Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Targeting of Nuclear γ-Tubulin in RB1-Negative Tumors

In addition to its cytosolic function, γ-tubulin is a chromatin-associated protein. Reduced levels of nuclear γ-tubulin increase the activity of E2 promoter-binding factors (E2F) and raise the levels of retinoblastoma (RB1) tumor suppressor protein. In tumor cells lacking RB1 expression, decreased γ-tubulin levels induce cell death. Consequently, impairment of the nuclear activity of γ-tubulin has been suggested as a strategy for targeted chemotherapy of RB1-deficient tumors; thus, tubulin inhibitors were tested to identify compounds that interfere with γ-tubulin. Interestingly, citral increased E2F activity but impaired microtubule dynamics while citral analogues, such citral dimethyl acetal (CDA), increased E2F activity without affecting microtubules. The cytotoxic effect of CDA on tumor cells was attenuated by increased expression of either RB1 or γ-tubulin, and increased by reduced levels of either RB1 or γ-tubulin. Mechanistic study, in silico and in vitro, demonstrated that CDA prevents GTP binding to γ-tubulin and suggested that the FDA-approved drug dimethyl fumarate is also a γ-tubulin inhibitor. Finally, in vivo growth of xenograft tumors carrying defects in the RB1 signaling pathway were inhibited by CDA treatment. These results demonstrate that inhibition of γ-tubulin has the potential to specifically target tumor cells and may aid in the design of safer and more efficient chemotherapeutic regimes. Implications: The in vivo antitumorigenic activity of γ-tubulin inhibitors paves the way for the development of a novel broad range targeted anticancer therapy that causes fewer side effects. Mol Cancer Res; 13(7); 1073–82. ©2015 AACR.
Isolation and cloning of human progesterone receptor isoform-b in CMV-eGFP vector

The progesterone receptor is a type of protein present inside cells, which is activated by the hormone progesterone (type of steroid hormone). In humans, a single PGR gene found on chromosome 11q22 encodes progesterone. There are two main types, A and B the difference lies in their molecular weight. Progesterone receptor isoform B functions tissue-specifically to mediate reproductive functions of progesterone in the present study we did cloning of progesterone receptor isoform B in expression vector CMV-eGFP. Gene cloning provides information about nucleotide sequence. Other motive of this is to manipulate the gene in various ways like genetic transformation. Genomic DNA was isolated from human blood. For cloning of PR-B and CMV-eGFP, restriction and ligation were done using appropriate conditions and concentrations. The resulting DNA was transformed into host organism (E.coli, DH5α). These were grown on kanamycin resistant agar plated. Colonies containing ligated PR-B with plasmid were then screened, purified and analysed using standard protocol. The desired CMV-eGFPC1-PR-B construct of 7523bp was obtained and stored at -20 o C.
Immune-mediated and lipid-mediated platelet function in atherosclerosis

Purpose of review Cardiovascular disease (CVD) is the leading cause of death and morbidity worldwide. Detailed knowledge of the mechanisms of atherosclerosis, the main underlying disease of CVD, will enable improved preventive and therapeutic options, thus potentially limiting the burden of vascular disease in aging societies. A large body of evidence illustrates the contribution of platelets to processes beyond their traditionally recognized role as mediators in thrombosis and hemostasis. Recent advances in molecular biology help to understand the complexity of atherosclerosis. Recent findings This article outlines the role of platelets as modulators of immune responses in the context of atherosclerosis. It provides a short overview of interactions between platelets and endothelial cells or immune cells via direct cell contact or soluble factors during atherogenesis. By means of some well examined, exemplary pathways (e.g. CD40/CD40L dyad), this article will discuss recent discoveries in immune-related function of platelets. We also focus on the relationship between platelets and the lipid metabolism highlighting potential consequences to atherosclerosis and dyslipidemia. Summary A better understanding of the molecular mechanisms of platelet-related immune activity allows their utilization as powerful diagnostic tools or targets of therapeutic intervention. Those findings might help to develop new classes of drugs which may supplement or replace classical anticoagulants and help clinicians to tackle CVD more efficiently.
Oxytocin Administered Centrally Facilitates Formation of a Partner Preference in Female Prairie Voles (Microtus ochrogaster)

Prairie voles (Microtus ochrogaster) are monogamous mammals that form male‐female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male‐female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimulation. Oxytocin has been implicated in mother‐infant bond formation. The present study tested the hypothesis that oxytocin participates in the partner preference component of pair bond formation in adult prairie voles. Ovariectomized female prairie voles were implanted with osmotic mini‐pumps releasing oxytocin (1–100 ng/h) or artificial cerebrospinal fluid (CSF). Pumps were implanted intracerebroventricularly or subcutaneously and females then were housed for 6 h with a male partner, followed by a preference test in which females could elect to spend time with either the partner or an unfamiliar male. Females in groups that received centrally‐administered oxytocin (10 or 100 ng/h), but not CSF, exhibited a significant preference for the partner present during infusion. The induction of a partner preference after oxytocin administration appeared specific for central oxytocin pathways as peripheral oxytocin administration was ineffective. Moreover, central administration of a selective oxytocin receptor antagonist inhibited the behavioral effect of exogenous oxytocin. These results suggest that oxytocin may be one factor contributing to the development of partner preferences in this monogamous rodent.
Human Cytomegalovirus Replicates Abortively in Polymorphonuclear Leukocytes after Transfer from Infected Endothelial Cells via Transient Microfusion Events

ABSTRACT Using a recently developed model for in vitro generation of pp65-positive polymorphonuclear leukocytes (PMNLs), we demonstrated that PMNLs from immunocompetent subjects may harbor both infectious human cytomegalovirus (HCMV) and viral products (pp65, p72, DNA, and immediate-early [IE] and pp67 late mRNAs) as early as 60 min after coculture with human umbilical vein endothelial cells (HUVEC) or human embryonic lung fibroblasts (HELF) infected with a clinical HCMV isolate (VR6110) or other wild-type strains. The number of PMNLs positive for each viral parameter increased with coculture time. Using HELF infected with laboratory-adapted HCMV strains, only very small amounts of viral DNA and IE and late mRNAs were detected in PMNLs. A cellular mRNA, the vascular cell adhesion molecule-1 mRNA, which is abundantly present in both infected and uninfected HUVEC, was detected in much larger amounts in PMNLs cocultured with VR6110-infected cells than in controls. Coculture of PMNLs with VR6110-infected permissive cells in the presence or absence of RNA, protein, and viral DNA synthesis inhibitors showed that only IE genes were transcribed in PMNLs during coculture. Synthesis of IE transcripts in PMNLs was also supported by the finding that only the copy number of IE mRNA (and not the DNA or the pp67 mRNA) per infected PMNL increased markedly with time, and the pp67 to IE mRNA copy number ratio changed from greater than 10 in infected HUVEC to less than 1 in cocultured PMNLs. Fluorescent probe transfer experiments and electron microscopy studies indicated that transfer of infectious virus and viral products from infected cells to PMNLs is likely to be mediated by microfusion events induced by wild-type strains only. In addition, HCMV pp65 and p72 were both shown to localize in the nucleus of the same PMNLs by double immunostaining. Two different mechanisms may explain the virus presence in PMNLs: (i) one major mechanism consists of transitory microfusion events (induced by wild-type strains only) of HUVEC or HELF and PMNLs with transfer of viable virus and biologically active viral material to PMNLs; and (ii) one minor mechanism, i.e., endocytosis, occurs with both wild-type and laboratory strains and leads to the acquisition of very small amounts of viral nucleic acids. In conclusion, HCMV replicates abortively in PMNLs, and wild-type strains and their products (as well as cellular metabolites and fluorescent dyes) are transferred to PMNLs, thus providing evidence for a potential mechanism of HCMV dissemination in vivo.
Perceived cervical cancer risk among women treated for high-grade cervical intraepithelial neoplasia: The importance of specific knowledge

Objective Women with high-grade cervical intraepithelial neoplasia (CIN) are at increased risk for developing cervical cancer. We examine how women with high-grade CIN perceive their own risk, and about pertinent knowledge concerning human high-risk papillomavirus (HPV), CIN and cervical cancer. Methods All patients who underwent first-time treatment of high-grade CIN (grade 2+) were followed-up at 6-months at the Karolinska University Hospital, Stockholm, Sweden and were invited to participate in the present study. This included completion of a questionnaire examining sociodemographic characteristics, self-perceived risk of cervical cancer without regular gynecologic follow-up, and 14 queries about HPV, CIN and cervical cancer knowledge, inter alia. Results The participation rate was 96.6%, with 479 women enrolled in this study. Over 75% were age 40 or younger, over half had completed university education. Most were married or co-living with their partner and were gainfully employed. On a scale scored from 10 (highest self-perceived risk of cervical cancer without regular gynecologic follow-up) to 1 (lowest self-perceived risk), 64% rated their risk ≥ 7; almost 30% viewed their risk ≤ 6 and 7.5% did not rate their risk. A Specific Knowledge Scale with six of the queries explained 58.3% of the total variance. Nearly 30% of the women answered four or fewer of the six queries correctly. The Specific Knowledge Scale predicted self-perceived cervical cancer risk (Odds ratio = 11.3, 95% Confidence Interval 5.6 − 22.6) after adjusting for age, income and education. Most of the women with low self-perceived cervical cancer risk did not rate their HPV-related knowledge as good. However, 32 predominantly university-educated women, with low self-perceived cervical cancer risk, considered their HPV-related knowledge good. Conclusion It is vital to effectively convey accurate information about these patients’ cervical cancer risk, needed preventive and follow-up measures, together with the relevant specific knowledge, for these women at increased risk for developing cervical cancer. Tailored programming to address these knowledge gaps is needed.
The impact of Involvement in CRM Initiative on Inter-functional Integration and Organizational Performance: Evidence from Pakistani Enterprises

Customer Relationship Management (CRM) is IT based system that manage customer long term relationship, and also inter-function relationship within the organization with the ultimate purpose of creating customer value by sharing concise, sufficient, accurate, reliable, and timely valuable information has greatly enhanced inter-functional integration (IFI) and organizational performance (OP). The purpose of this study is to examine the relationship among three constructs: 1) Involvement (IN) of marketing and IT departments in CRM initiative, 2) IFI, and 3) OP, and presents conceptual model based on this relationship in which involvement in CRM initiative can affect OP either directly or indirectly through IFI. Data collected based on online survey from 30 large companies in Pakistan are analyzed in accordance with research objectives by using correlation, descriptive statistics, simple linear regression and other statistical tools of SPSS. Research findings suggest that involvement in planning, implementation, and usage of CRM system has positive but no significant immediate effect on OP and instead that it improves OP via indirect significant and potential positive effect on IFI highlight the importance for management to endorse IFI and consider involvement of stakeholders in CRM initiative as enabler.
Screening and Brief Intervention in Primary Care Settings

Primary care practitioners are in a unique position to identify patients with potential alcohol problems and intervene when appropriate. Screening, the process by which practitioners can identify at-risk drinkers, can be followed by one-time or repeated short counseling sessions, known as brief interventions, which are designed to help the patient reduce drinking and minimize related problems. Varied levels of screening and brief intervention can be implemented in the primary care setting, depending on patient and physician factors. Although screening and brief intervention are valuable tools, they are underutilized in primary care practices. Strategies that may help increase physicians’ use of these techniques in the primary care setting include skills-based role-playing, performance feedback, clinical protocols, clinic-based education, and training by credible experts.
The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes

Objective: To measure the burden of infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) in the general population of England and Wales and to assess temporal changes in the incidence of HSV-1 infection in childhood. Methods: 4930 residual blood samples taken from people aged 0–69 years and submitted to 15 public health laboratories in England and Wales between January 1994 and June 1995, and 500 samples taken from people aged 10–14 years between November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV-2 using type specific ELISA assays. Results: The prevalence of antibody to HSV-1 in 10–14 year olds declined from 34% in samples collected in 1986–7 to 24% in samples collected in 1994–5 (p<0.001). HSV-1 antibody prevalence in adults increased with age and was higher in females than males, reaching 54% in females aged 25–30 years in 1994–5. In samples collected in 1994–5 from people aged 16–69 years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women. Conclusions: The incidence of HSV-1 infection in childhood is falling in England and Wales. The prevalence of HSV-2 infection in the general population is low, with the rate of infection significantly lower than that described for the general population in the United States and developing countries. The falling rate of HSV-1 infection in childhood may be one factor contributing to the increasing incidence of genital HSV-1 infection.
Paneth Cells in Intestinal Metaplasia of the Stomach and Duodenum of Man

The Paneth cells in intestinal metaplasia of stomach and the duodenum in human subjects were studied ultrastructurally, and the fine structures of these cells were compared. Paneth cells showed the ultrastructure of serozymogenic cells and secreted their secretory granules by merocrine process. The rod or tubular dense bodies were observed in the apical region of some Paneth cells. The structures may have some relation to the secretion of the secretory granules. The secretory granules with less dense layer in the periphery, which had never been described in the Paneth cell of man, were also observed. Morphologically intermediate cells between Paneth cell and goblet cell were found. Some of the Paneth cells might be phagocytized by undifferentiated crypt cells. The Paneth cells in intestinal metaplasia were fundamentally the same as those in duodenum at least in morphology. Difference between them was that Paneth cells with many phagolysosomes in the lower cytoplasm were observed more frequently in the duodenum than in intestinal metaplasia of the stomach. The physiological functions of the Paneth cell have been discussed. ACTA PATH. JAP. 27:677–695, 1977.
Application of ICHD-II Criteria for Headaches in a TMJ and Orofacial Pain Clinic

The aim of this study was to identify and diagnose headache in a temporomandibular joint and orofacial pain clinic population using the second edition of The International Classification of Headache Disorder criteria. In 502 temporomandibular disorder and orofacial pain patients, 246 patients (49%) were diagnosed with tension-type headache (TTH), followed by migraine without aura (14.5%), probable migraine (12.9%), migraine with aura (7%), probable TTH (4.8%) and cluster headache (0.2%). The prevalence of headaches was compared between male and female patients, and the prevalence of migraine was found to be higher in women than in men. In evaluating by age, the prevalence of migraine was highest in patients in their 20s and 30s and declined as age increased above 40. TTH showed the highest rate throughout all age groups, but it also decreased as age increased. In this study, the prevalence of migraine was lower than that reported in Dr Kim et al.'s study, and the prevalence of TTH much higher than that reported in the previous study. Of the headache patients, 81.1% presented with masseter muscle pain and 47.8% with temporal muscle pain. This finding suggests that pericranial muscle pain may be an inducing factor of primary headache.
WLC24-5: Adaptive Multi-Rate VoIP for IEEE 802.11 Wireless Networks with Link Adaptation Function

With the deployment of IEEE 802.11 wireless LANs, there is a strong requirement to support real-time applications with stringent QoS requirements on these networks. In order to improve the throughput in fluctuating wireless link conditions, IEEE 802.11 supports the link adaptation technique, which allows a wireless transmitter to select an appropriate transmission rate on a packet basis according to the wireless link conditions. However, if a lower transmission rate is selected because of deterioration of the wireless link conditions, packet delays and losses will be increased due to the poor bandwidth availability, especially when the traffic load is high, and as a result, the quality of real-time applications will significantly deteriorate. In this paper, we propose an adaptive multi-rate VoIP control scheme, which adapts the voice encoding rate and packetization interval according to the transmission rate in the PHY layer. We show that the proposed scheme achieves a significant improvement in the end-to-end delay and packet loss ratio of voice traffic in fluctuating wireless link conditions.
Five Empirical Essays on Corporate Taxation

This doctoral thesis presents five empirical essays on the impact of corporate taxes on companies’ decisions. All of its five papers are based on detailed and comprehensive micro datasets covering firm information of multinational companies. The five essays of this doctoral thesis analyze the tax impact on three of the most important decisions of corporations: the decision of how much to invest, the decision of how to finance such investments, and the decision of what group structures to embed the investments in. Three essays deal with the impact of taxes on investment and one essay each focuses on financing and on tax-induced group structuring. All five papers deal with corporate taxes. Three of them solely focus on the impact of profit taxes on corporations’ decisions, while the last two of them also take source taxes into account. Each of the five papers contains descriptive statistics and derives the tax hypotheses in detail. The five essays are titled as follows: 1. The Impact of Corporate Taxes on Investment 2. Investment Impact of Tax Loss Treatment 3. Empirical Evaluation of Interest Barrier Effects 4. The Impact of Tax Treaties and Repatriation Taxes on FDI Revisited 5. Form Follows Function? - Evidence on tax savings by multinational holding structures
Renal Failure in Mice with Gsα Deletion in Juxtaglomerular Cells

Background: Mice with deletion of Gsα in renin-producing cells (RC/FF mice) have been shown to have greatly reduced renin production and lack of responsiveness of renin secretion to acute stimuli. In addition, young RC/FF mice are hypotensive and have a vasopressin-resistant concentrating defect. In the present study we have determined the long-term effect on renal function, blood pressure, and renal pathology in this low renin and diuretic mouse model. Methods and Results: Urine osmolarity of RC/FF mice was decreased in all age groups. GFR measured at 7, 14 and 20 weeks of age declined progressively. Single nephron GFR similarly declined while fractional proximal fluid absorption was maintained. Expression levels of extracellular matrix proteins (collagen I, IV and fibronectin) and α-smooth muscle actin were increased in kidneys of RC/FF mice at 20 weeks, and this was accompanied by focal segmental glomerulosclerosis and periglomerular interstitial fibrosis. RC/FF mice showed a progressive reduction of body weight, an increase in urine albumin excretion, and an increase of blood pressure with aging. Conclusion: A chronic reduction of renin production in mice may be a risk factor in its own right, and does not protect renal function against the profibrotic influence of a chronically elevated urine flow.
Cloning and Characterization of PET100, a Gene Required for the Assembly of Yeast Cytochrome c Oxidase*

The biogenesis of cytochrome c oxidase in Saccharomyces cerevisiae requires a protein encoded by the nuclear gene, PET100. Cells carrying a recessive mutation (pet100-1) in PET100 are respiratory deficient and have reduced levels of cytochrome c oxidase activity. The PET100 gene has been cloned by complementation of pet100-1, sequenced and disrupted. PET100 is located adjacent to the PDC2 gene on chromosome IV and contains an open reading frame of 333 base pairs. The PET100 protein contains a possible membrane-spanning segment and a putative mitochondrial import sequence at its NH2 terminus. A strain carrying a null mutation in PET100 lacks cytochrome c oxidase activity and assembled cytochromes a and a3, but the other respiratory chain carriers are present. The respiratory-deficient phenotype of this strain is not rescued by added hemin or heme A. These findings indicate that the mutation is specific for cytochrome c oxidase and does not affect the biosynthesis of heme A. In addition, mitochondria from the strain carrying a null mutation in PET100 contain each of the subunit polypeptides of cytochrome c oxidase. Together, these findings suggest that PET100p is not required for the synthesis or localization of cytochrome c oxidase subunits to mitochondria, but is required at a later step in their assembly into an active holoenzyme.