Systemic signalling through translationally controlled tumour protein controls lateral root formation in Arabidopsis

The plant body plan and primary organs are established during embryogenesis. However, in contrast to animals, plants have the ability to generate new organs throughout their whole life. These give them an extraordinary developmental plasticity to modulate their size and architecture according to environmental constraints and opportunities. How this plasticity is regulated at the whole-organism level is elusive. Here we provide evidence for a role for translationally controlled tumour protein (TCTP) in regulating the iterative formation of lateral roots in Arabidopsis. AtTCTP1 modulates root system architecture through a dual function: as a general constitutive growth promoter enhancing root elongation and as a systemic signalling agent via mobility in the vasculature. AtTCTP1 encodes mRNAs with long-distance mobility between the shoot and roots. Mobile shoot-derived TCTP1 gene products act specifically to enhance the frequency of lateral root initiation and emergence sites along the primary root pericycle, while root elongation is controlled by local constitutive TCTP1 expression and scion size. These findings uncover a novel type for an integrative signal in the control of lateral root initiation and the compromise for roots between branching more profusely or elongating further. They also provide the first evidence in plants of an extracellular function of the vital, highly expressed ubiquitous TCTP1.This work was supported by The Australian National University and a Postgraduate Research Scholarship through the Australian Government Research Training Program

ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production

SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.This work was supported by Australian National Health and Medical Research Council Grant 1105857 (SB) and Career Development Fellowship 1035858 (AE

Multistage QTL mapping strategy in an advanced backcross cattle population

The aim of this study was to identify quantitative trait loci (QTL) affecting milk production traits in one advanced backcross Fleckvieh x Red Holstein population, that are identical by descent, according to both origin and effect.Genome wide scan and consequent QTL mapping by means of “selective DNA pooling” in the daughter design revealed two advanced backcross (Fleckvieh x Red Holstein) families segregating for QTL affecting protein percent (PP-QTL) on bovine chromosome 19 (BTA19). Identical by descent analysis indicated a 20 cM region as the most possible location of this QTL. After initial interval mapping in 20 granddaughter design families, six families segregating for PP-QTL in the same region were detected. PP-QTL segregating and related families were combined into a set of 11 granddaughter design families for intensive study performed with 21 microsatellite markers. Final interval mapping was able to confirm but not to refine the PP-QTL position. Combined linkage disequilibrium and linkage mapping refined the PP-QTL position. By this method we were able to locate highly significant PP-QTL in the region of 4-9 cM. Analyses performed on all available traits showed effects of the mapped QTL on milkability also. The analysis of estimated sires’ effects suggests rather one QTL with effect on both traits

The Comparison of Forensic-Psychiatric Traits between Female and Male Perpetrators of Murder or Attempted Murder

The aim of this investigation was to define more clearly specific forensic-psychiatric characteristics of female murder or attempted murder perpetrators. The retrospective method applied was based on the comparison of the data from forensic-psychiatric assessments carried out in the Center for Forensic Psychiatry, Psychiatric Hospital Vrapče, Zagreb, from 1983 to 1997 (including 70 female and 70 male subjects – who committed murder or attempted murder). Compared with men, female offenders were most often in some way emotionally related to their victims, and they were more often victimized themselves before committing the crime. In men alcoholism was a more significant circumstantial factor in the assessment of their accountability. Psychiatric security measures were more often given to male offenders. The intensity of aggression was lower in females than in males. This investigation reveals that there are some sex specific forensic-psychiatric traits of murder or attempted murder perpetrators. The obtained results could be of help in everyday forensic-psychiatric practice, both in assessments and treatment

Arthritis as a presentation of paraneoplastic syndrome: A case report

Paraneoplastic syndrome includes symptoms that occur far from the primary tumor, and despite unclear pathogenesis, these conditions are thought to be caused by substances secreted by the neoplasm or by the effect of antibodies directed at the tumor, which cross- react with other tissues

Effects of rising temperatures and [CO2] on the physiology of tropical forest trees

Using a mixture of observations and climate model outputs and a simple parametrization of leaf-level photosynthesis incorporating known temperature sensitivities, we find no evidence for tropical forests currently existing ‘dangerously close’ to their optimum temperature range. Our model suggests that although reductions in photosynthetic rate at leaf temperatures (TL) above 30°C may occur, these are almost entirely accountable for in terms of reductions in stomatal conductance in response to higher leaf-to-air vapour pressure deficits D. This is as opposed to direct effects of TL on photosynthetic metabolism. We also find that increases in photosynthetic rates associated with increases in ambient [CO2] over forthcoming decades should more than offset any decline in photosynthetic productivity due to higher D or TL or increased autotrophic respiration rates as a consequence of higher tissue temperatures. We also find little direct evidence that tropical forests should not be able to respond to increases in [CO2] and argue that the magnitude and pattern of increases in forest dynamics across Amazonia observed over the last few decades are consistent with a [CO2]-induced stimulation of tree growth

Understanding gene mutations driving autoimmune disease and lymphoid malignancy.

The pathogenesis of autoimmune diseases is poorly understood - this is explicit in our failure to effectively cure them. This thesis had two primary, interdependent, aims. The first was conceptual - to test the 'common root approach', designed to provide clues as to the cell-intrinsic effects of gene mutations in autoimmune disease, based on a priori knowledge of their recurrence and functional consequences in lymphoid cancer. The second was specific to a small set of carefully selected genes that are mutated in the germline to cause immune dysregulation and mutated somatically in lymphoid cancer - to determine their molecular and cellular effects in autoimmune disease. These genes included STAT3, EGR2 and CARDI 1. Collectively, they are some of the most recurrently somatically mutated genes In lymphoid cancer, and their mutations in the gerrnline cause immune dysregulation. I studied these genes in genome-edited mice to determine their roles in isolation from confounding genetic variation and environmental exposures - followed where possible by validation of my findings in humans patients with corresponding gerrnline mutations. The study of STAT3 revealed that gerrnline gain-of-function STAT3 mutations are su!tcient to cause pathology in mice, in isolation from additional genetic variation or environmental triggers. These mutations cause dramatic polyclonal expansion of effector COB T cells in mice and humans - cells in mice that are sensitive to inhibition of some signalling pathways but not of others. This study further revealed that STAT3 is a transcriptional regulator of co21tow CD23I0" age-associated B cells - such that STAT3 gain-of-function results in the accumulation, and qualitative change in mRNA and protein expression, of CD21 tow CD23·0w B cells. The study of EGR2 and EGR3 revealed that these transcription factors function in a cell-intrinsic and partially redundant manner to suppress the accumulation of two B cell populations enriched for self-reactive BCR specificities and aberrantly expanded in autoimmune and/or lympoproliferative disease - B1a cells and CD21I0"' CD2310"' age-associated B cells. Finally, the study of overactive CARD11 revealed that the gain-of-function Cardi 1M31JSK mutation has no significant cell-intrinsic effect in mouse B cells, but provides a cell-intrinsic advantage to activated CD4 and Treg cells. These findings demonstrate that the common root approach can be useful in the investigation of gene mutation-driven immune dysregulation

Reconfigurable Architectures for Cryptographic Systems

Field Programmable Gate Arrays (FPGAs) are suitable platforms for implementing cryptographic algorithms in hardware due to their flexibility, good performance and low power consumption. Computer security is becoming increasingly important and security requirements such as key sizes are quickly evolving. This creates the need for customisable hardware designs for cryptographic operations capable of covering a large design space. In this thesis we explore the four design dimensions relevant to cryptography - speed, area, power consumption and security of the crypto-system - by developing parametric designs for public-key generation and encryption as well as side-channel attack countermeasures. There are four contributions. First, we present new architectures for Montgomery multiplication and exponentiation based on variable pipelining and variable serial replication. Our implementations of these architectures are compared to the best implementations in the literature and the design space is explored in terms of speed and area trade-offs. Second, we generalise our Montgomery multiplier design ideas by developing a parametric model to allow rapid optimisation of a general class of algorithms containing loops with dependencies carried from one iteration to the next. By predicting the throughput and the area of the design, our model facilitates and speeds up design space exploration. Third, we develop new architectures for primality testing including the first hardware architecture for the NIST approved Lucas primality test. We explore the area, speed and power consumption trade-offs by comparing our Lucas architectures on CPU, FPGA and ASIC. Finally, we tackle the security issue by presenting two novel power attack countermeasures based on on-chip power monitoring. Our constant power framework uses a closed-loop control system to keep the power consumption of any FPGA implementation constant. Our attack detection framework uses a network of ring-oscillators to detect the insertion of a shunt resistor-based power measurement circuit on a device's power rail. This countermeasure is lightweight and has a relatively low power overhead compared to existing masking and hiding countermeasures

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+ T cell dysregulation and accumulation

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. To investigate whether these mutations are the cause or consequence of CD

The Possibility of Using Monte Carlo Method in the Case of Decision-Making under Conditions of Risk Concerning an Agricultural Economics Issue

Monte Carlo metoda je probabilistički računalni algoritam u kojem se vrijednost jedne ili više slučajnih varijabli zadaje funkcijom gustoće, a kojem je cilj predvidjeti sve moguće ishode procesa na koji je primijenjen te vjerojatnosti njihovog pojavljivanja. Kao takva, Monte Carlo metoda se pokazuje izuzetno korisnom u procesu donošenja odluka u uvjetima rizika. U radu se obrađuje primjer optimizacije funkcije s ciljem pronalaženja rješenja koje će u opisanom agroekonomskom problemu u uvjetima bez rizika donijeti najveći profit. Provodi se Monte Carlo simulacija te se rješenje pronalazi i u uvjetima rizika. U tu svrhu je napisan programski kôd.Monte Carlo method is a probabilistic computer algorithm in which the value of one or more random variables is given by the density function, and the goal of which is to predict all the possible outcomes of a process it has been applied to and the probability of their occurrence. As such, the Monte Carlo method proves to be extremely useful in the process of decision- making under conditions of risk. This paper discusses an example of function optimization with the aim of finding a solution that will deliver the highest profits in the described agricultural economics-related problem under risk-free conditions. A Monte Carlo simulation is carried out and the solution under conditions of risk is also found. For that purpose, a special program code was written