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Article ; Online: Climate Change Impacts on Microbiota in Beach Sand and Water: Looking Ahead.

Brandão, João / Weiskerger, Chelsea / Valério, Elisabete / Pitkänen, Tarja / Meriläinen, Päivi / Avolio, Lindsay / Heaney, Christopher D / Sadowsky, Michael J

International journal of environmental research and public health

2022 Volume 19, Issue 3

Abstract: Beach sand and water have both shown relevance for human health and their microbiology have been the subjects of study for decades. Recently, the World Health Organization recommended that recreational beach sands be added to the matrices monitored for ... ...

Abstract	Beach sand and water have both shown relevance for human health and their microbiology have been the subjects of study for decades. Recently, the World Health Organization recommended that recreational beach sands be added to the matrices monitored for enterococci and Fungi. Global climate change is affecting beach microbial contamination, via changes to conditions like water temperature, sea level, precipitation, and waves. In addition, the world is changing, and humans travel and relocate, often carrying endemic allochthonous microbiota. Coastal areas are amongst the most frequent relocation choices, especially in regions where desertification is taking place. A warmer future will likely require looking beyond the use of traditional water quality indicators to protect human health, in order to guarantee that waterways are safe to use for bathing and recreation. Finally, since sand is a complex matrix, an alternative set of microbial standards is necessary to guarantee that the health of beach users is protected from both sand and water contaminants. We need to plan for the future safer use of beaches by adapting regulations to a climate-changing world.
MeSH term(s)	Bathing Beaches ; Climate Change ; Environmental Monitoring ; Feces/microbiology ; Humans ; Microbiota ; Sand ; Water Microbiology
Chemical Substances	Sand
Language	English
Publishing date	2022-01-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19031444
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Article: Kilohertz droplet-on-demand serial femtosecond crystallography at the European XFEL station FXE.

Structural dynamics (Melville, N.Y.)

2024 Volume 11, Issue 2, Page(s) 24310

Abstract: X-ray Free Electron Lasers (XFELs) allow the collection of high-quality serial femtosecond crystallography data. The next generation of megahertz superconducting FELs promises to drastically reduce data collection times, enabling the capture of more ... ...

Abstract	X-ray Free Electron Lasers (XFELs) allow the collection of high-quality serial femtosecond crystallography data. The next generation of megahertz superconducting FELs promises to drastically reduce data collection times, enabling the capture of more structures with higher signal-to-noise ratios and facilitating more complex experiments. Currently, gas dynamic virtual nozzles (GDVNs) stand as the sole delivery method capable of best utilizing the repetition rate of megahertz sources for crystallography. However, their substantial sample consumption renders their use impractical for many protein targets in serial crystallography experiments. Here, we present a novel application of a droplet-on-demand injection method, which allowed operation at 47 kHz at the European XFEL (EuXFEL) by tailoring a multi-droplet injection scheme for each macro-pulse. We demonstrate a collection rate of 150 000 indexed patterns per hour. We show that the performance and effective data collection rate are comparable to GDVN, with a sample consumption reduction of two orders of magnitude. We present lysozyme crystallographic data using the Large Pixel Detector at the femtosecond x-ray experiment endstation. Significant improvement of the crystallographic statistics was made by correcting for a systematic drift of the photon energy in the EuXFEL macro-pulse train, which was characterized from indexing the individual frames in the pulse train. This is the highest resolution protein structure collected and reported at the EuXFEL at 1.38 Å resolution.
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2758684-4
ISSN	2329-7778
ISSN	2329-7778
DOI	10.1063/4.0000248
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Article ; Online: Climate Change Impacts on Microbiota in Beach Sand and Water

João Brandão / Chelsea Weiskerger / Elisabete Valério / Tarja Pitkänen / Päivi Meriläinen / Lindsay Avolio / Christopher D. Heaney / Michael J. Sadowsky

International Journal of Environmental Research and Public Health, Vol 19, Iss 1444, p

Looking Ahead

2022 Volume 1444

Abstract	Beach sand and water have both shown relevance for human health and their microbiology have been the subjects of study for decades. Recently, the World Health Organization recommended that recreational beach sands be added to the matrices monitored for enterococci and Fungi. Global climate change is affecting beach microbial contamination, via changes to conditions like water temperature, sea level, precipitation, and waves. In addition, the world is changing, and humans travel and relocate, often carrying endemic allochthonous microbiota. Coastal areas are amongst the most frequent relocation choices, especially in regions where desertification is taking place. A warmer future will likely require looking beyond the use of traditional water quality indicators to protect human health, in order to guarantee that waterways are safe to use for bathing and recreation. Finally, since sand is a complex matrix, an alternative set of microbial standards is necessary to guarantee that the health of beach users is protected from both sand and water contaminants. We need to plan for the future safer use of beaches by adapting regulations to a climate-changing world.
Keywords	climate change ; global warming ; beach sand ; FIB ; sand ; recreational water ; Medicine ; R
Subject code	333
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: New Case Detection by Cascade Testing in Familial Hypercholesterolemia: A Systematic Review of the Literature.

Lee, Christopher / Rivera-Valerio, Miriannie / Bangash, Hana / Prokop, Larry / Kullo, Iftikhar J

Circulation. Genomic and precision medicine

2019 Volume 12, Issue 11, Page(s) e002723

Abstract: Background: The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade ... ...

Abstract	Background: The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade testing programs in the US could be informed by approaches used elsewhere. Methods: We conducted a systematic review of published studies in the English language of cascade testing for familial hypercholesterolemia, which reported the number of index cases and number of relatives tested and specified methods of contacting relatives and testing modalities methods utilized. For each study, we calculated yield (proportion of relatives who test positive) and new cases per index case, to facilitate comparison. Results: We identified 10 studies from the literature that met inclusion criteria; the mean number of probands and relatives per study was 242 and 826, respectively. The average yield was 44.76% with a range of 30% to 60.5%, and the mean new cases per index case was 1.65 with a range of 0.22 to 8.0. New cases per index case tended to be greater in studies that used direct contact versus indirect contact (2.06 versus 0.86), tested beyond first-degree relatives versus only first-degree relatives (3.65 versus 0.80), used active sample collection versus collection at clinic (4.11 versus 1.06), and utilized genetic testing versus biochemical testing (2.47 versus 0.42). Conclusions: New case detection in familial hypercholesterolemia cascade testing programs tended to be higher with direct contact of relatives, testing beyond first-degree relatives, in-home-based sample collection, and genetic testing. These findings should be helpful for establishing cascade testing programs in the United States.
MeSH term(s)	Apolipoproteins B/genetics ; Genetic Testing ; Humans ; Hyperlipoproteinemia Type II/diagnosis ; Hyperlipoproteinemia Type II/genetics ; Mutation ; Pedigree ; Proprotein Convertase 9/genetics ; Receptors, LDL/genetics
Chemical Substances	Apolipoproteins B ; LDLR protein, human ; Receptors, LDL ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2019-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Systematic Review
ISSN	2574-8300
ISSN (online)	2574-8300
DOI	10.1161/CIRCGEN.119.002723
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Article ; Online: What About

St John, Julie / Reininger, Belinda / Balcazar, Hector / Valerio-Shewmaker, Melissa A / Beaudoin, Christopher E

Frontiers in public health

2021 Volume 9, Page(s) 689616

Abstract: This study tested whether a cancer education intervention ... ...

Abstract	This study tested whether a cancer education intervention affected
MeSH term(s)	Community Health Workers ; Cross-Sectional Studies ; Female ; Health Education ; Hispanic or Latino ; Humans ; Uterine Cervical Neoplasms
Language	English
Publishing date	2021-09-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2021.689616
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Article ; Online: Predictors of recognition of out of hospital cardiac arrest by emergency medical services call handlers in England: a mixed methods diagnostic accuracy study.

Watkins, Caroline L / Jones, Stephanie P / Hurley, Margaret A / Benedetto, Valerio / Price, Christopher I / Sutton, Christopher J / Quinn, Tom / Bangee, Munirah / Chesworth, Brigit / Miller, Colette / Doran, Dawn / Siriwardena, Aloysius Niroshan / Gibson, Josephine M E

Scandinavian journal of trauma, resuscitation and emergency medicine

2021 Volume 29, Issue 1, Page(s) 7

Abstract: Background: The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency ... ...

Abstract	Background: The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency Medical Service call handlers, resulting in delayed arrival at scene. Methods: Retrospective, mixed methods study including all suspected or confirmed OHCA patients transferred to one acute hospital from its associated regional Emergency Medical Service in England from 1/7/2013 to 30/6/2014. Emergency Medical Service and hospital data, including voice recordings of EMS calls, were analysed to identify predictors of recognition of OHCA by call handlers. Logistic regression was used to explore the role of the most frequently occurring (key) indicator symptoms and characteristics in predicting a correct dispatch for patients with OHCA. Results: A total of 39,136 dispatches were made which resulted in transfer to the hospital within the study period, including 184 patients with OHCA. The use of the term 'Unconscious' plus one or more of symptoms 'Not breathing/Ineffective breathing/Noisy breathing' occurred in 79.8% of all OHCAs, but only 72.8% of OHCAs were correctly dispatched as such. 'Not breathing' was associated with recognition of OHCA by call handlers (Odds Ratio (OR) 3.76). The presence of key indicator symptoms 'Breathing' (OR 0.29), 'Reduced or fluctuating level of consciousness' (OR 0.24), abnormal pulse/heart rate (OR 0.26) and the characteristic 'Female patient' (OR 0.40) were associated with lack of recognition of OHCA by call handlers (p-values < 0.05). Conclusions: There is a small proportion of calls in which cardiac arrest indicators are described but the call is not dispatched as such. Stricter adherence to dispatch protocols may improve call handlers' OHCA recognition. The existing dispatch protocol would not be improved by the addition of further terms as this would be at the expense of dispatch specificity.
MeSH term(s)	Aged ; Cardiopulmonary Resuscitation/methods ; Emergency Medical Service Communication Systems ; Emergency Medical Services ; England ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Out-of-Hospital Cardiac Arrest/diagnosis ; Predictive Value of Tests ; Respiration ; Retrospective Studies
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2455990-8
ISSN	1757-7241 ; 1757-7241
ISSN (online)	1757-7241
ISSN	1757-7241
DOI	10.1186/s13049-020-00823-9
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Article ; Online: Understanding conflict among experts working on controversial species

Valerio Donfrancesco / Benjamin L. Allen / Rob Appleby / Linda Behrendorff / Gabriel Conroy / Mathew S. Crowther / Christopher R. Dickman / Tim Doherty / Bronwyn A. Fancourt / Christopher E. Gordon / Stephen M. Jackson / Chris N. Johnson / Malcolm S. Kennedy / Loukas Koungoulos / Mike Letnic / Luke K.‐P. Leung / Kieren J. Mitchell / Bradley Nesbitt / Thomas Newsome /

Carlo Pacioni / Justine Phillip / Brad V. Purcell / Euan G. Ritchie / Bradley P. Smith / Danielle Stephens / Jack Tatler / Lily M. vanEeden / Kylie M. Cairns

Conservation Science and Practice, Vol 5, Iss 3, Pp n/a-n/a (2023)

A case study on the Australian dingo

2023

Abstract: Abstract Expert elicitation can be valuable for informing decision‐makers on conservation and wildlife management issues. To date, studies eliciting expert opinions have primarily focused on identifying and building consensus on key issues. Nonetheless, ... ...

Abstract	Abstract Expert elicitation can be valuable for informing decision‐makers on conservation and wildlife management issues. To date, studies eliciting expert opinions have primarily focused on identifying and building consensus on key issues. Nonetheless, there are drawbacks of a strict focus on consensus, and it is important to understand and emphasize dissent, too. This study adopts a dissensus‐based Delphi to understand conflict among dingo experts. Twenty‐eight experts participated in three rounds of investigation. We highlight disagreement on most of the issues explored. In particular, we find that disagreement is underpinned by what we call “conflict over values” and “conflict over evidence.” We also note the broader role played by distrust in influencing such conflicts. Understanding and recognizing the different elements shaping disagreement is critical for informing and improving decision‐making and can also enable critique of dominant paradigms in current practices. We encourage greater reflexivity and open deliberation on these aspects and hope our study will inform similar investigations in other contexts.
Keywords	carnivore ; conservation social sciences ; dissensus ; evidence ; human‐wildlife conflict ; values ; Ecology ; QH540-549.5 ; General. Including nature conservation ; geographical distribution ; QH1-199.5
Subject code	710
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2).

Day, James E H / Berdini, Valerio / Castro, Joan / Chessari, Gianni / Davies, Thomas G / Day, Philip J / St Denis, Jeffrey D / Fujiwara, Hideto / Fukaya, Satoshi / Hamlett, Christopher C F / Hearn, Keisha / Hiscock, Steven D / Holvey, Rhian S / Ito, Satoru / Kandola, Navrohit / Kodama, Yasuo / Liebeschuetz, John W / Martins, Vanessa / Matsuo, Kenichi /

Journal of medicinal chemistry

2024 Volume 67, Issue 6, Page(s) 4655–4675

Abstract: The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 ... ...

Abstract	The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.
MeSH term(s)	Humans ; Mice ; Animals ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Signal Transduction ; Receptor Protein-Tyrosine Kinases/metabolism ; Neoplasms ; Allosteric Site
Chemical Substances	Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2024-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c02118
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Article ; Online: Expression profile of key genes involved in DNA repair mechanisms in bovine cumulus cells cultured with bovine serum albumin or fetal calf serum.

Goetten, André Lucio Fontana / Koch, Júlia / Rocha, Cecília Constantino / Mezzalira, Alceu / Price, Christopher Allan / Portela, Valério Marques / Barreta, Marcos Henrique

Reproductive biology

2022 Volume 23, Issue 1, Page(s) 100709

Abstract: Cumulus cells from cumulus-oocyte complexes (COC) matured in vitro in serum-free medium show high incidence of apoptosis and DNA double-strand breaks (DSB). This study aimed to characterize the transcript expression profile of selected genes involved in ... ...

Abstract	Cumulus cells from cumulus-oocyte complexes (COC) matured in vitro in serum-free medium show high incidence of apoptosis and DNA double-strand breaks (DSB). This study aimed to characterize the transcript expression profile of selected genes involved in DNA repair mechanisms in bovine cumulus cells cultured with bovine serum albumin (BSA) or fetal calf serum (FCS). Briefly, bovine cumulus-oocyte complexes were in vitro matured with either, 0.4% BSA or 10% FCS for 3, 6, 12 or 24 h. The total RNA of cumulus cells was used for real-time PCR analysis. Transcript abundance of XRCC6, XRCC5, DNAPK, GAAD45B, TP53BP1, RAD50, RAD52, ATM and BRCA2 target genes changed as the IVM proceeded (P < 0.05). However, an interaction between protein source (FCS or BSA) and time was not detected (P ≥ 0.05). Cumulus cells from COCs matured with BSA presented higher mRNA expression of two genes compared to FCS group: TP53BP1 at 6 h and BRCA1 at 3, 6, 12 and 24 h (P < 0.05). In summary, our results showed for the first time the expression profile of the key genes involved in DSB repair mechanisms in cumulus cells obtained from bovine COCs matured with FCS or BSA. The higher mRNA expression of BRCA1 and TP53BP1 and lower mRNA expression of TNFAIP6 suggests an increase in apoptosis rate and DNA damage in cumulus cells cultured in BSA-supplemented medium and may explain, at least to some extent, the reduced developmental potential of bovine oocytes matured in serum-free medium.
MeSH term(s)	Female ; Animals ; Serum Albumin, Bovine ; Cumulus Cells/metabolism ; Oocytes/metabolism ; DNA Repair ; RNA, Messenger/metabolism ; Cells, Cultured
Chemical Substances	Serum Albumin, Bovine (27432CM55Q) ; RNA, Messenger
Language	English
Publishing date	2022-11-17
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2189316-0
ISSN	2300-732X ; 1642-431X
ISSN (online)	2300-732X
ISSN	1642-431X
DOI	10.1016/j.repbio.2022.100709
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Article: Development and characterization of an intra-articular fracture mediated model of post-traumatic osteoarthritis.

Valerio, Michael S / Pace, William A / Dolan, Connor P / Edwards, Jorge B / Janakiram, Naveena B / Potter, Benjamin K / Dearth, Christopher L / Goldman, Stephen M

Journal of experimental orthopaedics

2023 Volume 10, Issue 1, Page(s) 68

Abstract: ... modifying interventions.: Methods: Male rats were subject to a 0 Joule (J), 1 J, 3 J, or 5 J blunt-force ... of osteochondral degradation.: Results: High-energy (5 J) blunt impacts consistently induced IAF to the proximal ... tibia, distal femur, or both while lower energy (1 J and 3 J) impacts did not. CCL2 was found to be ...

Abstract	Purpose: This study aimed to develop and characterize a closed intra-articular fracture (IAF) mediated post-traumatic osteoarthritis (PTOA) model in rats to serve as a testbed for putative disease modifying interventions. Methods: Male rats were subject to a 0 Joule (J), 1 J, 3 J, or 5 J blunt-force impact to the lateral aspect of the knee and allowed to heal for 14 and 56 days. Micro-CT was performed at time of injury and at the specified endpoints to assess bone morphometry and bone mineral density measurements. Cytokines and osteochondral degradation markers were assayed from serum and synovial fluid via immunoassays. Histopathological analyses were performed on decalcified tissues and assessed for evidence of osteochondral degradation. Results: High-energy (5 J) blunt impacts consistently induced IAF to the proximal tibia, distal femur, or both while lower energy (1 J and 3 J) impacts did not. CCL2 was found to be elevated in the synovial fluid of rats with IAF at both 14- and 56-days post-injury while COMP and NTX-1 were upregulated chronically relative to sham controls. Histological analysis showed increased immune cell infiltration, increased osteoclasts and osteochondral degradation with IAF relative to sham. Conclusion: Based on results from the current study, our data indicates that a 5 J blunt-forced impact adequately and consistently induces hallmark osteoarthritic changes to the articular surface and subchondral bone at 56 days after IAF. Marked development of PTOA pathobiology suggest this model will provide a robust testbed for screening putative disease modifying interventions that might be translated to the clinic for militarily relevant, high-energy joint injuries.
Language	English
Publishing date	2023-07-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2780021-0
ISSN	2197-1153
ISSN	2197-1153
DOI	10.1186/s40634-023-00625-9
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