Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.

We previously demonstrated that reduced intrinsic electron transport chain (ETC) activity predicts and promotes sensitivity to the BCL-2 antagonist, venetoclax (Ven) in multiple myeloma (MM). Heme, an iron-containing prosthetic group, and metabolite is fundamental to maintaining ETC activity. Interrogation of the CD2 subgroup of MM from the CoMMpass trial (NCT01454297), which can be used as a proxy for Ven-sensitive MM (VS MM), shows reduced expression of the conserved heme biosynthesis pathway gene signature.

A home-based exercise programme attenuates fatigue in primary biliary cholangitis: Results from the EXCITED clinical trial.

Background & Aims: Fatigue is a commonly reported symptom of primary biliary cholangitis (PBC). We conducted a single-arm, open-label clinical trial to assess the efficacy of a physiotherapist-led home-based exercise programme (HBEP) in patients with PBC and moderate-to-severe fatigue (NCT04265235).

Methods: A 12-week individualised HBEP (aerobic + resistance based) was delivered to patients with a PBC-40 fatigue domain score ≥33.

Fluorometric Methods to Measure Bioavailable and Total Heme.

Heme b (iron protoporphyrin IX) is an essential but potentially cytotoxic cofactor, signaling molecule, and nutritional source of iron. Its importance in cell biology and metabolism is underscored by the fact that numerous diseases, including various cancers, neurodegenerative disorders, infectious diseases, anemias, and porphyrias, are associated with the dysregulation of heme synthesis, degradation, trafficking, and/or transport. Consequently, methods to measure, image, and quantify heme in cells are required to better understand the physiology and pathophysiology of heme.

Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease: A prospective, observational study.

Background: There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.

Aim: To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.

Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?

Background: Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the 'Fast Recovery' programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated.

Home-based exercise in patients with refractory fatigue associated with primary biliary cholangitis: a protocol for the EXerCise Intervention in cholesTatic LivEr Disease (EXCITED) feasibility trial.

Introduction: Fatigue is the most commonly reported symptom of the liver disease primary biliary cholangitis (PBC). It affects 40%-80% of patients, has no effective treatment and is associated with heightened mortality risk. The pathogenesis is unknown, but muscle bioenergetic abnormalities have been proposed to contribute.

Survival after resection of brain metastases with white light microscopy versus fluorescence-guidance: A matched cohort analysis of the Metastasys study data.

Background: Metastatic brain disease continues to have a dismal prognosis. Previous studies achieved a reduction of local recurrence rates by aggressively resecting the peritumoral zone (supramarginal resection) or using 5-aminolaevulinic acid (5-ALA) fluorescence. The aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection.

A ruthenium-platinum metal complex that binds to sarcin ricin loop RNA and lowers mRNA expression.

IT127 is a dinuclear transition metal complex that contains a Pt(ii) and a Ru(iii) metal center. We have shown that IT127 is significantly more effective in binding the 29-base sarcin ricin loop (SRL) RNA in comparison to Cisplatin, a hallmark anticancer agent. Binding site analysis shows that IT127 prefers purine bases and the GAGA tetraloop region of SRL RNA.

Mechanistic study of the hydrothermal reduction of palladium on the Tobacco mosaic virus.

The fundamental mechanisms governing reduction and growth of palladium on the genetically engineered Tobacco mosaic virus in the absence of an external reducer have been elucidated via in situ X-ray absorption spectroscopy. In recent years, many virus-inorganic materials have been synthesized as a means to produce high quality nanomaterials. However, the underlying mechanisms involved in virus coating have not been sufficiently studied to allow for directed synthesis.

Biomineral proteins from Mytilus edulis mantle tissue transcriptome.

The common blue mussel, Mytilus edulis, has a bimineralic shell composed of approximately equal proportions of the two major polymorphs of calcium carbonate: calcite and aragonite. The exquisite biological control of polymorph production is the focus of research interest in terms of understanding the details of biomineralisation and the proteins involved in the process of complex shell formation. Recent advances in ease and availability of pyrosequencing and assembly have resulted in a sharp increase in transcriptome data for invertebrate biominerals.

SAXS characterization of genetically engineered tobacco mosaic virus nanorods coated with palladium in the absence of external reducing agents.

Genetic modifications of the tobacco mosaic virus (TMV) coat proteins allow for an increase in the selective deposition and controlled growth of different metals onto the surface of the virus, making it an ideal biotemplate for metal nanowire formation. In the current process, TMV2Cys is coated sequentially with multiple uniform layers of palladium metal in aqueous solution under very mild conditions. Palladium nanowires of 300 nm in length and 30-40 nm in diameter have been created with this process.

Control of crystal polymorph in microfluidics using molluscan 28 kDa Ca²(+)-binding protein.

Biominerals produced by biological systems in physiologically relevant environments possess extraordinary properties that are often difficult to replicate under laboratory conditions. Understanding the mechanism that underlies the process of biomineralisation can lead to novel strategies in the development of advanced materials. Using microfluidics, we have demonstrated for the first time, that an extrapallial (EP) 28 kDa protein, located in the extrapallial compartment between mantle and shell of Mytilus edulis, can influence, at both micro- and nanoscopic levels, the morphology, structure and polymorph that is laid down in the shell ultrastructure.

Evaluation of the CSEC Community Intervention Project (CCIP) in five U.S. Cities.

In response to the commercial sexual exploitation of children (CSEC) within five U.S. cities, the CSEC Community Intervention Project (CCIP) was created to enhance collaboration among nongovernmental organization (NGO) representatives, law enforcement officials and prosecutors in Chicago, Atlantic City, Denver, Washington, D.

Screening of biomineralization using microfluidics.

Biomineralization is the process where biological systems produce well-defined composite structures such as shell, teeth, and bones. Currently, there is substantial momentum to investigate the processes implicated in biomineralization and to unravel the complex roles of proteins in the control of polymorph switching. An understanding of these processes may have wide-ranging significance in health care applications and in the development of advanced materials.

Structure of myelin P2 protein from equine spinal cord.

Equine P2 protein has been isolated from horse spinal cord and its structure determined to 2.1 A. Since equine myelin is a viable alternative to bovine tissue for large-scale preparations, characterization of the proteins from equine spinal cord myelin has been initiated.

The structural basis of light-harvesting in purple bacteria.

A typical purple bacterial photosynthetic unit consists of two types of light-harvesting complex (LH1 and LH2) together with a reaction centre. This short review presents a description of the structure of the LH2 complex from Rhodopseudomonas acidophila, which has recently been improved to a resolution of 2.0 A [Papiz et al.

Detergent structure in crystals of the integral membrane light-harvesting complex LH2 from Rhodopseudomonas acidophila strain 10050.

Integral membrane proteins are solubilized by their incorporation into a detergent micelle. The detergent micelle has a critical influence on the formation of a three-dimensional crystal lattice. The bulk detergent phase is not seen in X-ray crystal structures of integral membrane proteins, due to its disordered character.

Primary structure of equine myelin basic protein by mass spectrometry.

Equine myelin basic protein (MBP) has been isolated from spinal cord and shown to consist of a number of components (charge isomers) by alkaline-urea gel electrophoresis. Mass analyses of several of these components showed that each was posttranslationally modified and some have been identified. Component 1, the most cationic charge isomer, was sequenced by a combination of liquid chromatography and mass spectrometry of peptides obtained by proteolytic digestion.

Evidence for possible interactions between PLP and DM20 within the myelin sheath.

PLP and its smaller DM20 isoform constitute the major proteins of CNS myelin. Previous studies indicated a role for the proteins in maintaining the intraperiod line of the myelin sheath and the integrity of axons and suggested that both isoforms were necessary to provide these functions. The present study shows that each isoform is capable individually of inserting into compact myelin.

Derivative manipulation in the structure solution of the integral membrane LH2 complex.

The structure of the peripheral light-harvesting complex from Rhodopseudomonas acidophila strain 10050 was determined by multiple isomorphous replacement methods. The derivatization of the crystals was augmented by the addition of a backsoaking stage. The soak/backsoaked data comparison had greater isomorphism and showed simpler Patterson maps than the standard native/soak comparison.

Crystallization and preliminary X-ray crystallographic analysis of a vancomycin-N-acetyl-D-Ala-D-Ala complex.

A vancomycin-N-acetyl-D-Ala-D-Ala complex has been crystallized by the sitting-drop vapour-diffusion method using imidazole maleic buffer at pH 7.6. The novel crystals obtained belong to the space group P6322 with unit-cell parameters a = b = 73.

Assessment of cage use by laboratory-bred common marmosets (Callithrix jacchus).

The way in which breeding families of laboratory-born marmosets used the space provided by their cages, and a small protruding 'veranda', was assessed in order to determine the popularity of the veranda as a form of environmental enrichment, and the extent to which the marmosets confined themselves to only part of the cage. The veranda was found to be of enduring interest to the marmosets whose occupancy of this space was an order of magnitude greater than the rest of the cage. The upper part of the cage was preferred to the bottom half.