR inhibition. Even if highly sensitive for nonresponse, KRAS testing is not very specific. In fact, a limited but still considerable proportion of KRAS wild-type patients rapidly progress on treatment with an EGFR inhibitor. New potential molecular determinants of benefit from such treatment are under investigation and may further refine the selection of patients. Pharmacogenomic analyses and translational studies are also ongoing for exploring the field of acquired resistance to anti-EGFRs, since all patients eventually progress. New biological data are awaited for optimizing the use of molecular agents in colorectal cancer and for identifying promising targets that could allow to better understand and, potentially, overcome mechanisms of primary or secondary resistance to EGFR inhibitors.
An Efficient Morphological Reversible Contour/Edge Representation Using Overlapping Line Components

The paper proposes a new morphological reversible contour/edge representation algorithm for the representation of 2D binary shapes of digital images. The concise representation algorithm uses representative lines of different sizes and types to cover all the significant features of the binary contour/edge image. These well-characterized representative line segments, which may overlap among different types, take minimum representative points than that of most other prominent shape representation algorithms including MST and MSD. The new algorithm is computationally efficient than most other algorithms in the literature and is also capable of approximating edge images. The approximated outputs produced by the proposed algorithm by using minimal number of representative points are more natural to the original shapes than that of MST and MSD.
Cramér-Rao Lower Bounds on Covariance Matrix Estimation for Complex Elliptically Symmetric Distributions

This paper introduces the Cramér-Rao Lower Bounds (CRLBs) for the scatter matrix of Complex Elliptically Symmetric distributions and compares them to the performance of the (constrained-)ML estimators in the particular cases of complex Gaussian, Generalized Gaussian (GG) and t-distributed observation vectors. Numerical results confirm the goodness of the ML estimators and the advantage of taking into proper account a constraint on the matrix trace for small data size. The work is completed with the comparison with the performance of Tyler's matrix estimator that shows a very robust behavior in almost all the analyzed cases and with the CRLBs for the Complex Angular Elliptical distributions, whose Tyler's estimator is the ML one.
Adenovirus E1A Activation Domain Regulates H3 Acetylation Affecting Varied Steps in Transcription at Different Viral Promoters

Despite a wealth of data associating promoter and enhancer region histone N-terminal tail lysine acetylation with transcriptional activity, there are relatively few examples of studies that establish causation between these histone posttranslational modifications and transcription. While hypoacetylation of histone H3 lysines 18 and 27 is associated with repression, the step(s) in the overall process of transcription that is blocked at a hypoacetylated promoter is not clearly established in most instances. Studies presented here confirm that the adenovirus 2 large E1A protein activation domain interacts with p300, as reported previously (P. Pelka, J. N. G. Ablack, J. Torchia, A. S. Turnell, R. J. A. Grand, J. S. Mymryk, Nucleic Acids Res 37:1095–1106, 2009, https://doi.org/10.1093/nar/gkn1057), and that the resulting acetylation of H3K18/27 affects varied steps in transcription at different viral promoters. ABSTRACT How histone acetylation promotes transcription is not clearly understood. Here, we confirm an interaction between p300 and the adenovirus 2 large E1A activation domain (AD) and map the interacting regions in E1A by observing colocalization at an integrated lacO array of fusions of LacI-mCherry to E1A fragments with YFP-p300. Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. The results indicate that this E1A interaction with p300 is required for H3K18 and H3K27 acetylation at the E2early, E3, and E4 promoters and is required for TBP and Pol II association with the E2early promoter. In contrast, H3K18/27 acetylation was not required for TBP and Pol II association with the E3 and E4 promoters but was required for E4 transcription at a step subsequent to Pol II preinitiation complex assembly. IMPORTANCE Despite a wealth of data associating promoter and enhancer region histone N-terminal tail lysine acetylation with transcriptional activity, there are relatively few examples of studies that establish causation between these histone posttranslational modifications and transcription. While hypoacetylation of histone H3 lysines 18 and 27 is associated with repression, the step(s) in the overall process of transcription that is blocked at a hypoacetylated promoter is not clearly established in most instances. Studies presented here confirm that the adenovirus 2 large E1A protein activation domain interacts with p300, as reported previously (P. Pelka, J. N. G. Ablack, J. Torchia, A. S. Turnell, R. J. A. Grand, J. S. Mymryk, Nucleic Acids Res 37:1095–1106, 2009, https://doi.org/10.1093/nar/gkn1057), and that the resulting acetylation of H3K18/27 affects varied steps in transcription at different viral promoters.
TEST FOR INCOMPETENT COMMUNICATING BRANCHES IN THE SURGICAL TREATMENT OF VARICOSE VEINS

Before one decides which type of treatment the patient who has varicose veins is to undergo, certain tests must be performed. These are: 1. Test for the adequacy of the arterial circulation: The history of arterial competence, freedom from rubor on dependence or pallor on elevation, the palpation of the dorsalis pedis and posterior tibial arteries and the oscillometric readings. 2. Tests for the adequate functioning of the deep venous circulation (modified Perthes test): The leg is elevated and the veins are emptied. A tourniquet is applied to the upper thigh to constrict the saphenous vein return flow. The patient then walks around the room for five minutes. Absence of pain in the calf or definite swelling of the foot and ankle indicates patent deep veins. 3. Test for competence of the saphenous femoral valve (modified Trendelenburg test): The leg is elevated and the veins are emptied. The tourniquet is
Clinical Effects of Brown Seaweed, Undaria pinnatifida (wakame), on Blood Pressure in Hypertensive Subjects

This was conducted to examine the effects of brown seaweed (wakame) on blood pressure and serum biochemical parameters in hypertensive subjects. Of the 37 elderly out-patients with hypertension who started the study, 36 of them completed it. This study was a randomly assigned, case-controlled one. Nineteen patients received a daily dose of 5g of dried wakame powder packed in 12 capsules. Eighteen gender-matched subjects with age difference±2 years, and starting time of participation within±2 weeks, were selected as the control group. Patients visited the clinic every 4 weeks. The observation period was 8 weeks. In the wakame group, the average amount of wakame ingested was 3.3g. The systolic blood pressure (SBP) in this group dropped 13mmHg below the baseline (p<0.01) after 4 weeks, and 8mmHg (p<0.05) after 8 weeks. The diastolic blood pressure (DBP) decreased by 9mmHg (p<0.01) after 4 weeks and by 8mmHg (p<0.05) after 8 weeks. In the control group, no significant changes were seen in either SBP or DBP. However, the differences in reduction in SBP and DBP were significant between the wakame and control groups. Regarding clinical chemistry data, hypercholesterolemia in the wakame group decreased by 8% after 4 weeks. No other abnormal changes were observed in either group. We conclude that wakame has beneficial effects as a supplemental regimen in the treatment of hypertension.
p53 Is a Host Cell Regulator during Herpes Simplex Encephalitis

ABSTRACT p53 is a critical host cell factor in the cellular response to a broad range of stress factors. We recently reported that p53 is required for efficient herpes simplex virus 1 (HSV-1) replication in cell culture. However, a defined role for p53 in HSV-1 replication and pathogenesis in vivo remains elusive. In this study, we examined the effects of p53 on HSV-1 infection in vivo using p53-deficient mice. Following intracranial inoculation, p53 knockout reduced viral replication in the brains of mice and led to significantly reduced rates of mortality due to herpes simplex encephalitis. These results suggest that p53 is an important host cell regulator of HSV-1 replication and pathogenesis in the central nervous system (CNS). IMPORTANCE HSV-1 causes sporadic cases of encephalitis, which, even with antiviral therapy, can result in severe neurological defects and even death. Many host cell factors involved in the regulation of CNS HSV-1 infection have been investigated using genetically modified mice. However, most of these factors are immunological regulators and act via immunological pathways in order to restrict CNS HSV-1 infection. They therefore provide limited information on intrinsic host cell regulators that may be involved in the facilitation of CNS HSV-1 infection. Here we demonstrate that a host cell protein, p53, which has generally been considered a host cell restriction factor for various viral infections, is required for efficient HSV-1 replication and pathogenesis in the CNS of mice. This is the first report showing that p53 positively regulates viral replication and pathogenesis in vivo and provides insights into its molecular mechanism, which may suggest novel clinical treatment options for herpes simplex encephalitis.