Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis.

Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors.

Robust Fermi-Surface Morphology of CeRhIn_{5} across the Putative Field-Induced Quantum Critical Point.

We report a comprehensive de Haas-van Alphen (dHvA) study of the heavy-fermion material CeRhIn_{5} in magnetic fields up to 70 T. Several dHvA frequencies gradually emerge at high fields as a result of magnetic breakdown. Among them is the thermodynamically important β_{1} branch, which has not been observed so far.

Biochemical, cellular and structural characterization of novel and selective ERK3 inhibitors.

Triazolo[4,5-d]pyrimidin-5-amines were identified from kinase selectivity screening as novel ERK3 inhibitors with sub-100 nanomolar potencies in a biochemical assay using MK5 as substrate and with an attractive kinase selectivity profile. ERK3 crystal structures clarified the inhibitor binding mode in the ATP pocket with impact on A-loop, GC-loop and αC-helix conformations suggesting a potential structural link towards MK5 interaction via the FHIEDE motif. The inhibitors also showed sub-100 nM potencies in a cellular ERK3 NanoBRET assay and with excellent correlation to the biochemical ICs.

Selecting red blood cell units to perform RBCX in patients with sickle cell disease.

Red blood cell exchange (RBCX) is a standard option for treating or preventing complications in patients with sickle cell disease (SCD). According to the patient's blood volume, the amounts of red blood cells (RBC) to be exchanged and the practices of the apheresis and clinical teams, such treatment requires numerous red blood cell units (RBCUs) (3-15 RBCUs per procedure). To perform RBCXs safely and prevent the risk of alloimmunization, appropriate RBCUs must be selected and transfused to replace the sickled RBCs.

Automatic depletion with Spectra Optia allows a safe 16% reduction of red blood cell pack consumption in exchanged sickle cell anemia patients.

Background: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device.

Study Design And Methods: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed.

Immune hemolysis secondary to injection of contrast medium.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but sometimes severe side effect.

Case Report: We describe the case of a 32-year-old patient who presented a cardiovascular collapse and a severe hemolysis secondary to the injection of iomeprol, a contrast medium, after a carcinologic surgery.

Results: The evolution was favorable after blood transfusion and short catecholamine support.

Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons.

Postnatal maturation of the neurons whose main phenotype and basic synaptic contacts are already established includes neuronal growth, refinement of synaptic contacts, final steps of differentiation, programmed cell death period (PCD) etc. In the sympathetic neurons, postnatal maturation includes permanent end of the PCD that occurs with the same time schedule in vivo and in vitro suggesting that the process could be genetically determined. Also many other changes in the neuronal maturation could be permanent and thus based on stable changes in the genome expression.

Transfusion dependency at diagnosis and transfusion intensity during initial chemotherapy are associated with poorer outcomes in adult acute myeloid leukemia.

Blood transfusions can modify host immunity and clinical outcomes in hematological malignancies. One thousand sixty-seven patients with acute myeloid leukemia (AML) were studied for their transfusion dependency at initial presentation and transfusion frequency during induction chemotherapy. Three hundred five patients (29 %) showed initial dependence to red blood cell (RBC) transfusion and 109 (10 %) to platelet transfusion.

Selectivity mechanism of a bacterial homolog of the human drug-peptide transporters PepT1 and PepT2.

Peptide transporters of the PepT family have key roles in the transport of di- and tripeptides across membranes as well as in the absorption of orally administered drugs in the small intestine. We have determined structures of a PepT transporter from Shewanella oneidensis (PepT(So2)) in complex with three different peptides. The peptides bind in a large cavity lined by residues that are highly conserved in human PepT1 and PepT2.

Extracellular loop 4 of the proline transporter PutP controls the periplasmic entrance to ligand binding sites.

The Na(+)/proline symporter (PutP), like several other Na(+)-coupled symporters, belongs to the so-called LeuT-fold structural family, which features ten core transmembrane domains (cTMs) connected by extra- and intracellular loops. The role of these loops has been discussed in context with the gating function in the alternating access model of secondary active transport processes. Here we report the complete spin-labeling site scan of extracellular loop 4 (eL4) in PutP that reveals the presence of two α-helical segments, eL4a and eL4b.

The Na⁺/L-proline transporter PutP.

The Na⁺/L-proline transporter PutP is a member of the Na⁺/solute symporter family (TC 2A.21, SLC5), which contains several hundred proteins of pro- and eukaryotic origin. Within the family, the capability of L-proline uptake is restricted to proteins of prokaryotes.

Homology model of the Na+/proline transporter PutP of Escherichia coli and its functional implications.

Na(+)/solute symporters are essential membrane integrated proteins that couple the flow of Na(+) ions driven by electrochemical Na(+) gradients to the transport of solutes across biological membranes. Here, we used a combination of molecular modeling techniques and evolutionary conservation analysis to construct and validate a first model of the Na(+)/proline symporter PutP of Escherichia coli based on the crystal structure of the bacterial Na(+)/galactose symporter vSGLT. Ligand docking experiments were employed to gain information about residues involved in proline binding.

[A one-year survey of an emergency released group O red blood cell stock used by a surgical treatment center].

Objectives: Evaluation of a blood storage of six concentrates red blood cells of groupe O RH:-1KEL:-1 in a surgical emergency treatment center.

Patients And Methods: All patients transfused with this concentrates; main points of utilisation are analysed.

Conclusion: The concentrates, used by the anaesthesiologists, are part of the treatment strategy care in case of severe bleeding.

Function of transmembrane domain IX in the Na+/proline transporter PutP.

Selected residues of transmembrane domain (TM) IX were previously shown to play key roles in ligand binding and transport in members of the Na(+)/solute symporter family. Using the Na(+)/proline transporter PutP as a model, a complete Cys scanning mutagenesis of TM IX (positions 324 to 351) was performed here to further investigate the functional significance of the domain. G328, S332, Q345, and L346 were newly identified as important for Na(+)-coupled proline uptake.

[Transfusion protocols in hematopoietic stem cell allogeneic transplantation].

Hematopoietic stem cell (HSC) allogeneic transplantation is now commonly used as a therapeutic tool in patients with certain types of hematologic malignancies. Such patients, on account of severe pre-graft conditioning regimens, present with severe marrow aplasia justifying specific transfusion care. Given a complex immunological situation (immediately after transplantation, co-existence of two cell populations with different immunohematological characteristics), transfusion protocols must rest on clear and well-defined recommendations.

Simultaneous metal chelate affinity purification and endotoxin clearance of recombinant antibody fragments.

Endotoxins are frequent contaminants of recombinant proteins produced in Escherichia coli. Due to their adverse effects, endotoxins have to be removed from recombinant proteins prior their use in cell-based assays or parenteral application. Reduction of endotoxin to less than 10 EU mg(-1) is, however, one of the most problematic steps during protein purification from E.

Outcome of unrelated bone marrow donor searches in 174 children resulting in 45 patients transplanted in the HLA-matched and -mismatched situation.

The aim of the study was to evaluate the outcome of unrelated bone marrow donor (UBMD) searches initiated for 174 children between 1986 and 1997. Seven patients were registered twice so that a total of 181 UBMD searches took place. At the time of registration, patients suffered from hematological malignancies (n = 121), non-malignant hemopathies (n = 26) and inborn errors (n = 34).

High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation.

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.

Cryopreserved arterial homografts: preliminary study.

The use of arterial or venous allografts for vascular reconstruction was first reported in 1951, but long-term results have been disappointing. Rejection and inappropriate methods of preservation are the main reasons for failure. A successful solution to this problem could be achieved by programmed cryopreservation with cryoprotectant.

Nucleotide sequence and secondary structure of citrus exocortis and chrysanthemum stunt viroid.

The complete nucleotide sequence of citrus exocortis viroid (CEV, propagated in Gymura) and chrysanthemum stunt viroid (CSV, propagated in Cineraria) has been established, using labelling in vitro and direct RNA sequencing methods and a new screening procedure for the rapid selection of suitable RNA fragments from limited digests. The covalently closed circular single-stranded viroid RNAs consist of 371 (CEV) and 354 (CSV) nucleotides, respectively. As previously shown for potato spindle tuber viroid (PSTV, 359 nucleotides), CEV and CSV also contain a long polypurine sequence.