Protecting FPGA-Based Cryptohardware Implementations from Fault Attacks Using ADCs.

The majority of data exchanged between connected devices are confidential and must be protected against unauthorized access. To ensure data protection, so-called cryptographic algorithms are used. These algorithms have proven to be mathematically secure against brute force due to the key length, but their physical implementations are vulnerable against physical attacks. The physical implementation of these algorithms can result in the disclosure of information that can be used to access confidential data. Some of the most powerful hardware attacks presented in the literature are called fault injection attacks. These attacks involve introducing a malfunction into the normal operation of the device and then analyzing the data obtained by comparing them with the expected behavior. Some of the most common methods for injecting faults are the variation of the supply voltage and temperature or the injection of electromagnetic pulses. In this paper, a hardware design methodology using analog-to-digital converters (ADCs) is presented to detect attacks on cryptocircuits and prevent information leakage during fault injection attacks. To assess the effectiveness of the proposed design approach, FPGA-based ADC modules were designed that detect changes in temperature and supply voltage. Two setups were implemented to test the scheme against voltage and temperature variations and injections of electromagnetic pulses. The results obtained demonstrate that, in 100% of the cases, when the correct operating voltage and temperature range were established, the detectors could activate an alarm signal when the cryptographic module was attacked, thus avoiding confidential information leakage and protecting data from being exploited.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

Influence of vehicular emissions on the levels of polycyclic aromatic hydrocarbons (PAHs) in urban and industrial areas of La Plata, Argentina.

Polycyclic aromatic hydrocarbons (PAHs) are considered potentially toxic, even carcinogenic, because of their affection to public health and the environment. It is necessary to know their ambient levels and the origin of these pollutants in order to mitigate them. A concerning scenario is the one in which commercial/administrative, industrial, and residential activities coexist. In this context, Gran La Plata (Argentina) presents such characteristics, in addition to the presence of one of the most important petrochemical complexes in the country and intense vehicular traffic. The source apportionment of PAH emission in the region, associated to 10-µm and 2.5-µm particulate matter fractions, was studied. First, different missing value imputation methods were evaluated for PAH databases. GSimp presented a better performance, with mean concentrations of ∑PAHs of 65.8 ± 40.2 ng m-3 in PM10 and 39.5 ± 18.0 ng m-3 in PM2.5. For both fractions, it was found that the highest contribution was associated with low molecular weight PAHs (3 rings), with higher concentrations of anthracene. Emission sources were identified by using principal component analysis (PCA) together with multiple linear regression (MLR) and diagnostic ratios of PAHs. The results showed that the main emission source is associated with vehicular traffic in both fractions. Classification by discriminant analysis showed that emissions can be identified by region and that fluoranthene, benzo(a)anthracene, and anthracene in PM10 and anthracene and phenanthrene in PM2.5 are a characteristic of emissions from the petrochemical complex.

High field magnetometry with hyperpolarized nuclear spins.

Quantum sensors have attracted broad interest in the quest towards sub-micronscale NMR spectroscopy. Such sensors predominantly operate at low magnetic fields. Instead, however, for high resolution spectroscopy, the high-field regime is naturally advantageous because it allows high absolute chemical shift discrimination. Here we demonstrate a high-field spin magnetometer constructed from an ensemble of hyperpolarized 13C nuclear spins in diamond. They are initialized by Nitrogen Vacancy (NV) centers and protected along a transverse Bloch sphere axis for minute-long periods. When exposed to a time-varying (AC) magnetic field, they undergo secondary precessions that carry an imprint of its frequency and amplitude. For quantum sensing at 7T, we demonstrate detection bandwidth up to 7 kHz, a spectral resolution < 100mHz, and single-shot sensitivity of 410pT[Formula: see text]. This work anticipates opportunities for microscale NMR chemical sensors constructed from hyperpolarized nanodiamonds and suggests applications of dynamic nuclear polarization (DNP) in quantum sensing.

Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent in primary hepatocytes.

A number of G protein-coupled receptors (GPCRs) are now thought to use endocytosis to promote cellular cAMP signaling that drives downstream transcription of cAMP-dependent genes. We tested if this is true for the glucagon receptor (GCGR), which mediates physiological regulation of hepatic glucose metabolism via cAMP signaling. We show that epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh-7-Lunet cells after activation by glucagon within 5 min and transit via EEA1-marked endosomes shown previously to be sites of GPCR/Gs-stimulated production of cAMP. We further show that endocytosis potentiates cytoplasmic cAMP elevation produced by GCGR activation and promotes expression of phosphoenolpyruvate carboxykinase 1 (PCK1), the enzyme catalyzing the rate-limiting step in gluconeogenesis. We verify endocytosis-dependent induction of PCK1 expression by endogenous GCGRs in primary hepatocytes and show similar control of two other gluconeogenic genes (PGC1α and G6PC). Together, these results implicate the endosomal signaling paradigm in metabolic regulation by glucagon.

Modeling amplified arbitrary filtered heterodyne microwave photonic links.

We report an end-to-end analytic model for the computation of the figures of nerit (FOMs) of arbitrarily filtered and amplified heterodyne coherent microwave photonics (MWP) links. It is useful for evaluating the performance of complex systems where the final stage is employed for up/down-converting the radio frequency (RF) signal. We apply the model to a specific case of complex system representing the front-haul segment in a 5G link between the central office and the base station. The model can be however applied to a wider range of cases combining fiber and photonic chip elements and thus is expected to provide a useful and fast tool to analyze them in the design stage.

Experimental FIA Methodology Using Clock and Control Signal Modifications under Power Supply and Temperature Variations.

The security of cryptocircuits is determined not only for their mathematical formulation, but for their physical implementation. The so-called fault injection attacks, where an attacker inserts faults during the operation of the cipher to obtain a malfunction to reveal secret information, pose a serious threat for security. These attacks are also used by designers as a vehicle to detect security flaws and then protect the circuits against these kinds of attacks. In this paper, two different attack methodologies are presented based on inserting faults through the clock signal or the control signal. The optimization of the attacks is evaluated under supply voltage and temperature variation, experimentally determining the feasibility through the evaluation of different Trivium versions in 90 nm ASIC technology implementations, also considering different routing alternatives. The results show that it is possible to inject effective faults with both methodologies, improving fault efficiency if the power supply voltage decreases, which requires only half the frequency of the short pulse inserted into the clock signal to obtain a fault. The clock signal modification methodology can be extended to other NLFSR-based cryptocircuits and the control signal-based methodology can be applied to both block and stream ciphers.

Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms.

Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transported via sensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.

Modeling amplified arbitrary filtered microwave photonic links and systems.

Microwave photonic (MWP) links and systems will have more losses as their complexities increase and there will be a need for incorporating optical amplification. Here, we report results of an analytical model developed for amplified arbitrary filtered MWP systems that provides the expressions of the main figures of merit for intensity modulation direct detection. It contemplates the cases of power, intermediate and pre amplification. The model is applied to a long MWP link and then it is evaluated in a MWP reconfigurable filter implemented by means of a programmable waveguide mesh photonic integrated circuit.

Integrated photonic tunable basic units using dual-drive directional couplers.

Photonic integrated circuits based on waveguide meshes and multibeam interferometers call for large-scale integration of Tunable Basic Units (TBUs) that feature beam splitters and waveguides. This units are loaded with phase actuators to provide complex linear processing functionalities based on optical interference and can be reconfigured dynamically. Here, we propose and experimentally demonstrate, to the best of our knowledge, for the first time, a thermally actuated Dual-Drive Directional Coupler (DD-DC) design integrated on a silicon nitride platform. It operates both as a standalone optical component providing arbitrary optical beam splitting and common phase as well as a low loss and potentially low footprint TBU. Finally, we report the experimental demonstration of the first integrated triangular waveguide mesh arrangement using DD-DC based TBUs and provide an extended analysis of its performance and scalability.

Characterization and cancer risk assessment of VOCs in home and school environments in gran La Plata, Argentina.

Three areas are highlighted in Gran La Plata, Argentina: industrial, urban, and residential. In this work, the levels of volatile organic compounds (VOCs) in indoor air of homes and schools in those areas were analyzed, through the use of passive monitors. The study period is between 2007 and 2010. Higher levels of VOCs were found in homes and schools in the industrial zone, higher than the levels corresponding to urban and residential. Taking into account the relationship between indoor and outdoor levels of VOCs, they have ratios (I/O) between 1.5 and 10 are evidenced contributions of emission sources of VOCs both indoor and outdoor. Complementarily, we estimated the life time cancer risk (LCR) for benzene, styrene, trichloroethylene, and tetrachloroethylene in children who spend their time mostly in such indoor environments. The results show high LCR values for benzene, which exceed acceptable values for the US EPA.

The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation.

Vitamin B12 deficiency is common in older individuals. Circulating vitamin B12 concentration can be used to diagnose deficiency, but this test has substantial false positive and false negative rates. We conducted genome-wide association studies (GWAS) in which we resolved total serum vitamin B12 into the fractions bound to transcobalamin and haptocorrin: two carrier proteins with very different biological properties. We replicated reported associations between total circulating vitamin B12 concentrations and a common null variant in FUT2. This allele determines the secretor phenotype in which blood group antigens are found in non-blood body fluids. Vitamin B12 bound to haptocorrin (holoHC) remained highly associated with FUT2 rs601338 (p.Trp154Ter). Transcobalamin bound vitamin B12 (holoTC) was not influenced by this variant. HoloTC is the bioactive the form of the vitamin and is taken up by all tissues. In contrast, holoHC is only taken up by the liver. Using holoHC from individuals with known FUT2 genotypes, we demonstrated that FUT2 rs601338 genotype influences the glycosylation of haptocorrin. We then developed an experimental model demonstrating that holoHC is transported into cultured hepatic cells (HepG2) via the asialoglycoprotein receptor (ASGR). Our data challenge current published hypotheses on the influence of genetic variation on this clinically important measure and are consistent with a model in which FUT2 rs601338 influences holoHC by altering haptocorrin glycosylation, whereas B12 bound to non-glycosylated transcobalamin (i.e. holoTC) is not affected. Our findings explain some of the observed disparity between use of total B12 or holoTC as first-line clinical tests of vitamin B12 status.

Hábitos alimenticios de Leporinus friderici (Anostomidae: Teleostei) durante un ciclo hidrobiológico en el río Vaupés, Colombia / Feeding habits of Leporinus friderici (Anostomidae: Teleostei) during a hydrobiological cycle in Vaupés River, Colombia

ResumenLa especie más importante de la pesquería del río Vaupés es un pez conocido como Warakú tres puntos (Leporinus friderici), un carácido migratorio representativo del departamento del Vaupés, Colombia, de importancia para la seguridad alimentaria de comunidades indígenas. Con el propósito de contribuir en el conocimiento biológico básico de la especie, el presente estudio determinó los hábitos y preferencias alimenticias de Leporinus friderici durante un ciclo hidrobiológico (marzo 2014 a mayo 2015) en el río Vaupés, Colombia. Fueron muestreados tres lugares, dos a lo largo del río Vaupés (comunidades indígenas de Yacayacá y Santa Cruz) y uno en el río Cuduyarí afluente del río Vaupés (comunidad de Piracemo). Se analizaron 316 contenidos estomacales aplicando los métodos de frecuencia de ocurrencia (FO), índice gravimétrico (W), coeficiente de vacuidad (CV) e índice de importancia relativa (IIR). De igual modo, se determinaron parámetros físicos y químicos del agua superficial y profunda. La profundidad del río en época de aguas ascendentes fue de 3.7 ± 0.6 m, aguas altas de 5.9 ± 1.4 m, aguas descendentes 4.6 ± 1.3 m y en aguas bajas 2.4 ± 1.0 m; se registró mayor acidez y turbidez del agua en las ascendentes. El CV fue de 14.5 %; sin embargo, el CV alcanzó un valor del 40 % en aguas ascendentes. En general se observó una mayor FO de material vegetal en los estómagos de los individuos muestreados (44.4-66.7 %), seguido por los insectos (21.1-33.3 %, dietas secundarias). Los índices gravimétricos reflejaron que el material vegetal fue el ítem consumido en mayor cantidad, seguido de los insectos y en casi igual proporción invertebrados y material animal. Las diferencias en la composición de la dieta confirman la naturaleza oportunista de esta especie con predominio de hábitos omnívoros.Este estudio puede ser utilizado como parte integral del conocimiento de la ecología trófica de la especie, con el fin de crear estrategias para la protección del L. friderici en la región del Vaupés.

AbstractThe most important fish species of the Vaupes river is known as a Warakú tres puntos (Leporinus friderici), the most representative migratory Characidae from the Vaupés state, Colombia, with a significant importance in food security of indigenous communities. To contribute with the knowledge of its basic biology, we determined the habits and food preferences of Leporinus friderici, during one hydrobiological cycle (March 2014 to May 2015) in the Vaupés river, Colombia. Three sites were sampled, two of them along the Vaupés river (Yacayacá and Santa Cruz communities) and the other one in the Cuduyarí river, tributary of the Vaupés river (Piracemo community). Physical and chemical water parameters from the surface and depth level of the river were determined. Stomach contents from 316 fish were analyzed by frequency of occurrence (FO), gravimetric index, vacuity index (VI) and relative importance index (RII). Vaupés's average depth in ascending water period was of 3.7 ± 0.6 m, during rainy season of 5.9 ± 1.4 m, in descending water period of 4.6 ± 1.3 m and during dry season of 2.4 ± 1.0 m. The higher acidity and turbidity were observed during the ascending water period. The average VI was 14.5 % for the period, but it reached 40 % in descending waters. In general, a FO of plant material was the most frequent (44.4-66.7 %), followed by insects (21.1-33.3 %, secondary diets). The gravimetric indices showed that plant material was the most consumed item, followed by insects, and in almost in equal proportion, invertebrates and animal material. The differences in diet composition confirm the opportunistic nature of this species with a predominance of omnivorous habits. This study can be used as an integral part of the feeding ecology of L. friderici knowledge, in order to develop strategies for its protection in the Vaupés region because of its importance for local communities.

Glycolysis, Glutaminolysis, and Fatty Acid Synthesis Are Required for Distinct Stages of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). KSHV infection induces and requires multiple metabolic pathways, including the glycolysis, glutaminolysis, and fatty acid synthesis (FAS) pathways, for the survival of latently infected endothelial cells. To determine the metabolic requirements for productive KSHV infection, we induced lytic replication in the presence of inhibitors of different metabolic pathways. We found that glycolysis, glutaminolysis, and FAS are all required for maximal KSHV virus production and that these pathways appear to participate in virus production at different stages of the viral life cycle. Glycolysis and glutaminolysis, but not FAS, inhibit viral genome replication and, interestingly, are required for different early steps of lytic gene expression. Glycolysis is necessary for early gene transcription, while glutaminolysis is necessary for early gene translation but not transcription. Inhibition of FAS resulted in decreased production of extracellular virions but did not reduce intracellular genome levels or block intracellular virion production. However, in the presence of FAS inhibitors, the intracellular virions are noninfectious, indicating that FAS is required for virion assembly or maturation. KS tumors support both latent and lytic KSHV replication. Previous work has shown that multiple cellular metabolic pathways are required for latency, and we now show that these metabolic pathways are required for efficient lytic replication, providing novel therapeutic avenues for KS tumors.IMPORTANCE KSHV is the etiologic agent of Kaposi's sarcoma, the most common tumor of AIDS patients. KS spindle cells, the main tumor cells, all contain KSHV, mostly in the latent state, during which there is limited viral gene expression. However, a percentage of spindle cells support lytic replication and production of virus and these cells are thought to contribute to overall tumor formation. Our previous findings showed that latently infected cells are sensitive to inhibitors of cellular metabolic pathways, including glycolysis, glutaminolysis, and fatty acid synthesis. Here we found that these same inhibitors block the production of infectious virus from lytically infected cells, each at a different stage of viral replication. Therefore, inhibition of specific cellular metabolic pathways can both eliminate latently infected cells and block lytic replication, thereby inhibiting infection of new cells. Inhibition of metabolic pathways provides novel therapeutic approaches for KS tumors.

Expresión del síndrome metabólico frente a factores ambientales / Expression of metabolic syndrome against environmental factors / Expressão da síndrome metabólica frente a fatores ambientais

El Síndrome Metabólico (SM) se define como la asociación de alteraciones metabólicas e inflamatorias a nivel molecular, celular o hemodinámico, que pueden presentarse en forma simultánea o secuencial en un mismo individuo. Esto imprime un mayor riesgo de desarrollar diabetes y enfermedades cardiovasculares, teniendo como base la resistencia insulínica. Su diagnóstico se presenta cuando existe obesidad abdominal y dos o más componentes adicionales: triglicéridos elevados, lipoproteína de alta densidad (HDL) baja, alteración en la regulación de la glucemia y presión arterial alta. En este contexto, y dada su relación con los factores ambientales, el objetivo del presente trabajo fue evaluar la relación del SM en poblaciones expuestas a diferentes niveles de contaminación atmosférica, determinando dicha asociación mediante las respuestas obtenidas de una encuesta socioeconómica, de antecedentes de salud, y contrastándolas con análisis sanguíneos. Finalmente, los resultados obtenidos evidencian intercurrencias entre el grado de contaminación atmosférica y el SM.

The metabolic syndrome (MS) is defined as the association of metabolic disorders and inflammatory diseases at molecular, cellular or hemodynamic levels, which may occur simultaneously or sequentially in the same individual. This adds an increased risk of developing diabetes and cardiovascular disease, based on insulin resistance. MS diagnosis is made when there are two or more additional components and abdominal obesity: elevated triglycerides, high density lipoprotein (HDL) low, altered regulation of blood glucose and high blood pressure. In this context, and given its relationship with environmental factors, the objective of this study was to evaluate the relationship of MS in populations exposed to different levels of air pollution,determining the association with the responses obtained from a socio-economic survey and health history, and contrasting them with a blood test. Finally, the results show intercurrences between the degree of air pollution and SM.

A síndrome metabólica (SM) é definida como a associação de alterações metabólicas e inflamatórias em nível molecular, celular ou hemodinâmico, que podem ocorrer em forma simultânea ou sequencial num mesmo indivíduo. Isto adiciona um maior risco de desenvolver diabetes e doenças cardiovasculares, tendo como base a resistência à insulina. Seu diagnóstico ocorre quando há obesidade abdominal e dois ou mais componentes adicionais: aumento dos triglicerídeos, lipoproteína de alta densidade (HDL) baixa, alteração na regulação da glicemia e pressão arterial elevada. Neste contexto, e devido a sua relação com os fatores ambientais, o objetivo desse estudo foi avaliar a relação da SM em populações expostas a diferentes níveis de poluição do ar, determinando tal associação através das respostas obtidasa em um levantamento socioeconômico, histórico de saúde e em contraste com análises de sangue. Por fim, os resultados mostram intercorrências entre o grau de poluição do ar e a SM.

Autotrasplante dental: revisión de la literatura y presentación de dos casos / Autogenous tooth transplantation: a review of the literature and report of two cases

El autotrasplante dental se define como el traslado de un diente de su alveolo a un alveolo post-extracción o alveolo confeccionado quirúrgicamente, en la misma persona. Actualmente siguiendo los criterios de selección adecuados así como una técnica quirúrgica minuciosa puede resultar una alternativa terapéutica ideal en ciertos pacientes. Las tasas de éxito han aumentado con el tiempo alcanzando cifras mayores al90%. En el presente artículo se reportan dos casos de éxito de autotransplantesdentales y se revisan las indicaciones, contraindicaciones y criterios de éxito de los mismos.

Autogenous tooth transplantation is defined as the movement of a tooth from its socket to a post-extraction or surgically created socketin the same individual. Today, by following appropriate selection criteria and a refi ned surgical technique, this procedure can prove tobe an ideal therapeutic alternative in certain patients. Success rateshave increased over time, reaching as high as 90%. In this article, wepresent two cases of successful autogenous tooth transplantation and a review of the indications, contraindications, and success criteria associated with these.

Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival.

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of Kaposi's Sarcoma (KS). KSHV establishes a predominantly latent infection in the main KS tumor cell type, the spindle cell, which is of endothelial cell origin. KSHV requires the induction of multiple metabolic pathways, including glycolysis and fatty acid synthesis, for the survival of latently infected endothelial cells. Here we demonstrate that latent KSHV infection leads to increased levels of intracellular glutamine and enhanced glutamine uptake. Depletion of glutamine from the culture media leads to a significant increase in apoptotic cell death in latently infected endothelial cells, but not in their mock-infected counterparts. In cancer cells, glutamine is often required for glutaminolysis to provide intermediates for the tri-carboxylic acid (TCA) cycle and support for the production of biosynthetic and bioenergetic precursors. In the absence of glutamine, the TCA cycle intermediates alpha-ketoglutarate (αKG) and pyruvate prevent the death of latently infected cells. Targeted drug inhibition of glutaminolysis also induces increased cell death in latently infected cells. KSHV infection of endothelial cells induces protein expression of the glutamine transporter, SLC1A5. Chemical inhibition of SLC1A5, or knockdown by siRNA, leads to similar cell death rates as glutamine deprivation and, similarly, can be rescued by αKG. KSHV also induces expression of the heterodimeric transcription factors c-Myc-Max and related heterodimer MondoA-Mlx. Knockdown of MondoA inhibits expression of both Mlx and SLC1A5 and induces a significant increase in cell death of only cells latently infected with KSHV, again, fully rescued by the supplementation of αKG. Therefore, during latent infection of endothelial cells, KSHV activates and requires the Myc/MondoA-network to upregulate the glutamine transporter, SLC1A5, leading to increased glutamine uptake for glutaminolysis. These findings expand our understanding of the required metabolic pathways that are activated during latent KSHV infection of endothelial cells, and demonstrate a novel role for the extended Myc-regulatory network, specifically MondoA, during latent KSHV infection.

Viral activation of cellular metabolism.

To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for the replication of each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways.

Dengue virus induces and requires glycolysis for optimal replication.

UNLABELLED: Viruses rely on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. Dengue virus (DENV), a member of the Flaviviridae family, is one of the most important arthropod-borne human pathogens worldwide. We analyzed global intracellular metabolic changes associated with DENV infection of primary human cells. Our metabolic profiling data suggested that central carbon metabolism, particularly glycolysis, is strikingly altered during a time course of DENV infection. Glucose consumption is increased during DENV infection and depriving DENV-infected cells of exogenous glucose had a pronounced impact on viral replication. Furthermore, the expression of both glucose transporter 1 and hexokinase 2, the first enzyme of glycolysis, is upregulated in DENV-infected cells. Pharmacologically inhibiting the glycolytic pathway dramatically reduced DENV RNA synthesis and infectious virion production, revealing a requirement for glycolysis during DENV infection. Thus, these experiments suggest that DENV induces the glycolytic pathway to support efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat DENV infection in the future. IMPORTANCE: Approximately 400 million people are infected with dengue virus (DENV) annually, and more than one-third of the global population is at risk of infection. As there are currently no effective vaccines or specific antiviral therapies for DENV, we investigated the impact DENV has on the host cellular metabolome to identify metabolic pathways that are critical for the virus life cycle. We report an essential role for glycolysis during DENV infection. DENV activates the glycolytic pathway, and inhibition of glycolysis significantly blocks infectious DENV production. This study provides further evidence that viral metabolomic analyses can lead to the discovery of novel therapeutic targets to block the replication of medically important human pathogens.

Percepción del riesgo al cambio climático y sus efectos sobre la salud y enfermedades infecciosas en estudiantes universitarios, 2011 Santa Marta-Colombia / Risk perception of climate change and its impact on health and infectious diseases in undergraduate students, 2011 Santa Marta-Colombia

Introducción: La Organización Mundial de la Salud (OMS) ha denominado que el cambio climático es una amenaza para la salud pública, por lo tanto es necesario conocer la percepción del riesgo al cambio climático específicamente en los futuros profesionales de la salud. Materiales y Métodos: Se realizó una investigación de tipo cuantitativo descriptiva con muestreo aleatorio estratificado. Se realizaron análisis de Chi2 y regresión logística para identificar los factores asociados a la percepción del riesgo al cambio climático y al aumento de enfermedades infecciosas sensibles al cambio climático en estudiantes universitarios de las ciencias de la salud en la Universidad del Magdalena. Resultados: Por Chi2 se encontró que cerca del 69% de los estudiantes perciben el cambio climático como dañino y entre 50 y 59% de ellos perciben que las enfermedades infecciosas aumentarán como consecuencia del cambio climático. Por regresión logística se observó significancia estadística que los estudiantes que pertenecen al sexto semestre de estudios o semestres superiores tienen 60% más probabilidad de reconocer que pueden enfermarse por el cambio climático, 63% más probabilidad de percibir el cambio climático como dañino, relacionaron 2,2 veces más el aumento de la temperatura global con el aumento de enfermos con fiebre amarilla y dengue, también tienen 58% más posibilidad de relacionar el aumento de los casos. Discusión: Los estudiantes de los diferentes programas de salud que pertenecen al sexto semestre de estudios o superiores percibieron el cambio climático como una amenaza sobre la salud pública y lo asociaron con el aumento de enfermedades infecciosas, de esta manera, se puede considerar que los estudiantes de salud conforme avanzan en los semestres académicos perciben un mayor riesgo del cambio climático como una amenaza sobre la salud pública y un aumento de los enfermos por enfermedades infecciosas sensibles al cambio climático. Conclusiones: Se puede concluir que los estudiantes de ciencias de la salud de la Universidad del Magdalena conforme se encuentran en semestres superiores adquieren una mayor percepción del riesgo del impacto del cambio climático sobre la salud pública y sobre el aumento de las enfermedades infecciosas.

Introduction: The World Health Organization (WHO) has called that climate change is a threat to public health, it is therefore necessary to know the perception of risk to climate change specifically on future health professionals. Materials and Methods: Descriptive quantitative research was undertaken with stratified random sampling. Chi2 analysis and logistic regression were performed to identify factors associated with sensitive risk perception of climate change and increased climate change to infectious diseases. Results: By Chi2 was found that about 69% of students perceive climate change as harmful and between 50 and 59% of them perceive that infectious diseases will increase as a result of climate change. By logistic regression statistical significance was observed that students who belong to the sixth semester of study or higher semesters are 60% more likely to recognize that they can get sick from climate change, 63% more likely to perceive climate change as harmful, were associated 2.2 times plus the increase in global temperature to increase in patients with yellow fever and dengue, also have 58% more likely to relate the increase in cases of cholera and malaria, with respect to students belonging to lower semesters. Discussion: Students of different health programs that belong to the sixth semester of study or higher perceived climate change as a threat to public health and associated with increased infectious diseases, thus, can be considered health students as they progress in academic semesters perceive a greater risk of climate change as a threat to public health and an increase in sick for climate-sensitive infectious diseases. Conclusions: It can be concluded that students in health sciences at the University of Magdalena as found in higher semesters acquire a greater perception of risk from the impact of climate change on public health and the increase of infectious diseases.