Theory of tunneling spectroscopy in a Mn_12 single-electron transistor by density-functional theory methods

We consider tunneling transport through a Mn12 molecular magnet using spin density functional theory. A tractable methodology for constructing many-body wave functions from Kohn-Sham orbitals allows for the determination of spin-ependent matrix elements for use in transport calculations. The tunneling conductance at finite bias is characterized by peaks representing transitions between spin multiplets, separated by an energy on the order of the magnetic anisotropy. The energy splitting of the spin multiplets and the spatial part of their many-body wave functions, describing the orbital degrees of freedom of the excess charge, strongly affect the electronic transport, and can lead to negative differential conductance

Inelastic Scattering in Metal-H2-Metal Junctions

We present first-principles calculations of the dI/dV characteristics of an H2 molecule sandwiched between Au and Pt electrodes in the presence of electron-phonon interactions. The conductance is found to decrease by a few percentage at threshold voltages corresponding to the excitation energy of longitudinal vibrations of the H2 molecule. In the case of Pt electrodes, the transverse vibrations can mediate transport through otherwise non-transmitting Pt $d$-channels leading to an increase in the differential conductance even though the hydrogen junction is characterized predominately by a single almost fully open transport channel. In the case of Au, the transverse modes do not affect the dI/dV because the Au d-states are too far below the Fermi level. A simple explanation of the first-principles results is given using scattering theory. Finally, we compare and discuss our results in relation to experimental data.Comment: Accepted in Phys. Rev.

Experimental Biological Protocols with Formal Semantics

Both experimental and computational biology is becoming increasingly automated. Laboratory experiments are now performed automatically on high-throughput machinery, while computational models are synthesized or inferred automatically from data. However, integration between automated tasks in the process of biological discovery is still lacking, largely due to incompatible or missing formal representations. While theories are expressed formally as computational models, existing languages for encoding and automating experimental protocols often lack formal semantics. This makes it challenging to extract novel understanding by identifying when theory and experimental evidence disagree due to errors in the models or the protocols used to validate them. To address this, we formalize the syntax of a core protocol language, which provides a unified description for the models of biochemical systems being experimented on, together with the discrete events representing the liquid-handling steps of biological protocols. We present both a deterministic and a stochastic semantics to this language, both defined in terms of hybrid processes. In particular, the stochastic semantics captures uncertainties in equipment tolerances, making it a suitable tool for both experimental and computational biologists. We illustrate how the proposed protocol language can be used for automated verification and synthesis of laboratory experiments on case studies from the fields of chemistry and molecular programming

Lactoferrin and cancer disease prevention

Lactoferrin (LF) is an iron-binding glycoprotein that is composed of the transferrin family and is predominantly found in the products of the exocrine glands located in the gateways of the digestive, respiratory, and reproductive systems, suggesting a role in the non-specific defence against invading pathogens. Additionally, several physiological roles have been attributed to LF, namely regulation of iron homeostasis, host defence against infection and inflammation, regulation of cellular growth, and differentiation and protection against cancer development and metastasis. These findings have suggested LF's great potential therapeutic use in cancer disease prevention and/or treatment, namely as a chemopreventive agent. This review looks at the recent advances in understanding the mechanisms underlying the multifunctional roles of LF and future perspectives on its potential therapeutic applications.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/26064/2005

The role of osteopontin in tumour progression and metastasis in breast cancer

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data.Fundação para a Ciência e a Tecnologia (FC

Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure

Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia

Sociobiological Control of Plasmid copy number

Background:
All known mechanisms and genes responsible for the regulation of plasmid replication lie with the plasmid rather than the chromosome. It is possible therefore that there can be copy-up mutants. Copy-up mutants will have within host selective advantage. This would eventually result into instability of bacteria-plasmid association. In spite of this possibility low copy number plasmids appear to exist stably in host populations. We examined this paradox using a computer simulation model.

Model:
Our multilevel selection model assumes a wild type with tightly regulated replication to ensure low copy number. A mutant with slightly relaxed replication regulation can act as a “cheater” or “selfish” plasmid and can enjoy a greater within-host-fitness. However the host of a cheater plasmid has to pay a greater cost. As a result, in host level competition, host cell with low copy number plasmid has a greater fitness. Furthermore, another mutant that has lost the genes required for conjugation was introduced in the model. The non-conjugal mutant was assumed to undergo conjugal transfer in the presence of another conjugal plasmid in the host cell.

Results:
The simulatons showed that if the cost of carrying a plasmid was low, the copy-up mutant could drive the wild type to extinction or very low frequencies. Consequently, another mutant with a higher copy number could invade the first invader. This process could result into an increasing copy number. However above a certain copy number within-host selection was overcompensated by host level selection leading to a rock-paper-scissor (RPS) like situation. The RPS situation allowed the coexistence of high and low copy number plasmids. The non-conjugal “hypercheaters” could further arrest the copy numbers to a substantially lower level.

Conclusions:
These sociobiological interactions might explain the stability of copy numbers better than molecular mechanisms of replication regulation alone

Quantification of very low-abundant proteins in bacteria using the HaloTag and epi-fluorescence microscopy.

Cell biology is increasingly dependent on quantitative methods resulting in the need for microscopic labelling technologies that are highly sensitive and specific. Whilst the use of fluorescent proteins has led to major advances, they also suffer from their relatively low brightness and photo-stability, making the detection of very low abundance proteins using fluorescent protein-based methods challenging. Here, we characterize the use of the self-labelling protein tag called HaloTag, in conjunction with an organic fluorescent dye, to label and accurately count endogenous proteins present in very low numbers (<7) in individual Escherichia coli cells. This procedure can be used to detect single molecules in fixed cells with conventional epifluorescence illumination and a standard microscope. We show that the detection efficiency of proteins labelled with the HaloTag is ≥80%, which is on par or better than previous techniques. Therefore, this method offers a simple and attractive alternative to current procedures to detect low abundance molecules