The Marmara Sea Gateway since ~16 ky BP: non-catastrophic causes of paleoceanographic events in the Black Sea at 8.4 and 7.15 ky BP

The Late Quaternary history of connection of the Black Sea to the Eastern Mediterranean has been intensely debated. Ryan, Pitman and coworkers advocate two pulses of outflow from the Black Sea to the world ocean at ~16–14.7 ky BP and ~11–10 ky BP. From ~14.7–11 ky BP and from ~10–8.4 ky BP, they suggest that the level of the Black Sea fell to ~ -100 m. At 8.4 ky BP, they further claim that a catastrophic flood occurred in a geological instant, refilling the Black Sea with saline waters from the Mediterranean. In contrast, we continue to gather evidence from seismic profiles and dated cores in the Marmara Sea which demonstrate conclusively that the proposed flood did not occur. Instead, the Black Sea has been at or above the Bosphorus sill depth and flowing into the world ocean unabated since ~10.5 ky BP. This conclusion is based on continuous Holocene water-column stratification (leading to sapropel deposition in the Marmara Sea and the Aegean Sea), proxy indicators of sea-surface salinity, and migration of endemic species across the Bosphorus in both directions whenever appropriate hydrographic conditions existed in the strait. The two pulses of outflow documented by Ryan, Pitman and coworkers find support in our data, and we have modified our earlier interpretations so that these pulses now coincide with the development of mid-shelf deltas: \Delta 2 (16–14.7 ky BP) and \Delta 1 (10.5–9 ky BP) at the southern end of the Bosphorus Strait. However, continued Black Sea outflow after 9 ky BP prevented the northward advection of Mediterranean water and the entry of open-marine species into the Black Sea for more than 1000 years. Sufficient Mediterranean water to change the Sr-isotopic composition of slope and shelf water masses was not available until ~8.4 ky BP (along with the first arrival of many varieties of marine fauna and flora), whereas euryhaline molluscs did not successfully populate the Black Sea shelves until ~7.15 ky BP. Instead of relying on catastrophic events, we recognize a slow, progressive reconnection of the Black Sea to the world ocean, accompanied by significant time lags

Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A.

Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP·Xpo4·eIF5A export complex at 3.2 Å resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A’s complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses – in a chaperone-like manner – undesired interactions of eIF5A inside nuclei

Aktivnost arginaze u ovarijskim strukturama krava švicarske smeđe pasmine i njezinih križanaca.

Arginase is the last enzyme of the urea cycle. It catalyses the hydrolysis of L-arginine to L-ornitine and urea. The aim of this study was to investigate the presence of arginase activity in ovarian structures such as: Graaf follicles, GF (Medium and Large size, M- and L-size), Corpus Haemorrhagicum (CH), and various types of Corpus Luteum (CL) such as: cyclic CL (CCL), 2-4 month pregnancy CL (2-4 MCL) and 4-7 month pregnancy CL (4-7 MCL). Ovarian tissues of 62 cows (7-10 years old and Brown Swiss or its cross-breeds), collected from a local slaughterhouse, were used as material. The materials were divided into 6 experimental groups, as follows: MGF group (n = 7), LGF group (n = 21), CH group (n = 7), CCL group (n = 6), 2-4 MCL group (n = 9) and 4-7 MCL group (n = 12). Arginase activities were measured as 0.056 ± 0.017, 0.100 ± 0.016, 2.517 ± 0.521, 0.827 ± 0.190, 0.674 ± 0.106 and 0.833 ± 0.093 U/mg protein in all groups, respectively. Arginase activity in the CH group was significantly higher than that in the CCL, 2-4 MCL and 4-7 MCL groups (P<0.001). The lowest enzyme activity was in the MGF and LGF groups. Hence, it was concluded that the arginase enzyme might play a crucial role in cell division, proliferation and differentiation in the ovarian tissues (especially the CH) of mature cows.Arginaza je posljednji enzim u ciklusu ureje koji katalizira hidrolizu L-arginina u L-ornitin i ureju. Cilj istraživanja bio je utvrditi prisutnost aktivnosti arginaze u ovarijskim strukturama kao što su Graafovi folikuli, GF (srednje veliki - M i veliki - L), corpus haemorrhagicum (CH) i različiti tipovi corpus luteum (CL) kao što su ciklični (CCL), 2-4 mjeseca graviditetni (2-4 MCL) i 4-7 mjeseci graviditetni (4-7 MCL). Tkiva ovarija od 62 krave (švicarske smeđe pasmine i križanaca u dobi od 7 do 10 godina) prikupljena su u lokalnoj klaonici. Materijali su bili podijeljeni u 6 pokusnih skupina kako slijedi: MGF skupina (n = 7), LGF skupina (n = 21), CH skupina (n = 7), CCL skupina (n = 6), 2-4 MCL skupina (n = 9) i 4-7 MCL skupina (n = 12). Slijedom navedenih skupina, aktivnost arginaze bila je 0,056 ± 0,017, 0,100 ± 0,016, 2,517 ± 0,521, 0,827 ± 0,190, 0,674 ± 0,106 i 0,833 ± 0,093 U/mg. Aktivnost arginaze u CH skupini bila je signifikantno viša u odnosu na skupine CCL, 2-4 MCL i 4-7 MCL (P<0,001). Najniža aktivnost enzima bila je u skupinama MGF i LGF. Zaključeno je o mogućoj ključnoj ulozi aktivnosti enzima arginaze u diobi stanica, proliferaciji i diferencijaciji ovarijskih tkiva (osobito CH) kod odraslih krava

A panel of oxidative stress assays does not provide supplementary diagnostic information in Behcet's disease patients

Published onlineJournal ArticleBACKGROUND: Recent findings suggest a role of oxidative stress in the pathogenesis of Behcet's disease (BD), but the utility of oxidative stress-associated assays in offering diagnostic information or in the monitoring of disease activity is largely unassessed. OBJECTIVE AND METHODS: We aimed to measure oxidative and inflammatory markers, along with the markers of reactive nitrogen species, S-nitrosothiols and 3-nitrotyrosine, in BD patients (n = 100) and healthy volunteers (n = 50). These markers were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, disease activity and duration. RESULTS: Median values for erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, and IL-18 levels, as well as myeloperoxidase (MPO) activity, were statistically higher in the patient group compared to controls. Some inflammation markers (ESR, neutrophil and leukocyte counts) were statistically higher (p 0.05 in all statistical comparisons), nor was there any difference in median levels of these oxidative stress markers in active disease versus disease remission. S-nitrosothiols and 3-nitrotyrosine were undetectable in BD plasma. CONCLUSIONS: The application of oxidative stress-associated measures to BD blood samples offered no supplemental diagnostic or disease activity information to that provided by standard laboratory measures of inflammation. S-nitrosothiols and 3-nitrotyrosine appeared not to be markers for active BD; thus the search for biochemical markers that will indicate the active period should be continued with larger studies

Kabuki make-up syndrome: a case report

Kabuki make-up sendromu (KMS) mental retardasyon, gelisme geriligi ve multipl anomalilerle birlikte seyreden, nedeni bilinmeyen nadir görülen bir sendromdur. Olgular karakteristik bir yüz görünümüne (ektropion, kulak kepçelerinin genis ve düsük olması, genis alın, genis ve basık burun kökü) sahiptirler. Bu yazıda konusma bozuklugu, gözlerinde sık sık kızarıklık ve yasarma ile birlikte sık tekrarlayan kulak akıntısı nedeniyle basvuran ve karakteristik özellikleri ile KMS düsünülen 5 yasındaki bir kız olgu nadir görülmesi nedeniyle sunulmak istenmistir.Kabuki make-up syndrome (KMS) is a rare syndrome characterized by mental retardation, growth retardation and multiple abnormalities. The etiology is obscure. Patients present with typical facies characterized by ectropion of eyelids, a wide forehead, arched eyebrows and a depressed and broad nasal tip. In this paper we report a 5-year-old girl who presented with speech abnormalities, recurrent red eyes, epiphora and recurrent otitis media

Variability in the summer movements, habitat use and thermal biology of two fish species in a temperate river

The ability of fish to cope with warm water temperatures in summer depends on factors including their thermal traits and the ability of individuals to access cool-water refugia. Knowledge is highly limited on the in situ responses of many fishes to elevated summer temperatures, including whether they express behavioural thermoregulation. The responses of two riverine species to summer water temperatures were tested here using the movement metrics, spatial habitat use and body temperatures of individual European barbel Barbus barbus (‘barbel’) and common bream Abramis brama (‘bream’) versus river temperatures. Acoustic biotelemetry was applied in the lower River Severn basin, western Britain, in summer 2021 (barbel) and 2022 (bream), where individuals could move across > 150 km of river, including a tributary of cooler water. Across all individuals, bream occupied 37 km of river length (mainstem only), with low inter-individual variability in their spatial habitat use, movements and body temperatures. In contrast, barbel occupied 62 km of river (main river/tributary), with relatively high inter-individual variability in spatial habitat use, movements and body temperatures, with higher variation in body temperatures as river temperatures increased (maximum mean daily temperature difference between individuals on the same day: 4.2 °C). Although warmer individuals generally moved more, their activity was greatest at relatively low temperatures and higher flows, and neither species revealed any evidence of behavioural thermoregulation during elevated temperatures. Enabling phenotypically diverse fish populations to express their natural behaviours and thermal preferences in summer water temperatures thus requires maintaining their free-ranging in thermally heterogenous habitats

Massive hemoptysis and deep venous thrombosis presenting in a woman with Hughes-Stovin syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hughes-Stovin syndrome is a very rare disease with fewer than 30 cases reported in the literature. The disease is thought to be a variant of Behcet's disease and is defined by the presence of pulmonary artery aneurysm in association with peripheral venous thrombosis.</p> <p>Case presentation</p> <p>A previously healthy 23-year-old Saudi woman presented with massive hemoptysis a day prior to her admission to our hospital. She had a six-month history of recurrent fever, cough, dyspnea, and recurrent oral ulceration. Contrast-enhanced computed tomography scan of her chest and pulmonary angiogram demonstrated a single right-lower lobe pulmonary artery aneurysm. She underwent thoracotomy and right lower lobe resection. Her postoperative course was complicated by deep vein thrombosis. She also developed headache and papilledema, while a magnetic resonance imaging of her brain suggested vasculitis. Based on these clinical presentations, she was diagnosed and treated with Hughes-Stovin syndrome.</p> <p>Conclusion</p> <p>The majority of cases of Hughes-Stovin syndrome are reported among men, with only two cases occurring in women. A case of Hughes-Stovin syndrome occurring in a woman is presented in this report. She was treated successfully with multimodality treatment that includes surgery, steroids and cytotoxic agents.</p

Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19. However, their production in mammalian cells is not scalable to meet the global demand. Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS-CoV-2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X-ray and cryo-EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune-escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low-picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold-promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape-mutations