Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network

Despite the continued analysis of HDAC inhibitors in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

COMPLEX PROGRAM OF DIAGNOSTICS AND TREATMENT OF POLYTRAUMATIZED PATIENTS WITH II-III DEGREES OBESITY

The aim: Elaboration of the complex program of diagnostics and treatment of the polytraumatized overweight patients. Materials and methods: Clinical material was composed of 64 patients with the combined body trauma who suffered from II-III grade obesity. Results: Main principles of rendering the aid to the polytraumatized overweight patients included the pathophysiological and topographic features of the group. The obtained study results confirmed the credible difference of the traumatic disease progress in the patients with the normal weight and overweight patients which was the basis of our differential complex treatment program. The treatment tactics also had certain characteristics connected with the obesity. The development of RDS syndrome is a typical stage of the traumatic disease during the blunt thoracal trauma in case of obesity. The programmed and urgent relaparotomy, as a method of the stage treatment in the present group of patients, is the integral component of the blunt abdominal injury in case of obesity. Conclusions: The study results proved that our complex program of diagnostics and treatment of the polytraumatized patients shall be basic for the patients with II-III grade obesity.

Differential complex formation via paralogs in the human Sin3 protein interaction network

ABSTRACTDespite the continued analysis of HDAC inhibitor efficacy in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The functional attributes of these protein complexes remain poorly characterized in humans. Contributing to the poor definition of Sin3 complex attributes in higher eukaryotes is the presence of two Sin3 scaffolding proteins, SIN3A and SIN3B. Here we show that paralog switching influences the interaction networks of the Sin3 complexes. While SIN3A and SIN3B do have unique interaction network components, we find that SIN3A and SIN3B interact with a common set of proteins. Additionally, our results suggest that SIN3A and SIN3B may possess the capacity to form hetero-oligomeric complexes. While one principal form of SIN3B exists in humans, the analysis of rare SIN3B proteoforms provides insight into the domain organization of SIN3B. Together, these findings shed light on the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

Structurally conserved binding motifs of transcriptional regulators to notch nuclear effector CSL

This mini review discusses the protein complexes comprised of the universal Notch signaling transcription factor, CSL (CBF1/Su(H)/Lag-1), and its activating or repressing transcriptional coregulation partners. Many of these complex structures have been solved crystallographically as well as undergoing extensive binding studies with wild-type and mutant variants. Notch signaling is critically important in a large variety of basic biological processes: cell proliferation, differentiation, cell cycle control to name a few. Aberrant Notch thus remains a coveted target for pharmaceutical intervention. To that end, we provide a molecular-level summary of the similarities and differences in the Notch coregulator complexes that ultimately govern these processes. We highlight a conserved binding motif that multiple superficially unrelated proteins have adopted to become involved in Notch target gene regulation. As CSL-interacting small molecules begin to be characterized, this review will provide insight to potential binding sites and differential complex disruption. Impact statement Proper Notch signaling regulation is informed by many distinct protein complexes involving a single nuclear effector. A decade of research into these protein complexes yields multiple crystal structures and a wealth of binding data to guide drug development for Notch-related diseases – cancer, cardiovascular, development disorders.

On a spectral sequence for the cohomology of a nilpotent Lie algebra

Given a nilpotent Lie algebra 𝔫 we construct a spectral sequence which is derived from a filtration of its Chevalley–Eilenberg differential complex and converges to the Lie algebra cohomology of 𝔫. The limit of this spectral sequence gives a grading for the Lie algebra cohomology, except for the cohomology groups of degree 0, 1, dim 𝔫 - 1 and dim 𝔫 as we shall prove. We describe the spectral sequence associated to a nilpotent Lie algebra which is a direct sum of two ideals, one of them of dimension one, in terms of the spectral sequence of the co-dimension one ideal. Also, we compute the spectral sequence corresponding to each real nilpotent Lie algebra of dimension less than or equal to six.

High Precision Data Processing Method Based on the Complex-Step Differentiation

Finite differencing is a very commonly method used in numerical algorithms to compute derivatives, which is well known for its accurate precision. Besides, the best advantage of this method resides in the fact that it is extremely easy to implement. But the finite differencing may be in a dilemma. The reason is that if the step size is large, the precision is not satisfying, but if the step size is small, the error is increased due to subtractive cancellation. In this manuscript, a new method for differential, complex-step differentiation (CSD) is proposed, which uses complex computations to compute derivatives. We first give a detailed account of the principles of the complex-step differentiation. Then analyze the CSD method from two sides, error and efficiency. At last, the implementation of CSD in MATLAB is presented. Simulating results indicate that they are fitting well with the theoretical analysis.

GENERALIZED INVERSION OF THE HOCHSCHILD COBOUNDARY OPERATOR AND DEFORMATION QUANTIZATION

Using a derivative decomposition of the Hochschild differential complex we define a generalized inverse of the Hochschild coboundary operator. It can be applied for systematic computations of star products on Poisson manifolds.