פרסומים

AbstractThis study contributes to the understanding of the relationship between air temperature and convection by analyzing the characteristics of rainfall at the storm and convective rain cell scales. High spatial-temporal resolution (1-km, 5-min) estimates from a uniquely long weather radar record (24-year) were coupled with near-surface air temperature over Mediterranean and semiarid regions in the eastern Mediterranean. In the examined temperature range (5 to 25°C), the peak intensity of individual convective rain cells was found to increase with temperature, but at lower rate than the 7%°C-1 scaling expected from the Clausius-Clapeyron relation, while the area of the individual convective rain cells slightly decrease or, at most, remains unchanged. At the storm-scale, the areal convective rainfall was found to increase with warmer temperatures, whereas the areal non-convective rainfall and the storm-wide area decrease. This suggests an enhanced moisture convergence from the storm-wide extent towards the convective rain cells. Results indicate a reduction in the total rainfall amounts and an increased heterogeneity of the spatial structure of the storm rainfall for temperatures increasing up to 25°C. Thermodynamic conditions, analyzed using convective available potential energy, were determined to be similar between Mediterranean and semiarid regions. Limitation in the atmospheric moisture availability when shifting from Mediterranean to semiarid climates was detected and explains the suppression of the intensity of the convective rain cells when moving towards drier regions. The relationships obtained in this study are relevant for nearby regions characterized by Mediterranean and semiarid climates.

A novel quantitative assessment of late Holocene precipitation in the Levant is presented, including mean and variance of annual precipitation and their trends. A stochastic framework was utilized and allowed, possibly for the first time, linking high-quality, reconstructed rises/declines in Dead Sea levels with precipitation trends in its watershed. We determined the change in mean annual precipitation for 12 specific intervals over the past 4500 yr, concluding that: (1) the twentieth century was substantially wetter than most of the late Holocene; (2) a representative reference value of mean annual precipitation is 75% of the present-day parameter; (3) during the late Holocene, mean annual precipitation ranged between -17 and +66% of the reference value (-37 to +25% of present-day conditions); (4) the driest intervals were 1500–1200 BC and AD 755–890, and the wettest intervals were 2500–2460 BC, 130–40 BC, AD 350–490, and AD 1770–1940; (5) lake-level rises and declines probably occurred in response to trends in precipitation means and are less likely to occur when precipitation mean is constant; (6) average trends in mean annual precipitation during intervals of >=200 yr did not exceed 15mm per decade. The precipitation trends probably reflect shifts in eastern Mediterranean cyclone tracks.

The Sahara was wetter and greener during multiple interglacial periods of the Quaternary, when some have suggested it featured very large (mega) lakes, ranging in surface area from 30,000 to 350,000km2. In this paper, we review the physical and biological evidence for these large lakes, especially during the African Humid Period (AHP) 11–5 ka. Megalake systems from around the world provide a checklist of diagnostic features, such as multiple well-defined shore- line benches, wave-rounded beach gravels where coarse material is present, landscape smoothing by lacustrine sediment, large-scale deltaic deposits, and in places, tufas encrusting shorelines. Our survey reveals no clear evidence of these fea- tures in the Sahara, except in the Chad basin. Hydrologic modeling of the proposed megalakes requires mean annual rain- fall >=1.2 m/yr and a northward displacement of tropical rainfall belts by >=1000 km. Such a profound displacement is not supported by other paleo-climate proxies and comprehensive climate models, challenging the existence of megalakes in the Sahara. Rather than megalakes, isolated wetlands and small lakes are more consistent with the Sahelo-Sudanian paleoenvironment that prevailed in the Sahara during the AHP. A pale-green and discontinuously wet Sahara is the like- lier context for human migrations out of Africa during the late Quaternary.

The mechanisms by which stem cell (SC) quiescence is regulated to allow normal regeneration are poorly understood. Here, we show that the mesenchymal niche of the hair follicle, the dermal papilla (DP), governs the properties of quiescent SCs in the bulge despite its relatively distant location. The DP induces regeneration by downregulating bulge-dependent inhibitory effects that restrain the intrinsic proliferation features of primed progenitors. Once regeneration initiates, the DP orchestrates Shh expression in primed-progenitor descendants by an autoregulatory circuit to restrict Shh expression to the DP vicinity and to confine Shh levels to act only on nearby cells. As the DP moves away from the bulge, quiescent SCs are exposed to Shh transiently. This ensures a short period of quiescent SC activation required for normal regeneration. Furthermore, our findings show that Shh signaling in the DP fine-tunes Wnt signaling activity and reveal the importance of signaling cross talk in coordinating regeneration pace.

Background: Bone marrow mesenchymal stem cells (bmMSC) may play a role in the regulation of maturation, proliferation, and functional activation of lymphocytes, though the exact mechanisms are unknown. MSC-derived exosomes induce a regulatory response in the function of B, T, and monocyte-derived dendritic cells. Here, we evaluated the specific inhibition of human lymphocytes by bmMSC-derived exosomes and the effects on B-cell function. Methods: Exosomes were isolated from culture media of bmMSC obtained from several healthy donors. The effect of purified bmMSC-derived exosomes on activated peripheral blood mononuclear cells (PBMCs) and isolated B and T lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester assay. Using the Illumina sequencing platform, mRNA profiling was performed on B-lymphocytes activated in the presence or absence of exosomes. Ingenuity(R) pathway analysis software was applied to analyze pathway networks, and biological functions of the differentially expressed genes. Validation by RT-PCR was performed. The effect of bmMSC-derived exosomes on antibody secretion was measured by ELISA. Results: Proliferation of activated PBMCs or isolated T and B cells co-cultured with MSC-derived exosomes decreased by 37, 23, and 18%, respectively, compared to controls. mRNA profiling of activated B-lymphocytes revealed 186 genes that were differentially expressed between exosome-treated and control cells. We observed down- and up-regulation of genes that are involved in cell trafficking, development, hemostasis, and immune cell function. RNA-Seq results were validated by real time PCR analysis for the expression of CXCL8 (IL8) and MZB1 genes that are known to have an important role in immune modulation. Functional alterations were confirmed by decreased IgM production levels. Consistent results were demonstrated among a wide variety of healthy human bmMSC donors. Conclusion: Our data show that exosomes may play an important role in immune regulation. They inhibit proliferation of several types of immune cells. In B-lymphocytes they modulate cell function by exerting differential expression of the mRNA of relevant genes. The results of this study help elucidate the mechanisms by which exosomes induce immune regulation and may contribute to the development of newer and safer therapeutic strategies.

This study expands the Metastatistical Extreme Value (MEV) framework to sub-daily rainfall frequency analysis and compares it to extreme value theory methods in presence of short records and measurement errors. Ordinary events are identified based on the temporal autocorrelation of hourly data and modeled with a Weibull distribution. MEV is compared to extreme value theory methods in the estimation of long return period quantiles from actual data (160 rain gauges with at least 60-year record in the contiguous United States) and on synthetic data perturbed with measurement errors typical of remote sensing rainfall estimation. MEV tends to underestimate the 100-year return period quantiles of hourly rainfall when 5–20 years of actual data are used, but presents diminished uncertainty. When a good model of the ordinary events and adequate number of events per year are available, MEV is able to provide information on the 100-year return period quantiles from 10–20, or even 5 years of data with significantly reduced uncertainty (\textless30% uncertainty for 5-year records). MEV estimates of 100-year return period quantiles from short records are much less sensitive than extreme value theory methods to additive/multiplicative errors, presence of cap values in the estimates, and missing of extreme values. Results from this study strongly support the use of MEV for rainfall frequency analyses based on remotely sensed datasets.

Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR-16-1* and miR-16-2* “passenger” strands as well as the “lead” miR-16 strand possess strong tumor suppressive functions in human OS. We report different although strongly overlapping functions for miR-16-1* and miR-16-2* in OS cells. Ectopic expression of these miRNAs affected primary tumor growth, metastasis seeding, and chemoresistance and invasiveness of human OS cells. Loss-of-function experiments verified tumor suppressive functions of these miRNAs at endogenous levels of expression. Using RNA immunoprecipitation (RIP) assays, we identify direct targets of miR-16-1* and miR-16-2* in OS cells. Furthermore, validation experiments identified FGFR2 as a direct target for miR-16-1* and miR-16-2*. Overall, our findings underscore the importance of passenger strand miRNAs in osteosarcomagenesis.Novelty and Impact Osteosarcoma (OS) can be a fatal disease. MicroRNAs (miRNAs) play crucial roles in osteosarcomagenesis. In this study, we identify miR-16-1* and miR-16-2* as strong tumor suppressors and anti-metastatic genes in OS. This is the first report demonstrating tumor suppressive functions of passenger strands of these miRNAs in OS. Given that MIR-16-1 is located in 13q14 region that is commonly deleted in several human malignancies, our findings shed light on oncogenic mechanisms triggered by 13q14 deletion.AbbreviationsOSosteosarcomamiRISCmicroRNA-induced silencing complexmRNAmessenger RNACLLchronic lymphocytic leukemiaRIPRNA Immunoprecipitation

Reducing insulin/IGF-1 signaling (IIS) extends lifespan, promotes protein homeostasis (proteostasis), and elevates stress resistance of worms, flies, and mammals. How these functions are orchestrated across the organism is only partially understood. Here, we report that in the nematode Caenorhabditis elegans, the IIS positively regulates the expression of caveolin-1 (cav-1), a gene which is primarily expressed in neurons of the adult worm and underlies the formation of caveolae, a subtype of lipid microdomains that serve as platforms for signaling complexes. Accordingly, IIS reduction lowers cav-1 expression and lessens the quantity of neuronal caveolae. Reduced cav-1 expression extends lifespan and mitigates toxic protein aggregation by modulating the expression of aging-regulating and signaling-promoting genes. Our findings define caveolae as aging-governing signaling centers and underscore the potential for cav-1 as a novel therapeutic target for the promotion of healthy aging.

אריך אוארבך (1957-1892) היה פילולוג יהודי גרמני דגול, חוקר ספרות השוואתית, היסטוריון ומבקר ספרות. ספר זה מציג מחדש את הביוגרפיה הרעיונית של יצירתו במסכת תמציתית ובהירה, הממחישה את התהוות היצירה לצד התמורות הדרמטיות בנות הזמן - עליית הפשיזם בגרמניה והמהפכה הנאצית שהעלתה את היטלר לשלטון ודחקה את אוארבך לגלות באיסטנבול. בספר זה נבחנים חייו, זמנו ועבודתו של אוארבך מנקודת מבט קונטקסטואלית, המביאה בחשבון את הרקע ההיסטורי והאידאולוגי - את ניצחונן של הפילולוגיה הארית וההיסטוריוגרפיה הנאצית, המבוססות על גזענות ועל אנטישמיות. אלו עקרו כליל את התנ"ך העברי, הברית הישנה, מן התרבות הגרמנית ומן הציוויליזציה המערבית. בתגובה חיבר אוארבך אפולוגיה (Apologia), כתב הגנה על המסורת ההומניסטית היהודית־נוצרית של המערב בימים שזו עמדה בפני הסכנה הגדולה ביותר לקיומה – תיאור המו"ל

"During 1942, the decisive battles of Stalingrad and El Alamein raged and the Nazi genocide was at its lethal peak. The Pen Confronts the Sword examines the shared motives behind four remarkable texts German exiles began writing that year: Thomas Mann’s Doctor Faustus (1947); Ernst Cassirer’s The Myth of the State (1946); Erich Auerbach’s Mimesis: The Representation of Reality in Western Literature (1946); and Max Horkheimer and Theodor Adorno’s Dialectic of Enlightenment (1944). Each identified a specific danger in Nazi ideology and mustered new theories, approaches, and sources to combat it. The books aimed to expose the encompassing catastrophes of German culture (Mann), politics (Cassirer), philology (Auerbach), and philosophy and sociology (Horkheimer and Adorno). Their scope, mastery, and sense of urgency constitute a comprehensive Kulturkampf (culture war) against Nazi barbarism. Avihu Zakai cogently analyzes each work, explains the context of its creation, and draws connections between these four landmark books in Western intellectual history" – Publisher’s Description