Environmental Factors Linked to Harmful Algal Bloom Induced Shellfish Toxicity in Cobscook Bay, Maine

The Gulf of Maine experiences annual closures of shellfish harvesting due to the accumulation of toxins resulting from harmful algal blooms of the dinoflagellate Alexandrium spp. If ingested by humans, these toxins can cause paralytic shellfish poisoning. The factors affecting the timing, location, and magnitude of these events remain poorly understood. Previous work found no obvious correlations between Gulf of Maine oceanographic variability and interannual variability in toxicity in the strongly tidally mixed eastern Maine coastal region in the vicinity of Cobscook Bay. Using 21 years (1985-2005) of Maine Department of Marine Resources shellfish toxicity data, interannual variability in two metrics of annual toxicity, maximum magnitude and integrated total annual toxicity, are examined for relationships to a suite of environmental variables. Consistent with earlier work, no correlation was found between toxicity and oceanographic variables, even when individual station toxicity was compared to very proximate variables such as local sea surface temperature and river discharge. However, correlations between toxicity and two variables indicative of local weather, dew point and atmospheric pressure, both suggest a link between increased toxicity and clearer skies/ drier air. As no correlation was evident between toxicity and local precipitation, we hypothesize that the link is through light availability in this persistently foggy section of coast

Organization of spatiotemporal information and relational memory in the hippocampus

This work examines the role of the hippocampus and relational memory in organizing episodic memory during navigation and reconstruction. Navigation is a critical component in most organisms’ survival. Reconstruction, on the other hand, provides an incredibly rich method of evaluating the precise information remembered by an individual after attempting to learn and remember that information. Through validating the computational framework in this work on amnesic patients with hippocampal damage, an understanding of some of the specific types of relations which rely on the hippocampus can be established. Then, this framework can be applied to a much more complex, spatiotemporal navigation and reconstruction task in healthy individuals to gain a wider perspective on the organization of episodic memory, which is known to critically rely on the hippocampus. The first experiment and associated analysis framework presented in this document (Chapter 2) uses spatial reconstruction to establish that not all types of spatial relations are impaired in hippocampal damaged patients. In particular, the arbitrary, identity-location relations (i.e. those relationships where the element being bound could have just as easily been anything) are critically impaired in hippocampal damaged patients while location information, disregarding identity, is not. The use of reconstruction in this context allows for the establishment of a set of critical computational metrics which relate to hippocampal function in reconstruction which can then be applied to other reconstruction tasks in healthy individuals to learn more about the wider structure and organization of memory. In the second experiment (Chapters 3 and 4), the methodologies which were applied to hippocampal damaged patients in the first experiment are applied to a novel Spatiotemporal Navigation Task in healthy young adults. In this task, participants are not just asked to study and reconstruct items in space, but instead, participants are asked to, in Virtual Reality, navigate space and time (via normal movement and simulated Time Travel) and study, then reconstruct the locations of events in spacetime. The computational framework established in the previous chapter is then applied to show that relational memory errors in time are far more common in this task than in space, suggesting differences in representations between these two domains even when the navigation and exploration of the domains are put on a more equal footing. Additionally, in time, these relational memory errors are far more likely to occur within a shared contextual region than should occur by chance. In fact, this error (temporal relational memory error within a context) gets worse across the first 3 trials, suggesting a systematic bias due to context. Finally, a more traditional bias, the context boundary effect (i.e. a “squishing” of within context temporal locations and “stretching” of across context temporal locations) is observed even though participants are allowed to reexplore the contexts arbitrarily, multiple times. This suggests that the context boundaries are having a profound impact on both the distance judgements and relational memory structure associated with events in spacetime. Finally, in the fourth chapter, the navigation component of the previous Spatiotemporal Navigation Task is examined to determine if changes in study time navigation and exploration relate to changes in the various test metrics discussed in the previous chapter. More rapid improvements in spatial and temporal navigation are shown to relate to more rapid improvements in memory in those domains, separably, suggesting that spatial and temporal representations may in some way be separable in this task in both the relational representations and the navigation strategies supporting those representations. Relational memory improvements are shown to be uniquely tied to changes in navigation complexity and systematicity, pointing to an interplay between in-the-moment, memory-guided decision making and subsequent relational memory efficacy. Context boundaries are suggested to act as more of a discriminatory feature (at least in this task) than one used to strengthen within-context relational memory organization accuracy as there is a significant relationship between changes in context boundary crossing and both the context boundary effect and across-context temporal relational memory errors. Finally, a preference towards exploring an otherwise temporally-flexible environment in the implied, forward order with increasing contiguity is suggested to be a critical element in improving temporal, relational, and contextual memory organization. Taken together, this work shows the richness of spatiotemporal navigation and reconstruction in observing the complex interplay between navigation in space, navigation in time and how these ultimately may relate to navigation in memory. Through embracing principled approaches to analysis of behavioral data, and the inclusion of complex behavioral mechanics (such as simulated time travel), this work extends our understanding of the role of hippocampal relational memory and overall memory organization

Osteoarthritis of the knee - biochemical aspect of applied therapies: a review

The most prevalent form of arthritis is osteoarthritis (OA) of the knee, which is characterized by a degeneration of articular cartilage resulting in the development of osteophytes, or bone spurs. Main goals of OA treatment are to reduce pain, slow the disease progression, and improve joint function and the quality of life. The purpose of this study was to verify all the therapies recommended by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) from the biochemical point of view. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of eicosanoids, whereas paracetamol prevents the production of prostaglandin (PG) by interacting with peroxidase (POX) site of the prostaglandin H2 synthase complex. Tramadol is an opioid that has a dual mechanism of action: it binds to the μ-opioid receptor and it inhibits serotonin and adrenaline. Corticosteroids, which are also prescribed for OA pain, inhibit the activity of phospholipase A2 and block the synthesis of arachidonate-derived eicosanoids. Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are drugs that are well tolerated by patients and help to restore proteoglycan matrix of the cartilage. These drugs include compounds that naturally build articular cartilage. The articular cartilage, as well as the bone located around the cartilage, are destroyed as osteoarthritis progresses. Thus, bisphosphonates, commonly used in the treatment of osteoporosis, were evaluated as potential therapy. However, there is no official recommendation for their use in therapy. The aim of the study was to analyze the biochemical mechanisms of principal drugs used for the treatment of knee OA. Therefore, a narrative review summarizing the current knowledge regarding the applied therapies was prepared

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast

In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth-­dependent signals control cell growth and the cell cycle

Genetski deverzitet u okviru fragmenta gena myo15a, odgovornog za sluh u populaciji životinja familije canidae u uslovima farmskog i slobodnog uzgoja

The gene MYO15A is involved in the production of a protein included in the group of motor proteins known as myosins. Myosin XVA is located in the inner ear, the pituitary gland and other tissues, and has a substantial influence on the hearing process. Mutations in this gene cause amino acid substitutions in the conserved motor domain of the myosin chain, leading to shortening of the stereocilia in the hair cells, so that the function of myosin XVA is impaired. A research hypothesis was put forth that mutations in the gene responsible for the hearing process in animals of the Canidae family can cause hypoacusis, as well as substantial behavioural changes in dogs (ranging from timidity to aggressive behaviour). The study determined SNP polymorphism in a fragment of the gene MYO15A, which can cause hearing disorders or hypoacusis, in wild and farmed individuals of the Canidae family.Gen MYO15A je uključen u stvaranje proteina iz grupe motornih proteina - miozina. Miozin XVA je lociran u unutrašnjem uhu, hipofi zi i drugim tkivima, i značajno utiče na slušni proces. Mutacije u ovom genu izazivaju supstitucije aminokiselina u konzervisanom motornom domenu lanca miozina, što dovodi do skraćenja stereocilija slušnih ćelija, a kao posledica dolazi do poremećaja funkcije XVA miozina. Postavljena je istraživačka hipoteza koja je pretpostavljala da mutacije u genu koji je odgovoran za slušni proces kod životinja familije Canidae mogu da izazovu hipoakustiku kao i značajne promene u ponašanju pasa, od povučenosti i straha do agresivnosti. Ispitivanjem je determinisan SNP polimorfi zam u fragmentu gena MYO15A koji može da dovede do poremećaja sluha kako kod divljih tako i kod farmski uzgajanih životinja familije Canidae

Ty1 integrase overexpression leads to integration of non-Ty1 DNA fragments into the genome of Saccharomyces cerevisiae

The integrase of the Saccharomyces cerevisiae retrotransposon Ty1 integrates Ty1 cDNA into genomic DNA likely via a transesterification reaction. Little is known about the mechanisms ensuring that integrase does not integrate non-Ty DNA fragments. In an effort to elucidate the conditions under which Ty1 integrase accepts non-Ty DNA as substrate, PCR fragments encompassing a selectable marker gene were transformed into yeast strains overexpressing Ty1 integrase. These fragments do not exhibit similarity to Ty1 cDNA except for the presence of the conserved terminal dinucleotide 5′-TG-CA-3′. The frequency of fragment insertion events increased upon integrase overexpression. Characterization of insertion events by genomic sequencing revealed that most insertion events exhibited clear hallmarks of integrase-mediated reactions, such as 5 bp target site duplication and target site preferences. Alteration of the terminal dinucleotide abolished the suitability of the PCR fragments to serve as substrates. We hypothesize that substrate specificity under normal conditions is mainly due to compartmentalization of integrase and Ty cDNA, which meet in virus-like particles. In contrast, recombinant integrase, which is not confined to virus-like particles, is able to accept non-Ty DNA, provided that it terminates in the proper dinucleotide sequence

Environmental and Genetic Determinants of Colony Morphology in Yeast

Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic bases of this phenotype and the key environmental signals involved in its induction have heretofore remained poorly understood. By surveying multiple strain backgrounds and a large number of growth conditions, we show that limitation for fermentable carbon sources coupled with a rich nitrogen source is the primary trigger for the colony morphology response in budding yeast. Using knockout mutants and transposon-mediated mutagenesis, we demonstrate that two key signaling networks regulating this response are the filamentous growth MAP kinase cascade and the Ras-cAMP-PKA pathway. We further show synergistic epistasis between Rim15, a kinase involved in integration of nutrient signals, and other genes in these pathways. Ploidy, mating-type, and genotype-by-environment interactions also appear to play a role in the controlling colony morphology. Our study highlights the high degree of network reuse in this model eukaryote; yeast use the same core signaling pathways in multiple contexts to integrate information about environmental and physiological states and generate diverse developmental outputs

Sudden and gradual responses of phytoplankton to global climate change: case studies from two large, shallow lakes (Balaton, Hungary and the Neusiedlersee Austria/Hungary)

This paper analyses two phytoplankton long-term datasets; both are from large, temperate shallow lakes. The main difference between them is that phytoplankton growth in Lake Balaton remained severely P-limited despite P-driven eutrophication during the last 30 years, whereas extremely high turbidity causes a permanent light limitation in Neusiedlersee and therefore an increase in P-loadings did not result in a similar increase in phytoplankton biomass. Neusiedlersee is a (slightly) saline inland lake. In Lake Balaton, the blue-green alga Cylindrospermopsis raciborskii blooms invariably if the July-august temperature deviates positively from a 30-year average by ca. 2 °C. A supposed global warming is predicted to cause a higher frequency (but not intensity!) of these blooms. Neusiedlersee is very shallow and therefore regulation techniques cannot prevent water levels sinking in successive dry years. Annual averages of phytoplankton seem to follow quite a regular, wave-like cyclicity. Such cycles can be recognised in the population records of the characteristic species. Similar changes were seen in changes of water level, conductivity, inorganic-P, inorganic N-forms and nutrient ratios. How phytoplankton species can follow a climatic cycle that covers 200 to 500 generations has not yet become clear. Because of reasons discussed in the paper, neither of the two cases can be generalised; each is quite individual

Molecular interactions between Hel2 and RNA supporting ribosome-associated quality control

Ribosome-associated quality control (RQC) pathways monitor and respond to stalling of the translating ribosome. Here the authors show that the ribosome associated RQC factor Hel2/ZNF598, an E3 ubiquitin ligase, generally interacts with mRNAs in the vicinity of stop codons