Welding PROxAb Shuttles: A Modular Approach for Generating Bispecific Antibodies via Site-Specific Protein-Protein Conjugation.

Targeted protein degradation is an innovative therapeutic strategy to selectively eliminate disease-causing proteins. Exemplified by proteolysis-targeting chimeras (PROTACs), they have shown promise in overcoming drug resistance and targeting previously undruggable proteins. However, PROTACs face challenges, such as low oral bioavailability and limited selectivity.

LiSn, the Most Lithium-Rich Binary Stannide: A Combined Experimental and Computational Study.

From reaction of excess lithium with tin, we isolate well-crystallized LiSn and solve the crystal structure from single-crystal X-ray diffraction data. The orthorhombic structure (space group ) features the same coordination polyhedra around tin and lithium as previously predicted by electronic structure calculations for this composition, however differently arranged. An extensive analysis, including thermodynamic integration using Langevin dynamics in combination with a machine-learning potential (moment tensor potential), is conducted to understand the thermodynamic stability of this LiSn structure observed in our experiments.

Analysis of the functional interaction of Arabidopsis starch synthase and branching enzyme isoforms reveals that the cooperative action of SSI and BEs results in glucans with polymodal chain length distribution similar to amylopectin.

Starch synthase (SS) and branching enzyme (BE) establish the two glycosidic linkages existing in starch. Both enzymes exist as several isoforms. Enzymes derived from several species were studied extensively both in vivo and in vitro over the last years, however, analyses of a functional interaction of SS and BE isoforms are missing so far.

A new species of the Gekko japonicus group (Squamata: Sauria: Gekkonidae) from the border region between China and Vietnam.

We describe a new species of the genus Gekko on the basis of 25 specimens from southern China and northern Vietnam. Gekko adleri sp. nov.

A new species of Hemiphyllodactylus (Reptilia: Gekkonidae) from northern Vietnam.

We describe a new species of the genus Hemiphyllodactylus on the basis of four specimens from Cao Bang Province, northern Vietnam. Hemiphyllodactylus zugi sp. nov.

Endpoints of drug discovery for menopausal vasomotor symptoms: interpretation of data from a proxy of disease.

Objective: Estrogen supplementation is considered a reliable therapeutic approach to symptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation. Implication of changes in central neurotransmission in the pathogenesis of hot flashes has prompted the off-label use of serotonergic and γ-aminobutyric acid-ergic drugs as a therapeutic alternative, claiming similarity of outcomes to those of estrogen treatment.

Methods: Using telemetric recordings in a rat model of estrogen deficit-induced vasomotor dysregulation, we compared the long- and short-term effects of estrogen supplementation and treatment with neuropharmaceuticals (venlafaxine, desvenlafaxine, fluoxetine, agomelatine, gabapentin) on endpoints of thermoregulation.

Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).

In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy. The present study investigated R-maintenance after R-chemotherapy. Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM).

Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing.

Clinical features of Opitz BBB/G syndrome are confined to defects of the developing ventral midline, whereas the causative gene, MID1, is ubiquitously expressed. Therefore, a non-redundant physiological function of the MID1 product appears to be developmentally restricted. Here, we report the identification of several alternative MID1 exons in human, mouse and fugu.

MLL-mediated transcriptional gene regulation investigated by gene expression profiling.

The human mixed lineage leukemia (MLL) gene is involved in about 50 different chromosomal translocations, associated with the disease phenotype of acute leukemia. However, the normal function of MLL is less understood. Homozygous knockouts of murine Mll were embryonal lethal, while heterozygous disruption led to aberrant hox gene expression associated with skeletal malformations, growth retardation, and impaired hematopoiesis.

Duplication of the MID1 first exon in a patient with Opitz G/BBB syndrome.

Opitz G/BBB syndrome is a malformation syndrome of the ventral midline mainly characterized by hypertelorism, swallowing difficulties, hypospadias and developmental delay. SSCP analysis and genomic sequencing of the MID1 open reading frame have identified mutations in 80% of the families with X-linked inheritance. However, in many patients the underlying genetic defect remains undetected by these techniques.