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Institution

University of Zurich

EducationZurich, Switzerland
About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.


Papers
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Journal ArticleDOI
TL;DR: Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever.
Abstract: Background Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life-threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status. Methodology/Principal Findings We conducted a systematic review of published morbidity and mortality studies and databases to extract information on disease incidence and case fatality ratios. Linear regression and Monte Carlo modelling were used to obtain age and gender-adjusted estimates of disease morbidity for countries and Global Burden of Disease (GBD) and WHO regions. We estimated mortality using models that incorporated age and gender-adjusted disease morbidity and case fatality ratios. The review identified 80 studies on disease incidence from 34 countries that met quality criteria. In certain regions, such as Africa, few quality assured studies were identified. The regression model, which incorporated country-specific variables of population structure, life expectancy at birth, distance from the equator, tropical island, and urbanization, accounted for a significant proportion (R2 = 0.60) of the variation in observed disease incidence. We estimate that there were annually 1.03 million cases (95% CI 434,000–1,750,000) and 58,900 deaths (95% CI 23,800–95,900) due to leptospirosis worldwide. A large proportion of cases (48%, 95% CI 40–61%) and deaths (42%, 95% CI 34–53%) were estimated to occur in adult males with age of 20–49 years. Highest estimates of disease morbidity and mortality were observed in GBD regions of South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa. Conclusions/Significance Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated

1,090 citations

Journal ArticleDOI
26 Nov 1999-Science
TL;DR: Observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt in a human breast cancer cell line.
Abstract: Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, or differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.

1,089 citations

Journal ArticleDOI
11 Jun 2015-Nature
TL;DR: It is shown that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia.
Abstract: The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.

1,088 citations

Journal ArticleDOI
TL;DR: Patients with Ehlers–Danlos syndrome type IV are at risk for arterial, bowel, and uterine rupture, but the timing of these events, their frequency, and the course of the disease are not well documented.
Abstract: Background Ehlers–Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture, but the timing of these events, their frequency, and the course of the disease are not well documented. Methods We reviewed the clinical and family histories of and medical and surgical complications in 220 index patients with biochemically confirmed Ehlers–Danlos syndrome type IV and 199 of their affected relatives. We identified the underlying COL3A1 mutation in 135 index patients. Results Complications were rare in childhood; 25 percent of the index patients had a first complication by the age of 20 years, and more than 80 percent had had at least one complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about a quarter of complications but rarely l...

1,083 citations

Journal ArticleDOI
25 Sep 2014-Nature
TL;DR: A crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5′-NGG-3′ PAM is reported, revealing that the PAM motif resides in a base-paired DNA duplex.
Abstract: The CRISPR-associated protein Cas9 is an RNA-guided endonuclease that cleaves double-stranded DNA bearing sequences complementary to a 20-nucleotide segment in the guide RNA. Cas9 has emerged as a versatile molecular tool for genome editing and gene expression control. RNA-guided DNA recognition and cleavage strictly require the presence of a protospacer adjacent motif (PAM) in the target DNA. Here we report a crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5'-NGG-3' PAM. The structure reveals that the PAM motif resides in a base-paired DNA duplex. The non-complementary strand GG dinucleotide is read out via major-groove interactions with conserved arginine residues from the carboxy-terminal domain of Cas9. Interactions with the minor groove of the PAM duplex and the phosphodiester group at the +1 position in the target DNA strand contribute to local strand separation immediately upstream of the PAM. These observations suggest a mechanism for PAM-dependent target DNA melting and RNA-DNA hybrid formation. Furthermore, this study establishes a framework for the rational engineering of Cas9 enzymes with novel PAM specificities.

1,082 citations


Authors

Showing all 51384 results

NameH-indexPapersCitations
Richard A. Flavell2311328205119
Peer Bork206697245427
Thomas C. Südhof191653118007
Stuart H. Orkin186715112182
Ruedi Aebersold182879141881
Tadamitsu Kishimoto1811067130860
Stanley B. Prusiner16874597528
Yang Yang1642704144071
Tomas Hökfelt158103395979
Dan R. Littman157426107164
Hans Lassmann15572479933
Matthias Egger152901184176
Lorenzo Bianchini1521516106970
Robert M. Strieter15161273040
Ashok Kumar1515654164086
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023265
20221,039
20218,997
20208,398
20197,336
20186,832