Diversity and Localization of Bacterial Endosymbionts from Whitefly Species Collected in Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

Novel insights into the genomic basis of citrus canker based on the genome sequences of two strains of Xanthomonas fuscans subsp. aurantifolii

Abstract Background Citrus canker is a disease that has severe economic impact on the citrus industry worldwide. There are three types of canker, called A, B, and C. The three types have different phenotypes and affect different citrus species. The causative agent for type A is Xanthomonas citri subsp. citri, whose genome sequence was made available in 2002. Xanthomonas fuscans subsp. aurantifolii strain B causes canker B and Xanthomonas fuscans subsp. aurantifolii strain C causes canker C. Results We have sequenced the genomes of strains B and C to draft status. We have compared their genomic content to X. citri subsp. citri and to other Xanthomonas genomes, with special emphasis on type III secreted effector repertoires. In addition to pthA, already known to be present in all three citrus canker strains, two additional effector genes, xopE3 and xopAI, are also present in all three strains and are both located on the same putative genomic island. These two effector genes, along with one other effector-like gene in the same region, are thus good candidates for being pathogenicity factors on citrus. Numerous gene content differences also exist between the three cankers strains, which can be correlated with their different virulence and host range. Particular attention was placed on the analysis of genes involved in biofilm formation and quorum sensing, type IV secretion, flagellum synthesis and motility, lipopolysacharide synthesis, and on the gene xacPNP, which codes for a natriuretic protein. Conclusion We have uncovered numerous commonalities and differences in gene content between the genomes of the pathogenic agents causing citrus canker A, B, and C and other Xanthomonas genomes. Molecular genetics can now be employed to determine the role of these genes in plant-microbe interactions. The gained knowledge will be instrumental for improving citrus canker control.

Analisi di pushover 3D per strutture in c.a.

In the present study, a new pushover procedure for 3D frame structures is proposed, based on the application of a set of horizontal force and torque distributions at each floor level; in order to predict the most severe configurations of an irregular structure subjected to an earthquake, more than one pushover analysis has to be performed. The proposed method is validated by a consistent comparison of results from static pushover and dynamic simulations in terms of different response parameters, such as displacements, rotations, floor shears and floor torques. Starting from the linear analysis, the procedure is subsequently extended to the nonlinear case. The results confirm the effectiveness of the proposed procedure to predict the structural behaviour in the most severe configurations.

Las actas con acuerdo en la Ley General Tributaria y en el Derecho Comparado

È la nostra intenzione, per mezzo di questa ricerca, effettuare uno studio metodico del procedure tributaria con gli actas con acuerdo, che costituisce una riflessione fedele delle tecniche convenzionali usate allo scopo di dare più sicurezza giurídica al contribuente ed evitare la formazione delle controversie inutili quando stabilisce la possibilità di raggiungere un accordo con la Amministrazione Finanziaria, per la indeterminatezza e la difficoltà che esistono nel sistema fiscale che ordina, per quanto l’interpretazione e l’applicazione della norma si riferisce. Per la realizzaione di questa ricerca ha usato i materiali possiedono del ambito giuridico, questo è, dottrina, giurisprudenza e il Diritto positive, tanto nazionale (spagnolo) quanto straniero, perché l’analisi interrotta di queste fonti, mette di rilievo adi atti relativi a lei actas con acuerdo, di cui la risposta non ha essere pacifica né l’uno né l’altro unanime, poichè abbiamo occasione da analizzare in questo lavoro che prova a contribuire nel minim misurato allo studio su questo tipo specifico di actas e, allo stesso tempo, per effettuare le considerazioni de lege ferenda sul relativo regime legale. Giustificato l’interesse dell’oggetto di studio e dei mezzi tematichi usare, risulta opportuno esporre dopo, il soddisfare di base che è stato seguito per l’elaborazione del lavoro, che consiste di quattro capitoli, a quale va fare il riferimento. Abbiamo considerato indovinato per cominciare, dedicare il capitolo I, titolato “Natura legale degli actas con acuerdo” all’analisi della domanda circa l’inserzione negli accordi nelle procedure fiscali, prendente como l’ipotesi di partenza la scrittura dall’articolo 88 dalla Legge dal Regime Giuridico delle Amministrazioni Pubbliche e la Procedura Amministrativa Comune, dall’applicazione ausiliaria alle procedure fiscale e da quale la possibilità è introdotta di fare gli accordi, i patti o i contratti fra l’Ammistrazione e gli amministrate che possono avere la considerazione dei rimorchi delle procedure amministrative o, a tali introduce dentro con il carattere precedente al relativo completamento, incomparabile con esso unilateralità caratteristico delle prestazioni amministrative. Anche se, dato che relativo adattato messo in funzione all’interno nell sistema fiscale, l’approvazione di una norma specifica, sarebbe consigliabile, che regola l’accordo corrispondente o l’accordo, perché solamente finora, le valutazioni specifiche sono state regolate soltanto como quale sono oggetto di analisi. Quando abbiamo fato l’esame delle caratteristiche che sono conformi la compilazione convenzizonale della procedura ed all’interno di questo primo capitolo, là sono imbarcati in il dibattito doctrinal discutibile su uno alle funzioni decisive degli actas con acuerdo, poichè è quello della sua natura legale, con l’obiettivo per incorniciarlo nella categoria di tecnica di patticio o di atto amministrativo, poiché del telaio in uno o l’altro, saranno fatti derivi il regime legale e le relative conseguenze; e così, dopo l’esame specifico di ogni delle teorie formulate, rendere specificamente la natura legale che abbiamo considerato più misura a la realtà di questa figura. D’altra parte, il secondo dei capitoli accende “La prospettiva dogmatica e costituzionale degli actas con acuerdo”, in cui ci siamo avvicinati alla compatibilità di questa figura con i principii principali del Finanziario che la costituzione spagnola allo scopo di ottenere un Sistema Finanziario del justo; e reso specifico nel principio di capacità contributiva, nel principio di uguaglianza, nel principio di legalità, nel principio di tutela giurisdizionale effetiva, nel principio di certezza e nel indisponibilità del credito tributario. L’analisi nel Diritto comparato è di base nello studio su tutta l’istituzione legale, non solo per affrontante le possibili carenze del nostro sistema fiscale, ma anche per capire la stessa realtà legale, per quel motivo, noi ha dedicato il terzo dei capitoli, “Risoluzione convenzionale delle polemiche del Finanziario nel quadro del Diritto comparato”, fare una descrizione separata del regime legale di ogni delle figure attuali dei differenti sisteme studiati; ma concentrandosi il nostro studio nella modalitá del accertamento con adesione di sistema italiano, perché gli actas con acuerdo sono basati, in grande misura, in questo modello, ragione per la quale il relativo esame concederà rilevare i problemi ed i successi principali, tanto teorico quanto pratico, che la relativa applizcazione ha causato in Italia e trasferirla all’ordenamento spagnolo. Il capitolo IV, “Regime legale degli actas con acuerdo”, costituisce il nucleo della nostra ricerca quando si avvicina l’esame della relativa portata dell’applicazione, obiettivo come tanto soggettivo, di questa categoria specifica delle Ufficio dell’Entrate, i preventivi che il legislatore depositato giù in moda da potere invitare l’attuario di controllo al contribuente per regolarizzare la sua situazione finanziaria prima dell’esistenza dei concetti legali indetermine, concretion della norma legale o della realizzazione delle misure, delle valutazioni o delle valutazioni per la determinazione dell’obbligo finanziario; così como la procedura che deve essere seguita, i requisiti richiesti per i relativo abbonamento, si sono riferiti all’autorizzazione dall’organo competente per liquidare i debiti, la costituzione della garanzia dovuta per assicurare i tutela dell credito tributario egli effetti legali derivato dalla relativa formalizzazione. Per concludere la nostra ricerca, poichè è tradizionale in questi casi, un’ultima sezione è dedicata per riunire le conclusioni principali che derivano dallo studio si sono presentate nelle pagine precedere, provante a fornire una visione globale delle domande imbarcate nel lavoro, così como dei problemi provocati e, nel relativo caso, delle soluzioni possibili.

Food Safety and Mineral Oil Contaminated Paperboard Packaging: an Analytical Challenge and a Migration Study

Food packaging protects food, but it can sometimes become a source of undesired contaminants. Paper based materials, despite being perceived as “natural” and safe, can contain volatile contaminants (especially if made from recycled paper) able to migrate to food, as mineral oil, phthalates and photoinitiators. Mineral oil is a petroleum product used as printing ink solvent for newspapers, magazines and packaging. From paperboard printing and from recycled fibers (if present), mineral oil migrates into food, even if dry, through the gas phase. Its toxicity is not fully evaluated, but a temporary Acceptable Daily Intake (ADI) of 0.6 mg kg-1 has been established for saturated mineral oil hydrocarbons (MOSH), while aromatic hydrocarbons (MOAH) are more toxic. Extraction and analysis of MOSH and MOAH is difficult due to the thousands of molecules present. Extraction methods for packaging and food have been optimized, then applied for a “shopping trolley survey” on over 100 Italian and Swiss market products. Instrumental analyses were performed with online LC-GC/FID. Average concentration of MOSH in paperboards was 626 mg kg-1. Many had the potential of contaminating foods exceeding temporary ADI tens of times. A long term migration study was then designed to better understand migration kinetics. Egg pasta and müesli were chosen as representative (high surface/weight ratio). They were stored at different temperatures (4, 20, 30, 40 and 60°C) and conditions (free, shelved or boxed packs) for 1 year. MOSH and MOAH kinetic curves show that migration is a fast process, mostly influenced by temperature: in egg pasta (food in direct contact with paperboard), half of MOSH is transferred to food in a week at 40°C and in 8 months at 20°C. The internal plastic bag present in müesli slowed down the startup of migration, creating a “lag time” in the curves.

Entwicklung eines Pikoliter-Tropfengenerators für die Massenspektrometrische Spuren- und Speziesanalytik

Die Dissertationsschrift beschäftigt sich mit der Entwicklung und Anwendung einer alternativen Probenzuführungstechnik für flüssige Proben in der Massenspektrometrie. Obwohl bereits einige Anstrengungen zur Verbesserung unternommen wurden, weisen konventionelle pneumatische Zerstäuber- und Sprühkammersysteme, die in der Elementspurenanalytik mittels induktiv gekoppeltem Plasma (ICP) standardmäßig verwendet werden, eine geringe Gesamteffizienz auf. Pneumatisch erzeugtes Aerosol ist durch eine breite Tropfengrößenverteilung gekennzeichnet, was den Einsatz einer Sprühkammer bedingt, um die Aerosolcharakteristik an die Betriebsbedingungen des ICPs anzupassen.. Die Erzeugung von Tropfen mit einer sehr engen Tropfengrößenverteilung oder sogar monodispersen Tropfen könnte die Effizienz des Probeneintrags verbessern. Ein Ziel dieser Arbeit ist daher, Tropfen, die mittels des thermischen Tintenstrahldruckverfahrens erzeugt werden, zum Probeneintrag in der Elementmassenspektrometrie einzusetzen. Das thermische Tintenstrahldruckverfahren konnte in der analytischen Chemie im Bereich der Oberflächenanalytik mittels TXRF oder Laserablation bisher zur gezielten, reproduzierbaren Deposition von Tropfen auf Oberflächen eingesetzt werden. Um eine kontinuierliche Tropfenerzeugung zu ermöglichen, wurde ein elektronischer Mikrokontroller entwickelt, der eine Dosiereinheit unabhängig von der Hard- und Software des Druckers steuern kann. Dabei sind alle zur Tropfenerzeugung relevanten Parameter (Frequenz, Heizpulsenergie) unabhängig voneinander einstellbar. Die Dosiereinheit, der "drop-on-demand" Aerosolgenerator (DOD), wurde auf eine Aerosoltransportkammer montiert, welche die erzeugten Tropfen in die Ionisationsquelle befördert. Im Bereich der anorganischen Spurenanalytik konnten durch die Kombination des DOD mit einem automatischen Probengeber 53 Elemente untersucht und die erzielbare Empfindlichkeiten sowie exemplarisch für 15 Elemente die Nachweisgrenzen und die Untergrundäquivalentkonzentrationen ermittelt werden. Damit die Vorteile komfortabel genutzt werden können, wurde eine Kopplung des DOD-Systems mit der miniaturisierten Fließinjektionsanalyse (FIA) sowie miniaturisierten Trenntechniken wie der µHPLC entwickelt. Die Fließinjektionsmethode wurde mit einem zertifizierten Referenzmaterial validiert, wobei für Vanadium und Cadmium die zertifizierten Werte gut reproduziert werden konnten. Transiente Signale konnten bei der Kopplung des Dosiersystems in Verbindung mit der ICP-MS an eine µHPLC abgebildet werden. Die Modifikation der Dosiereinheit zum Ankoppeln an einen kontinuierlichen Probenfluss bedarf noch einer weiteren Reduzierung des verbleibenden Totvolumens. Dazu ist die Unabhängigkeit von den bisher verwendeten, kommerziell erhältlichen Druckerpatronen anzustreben, indem die Dosiereinheit selbst gefertigt wird. Die Vielseitigkeit des Dosiersystems wurde mit der Kopplung an eine kürzlich neu entwickelte Atmosphärendruck-Ionisationsmethode, die "flowing atmospheric-pressure afterglow" Desorptions/Ionisations Ionenquelle (FAPA), aufgezeigt. Ein direkter Eintrag von flüssigen Proben in diese Quelle war bislang nicht möglich, es konnte lediglich eine Desorption von eingetrockneten Rückständen oder direkt von der Flüssigkeitsoberfläche erfolgen. Die Präzision der Analyse ist dabei durch die variable Probenposition eingeschränkt. Mit dem Einsatz des DOD-Systems können flüssige Proben nun direkt in die FAPA eingetragen, was ebenfalls das Kalibrieren bei quantitativen Analysen organischer Verbindungen ermöglicht. Neben illegalen Drogen und deren Metaboliten konnten auch frei verkäufliche Medikamente und ein Sprengstoffanalogon in entsprechend präpariertem reinem Lösungsmittel nachgewiesen werden. Ebenso gelang dies in Urinproben, die mit Drogen und Drogenmetaboliten versetzt wurden. Dabei ist hervorzuheben, dass keinerlei Probenvorbereitung notwendig war und zur Ermittlung der NWG der einzelnen Spezies keine interne oder isotopenmarkierte Standards verwendet wurden. Dennoch sind die ermittelten NWG deutlich niedriger, als die mit der bisherigen Prozedur zur Analyse flüssiger Proben erreichbaren. Um im Vergleich zu der bisher verwendeten "pin-to-plate" Geometrie der FAPA die Lösungsmittelverdampfung zu beschleunigen, wurde eine alternative Elektrodenanordnung entwickelt, bei der die Probe länger in Kontakt mit der "afterglow"-Zone steht. Diese Glimmentladungsquelle ist ringförmig und erlaubt einen Probeneintrag mittels eines zentralen Gasflusses. Wegen der ringförmigen Entladung wird der Name "halo-FAPA" (h-FAPA) für diese Entladungsgeometrie verwendet. Eine grundlegende physikalische und spektroskopische Charakterisierung zeigte, dass es sich tatsächlich um eine FAPA Desorptions/Ionisationsquelle handelt.

Zelluläre und molekulare Mechanismen der angeborenen Immunität

Die myeloide Zelllinie MUTZ-3 konnte als geeignetes Modellsystem zur Charakterisierung der TREM-1-Signaltransduktion etabliert werden, da diese TREM-1 und dessen essentielles Adaptermoleküle DAP12 funktional exprimiert. Übereinstimmend mit bisherigen Daten wurden die Kinasen PI3K und p38-MAPK als wichtige Regulatoren in der Signalweiterleitung nach TREM-1-Aktivierung identifiziert, wobei sich einige Unterschiede in der exakten Signalhierarchie zwischen monozytären und granulozytären Zellen ergaben. So erfolgt die Aktivierung von PI3K und p38-MAPK in PMN unabhängig voneinander und in monozytären Zellen findet die Aktivierung von p38-MAPK vor der Akt-Phosphorylierung statt und ist für Letztere notwendig. Zudem ist die Ca2+-Mobilisierung in PMN nur von PI3K abhängig und in monozytären Zellen von PI3K und p38-MAPK. Bei der durch TLR- oder NLR-Koligation gesteigerten TREM-1-Aktivierung sind PI3K und p38-MAPK ebenfalls zentrale Regulatoren. Es ergaben sich ebenfalls Unterschiede in der exakten TREM-1-Signaltransduktion.rnrnEin Mausmodell für invasive Aspergillose (IA) wurde erfolgreich etabliert, wobei die wichtige Rolle der PMN bei der Abwehr von Pilzinfektionen durch deren Depletion mit unterschiedlichen Antikörpern belegt wurde. Für das Abtöten von A. fumigatus-Konidien sind oxidative und nicht-oxidative PMN-Effektormechanismen notwendig. Dabei konnte die essentielle Rolle der oxidativen PMN-Effektorfunktionen anhand NADPH-Oxidase-defizienter p47phox-/- und gp91phox-/- Mäuse für das Überleben von Pilzinfektionen gezeigt werden. Dagegen war die Infektion von Neutrophiler Elastase defizienter ELANE Mäuse nicht letal. Dies deutet darauf hin, dass diese als prototypische Serinprotease und wichtiger Bestandteil der NET-Formation nicht essentiell für das Überleben von IA ist oder durch andere, nicht-oxidative Effektormechanismen kompensiert werden kann. Keinen Einfluss auf die IA hatte die Depletion von Arginin mittels ADI-PEG, da weder das Überleben der Mäuse noch das Abtöten der Pilzkonidien beeinflusst wurde. Außerdem wurden keine Veränderung in der Einwanderung und Aktivierung von PMN nach Infektion quantifiziert. Dagegen induzierte die Defizienz in ADAMTS13 (ADAMTS13-/- Mäuse) eine verminderte Rekrutierung von PMN, einhergehend mit erhöhter Mortalität, vermindertem Abtöten von A. fumigatus-Konidien und erhöhter Schädigung der Lunge bei IA. Da in vitro keine generellen oder pilzspezifischen Defekte der PMN quantifiziert wurden, muss ADAMTS13 die Einwanderung der PMN beeinflussen. Normalerweise spaltet die Protease ADAMTS13 den von-Willebrand-Faktor (vWF), der die Quervernetzung und das Anhaften von Blutplättchen an beschädigte Gefäßwände steuert. Ob und wie ADAMTS13 oder der vWF die verminderte PMN-Einwanderung bei Pilzinfektionen verursacht, muss weiter untersucht werden.rnrnZusammenfassend verbessern die erhaltenen Daten für eine zellspezifische TREM-1-Signaltransduktion, ein von oxidativen und nicht-oxidativen PMN-Effektorfunktionen abhängiges sowie Arginin-unabhängiges Abtöten vom Pilz A. fumigatus als auch der Einfluss von ADAMTS13 und vWF bei der Rekrutierung von PMN nach A. fumigatus-Infektion unser Verständnis der angeborenen Immunität. Diese Erkenntnisse dienen der zukünftigen Entwicklung von Therapien zur Behandlung von schweren Entzündungsreaktionen wie Aspergillose und Sepsis.

Sviluppo di trattamenti termici per l'ottenimento di una struttura ausferritica ad alta resistenza e tenacità nell'acciaio 56SiCr7

L’attività di tesi è stata rivolta allo sviluppo e messa a punto del trattamento termico di austempering per un acciaio ad alto contenuto di Si. Scopo della ricerca è stato valutare la possibilità di effettuare il trattamento termico secondo metodiche industriali analoghe a quelle utilizzate per il trattamento delle ghise sferoidali austemperate (ADI). Si sono studiati in particolare gli effetti dei tempi e delle temperature del trattamento sulle microstrutture e le proprietà meccaniche dell'acciaio. I risultati della sperimentazione e delle analisi hanno permesso di definire i parametri ottimali del processo di austempering, al fine di ottenere una microstruttura ausferritica in grado di garantire al contempo elevata resistenza e buona tenacità e duttilità.

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >=200 Cells/ L in the Post-Combination Antiretroviral Therapy Era

Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0–21.1 per 1000 PYFU) with current CD4 200–349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6–4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500–749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10–1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79–1.07), compared to a current CD4 of 750–999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25–1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01–1.25), comparing persons with a current CD4 of 500–749 cells/µL to 750–999 cells/µL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500–749 cells/µL compared to those with a CD4 count of 750–999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Dead Sea lake level for the last 260 ka

The rain regime of the Levant during the late Quaternary was controlled primarily by Mediterranean cyclonic systems associated with North Atlantic climate shifts. Lake levels in the Dead Sea basin have been robust recorders of the regional hydrology and generally indicate highstand (wet) conditions throughout glacial intervals and lowstands (dry) during interglacials. However, sporadic deposition of travertines and speleothems occurred in the Negev Desert and Arava Valley during past interglacials, suggesting intrusions of humidity from southern sources probably in association with enhanced activity of mid-latitude Red Sea synoptic troughs and/or low-latitude tropical plumes. The southerly incursions of wetness were superimposed on the long-term interglacial Levantine arid conditions, as reflected by the current prevailing hyperaridity, and could have had an important impact on human migra- tion through the Red Sea-Dead Sea corridor.