Urgent considerations for assessment of coma in the emergency department

Not speaking, closed eyes, absent response to tactile, verbal or noxious stimuli are characteristic of comatose patients. Many causes of coma have been identified and reported in the literature. However, other causes might require extensive assessment and evaluation approaches. The attending physicians start with the baseline support of life for the affected patients, followed by rapid assessment and evaluation of the etiology and pathophysiology and adequate physical examination. In addition, it requires imaging and laboratory investigations whenever needed to determine the most appropriate management plan. In this literature review, we have conducted a brief discussion about the urgent considerations for the assessment of coma in the emergency department. Many causes can attribute to the development of coma. Therefore, adequate assessment and evaluation is a key component in the management of the affected patients in the emergency department. Moreover, the management approach might differ based on the underlying etiology. Nevertheless, caring for breathing, circulation, management of the airways, and stabilization are the main steps that should be done for each comatose patient. Physical examination is also critical in such situations, where imaging or conducting laboratory tests might not be suitable for some patients. Finally, the treatment plan should be directed based on the underlying etiology of coma.

The Eyes Absent proteins in development and in developmental disorders

The Eyes Absent (EYA) transactivator-phosphatase proteins are important contributors to cell-fate determination processes and to the development of multiple organs. The transcriptional regulatory activity as well as the protein tyrosine phosphatase activities of the EYA proteins can independently contribute to proliferation, differentiation, morphogenesis and tissue homeostasis in different contexts. Aberrant EYA levels or activity are associated with numerous syndromic and non-syndromic developmental disorders, as well as cancers. Commensurate with the multiplicity of biochemical activities carried out by the EYA proteins, they impact upon a range of cellular signaling pathways. Here, we provide a broad overview of the roles played by EYA proteins in development, and highlight the molecular signaling pathways known to be linked with EYA-associated organ development and developmental disorders.

EPCT-17. DEVELOPING EYA PHOSPHATASE INHIBITORS WITH ON-TARGET EFFECTS IN SHH-MEDULLOBLASTOMA

Medulloblastoma, one of the most frequent malignant pediatric brain tumors, encompasses four molecularly and clinically distinct cancers. Sonic hedgehog (SHH)-subtype medulloblastoma constitutes about 30% of medulloblastomas, and therapies targeting the SHH pathway can lead to new highly selective treatment. The haloacid dehalogenase (HAD) phosphatase Eyes Absent 1 (EYA1) is critically involved in the development and progression of SHH-medulloblastoma: Eya1 is highly expressed in SHH-medulloblastomas, and single cell sequencing indicates that Eya1 is a consistent feature that can be detected in every individual cancer cell. Inhibition of EYA1 interrupts SHH pathway signaling. During normal development, EYA1 promotes symmetric division of cerebellar granule cell precursors (GCPs), the cells of origin for SHH-subtype medulloblastoma, and reduced levels of EYA1 decrease medulloblastoma mortality rates in mouse models. Therefore, targeting EYA1 may be a novel therapeutic avenue for these pediatric cancers. Benzarone derivatives have been suggested as allosteric EYA-inhibitors, and benzarone provides a promising platform for chemical derivatives. Here, we develop 60 novel benzarone derivatives and assess their efficacy in inhibiting SHH-medulloblastoma growth through the inhibition of EYA1. Several of the new compounds inhibit EYA1 phosphotyrosine phosphatase activity in a cell-based assay, interrupt SHH pathway, and prevent SHH-medulloblastoma growth in vitro. Our results show that these novel benzarone derivatives are a new promising avenue for developing therapeutics for pediatric SHH-medulloblastoma via inhibition of EYA phosphatases.

The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases

Here, we review the haloacid dehalogenase (HAD) class of protein phosphatases, with a particular emphasis on an unusual group of enzymes, the eyes absent (EYA) family. EYA proteins have the unique distinction of being structurally and mechanistically classified as HAD enzymes, yet, unlike other HAD phosphatases, they are protein tyrosine phosphatases (PTPs). Further, the EYA proteins are unique among the 107 classical PTPs in the human genome because they do not use a Cysteine residue as a nucleophile in the dephosphorylation reaction. We will provide an overview of HAD phosphatase structure-function, describe unique features of the EYA family and their tyrosine phosphatase activity, provide a brief summary of the known substrates and cellular functions of the EYA proteins, and speculate about the evolutionary origins of the EYA family of proteins.

A new species of the cave-fish genus Lucifuga (Ophidiiformes, Bythitidae), from eastern Cuba

Recently, a barcoding study and a molecular phylogenetic analysis of the Cuban species of the cave-fish genus Lucifuga Poey, 1858 revealed the existence of different evolutionary lineages that were previously unknown or passed unnoticed by morphological scrutiny (i.e., cryptic candidate species). In the present study, Lucifuga gibarensis is described as a new species restricted to anchialine caves in the northeastern karst region of the main island. The species was earlier described as a variety of Lucifuga dentata, but since the name was introduced as a variety after 1960, it is deemed to be infrasubspecific and unavailable according to the International Code of Zoological Nomenclature Art. 15.2. The new species differs from L. dentata by pigmented eyes vs. eyes absent and lack of palatine teeth vs. present. Lucifuga gibarensis seems to be most similar to the Bahamian species L. lucayana by showing pigmented eyes, 13 or 14 precaudal vertebrae and ten caudal fin rays. However, differs from it by a larger size of the pigmented eye (1.1–1.9 vs. 0.9–1.0% SL) and number of posterior lateral line neuromasts (30–33 vs. 34–35).

EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology inDrosophila

Organisms possess photoperiodic timing mechanisms to detect variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that, inDrosophila melanogaster, EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses. We observed that tissue-specific genetic manipulation ofeyaexpression is sufficient to disrupt the ability of flies to sense seasonal cues, thereby altering the extent of female reproductive dormancy. Specifically, we observed that EYA proteins, which peak at night in short photoperiod and accumulate at higher levels in the cold, promote reproductive dormancy in femaleD. melanogaster. Furthermore, we provide evidence indicating that the role of EYA in photoperiodism and temperature sensing is aided by the stabilizing action of the light-sensitive circadian clock protein TIMELESS (TIM). We postulate that increased stability and level of TIM at night under short photoperiod together with the production of cold-induced and light-insensitive TIM isoforms facilitate EYA accumulation in winter conditions. This is supported by our observations thattimnull mutants exhibit reduced incidence of reproductive dormancy in simulated winter conditions, while flies overexpressingtimshow an increased incidence of reproductive dormancy even in long photoperiod.

Atlantiphoxus wajapi n. gen., n. sp. (Crustacea: Amphipoda: Phoxocephalidae), a new deep-sea amphipod from the southwestern Atlantic

A new genus and species of the family Phoxocephalidae is here described with material collected during the Mini Biological Trawl Project at 224 and 500 m depth off Brazil’s southeastern coast in the states of Rio de Janeiro and São Paulo. Atlantiphoxus wajapi n. gen., n. sp. can be grouped in the subfamily Phoxocephalinae and seems to be morphologically close to Fuegiphoxus Barnard and Barnard, 1980 and Parharpinia Stebbing, 1899. However it can be easily distinguished within the phoxocephalids by the following characters: deep pereonites with small coxae; rostrum unconstricted; eyes absent; man­dible molar not triturative, but as a small hump with 3 multicuspidate stout setae; pereopods 3-4 with stout dactylus; pereopod 5 basis strongly tapering distally; pereopod 7 basis anterodistal corner with a row of long plumose setae; dactylus elongate. Epimeral plate 3 posteroventral margin strongly produced.