128 research outputs found
Farsighted Risk Mitigation of Lateral Movement Using Dynamic Cognitive Honeypots
Lateral movement of advanced persistent threats has posed a severe security
challenge. Due to the stealthy and persistent nature of the lateral movement,
defenders need to consider time and spatial locations holistically to discover
latent attack paths across a large time-scale and achieve long-term security
for the target assets. In this work, we propose a time-expanded random network
to model the stochastic service links in the user-host enterprise network and
the adversarial lateral movement. We design cognitive honeypots at idle
production nodes and disguise honey links as service links to detect and deter
the adversarial lateral movement. The location of the honeypot changes randomly
at different times and increases the honeypots' stealthiness. Since the
defender does not know whether, when, and where the initial intrusion and the
lateral movement occur, the honeypot policy aims to reduce the target assets'
Long-Term Vulnerability (LTV) for proactive and persistent protection. We
further characterize three tradeoffs, i.e., the probability of interference,
the stealthiness level, and the roaming cost. To counter the curse of multiple
attack paths, we propose an iterative algorithm and approximate the LTV with
the union bound for computationally efficient deployment of cognitive
honeypots. The results of the vulnerability analysis illustrate the bounds,
trends, and a residue of LTV when the adversarial lateral movement has infinite
duration. Besides honeypot policies, we obtain a critical threshold of
compromisability to guide the design and modification of the current system
parameters for a higher level of long-term security. We show that the target
node can achieve zero vulnerability under infinite stages of lateral movement
if the probability of movement deterrence is not less than the threshold
Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice.
Small non-coding RNAs (sncRNAs) are potential vectors at the interface between genes and environment. We found that traumatic stress in early life altered mouse microRNA (miRNA) expression, and behavioral and metabolic responses in the progeny. Injection of sperm RNAs from traumatized males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring.We thank M. Rassoulzadegan and V. Grandjean for help with the sperm
purification, F. Manuella and H. Hörster for assistance with the MSUS paradigm,
H. Welzl for help with behavior, G. Vernaz for help with western blotting,
R. Tweedie-Cullen and P. Nanni for help with mass spectrometry, A. Patrignani
for advice on DNA and RNA quality assessment, and A. Chen and A. Brunner for
constructive discussions. This work was supported by the Austrian Academy of
Sciences, the University of Zürich, the Swiss Federal Institute of Technology,
Roche, the Swiss National Science Foundation, and The National Center of
Competence in Research “Neural Plasticity and Repair”. P.S. was supported by a
Gonville and Caius College fellowship.This is the accepted manuscript. The final version is available in Nature Neuroscience 17, 667–669 (2014), doi:10.1038/nn.369
Gait kinematic analysis in patients with a mild form of central cord syndrome
<p>Abstract</p> <p>Background</p> <p>Central cord syndrome (CCS) is considered the most common incomplete spinal cord injury (SCI). Independent ambulation was achieved in 87-97% in young patients with CCS but no gait analysis studies have been reported before in such pathology. The aim of this study was to analyze the gait characteristics of subjects with CCS and to compare the findings with a healthy age, sex and anthropomorphically matched control group (CG), walking both at a self-selected speed and at the same speed.</p> <p>Methods</p> <p>Twelve CCS patients and a CG of twenty subjects were analyzed. Kinematic data were obtained using a three-dimensional motion analysis system with two scanner units. The CG were asked to walk at two different speeds, at a self-selected speed and at a slower one, similar to the mean gait speed previously registered in the CCS patient group. Temporal, spatial variables and kinematic variables (maximum and minimum lower limb joint angles throughout the gait cycle in each plane, along with the gait cycle instants of occurrence and the joint range of motion - ROM) were compared between the two groups walking at similar speeds.</p> <p>Results</p> <p>The kinematic parameters were compared when both groups walked at a similar speed, given that there was a significant difference in the self-selected speeds (p < 0.05). Hip abduction and knee flexion at initial contact, as well as minimal knee flexion at stance, were larger in the CCS group (p < 0.05). However, the range of knee and ankle motion in the sagittal plane was greater in the CG group (p < 0.05). The maximal ankle plantar-flexion values in stance phase and at toe off were larger in the CG (p < 0.05).</p> <p>Conclusions</p> <p>The gait pattern of CCS patients showed a decrease of knee and ankle sagittal ROM during level walking and an increase in hip abduction to increase base of support. The findings of this study help to improve the understanding how CCS affects gait changes in the lower limbs.</p
The sperm factor: paternal impact beyond genes
The fact that sperm carry more than the paternal DNA has only been discovered just over a decade ago. With this discovery, the idea that the paternal condition may have direct implications for the fitness of the offspring had to be revisited. While this idea is still highly debated, empirical evidence for paternal effects is accumulating. Male condition not only affects male fertility but also offspring early development and performance later in life. Several factors have been identified as possible carriers of non-genetic information, but we still know little about their origin and function and even less about their causation. I consider four possible non-mutually exclusive adaptive and non-adaptive explanations for the existence of paternal effects in an evolutionary context. In addition, I provide a brief overview of the main non-genetic components found in sperm including DNA methylation, chromatin modifications, RNAs and proteins. I discuss their putative functions and present currently available examples for their role in transferring non-genetic information from the father to the offspring. Finally, I identify some of the most important open questions and present possible future research avenues
Sexual Selection Halts the Relaxation of Protamine 2 among Rodents
Sexual selection has been proposed as the driving force promoting the rapid evolutionary changes observed in some reproductive genes including protamines. We test this hypothesis in a group of rodents which show marked differences in the intensity of sexual selection. Levels of sperm competition were not associated with the evolutionary rates of protamine 1 but, contrary to expectations, were negatively related to the evolutionary rate of cleaved- and mature-protamine 2. Since both domains were found to be under relaxation, our findings reveal an unforeseen role of sexual selection: to halt the degree of degeneration that proteins within families may experience due to functional redundancy. The degree of relaxation of protamine 2 in this group of rodents is such that in some species it has become dysfunctional and it is not expressed in mature spermatozoa. In contrast, protamine 1 is functionally conserved but shows directed positive selection on specific sites which are functionally relevant such as DNA-anchoring domains and phosphorylation sites. We conclude that in rodents protamine 2 is under relaxation and that sexual selection removes deleterious mutations among species with high levels of sperm competition to maintain the protein functional and the spermatozoa competitive
Identification and characterization of microRNAs expressed in the African malaria vector Anopheles funestus life stages using high throughput sequencing
Background: Over the past several years, thousands of microRNAs (miRNAs) have been identified in the genomes of various insects through cloning and sequencing or even by computational prediction. However, the number of miRNAs identified in anopheline species is low and little is known about their role. The mosquito Anopheles funestus is one of the dominant malaria vectors in Africa, which infects and kills millions of people every year. Therefore, small RNA molecules isolated from the four life stages (eggs, larvae, pupae and unfed adult females) of An. funestus were sequenced using next generation sequencing technology. Results: High throughput sequencing of four replicates in combination with computational analysis identified 107 mature miRNA sequences expressed in the An. funestus mosquito. These include 20 novel miRNAs without sequence identity in any organism and eight miRNAs not previously reported in the Anopheles genus but are known in non-anopheles mosquitoes. Finally, the changes in the expression of miRNAs during the mosquito development were determined and the analysis showed that many miRNAs have stage-specific expression, and are co-transcribed and co-regulated during development. Conclusions: This study presents the first direct experimental evidence of miRNAs in An. funestus and the first profiling study of miRNA associated with the maturation in this mosquito. Overall, the results indicate that miRNAs play important roles during the growth and development. Silencing such molecules in a specific life stage could decrease the vector population and therefore interrupt malaria transmission.IS
Spermatogonial Stem Cell Niche and Spermatogonial Stem Cell Transplantation in Zebrafish
Background
Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis, and reside within a specific microenvironment in the testes called “niche” which regulates stem cell properties, such as, self-renewal, pluripotency, quiescence and their ability to differentiate.
Methodology/Principal Findings
Here, we introduce zebrafish as a new model for the study of SSCs in vertebrates. Using 5′-bromo-2′-deoxyuridine (BrdU), we identified long term BrdU-retaining germ cells, type A undifferentiated spermatogonia as putative stem cells in zebrafish testes. Similar to rodents, these cells were preferentially located near the interstitium, suggesting that the SSC niche is related to interstitial elements and might be conserved across vertebrates. This localization was also confirmed by analyzing the topographical distribution of type A undifferentiated spermatogonia in normal, vasa::egfp and fli::egfp zebrafish testes. In the latter one, the topographical arrangement suggested that the vasculature is important for the SSC niche, perhaps as a supplier of nutrients, oxygen and/or signaling molecules. We also developed an SSC transplantation technique for both male and female recipients as an assay to evaluate the presence, biological activity, and plasticity of the SSC candidates in zebrafish.
Conclusions/Significance
We demonstrated donor-derived spermato- and oogenesis in male and female recipients, respectively, indicating the stemness of type A undifferentiated spermatogonia and their plasticity when placed into an environment different from their original niche. Similar to other vertebrates, the transplantation efficiency was low. This might be attributed to the testicular microenvironment created after busulfan depletion in the recipients, which may have caused an imbalance between factors regulating self-renewal or differentiation of the transplanted SSCs
Paternal effects on early embryogenesis
Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field
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