Studies of the horizontal vestibulo-ocular reflex on STS 7 and 8

Unpaced voluntary horizontal head oscillation was used to study the Vestibulo-Ocular Reflex (VOR) on Shuttle flights STS 7 and 8. Ten subjects performed head oscillations at 0.33 Hz + or - 30 deg amplitude under the followng conditions: VVOR (visual VOR), eyes open and fixed on a stationary target; VOR-EC, with eyes closed and fixed on the same target in imagination; and VOR-S (VOR suppression), with eyes open and fixed on a head-synchronized target. Effects of weightlessness, flight phase, and Space Motion Sickness (SMS) on head oscillation characteristics were examined. A significant increase in head oscillation frequency was noted inflight in subjects free from SMS. In subjects susceptible to SMS, frequency was reduced during their Symptomatic period. The data also suggest that the amplitude and peak velocity of head oscillation were reduced early inflight. No significant changes were noted in reflex gain or phase in any of the test conditions; however, there was a suggestion of an increase in VVOR and VOR-ES gain early inflight in asymptomatic subjects. A significant difference in VOR-S was found between SMS susceptible and non-susceptible subjects. There is no evidence that any changes in VOR characteristics contributed to SMS

Novel PITX2 Homeodomain-Contained Mutations from ATRIAL Fibrillation Patients Deteriorate Calcium Homeostasis

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the human population, with an estimated incidence of 1¿2% in young adults but increasing to more than 10% in 80+ years patients. Pituitary Homeobox 2, Paired Like Homeodomain 2 (PITX2c) loss-of-function in mice revealed that this homeodomain (HD)-containing transcription factor plays a pivotal role in atrial electrophysiology and calcium homeostasis and point to PITX2 as a candidate gene for AF. To address this issue, we recruited 31 AF patients for genetic analyses of both the known risk alleles and PITX2c open reading frame (ORF) re-sequencing. We found two-point mutations in the homedomain of PITX2 and three other variants in the 5¿untranslated region. A 65 years old male patient without 4q25 risk variants but with recurrent AF displayed two distinct HD-mutations, NM_000325.5:c.309G>C (Gln103His) and NM_000325.5:c.370G>A (Glu124Lys), which both resulted in a change within a highly conserved amino acid position. To address the functional impact of the PITX2 HD mutations, we generated plasmid constructs with mutated version of each nucleotide variant (MD4 and MD5, respectively) as well as a dominant negative control construct in which the PITX2 HD was lacking (DN). Functional analyses demonstrated PITX2c MD4 and PITX2c MD5 decreased Nppa-luciferase transactivation by 50% and 40%, respectively, similar to the PITX2c DN (50%), while Shox2 promoter repression was also impaired. Co-transactivation with other cardiac-enriched co-factors, such as Gata4 and Nkx2.5, was similarly impaired, further supporting the pivotal role of these mutations for correct PITX2c function. Furthermore, when expressed in HL1 cardiomyocyte cultures, the PITX2 mutants impaired endogenous expression of calcium regulatory proteins and induced alterations in sarcoplasmic reticulum (SR) calcium accumulation. This favored alternating and irregular calcium transient amplitudes, causing deterioration of the beat-to-beat stability upon elevation of the stimulation frequency. Overall this data demonstrate that these novel PITX2c HD-mutations might be causative of atrial fibrillation in the carrier.This work was supported by grants from The Spanish Ministry of Science Innovation and Universities [SAF2017-88019-C3-1-R] to L.H.-M. V.J.-S. was employed by CIBERCV [RD12/0042/0002] grant. Work was also supported by a PhD scholarship [FPU18/01250] to S.C., and partially funded by grants from Generalitat de Catalunya [SGR2017-1769] and Fundació Marato TV3 [20152030] to L.H.-M., a translational CNIC grant [2009/08] to D.F., R.C. and L.H.-M. and a grant-in-aid from the Junta de Andalucia Regional Council to D.F. and A.A. [CTS-446]

Standardised inventories of spiders (Arachnida, Araneae) of Macaronesia II: The native forests and dry habitats of Madeira archipelago (Madeira and Porto Santo islands)

Here we present the data obtained from the samples collected as part of a large research project (MACDIV) which aims at understanding the drivers of spider (Araneae) community assembly in Macaronesian islands. To obtain the data, we applied the sampling protocol COBRA (Conservation Oriented Biodiversity Rapid Assessment), in twelve 50 m x 50 m native forest plots and five dry habitat plots on the island of Madeiraand in 5 dry habitat plots on the island of Porto Santo. Through this publication, we contribute to the knowledge of the arachnofauna of the Madeiran archipelago.info:eu-repo/semantics/publishedVersio

Alternative splicing of the human gene SYBL1 modulates protein domain architecture of longin VAMP7/TI-VAMP, showing both non-SNARE and synaptobrevin-like isoforms

<p>Abstract</p> <p>Background</p> <p>The control of intracellular vesicle trafficking is an ideal target to weigh the role of alternative splicing in shaping genomes to make cells. Alternative splicing has been reported for several Soluble <it>N</it>-ethylmaleimide-sensitive factor Attachment protein REceptors of the vesicle (v-SNAREs) or of the target membrane (t-SNARES), which are crucial to intracellular membrane fusion and protein and lipid traffic in Eukaryotes. However, splicing has not yet been investigated in Longins, i.e. the most widespread v-SNAREs. Longins are essential in Eukaryotes and prototyped by VAMP7, Sec22b and Ykt6, sharing a conserved N-terminal Longin domain which regulates membrane fusion and subcellular targeting. Human VAMP7/TI-VAMP, encoded by gene SYBL1, is involved in multiple cell pathways, including control of neurite outgrowth.</p> <p>Results</p> <p>Alternative splicing of SYBL1 by exon skipping events results in the production of a number of VAMP7 isoforms. In-frame or frameshift coding sequence modifications modulate domain architecture of VAMP7 isoforms, which can lack whole domains or domain fragments and show variant or extra domains. Intriguingly, two main types of VAMP7 isoforms either share the inhibitory Longin domain and lack the fusion-promoting SNARE motif, or vice versa. Expression analysis in different tissues and cell lines, quantitative real time RT-PCR and confocal microscopy analysis of fluorescent protein-tagged isoforms demonstrate that VAMP7 variants have different tissue specificities and subcellular localizations. Moreover, design and use of isoform-specific antibodies provided preliminary evidence for the existence of splice variants at the protein level.</p> <p>Conclusions</p> <p>Previous evidence on VAMP7 suggests inhibitory functions for the Longin domain and fusion/growth promoting activity for the Δ-longin molecule. Thus, non-SNARE isoforms with Longin domain and non-longin SNARE isoforms might have somehow opposite regulatory functions. When considering splice variants as "natural mutants", evidence on modulation of subcellular localization by variation in domain combination can shed further light on targeting determinants. Although further work will be needed to characterize identified variants, our data might open the route to unravel novel molecular partners and mechanisms, accounting for the multiplicity of functions carried out by the different members of the Longin proteins family.</p

Оценка характеристик перемешивания хэш-функций семейства MD

Матрично-графовый подход (МГП), нашедший успешное применение к оценке свойств итеративных блочных шифров и генераторов ключевого расписания, впервые представлен как инструмент оценивания перемешивающих свойств алгоритмов хэширования. Особенность применения МГП к хэш-функциям связана с неочевидностью построения перемешивающих матриц, характеризующих зависимость битов сгенерированного хэш-значения от битов исходного сообщения. Для хэш-функций MD4, MD5, SHA-1, SHA-256 построены перемешивающие матрицы порядка 512 + n, где n — длина блока, с которым оперирует односторонняя функция сжатия алгоритма хэширования при обработке 512-битового блока входного сообщения (n = 128 для MD4 и MD5, n = 160 для SHA-1 и n = 256 для SHA-256). К исследованным характеристикам перемешивания относятся локальные экспоненты перемешивающих матриц, то есть для каждой матрицы M определено наименьшее натуральное число y, такое, что при любом натуральном т y положительны все столбцы матрицы Мт с номерами 513, 514,..., 512 + n. Значения локальных экспонентов являются нижними оценками числа итераций, после которых каждый бит сгенерированного хэш-значения может существенно зависеть от всех битов исходного сообщения. Полученные значения (y = 21 для MD4, MD5, SHA-256 и y = 23 для SHA-1) косвенно свидетельствуют о схожих криптографических качествах рассмотренных алгоритмов хэширования, несмотря на варианты их усиления за счёт увеличения длины блока и усложнения функци

On the Security of HMAC and NMAC Based on HAVAL, MD4, MD5, SHA-0 and SHA-1

HMAC is a widely used message authentication code and a pseudorandom function generator based on cryptographic hash functions such as MD5 and SHA-1. It has been standardized by ANSI, IETF, ISO and NIST. HMAC is proved to be secure as long as the compression function of the underlying hash function is a pseudorandom function. In this paper we devise two new distinguishers of the structure of HMAC, called {\em differential} and {\em rectangle distinguishers}, and use them to discuss the security of HMAC based on HAVAL, MD4, MD5, SHA-0 and SHA-1. We show how to distinguish HMAC with reduced or full versions of these cryptographic hash functions from a random function or from HMAC with a random function. We also show how to use our differential distinguisher to devise a forgery attack on HMAC. Our distinguishing and forgery attacks can also be mounted on NMAC based on HAVAL, MD4, MD5, SHA-0 and SHA-1. Furthermore, we show that our differential and rectangle distinguishers can lead to second-preimage attacks on HMAC and NMAC