Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress.

Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo

Impact of various essential oils and plant extracts on the characterization of the composite seaweed hydrocolloid and gac pulp (Momordica cochinchinensis) edible film

Edible films and coatings have currently received increasing interest because of their potential in food applications. This study examined the effect of incorporated essential oils and natural plant extracts on the characteristics of the composite seaweed hydrocolloid and gac pulp films. Films were prepared by a casting technique, followed by measurement of physical, optical, barrier, mechanical, and structural properties. The results showed that adding plant oils and extracts significantly affected the physical, optical, mechanical, and structural properties of the composite films. Incorporation of the essential oils resulted in a reduction in moisture content and opacity while increasing values for Hue angle and elongation at break of the composite films. Besides, incorporation of the plant extracts showed increases in thickness, opacity, Delta E, Chroma, and elongation at the break, while there is a decrease in the Hue angle values of the composite films. In conclusion, incorporating plant essential oils and extracts into composite seaweed hydrocolloid and gac pulp films can enhance film properties, which can potentially be applied in food products

Local field potentials in a pre-motor region predict learned vocal sequences

Neuronal activity within the premotor region HVC is tightly synchronized to, and crucial for, the articulate production of learned song in birds. Characterizations of this neural activity detail patterns of sequential bursting in small, carefully identified subsets of neurons in the HVC population. The dynamics of HVC are well described by these characterizations, but have not been verified beyond this scale of measurement. There is a rich history of using local field potentials (LFP) to extract information about behavior that extends beyond the contribution of individual cells. These signals have the advantage of being stable over longer periods of time, and they have been used to study and decode human speech and other complex motor behaviors. Here we characterize LFP signals presumptively from the HVC of freely behaving male zebra finches during song production to determine if population activity may yield similar insights into the mechanisms underlying complex motor-vocal behavior. Following an initial observation that structured changes in the LFP were distinct to all vocalizations during song, we show that it is possible to extract time-varying features from multiple frequency bands to decode the identity of specific vocalization elements (syllables) and to predict their temporal onsets within the motif. This demonstrates the utility of LFP for studying vocal behavior in songbirds. Surprisingly, the time frequency structure of HVC LFP is qualitatively similar to well-established oscillations found in both human and non-human mammalian motor areas. This physiological similarity, despite distinct anatomical structures, may give insight into common computational principles for learning and/or generating complex motor-vocal behaviors.Fil: Brown, Daril E.. University of California at San Diego; Estados UnidosFil: Chavez, Jairo I.. University of California at San Diego; Estados UnidosFil: Nguyen, Derek H.. University of California at San Diego; Estados UnidosFil: Kadwory, Adam. University of California at San Diego; Estados UnidosFil: Voytek, Bradley. University of California at San Diego; Estados UnidosFil: Arneodo, Ezequiel Matías. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Gentner, Timothy Q.. University of California at San Diego; Estados UnidosFil: Gilja, Vikash. University of California at San Diego; Estados Unido

BRACELET: Hierarchical Edge-Cloud Microservice Infrastructure for Scientific Instruments’ Lifetime Connectivity

Recent advances in cyber-infrastructure have enabled digital data sharing and ubiquitous network connectivity between scientific instruments and cloud-based storage infrastructure for uploading, storing, curating, and correlating of large amounts of materials and semiconductor fabrication data and metadata. However, there is still a significant number of scientific instruments running on old operating systems that are taken offline and cannot connect to the cloud infrastructure, due to security and performance concerns. In this paper, we propose BRACELET - an edge-cloud infrastructure that augments the existing cloud-based infrastructure with edge devices and helps to tackle the unique performance and security challenges that scientific instruments face when they are connected to the cloud through public network. With BRACELET, we put a networked edge device, called cloudlet, in between the scientific instruments and the cloud as the middle tier of a three-tier hierarchy. The cloudlet will shape and protect the data traffic from scientific instruments to the cloud, and will play a foundational role in keeping the instruments connected throughout its lifetime, and continuously providing the otherwise missing performance and security features for the instrument as its operating system ages.NSF Award Number 1659293NSF Award Number 1443013Ope

4CeeD: Real-Time Data Acquisition and Analysis Framework for Material-related Cyber-Physical Environments

In this paper, we propose a data acquisition and analysis framework for materials-to-devices processes, named 4CeeD, that focuses on the immense potential of capturing, accurately curating, correlating, and coordinating materials-to-devices digital data in a real-time and trusted manner before fully archiving and publishing them for wide access and sharing. In particular, 4CeeD consists of: (i) a curation service for collecting data from experimental instruments, curating, and wrapping of data with extensive metadata in real-time and in a trusted manner, (ii) a cloudlet for caching collected data from curation service and coordinating data transfer with the back-end, and (iii) a cloud-based coordination service for storing data, extracting meta-data, analyzing and finding correlations among the data. Our evaluation results show that our proposed approach is able to help researchers significantly save time and cost spent on experiments, and is efficient in dealing with high-volume and fast-changing workload of heterogeneous types of experimental data.National Science Foundation/NSF ACI 1443013Ope

Vanadium Complexes Are in vitro Inhibitors of Leishmania Secreted Acid Phosphatases

Leishmaniasis is a parasitic disease caused by the protozoa Leishmania. These organisms secrete acid phosphatases during their growth cycle as an important part of cell targeting to host macrophage cells thus allowing for a successful infection. Secreted acid phosphatases (SAP) are reported to play a significant role in the survival of Leishmania cells, thus evaluation of these enzymes is of interest. The inhibition of SAP can be the focus of a new drug therapy. We tested for SAP activity from Leishmania tarentolae following the addition of a series of vanadium complexes including decavanadate. Cell cultures at different stages in their growth curve were harvested by centrifugation and supernatant was collected. The SAP activity in the supernatant was assayed with the artificial substrate p-nitrophenylphosphate (pNPP). Incubation with orthovanadate resulted in a decrease in activity of 18% ± 1 relative to the control, in comparison to decavanadate, which resulted in a 35% ± 4 decrease in activity. Other vanadium complexes showed smaller inhibitory effects than orthovanadate. Some vanadium complexes appeared to have an effect on reducing cell clumping when compared to control cells. The SAP was partially isolated through anion exchange chromatography and results indicate that SAP isozyme forms are present in the supernatant from cells. Future work is focused on obtaining recombinant enzyme which can be more completely characterized for inhibition by vanadium complexes

Toward an understanding of tourists’ authentic heritage experiences: Evidence from Hong Kong

Authenticity in tourism has been a topic of discussion since the 1960s, but the concept is still to be fully developed. This study focuses on tourists’ perceptions of authenticity, and in particular how they evaluate authentic heritage experiences. The appearance and physical settings of attractions were found to be the initial and most important indicators of authentic or inauthentic experiences. Other criteria for assessing the authenticity of heritage experiences include the presence of local culture and customs, constructed elements, commodification, and atmosphere

CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment