Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations

According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity

Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats

Painful stimuli during neonatal stage may affect brain development and contribute to abnormal behaviors in adulthood. Very few specific therapies are available for this developmental disorder. A better understanding of the mechanisms and consequences of painful stimuli during the neonatal period is essential for the development of effective therapies. In this study, we examined brain reactions in a neonatal rat model of peripheral inflammatory pain. We focused on the inflammatory insult-induced brain responses and delayed changes in behavior and pain sensation. Postnatal day 3 pups received formalin injections into the paws once a day for 3 days. The insult induced dysregulation of several inflammatory factors in the brain and caused selective neuronal cell death in the cortex, hippocampus and hypothalamus. On postnatal day 21, rats that received the inflammatory nociceptive insult exhibited increased local cerebral blood flow in the somatosensory cortex, hyperalgesia, and decreased exploratory behaviors. Based on these observations, we tested recombinant human erythropoietin (rhEPO) as a potential treatment to prevent the inflammatory pain-induced changes. rhEPO treatment (5,000 U/kg/day, i.p.), coupled to formalin injections, ameliorated neuronal cell death and normalized the inflammatory response. Rats that received formalin plus rhEPO exhibited normal levels of cerebral blood flow, pain sensitivity and exploratory behavior. Treatment with rhEPO also restored normal brain and body weights that were reduced in the formalin group. These data suggest that severe inflammatory pain has adverse effects on brain development and rhEPO may be a possible therapy for the prevention and treatment of this developmental disorder

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

The contribution of virtual enterprises to competence-based learning: an assessment from the students’ perspective: Case study

The use of virtual enterprises has evolved from secondary, vocational and professional education to the university level, becoming in recent times a relevant experiential e-learning tool based on the simulation of the functioning of a company. The purpose of this study is to analyze the perspective of students taking part in virtual enterprises about their acquisition of generic and specific managerial skills fostered by this e-learning methodology. We analyzed data of 76 students from Faculties of Business and Economics, who had participated during the academic year 2014-2015 in a virtual company during the development of their degrees at two different Italian universities, University of Bologna and Parma. Our results show that the most valued generic skills were related to the capacity of learning and adaptation, problem solving and teamwork, whilst the least valued ones were related to the skills of communication and interaction with people of other countries and cultures. In the case of specific managerial skills, the most valued ones were about understanding managerial concepts and the role and functions of economic agents, and the least valued were skills related to providing managerial advice, dealing with risks and analyzing financial statements. Besides, the analyses conducted to determine the existence of a learning profile in the students reveal that the skills acquired were quite similar, not being affected by the students’ gender or the economic activity developed by the virtual enterprise. This study makes a contribution in terms of the effectiveness of virtual enterprises for competence-based learning

Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells

Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs

Evidence for the Decay D0→K+π−π+π−D^0\to K^+ \pi^-\pi^+\pi^-

We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9 fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay can occur either through a doubly Cabibbo-suppressed process or through mixing to a D0bar followed by a Cabibbo-favored process. Our result for the time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is (0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space), which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays

We have measured the first and second moments of the hadronic mass-squared distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 - M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170 GeV^4, where M_D[Bar] is the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| = 0.0404 +- 0.0013.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Observation of the Ωc0\Omega_{c}^{0} Charmed Baryon at CLEO

The CLEO experiment at the CESR collider has used 13.7 fb$^{-1}$ of data to search for the production of the $\Omega_c^0$ (css-ground state) in $e^{+}e^{-}$ collisions at $\sqrt{s} \simeq 10.6$ {\rm GeV}. The modes used to study the $\Omega_c^0$ are $\Omega^- \pi^+$, $\Omega^- \pi^+ \pi^0$, $\Xi^- K^- pi^+ \pi^+$, $\Xi^0 K^- pi^+$, and $\Omega^- \pi^+ \pi^- \pi^+$. We observe a signal of 40.4$\pm$9.0(stat) events at a mass of 2694.6$\pm$2.6(stat)$\pm$1.9(syst) {\rm MeV/$c^2$}, for all modes combined.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

Background and Objectives: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study

Observation of B→ϕKB\to \phi K and B→ϕK∗B\to \phi K^{*}

We have studied two-body charmless hadronic decays of $B$ mesons into the final states phi K and phi K^*. Using 9.7 million $B\bar{B}$ pairs collected with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0 with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6) x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the statistical significance is not overwhelming for these modes we determine upper limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN