Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke.

Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating poststroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a forelimb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the peri-infarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in peri-infarct cortex. This effect is sensitive to competition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ-lineage-tracing mice, SVZ-derived neurons synaptically integrate into the peri-infarct cortex; these effects are enhanced with forelimb overuse. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for poststroke recovery

Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation.

Deregulated c-myc gene expression is associated with many human and animal cancers. Myc overexpression promotes the growth of blood and lymphatic vessels, which is due in part to induction of growth factors including vascular endothelial growth factor (VEGF). We determined that the P493-6 human B-cell line increases VEGF production 10-fold upon Myc overexpression. Myc overexpression in avian B cells similarly resulted in high level VEGF production. Real-time RT-PCR analyses showed that Myc did not alter the VEGF mRNA content of these cell lines, indicating that a post-transcriptional mechanism regulates VEGF production. VEGF mRNA translation was examined by RT-PCR analysis of monosome and polysome sucrose gradient fractions from Myc-on and Myc-off P493-6 cells. Myc increased VEGF mRNA translation initiation, as VEGF mRNA loading onto polysomes increased 14-fold in Myc-on cells, and the number of ribosomes loaded per VEGF mRNA increased threefold. This translational regulation is specific to VEGF mRNA, as total polysomes show the same sucrose gradient profile in Myc-on and Myc-off cells, with no change in the percent ribosomes in polysomes, or in the number of ribosomes per polysomal mRNA. Myc stimulates VEGF production by a rapamycin- and LY294002-sensitive pathway, which does not involve alteration of eIF4E activity

Securing the Invisible Thread: A Comprehensive Analysis of BLE Tracker Security in Apple AirTags and Samsung SmartTags

This study presents an in-depth analysis of the security landscape in Bluetooth Low Energy (BLE) tracking systems, with a particular emphasis on Apple AirTags and Samsung SmartTags, including their cryptographic frameworks. Our investigation traverses a wide spectrum of attack vectors such as physical tampering, firmware exploitation, signal spoofing, eavesdropping, jamming, app security flaws, Bluetooth security weaknesses, location spoofing, threats to owner devices, and cloud-related vulnerabilities. Moreover, we delve into the security implications of the cryptographic methods utilized in these systems. Our findings reveal that while BLE trackers like AirTags and SmartTags offer substantial utility, they also pose significant security risks. Notably, Apple's approach, which prioritizes user privacy by removing intermediaries, inadvertently leads to device authentication challenges, evidenced by successful AirTag spoofing instances. Conversely, Samsung SmartTags, designed to thwart beacon spoofing, raise critical concerns about cloud security and user privacy. Our analysis also highlights the constraints faced by these devices due to their design focus on battery life conservation, particularly the absence of secure boot processes, which leaves them susceptible to OS modification and a range of potential attacks. The paper concludes with insights into the anticipated evolution of these tracking systems. We predict that future enhancements will likely focus on bolstering security features, especially as these devices become increasingly integrated into the broader IoT ecosystem and face evolving privacy regulations. This shift is imperative to address the intricate balance between functionality and security in next-generation BLE tracking systems

p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis.

The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics

Convective suppression before and during the United States Northern Great Plains flash drought of 2017

Flash droughts tend to be disproportionately destructive because they intensify rapidly and are difficult to prepare for. We demonstrate that the 2017 US Northern Great Plains (NGP) flash drought was preceded by a breakdown of land–atmosphere coupling. Severe drought conditions in the NGP were first identified by drought monitors in late May 2017 and rapidly progressed to exceptional drought in July. The likelihood of convective precipitation in May 2017 in northeastern Montana, however, resembled that of a typical August when rain is unlikely. Based on the lower tropospheric humidity index (HIlow), convective rain was suppressed by the atmosphere on nearly 50&thinsp;% of days during March in NE Montana and central North Dakota, compared to 30&thinsp;% during a normal year. Micrometeorological variables, including potential evapotranspiration (ETp), were neither anomalously high nor low before the onset of drought. Incorporating convective likelihood to drought forecasts would have noted that convective precipitation in the NGP was anomalously unlikely during the early growing season of 2017. It may therefore be useful to do so in regions that rely on convective precipitation.</p