Regulatory T Cells: Potential Target in Anticancer Immunotherapy

SummaryThe concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed

Structural and Electronic Properties of Small Neutral (MgO)n Clusters

Ab initio Perturbed Ion (PI) calculations are reported for neutral stoichiometric (MgO)n clusters (n<14). An extensive number of isomer structures was identified and studied. For the isomers of (MgO)n (n<8) clusters, a full geometrical relaxation was considered. Correlation corrections were included for all cluster sizes using the Coulomb-Hartree-Fock (CHF) model proposed by Clementi. The results obtained compare favorably to the experimental data and other previous theoretical studies. Inclusion of correlaiotn is crucial in order to achieve a good description of these systems. We find an important number of new isomers which allows us to interpret the experimental magic numbers without the assumption of structures based on (MgO)3 subunits. Finally, as an electronic property, the variations in the cluster ionization potential with the cluster size were studied and related to the structural isomer properties.Comment: 24 pages, LaTeX, 7 figures in GIF format. Accepted for publication in Phys. Rev.

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Structural Transitions and Global Minima of Sodium Chloride Clusters

In recent experiments on sodium chloride clusters structural transitions between nanocrystals with different cuboidal shapes were detected. Here we determine reaction pathways between the low energy isomers of one of these clusters, (NaCl)35Cl-. The key process in these structural transitions is a highly cooperative rearrangement in which two parts of the nanocrystal slip past one another on a {110} plane in a direction. In this way the nanocrystals can plastically deform, in contrast to the brittle behaviour of bulk sodium chloride crystals at the same temperatures; the nanocrystals have mechanical properties which are a unique feature of their finite size. We also report and compare the global potential energy minima for (NaCl)NCl- using two empirical potentials, and comment on the effect of polarization.Comment: extended version, 13 pages, 8 figures, revte

Novel transparent nanocomposite films based on chitosan and bacterial cellulose

New nanocomposite films based on different chitosan matrices (two chitosans with different DPs and one water soluble derivative) and bacterial cellulose were prepared by a fully green procedure by casting a water based suspension of chitosan and bacterial cellulose nanofibrils. The films were characterized by several techniques, namely SEM, AFM, X-ray diffraction, TGA, tensile assays and visible spectroscopy. They were highly transparent, flexible and displayed better mechanical properties than the corresponding unfilled chitosan films. These new renewable nanocomposite materials also presented reasonable thermal stability and low O(2) permeability.FCT - SFRH/BD/41388/ 2007FCT - SFRH/BPD/38515/200

Primary angiosarcoma of the ovary with prominent fibrosis of the ovarian stroma. Case report of an 81-year old patient

Primary angiosarcoma of the ovary (AS) is a rare entity with only 31 reported cases. The majority are pure angiosarcomas, the remainder are associated either with teratomas or conventional epithelial tumors. More than 50% of ovarian AS are disseminated at the time of diagnosis, the minority is detected in stage I. The prognosis of ovarian angiosarcoma in general is poor. Most reports refer to younger individuals, aged from 7 to 46 years, and only 2 case reports could be found for patients older than 64 years. Here we present a very unusual case of angiosarcoma in a 81-year-old patient

Association of HLA class I with severe acute respiratory syndrome coronavirus infection

BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results