Probing large scale filaments with HI and 3^3HeII

We explore the observability of the neutral hydrogen (HI) and the singly-ionized isotope helium-3 ($^3$HeII) in the intergalactic medium (IGM) from the Epoch of Reionization down to the local Universe. The hyperfine transition of $^3$HeII, which is not as well known as the HI transition, has energy splitting corresponding to 8 cm. It also has a larger spontaneous decay rate than that of neutral hydrogen, whereas its primordial abundance is much smaller. Although both species are mostly ionized in the IGM, the balance between ionization and recombination in moderately high density regions renders them abundant enough to be observed. We estimate the emission signal of both hyperfine transitions from large scale filamentary structures and discuss the prospects for observing them with current and future radio telescopes. We conclude that HI in filaments is possibly observable even with current telescopes after 100 hours of observation. On the other hand, $^3$HeII is only detectable with future telescopes, such as SKA, after the same amount of time.Comment: 21 pages, 13 figures, 2 tables, accepted to MNRA

Clinical Anatomy of the Frenulum of the Oral Vestibule.

Introduction The frenula of the oral vestibule include the labial and buccal frenula. Abnormal labial and buccal frenula can affect facial esthetics and oral cavity function by retracting the gingival margin, creating a median diastema, and limiting lip movement. Because of the lack of information on these structures, we aimed to clarify their anatomy. Methods A total of 34 sides from 17 fresh frozen cadaveric Caucasian heads were used in the present study. The specimens were derived from 11 male and 6 female adult cadavers. The relationships between the frenulum of the mucosa and the tissue underneath the mucosa was observed. Results The buccal frenulum was formed by the border of mimetic muscles and connective tissues. Comparitively, the labial frenulum was only formed by taut connective tissue. Conclusion We found that the buccal and labial frenula have different compositions. This finding may have relevance both in oral surgery and in various cosmetic procedures near the oral vestibule

Reversal of neuroinflammation in novel GS model mice by single i.c.v. administration of CHO-derived rhCTSA precursor protein

Galactosialidosis (GS) is a lysosomal cathepsin A (CTSA) deficiency. It associates with a simultaneous decrease of neuraminidase 1 (NEU1) activity and sialylglycan storage. Central nervous system (CNS) symptoms reduce the quality of life of juvenile/adult-type GS patients, but there is no effective therapy. Here, we established a novel GS model mouse carrying homozygotic Ctsa IVS6+1g→a mutation causing partial exon 6 skipping with concomitant deficiency of Ctsa/Neu1. The GS mice developed juvenile/adult GS-like symptoms, such as gargoyle-like face, edema, proctoprosia due to sialylglycan accumulation, and neurovisceral inflammation, including activated microglia/macrophage appearance and increase of inflammatory chemokines. We produced human CTSA precursor proteins (proCTSA), a homodimer carrying terminal mannose 6-phosphate (M6P)-type N-glycans. The CHO-derived proCTSA was taken up by GS patient-derived fibroblasts via M6P receptors and delivered to lysosomes. Catalytically active mature CTSA showed a shorter half-life due to intralysosomal proteolytic degradation. Following single i.c.v. administration, proCTSA was widely distributed, restored the Neu1 activity, and reduced the sialylglycans accumulated in brain regions. Moreover, proCTSA suppressed neuroinflammation associated with reduction of activated microglia/macrophage and up-regulated Mip1α. The results show therapeutic effects of intracerebrospinal enzyme replacement utilizing CHO-derived proCTSA and suggest suppression of CNS symptoms

Przypadek przejściowego bloku przedsionkowo-komorowego z przewodzeniem 2:1, który ustąpił po suplementacji tyroksyną zastosowaną w celu leczenia subklinicznej postaci niedoczynności tarczycy

Mężczyznę w wieku 42 lat przyjęto do szpitala, w którym pracują autorzy niniejszego doniesienia, z powodu napadów kołatania serca. W holterowskim badaniu EKG wykazano blok przedsionkowo-komorowy (AV) z przewodzeniem 2:1 oraz bradykardię z minimalną częstością akcji serca wynoszącą 44 uderzenia/min. Stwierdzono obecność wskazań do przeprowadzenia dalszych badań elektrofizjologicznych oraz do wszczepienia rozrusznika serca. Wyniki badań laboratoryjnych wykonanych w dniu przyjęcia wykazały podwyższone stężenie tyreotropiny przy prawidłowym stężeniu tyroksyny. W celu wykluczenia czynnościowego bloku AV przez 2 tygodnie podawano pacjentowi tyroksynę, zaś w holterowskim badaniu EKG wykonanym po tym okresie wykazano znaczącą poprawę częstości akcji serca bez obecności bloku AV lub długotrwałych przerw w przewodzeniu. Na tej podstawie uznano, że ciężka bradykardia oraz blok AV z przewodzeniem 2:1 wynikały z subklinicznej postaci niedoczynności tarczycy, a przyjmowanie tyroksyny całkowicie wyeliminowało istniejące objawy. (Folia Cardiologica Excerpta 2006; 1: 448-451

Design and synthesis of orexin 1 receptor-selective agonists

Orexins are a family of neuropeptides that regulate various physiological events such as sleep/wakefulness as well as emotional and feeding behavior, and that act on two G-protein-coupled receptors, i.e., the orexin 1 (OX1R) and orexin 2 receptors (OX2R). Since the discovery that dysfunction of the orexin/OX2R system causes the sleep disorder narcolepsy, several OX2R-selective and OX1/2R dual agonists have been disclosed. However, an OX1R-selective agonist has not yet been reported, despite the importance of the biological function of OX1R. Herein, we report the discovery of a potent OX1R-selective agonist, (R,E)-3-(4-methoxy-3-(N-(8-(2-(3-methoxyphenyl)-N-methylacetamido)-5,6,7,8-tetrahydronaphthalen-2-yl)sulfamoyl)phenyl)-N-(pyridin-4-yl)acrylamide ((R)-YNT-3708; EC50 = 7.48 nM for OX1R; OX2R/OX1R EC50 ratio = 22.5). Unlike the OX2R-selective agonist, the OX1R-selective agonist (R)-YNT-3708 exhibited antinociceptive and reinforcing effects in mice more potently than the dual agonist