Enzymatic Cascades for Stereoselective and Regioselective Amide Bond Assembly.

Amide bond formation is fundamental in nature and is widely used in the synthesis of pharmaceuticals and other valuable products. Current methods for amide synthesis are often step and atom inefficient, requiring the use of protecting groups, deleterious reagents and organic solvents that create significant waste. The development of cleaner and more efficient catalytic methods for amide synthesis remains an urgent unmet need.

Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin.

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1, that prevents persistent RAD51 foci without or after DNA damage and genotoxic chromatin association in cells.

Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin.

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated.

Cryptic enzymatic assembly of peptides armed with β-lactone warheads.

Nature has evolved biosynthetic pathways to molecules possessing reactive warheads that inspired the development of many therapeutic agents, including penicillin antibiotics. Peptides armed with electrophilic warheads have proven to be particularly effective covalent inhibitors, providing essential antimicrobial, antiviral and anticancer agents. Here we provide a full characterization of the pathways that nature deploys to assemble peptides with β-lactone warheads, which are potent proteasome inhibitors with promising anticancer activity.

Thermal Transport and Mechanical Stress Mapping of a Compression Bonded GaN/Diamond Interface for Vertical Power Devices.

Bonding diamond to the back side of gallium nitride (GaN) electronics has been shown to improve thermal management in lateral devices; however, engineering challenges remain with the bonding process and characterizing the bond quality for vertical device architectures. Here, integration of these two materials is achieved by room-temperature compression bonding centimeter-scale GaN and a diamond die via an intermetallic bonding layer of Ti/Au. Recent attempts at GaN/diamond bonding have utilized a modified surface activation bonding (SAB) method, which requires Ar fast atom bombardment immediately followed by bonding within the same tool under ultrahigh vacuum (UHV) conditions.

Inversion for Thermal Properties with Frequency Domain Thermoreflectance.

3D integration of multiple microelectronic devices improves size, weight, and power while increasing the number of interconnections between components. One integration method involves the use of metal bump bonds to connect devices and components on a common interposer platform. Significant variations in the coefficient of thermal expansion in such systems lead to stresses that can cause thermomechanical and electrical failures.

Phosphoregulation of the checkpoint kinase Mec1.

Yeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. Mec1, in complex with Ddc2, is a 'sensor' of single stranded DNA, and phosphorylates numerous cell cycle and DNA repair factors to enforce cell cycle arrest and facilitate repair. Over the last several years, new techniques - particularly in structural biology - have provided molecular mechanisms for Mec1 function.

Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5-Sfr1.

Homologous recombination (HR) is a major pathway for the repair of DNA double-strand breaks, the most severe form of DNA damage. The Rad51 protein is central to HR, but multiple auxiliary factors regulate its activity. The heterodimeric Swi5-Sfr1 complex is one such factor.

A DNA damage-induced phosphorylation circuit enhances Mec1 Ddc2 recruitment to Replication Protein A.

The cell cycle checkpoint kinase Mec1 and its integral partner Ddc2 are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function.

Dominant carnivore loss benefits native avian and invasive mammalian scavengers.

Scavenging by large carnivores is integral for ecosystem functioning by limiting the build-up of carrion and facilitating widespread energy flows. However, top carnivores have declined across the world, triggering trophic shifts within ecosystems. Here, we compare findings from previous work on predator decline against areas with recent native mammalian carnivore loss.

Spatial pattern analysis of line-segment data in ecology.

The spatial analysis of linear features (lines and curves) is a challenging and rarely attempted problem in ecology. Existing methods are typically expressed in abstract mathematical formalism, making it difficult to assess their relevance and transferability into an ecological setting. We introduce a set of concrete and accessible methods to analyze the spatial patterning of line-segment data.

Parsimonious model selection using information theory: a modified selection rule.

Information-theoretic approaches to model selection, such as Akaike's information criterion (AIC) and cross validation, provide a rigorous framework to select among candidate hypotheses in ecology, yet the persistent concern of overfitting undermines the interpretation of inferred processes. A common misconception is that overfitting is due to the choice of criterion or model score, despite research demonstrating that selection uncertainty associated with score estimation is the predominant influence. Here we introduce a novel selection rule that identifies a parsimonious model by directly accounting for estimation uncertainty, while still retaining an information-theoretic interpretation.

Steady-state methods for measuring in-plane thermal conductivity of thin films for heat spreading applications.

The development of high thermal conductivity thin film materials for the thermal management of electronics requires accurate and precise methods for characterizing heat spreading capability, namely, in-plane thermal conductivity. However, due to the complex nature of thin film thermal property measurements, resolving the in-plane thermal conductivity of high thermal conductivity anisotropic thin films with high accuracy is particularly challenging. Capable transient techniques exist; however, they usually measure thermal diffusivity and require heat capacity and density to deduce thermal conductivity.

Roadkill islands: Carnivore extinction shifts seasonal use of roadside carrion by generalist avian scavenger.

Global road networks facilitate habitat modification and are integral to human expansion. Many animals, particularly scavengers, use roads as they provide a reliable source of food, such as carrion left after vehicle collisions. Tasmania is often cited as the 'roadkill capital of Australia', with the isolated offshore islands in the Bass Strait experiencing similar, if not higher, levels of roadkill.

Regulation of DNA break repair by RNA.

Genomic stability is critical for cell survival and its effective repair when damaged is a vital process for preserving genetic information. Failure to correctly repair the genome can lead to the accumulation of mutations that ultimately drives carcinogenesis. Life has evolved sophisticated surveillance, repair pathways, and mechanisms to recognize and mend genomic lesions to preserve its integrity.

Mechanism of auto-inhibition and activation of Mec1 checkpoint kinase.

In response to DNA damage or replication fork stalling, the basal activity of Mec1 is stimulated in a cell-cycle-dependent manner, leading to cell-cycle arrest and the promotion of DNA repair. Mec1 dysfunction leads to cell death in yeast and causes chromosome instability and embryonic lethality in mammals. Thus, ATR is a major target for cancer therapies in homologous recombination-deficient cancers.

Continuing to look in the mirror: A review of neuroscientific evidence for the broken mirror hypothesis, EP-M model and STORM model of autism spectrum conditions.

The mirror neuron system has been argued to be a key brain system responsible for understanding the actions of others and for imitation. It has therefore been proposed that problems within this system could explain the social difficulties experienced by people with autism spectrum condition. This idea is referred to as the broken mirror hypothesis.

Bulk-like Intrinsic Phonon Thermal Conductivity of Micrometer-Thick AlN Films.

Aluminum nitride (AlN) has garnered much attention due to its intrinsically high thermal conductivity. However, engineering thin films of AlN with these high thermal conductivities can be challenging due to vacancies and defects that can form during the synthesis. In this work, we report on the cross-plane thermal conductivity of ultra-high-purity single-crystal AlN films with different thicknesses (∼3-22 μm) via time-domain thermoreflectance (TDTR) and steady-state thermoreflectance (SSTR) from 80 to 500 K.

New horizons in iron deficiency anaemia in older adults.

Iron deficiency anaemia (IDA) is common in older adults and associated with a range of adverse outcomes. Differentiating iron deficiency from other causes of anaemia is important to ensure appropriate investigations and treatment. It is possible to make the diagnosis reliably using simple blood tests.

Interfacial Thermal Conductance across Room-Temperature-Bonded GaN/Diamond Interfaces for GaN-on-Diamond Devices.

The wide bandgap, high-breakdown electric field, and high carrier mobility makes GaN an ideal material for high-power and high-frequency electronics applications, such as wireless communication and radar systems. However, the performance and reliability of GaN-based high-electron-mobility transistors (HEMTs) are limited by the high channel temperature induced by Joule heating in the device channel. Integration of GaN with high thermal conductivity substrates can improve the heat extraction from GaN-based HEMTs and lower the operating temperature of the device.

Structures and regulations of ATM and ATR, master kinases in genome integrity.

Homologous recombination (HR) is a faithful repair mechanism for double stranded DNA breaks. Two highly homologous master kinases, the tumour suppressors ATM and ATR (Tel1 and Mec1 in yeast), coordinate cell cycle progression with repair during HR. Despite their importance, our molecular understanding of these apical coordinators has been limited, in part due to their large sizes.

Structural basis of homologous recombination.

Homologous recombination (HR) is a pathway to faithfully repair DNA double-strand breaks (DSBs). At the core of this pathway is a DNA recombinase, which, as a nucleoprotein filament on ssDNA, pairs with homologous DNA as a template to repair the damaged site. In eukaryotes Rad51 is the recombinase capable of carrying out essential steps including strand invasion, homology search on the sister chromatid and strand exchange.