Using Fundamental Measure Theory to Treat the Correlation Function of the Inhomogeneous Hard-Sphere Fluid

We investigate the value of the correlation function of an inhomogeneous hard-sphere fluid at contact. This quantity plays a critical role in Statistical Associating Fluid Theory (SAFT), which is the basis of a number of recently developed classical density functionals. We define two averaged values for the correlation function at contact, and derive formulas for each of them from the White Bear version of the Fundamental Measure Theory functional, using an assumption of thermodynamic consistency. We test these formulas, as well as two existing formulas against Monte Carlo simulations, and find excellent agreement between the Monte Carlo data and one of our averaged correlation functions

Using fundamental measure theory to treat the correlation function of the inhomogeneous hard-sphere fluid

We investigate the value of the correlation function of an inhomogeneous hard-sphere fluid at contact. This quantity plays a critical role in statistical associating fluid theory, which is the basis of a number of recently developed classical density functionals. We define two averaged values for the correlation function at contact and derive formulas for each of them from the White Bear version of the fundamental measure theory functional, using an assumption of thermodynamic consistency. We test these formulas, as well as two existing formulas, against Monte Carlo simulations and find excellent agreement between the Monte Carlo data and one of our averaged correlation functions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Harmonization and standardization of nucleus pulposus cell extraction and culture methods

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab‐to‐lab variability jeopardizes the much‐needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods: The most commonly applied methods for NP cell extraction, expansion, and re‐differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re‐differentiation media and techniques were also investigated. Results: Recommended protocols are provided for extraction, expansion, and re‐differentiation of NP cells from common species utilized for NP cell culture. Conclusions: This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species‐specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross‐lab comparisons on NP cells worldwide

Sub-picosecond, table-top x-ray absorption spectroscopy using superconducting microcalorimeters

We present time-resolved X-ray absorption measurements of vanadium dioxide using ionizations radiation generated by a femtosecond pulsed laser source in combination with superconducting microcalorimeters capable of measuring energies of individual radiation quanta

Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules

MHC class I molecules display peptides from endogenous and viral proteins for immunosurveillance by cytotoxic T lymphocytes (CTL). The importance of the class I pathway is emphasised by the remarkable strategies employed by different viruses to downregulate surface class I and avoid CTL recognition. The K3 gene product from Kaposi's sarcoma-associated herpesvirus (KSHV) is a viral ubiquitin E3 ligase which ubiquitinates and degrades cell surface MHC class I molecules. We now show that modification of K3-associated class I by lysine-63-linked polyubiquitin chains is necessary for their efficient endocytosis and endolysosomal degradation and present three lines of evidence that monoubiquitination of class I molecules provides an inefficient internalisation signal. This lysine-63-linked polyubiquitination requires both UbcH5b/c and Ubc13-conjugating enzymes for initiating mono- and subsequent polyubiquitination of class I, and the clathrin-dependent internalisation is mediated by the epsin endocytic adaptor. Our results explain how lysine-63-linked polyubiquitination leads to degradation by an endolysosomal pathway and demonstrate a novel mechanism for endocytosis and endolysosomal degradation of class I, which may be applicable to other receptors