Interaction Study of MADS-Domain Proteins in Tomato

MADS-domain proteins are important transcription factors involved in many biological processes of plants. Interactions between MADS-domain proteins are essential for their functions. In tomato (Solanum lycopersicum), the number of MIKCc-type MADSdomain proteins identified has totalled 36, but a largescale interaction assay is lacking. In this study, 22 tomato MADS-domain proteins were selected from six functionally important subfamilies of the MADS-box gene family, to create the first large-scale tomato protein interaction network. Compared with Arabidopsis and petunia (Petunia hybrida), protein interaction patterns in tomato displayed both conservation and divergence. The majority of proteins that can be identified as putative orthologues exhibited conserved interaction patterns, and modifications were mostly found in genes underlining traits unique to tomato. JOINTLESS and RIN, characterized for their roles in abscission zone development and fruit ripening, respectively, showed enlarged interaction networks in comparison with their Arabidopsis and petunia counterparts. Novel interactions were also found for members of the expanded subfamilies, such as those represented by AP1/FUL and AP3/PI MADS-domain proteins. In search for higher order complexes, TM5 was found to be the preferred bridge among the five SEP-like proteins. Additionally, 16 proteins with the MADS-domain removed were used to assess the role of the MADS-domain in protein–protein interactions. The current work provides important knowledge for further functional and evolutionary study of the MADSbox genes in tomato

Spontaneous expectoration of pulmonary metastases in a child with osteogenic sarcoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148355/1/pbc27611.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148355/2/pbc27611_am.pd

A phase I trial of the trifunctional anti Her2 × anti CD3 antibody ertumaxomab in patients with advanced solid tumors

Background: Ertumaxomab (ertu) is a bispecific, trifunctional antibody targeting Her2/neu, CD3 and the Fcγ-receptors I, IIa, and III forming a tri-cell complex between tumor cell, T cell and accessory cells. Methods: Patients (pts) with Her2/neu (1+/SISH positive, 2+ and 3+) expressing tumors progressing after standard therapy were treated to investigate safety, tolerability and preliminary efficacy. In this study, ertu was applied i.v. in 2 cycles following a predefined dose escalating scheme. Each cycle consisted of five ascending doses (10–500 μg) applied weekly within 28 days with a 21 day treatment-free interval. If 2 pts experienced a dose limiting toxicity (DLT) at a given dose level, the maximum tolerated dose (MTD) had been exceeded. Results: Fourteen heavily pretreated pts (e.g. breast, rectal, gastric cancer) were enrolled in the four main cohorts. Three (21 %) pts had to be replaced. Two serious adverse events (SAE) with possible relation to the investigational drug were seen, both fully reversible. A DLT was not detected. Consequently, the MTD could not be determined. All adverse events (AE) were transient and completely reversible. Most frequent AEs were fatigue (14/14), pain (13/14), cephalgia (12/14), chills (11/14), nausea (8/14), fever (7/14), emesis (7/14) and diarrhea (5/14). Single doses up to 300 μg were well tolerated (total dose up to 800 μg per cycle). We observed one partial remission and two disease stabilizations after first treatment cycle. Conclusions: Single doses up to 300 μg could be safely administered in an escalating dose scheme. Immunological responses and clinical activity warrant further evaluation in patients with Her2 over expressing tumors. Trial registration EudraCT number: 2011-003201-14; ClinicalTrials.gov identifier: NCT0156941

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

Immunotherapy with FBTA05 (Bi20), a trifunctional bispecific anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion (DLI) in relapsed or refractory B-cell lymphoma after allogeneic stem cell transplantation: study protocol of an investigator-driven, open-label, non-randomized, uncontrolled, dose-escalating Phase I/II-trial

BACKGROUND: Patients with B cell malignancies refractory to allogeneic stem cell transplantation (SCT) can be treated by subsequent immunotherapy with donor lymphocyte infusions (DLI). But unlike myeloid leukemia, B cell leukemia and lymphoma are less sensitive to allogeneic adoptive immunotherapy. Moreover, the beneficial graft-versus-lymphoma (GVL) effect may be associated with moderate to severe graft-versus-host disease (GVHD). Thus, novel therapeutic approaches augmenting the anti-tumor efficacy of DLI and dissociating the GVL effect from GVHD are needed. The anti-CD20 x anti-CD3 trifunctional bispecific antibody (trAb) FBTA05 may improve the targeting of tumor cells by redirecting immune allogeneic effector cells while reducing the risk of undesirable reactivity against normal host cells. Hence, FBTA05 may maximize GVL effects by simultaneously decreasing the incidence and severity of GVHD. METHODS/DESIGN: Based on this underlying treatment concept and on promising data taken from preclinical results and a small pilot study, an open-label, non-randomized, uncontrolled, dose-escalating phase I/II-study is conducted to evaluate safety and preliminary efficacy of the investigational antibody FBTA05 in combination with DLI for patients suffering from rituximab- and/or alemtuzumab-refractory, CD20-positive low- or high-grade lymphoma after allogeneic SCT. During the first trial phase with emphasis on dose escalation a maximum of 24 patients distributed into 4 cohorts will be enrolled. For the evaluation of preliminary efficacy data a maximum of 12 patients (6 patients with low-grade lymphoma and/or Chronic Lymphocytic Leukemia (CLL) / 6 patients with high-grade or aggressive lymphoma) will attend the second phase of this clinical trial. DISCUSSION: Promising data (e.g. induction of cellular immunity; GVL predominance over GVHD; achievement of partial or complete responses; prolongation of time-to-progression) obtained from this phase I/II trial would represent the first milestone in the clinical evaluation of a novel immunotherapeutic concept for treatment-resistant low- and high-grade lymphoma and NHL patients in relapse. TRIAL REGISTRATION: NCT0113857

Rupture process of large earthquakes in the northern Mexico subduction zone

The Cocos plate subducts beneath North America at the Mexico trench. The northernmost segment of this trench, between the Orozco and Rivera fracture zones, has ruptured in a sequence of five large earthquakes from 1973 to 1985; the Jan. 30, 1973 Colima event ( M s 7.5) at the northern end of the segment near Rivera fracture zone; the Mar. 14, 1979 Petatlan event ( M s 7.6) at the southern end of the segment on the Orozco fracture zone; the Oct. 25, 1981 Playa Azul event ( M s 7.3) in the middle of the Michoacan “gap”; the Sept. 19, 1985 Michoacan mainshock ( M s 8.1); and the Sept. 21, 1985 Michoacan aftershock ( M s 7.6) that reruptured part of the Petatlan zone. Body wave inversion for the rupture process of these earthquakes finds the best: earthquake depth; focal mechanism; overall source time function; and seismic moment, for each earthquake. In addition, we have determined spatial concentrations of seismic moment release for the Colima earthquake, and the Michoacan mainshock and aftershock. These spatial concentrations of slip are interpreted as asperities; and the resultant asperity distribution for Mexico is compared to other subduction zones. The body wave inversion technique also determines the Moment Tensor Rate Functions ; but there is no evidence for statistically significant changes in the moment tensor during rupture for any of the five earthquakes. An appendix describes the Moment Tensor Rate Functions methodology in detail.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43169/1/24_2004_Article_BF00875970.pd

Notes upon the emotionality of a schizophrenic patient and its relation to problems of technique

It seems justifiable to inquire into the specific factors which make the emotionality of a schizophrenic patient different from that of other patients and to investigate to what extent this specificity of schizophrenic emotionality might require specific changes in the psychoanalytic technique. Although I do not think that this paper can really live up to the full requirements of such an ambitious undertaking, it nevertheless may contribute modestly to it. My speculations began during a phase of the treatment of a schizophrenic patient; long after her acute condition had subsided I thought I observed-within clinically pertinent areas-a specific relationship between the patient's ego structure and her emotions. It seems to me that this relationship might allow generalization in terms of a basic defect with which a schizophrenic patient has to struggle, although in various phases of the disease and of the treatment the phenomenology of schizophrenic emotionality differs unquestionably in significant aspects. However, before delving into the subject matter, a few general points must be raised in reference to the psychoanalytic theory of emotions