2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding.

The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive.

2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

Dissecting the Conformational Heterogeneity of Stem-Loop Substructures of the Fifth Element in the 5'-Untranslated Region of SARS-CoV-2.

Throughout the family of coronaviruses, structured RNA elements within the 5' region of the genome are highly conserved. The fifth stem-loop element from SARS-CoV-2 (5_SL5) represents an example of an RNA structural element, repeatedly occurring in coronaviruses. It contains a conserved, repetitive fold within its substructures SL5a and SL5b.

Future Treatment Strategies for Cancer Patients Combining Targeted Alpha Therapy with Pillars of Cancer Treatment: External Beam Radiation Therapy, Checkpoint Inhibition Immunotherapy, Cytostatic Chemotherapy, and Brachytherapy.

Cancer is one of the most complex and challenging human diseases, with rising incidences and cancer-related deaths despite improved diagnosis and personalized treatment options. Targeted alpha therapy (TαT) offers an exciting strategy emerging for cancer treatment which has proven effective even in patients with advanced metastatic disease that has become resistant to other treatments. Yet, in many cases, more sophisticated strategies are needed to stall disease progression and overcome resistance to TαT.

Hot Carrier Nanowire Transistors at the Ballistic Limit.

We demonstrate experimentally nonequilibrium transport in unipolar quasi-1D hot electron devices reaching the ballistic limit at room temperature. The devices are realized with heterostructure engineering in nanowires to obtain dopant- and dislocation-free 1D-epitaxy and flexible bandgap engineering. We show experimentally the control of hot electron injection with a graded conduction band profile and the subsequent filtering of hot and relaxed electrons with rectangular energy barriers.

The 5'-terminal stem-loop RNA element of SARS-CoV-2 features highly dynamic structural elements that are sensitive to differences in cellular pH.

We present the nuclear magnetic resonance spectroscopy (NMR) solution structure of the 5'-terminal stem loop 5_SL1 (SL1) of the SARS-CoV-2 genome. SL1 contains two A-form helical elements and two regions with non-canonical structure, namely an apical pyrimidine-rich loop and an asymmetric internal loop with one and two nucleotides at the 5'- and 3'-terminal part of the sequence, respectively. The conformational ensemble representing the averaged solution structure of SL1 was validated using NMR residual dipolar coupling (RDC) and small-angle X-ray scattering (SAXS) data.

mA Methylation of Transcription Leader Sequence of SARS-CoV-2 Impacts Discontinuous Transcription of Subgenomic mRNAs.

The SARS-CoV-2 genome has been shown to be mA methylated at several positions in vivo. Strikingly, a DRACH motif, the recognition motif for adenosine methylation, resides in the core of the transcriptional regulatory leader sequence (TRS-L) at position A74, which is highly conserved and essential for viral discontinuous transcription. Methylation at position A74 correlates with viral pathogenicity.

Structure of an internal loop motif with three consecutive U•U mismatches from stem-loop 1 in the 3'-UTR of the SARS-CoV-2 genomic RNA.

The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5'- and 3'-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups.

NMR characterization and ligand binding site of the stem-loop 2 motif from the Delta variant of SARS-CoV-2.

The stem-loop 2 motif (s2m) in SARS-CoV-2 (SCoV-2) is located in the 3'-UTR. Although s2m has been reported to display characteristics of a mobile genomic element that might lead to an evolutionary advantage, its function has remained unknown. The secondary structure of the original SCoV-2 RNA sequence (Wuhan-Hu-1) was determined by NMR in late 2020, delineating the base-pairing pattern and revealing substantial differences in secondary structure compared to SARS-CoV-1 (SCoV-1).

NMR H,F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA.

Development of new antiviral medication against the beta-coronavirus SARS-CoV-2 (SCoV2) is actively being pursued. Both NMR spectroscopy and crystallography as structural screening technologies have been utilised to screen the viral proteome for binding to fragment libraries. Here, we report on NMR screening of elements of the viral RNA genome with two different ligand libraries using H-NMR-screening experiments and H and F NMR-screening experiments for fluorinated compounds.

Growth and fatty acid composition of pikeperch (Sander lucioperca L., 1758) larvae under altered feeding protocol including the copepod Apocyclops panamensis (Marsh, 1913).

Alternative live feeds for small and sensitive fish early life stages such as pikeperch (Sander lucioperca L., 1758) can improve the larval quantity, quality and performance in aquaculture. Therefore, this study evaluated the cyclopoid copepod Apocyclops panamensis (Marsh, 1913) as live feed for pikeperch larviculture from day 11 post hatch (dph) in two independent experiments.

High-resolution structure of stem-loop 4 from the 5'-UTR of SARS-CoV-2 solved by solution state NMR.

We present the high-resolution structure of stem-loop 4 of the 5'-untranslated region (5_SL4) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) genome solved by solution state nuclear magnetic resonance spectroscopy. 5_SL4 adopts an extended rod-like structure with a single flexible looped-out nucleotide and two mixed tandem mismatches, each composed of a G•U wobble base pair and a pyrimidine•pyrimidine mismatch, which are incorporated into the stem-loop structure. Both the tandem mismatches and the looped-out residue destabilize the stem-loop structure locally.

Cell-free transcription-translation system: a dual read-out assay to characterize riboswitch function.

Cell-free protein synthesis assays have become a valuable tool to understand transcriptional and translational processes. Here, we established a fluorescence-based coupled in vitro transcription-translation assay as a read-out system to simultaneously quantify mRNA and protein levels. We utilized the well-established quantification of the expression of shifted green fluorescent protein (sGFP) as a read-out of protein levels.

Omega-3 versus Omega-6: Are We Underestimating the Ecological Significance of Arachidonic Acid in Aquatic Systems?

The long-chain polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA, ω-3, or n-3) and arachidonic acid (ARA, ω-6 or n-6) are known to have distinct physiological functions, yet can both support growth and reproduction of consumers, raising the question of whether EPA and ARA are ecologically substitutable dietary resources. We explored the relative importance of EPA and ARA for the growth and reproduction of the freshwater keystone herbivore in a life-history experiment. Both PUFA were supplemented in a concentration-dependent manner to a PUFA-free diet, separately and in combination (50% EPA: 50% ARA mixture).

Pulse overlap artifacts and double quantum coherence spectroscopy.

The double quantum coherence (DQC) signal in nonlinear spectroscopy gives information about the many-body correlation effects not easily available by other methods. The signal is short-lived, consequently, a significant part of it is generated during the pulse overlap. Since the signal is at two times the laser frequency, one may intuitively expect that the pulse overlap-related artifacts are filtered out by the Fourier transform.

Photoperiodic adaptation of and clock gene expression in seasonal populations of .

Changes in day-length entrain the endogenous clock of organisms leading to complex responses to photoperiod. In long-lived organisms experiencing several seasons this response of the clock to photoperiod is phenotypically plastic. However, short-lived organisms often experience a single season without pronounced changes in day-length.

The COVID19-NMR Consortium: A Public Report on the Impact of this New Global Collaboration.

The outbreak of COVID-19 in December 2019 required the formation of international consortia for a coordinated scientific effort to understand and combat the virus. In this Viewpoint Article, we discuss how the NMR community has gathered to investigate the genome and proteome of SARS-CoV-2 and tested them for binding to low-molecular-weight binders. External factors including extended lockdowns due to the global pandemic character of the viral infection triggered the transition from locally focused collaborative research conducted within individual research groups to digital exchange formats for immediate discussion of unpublished results and data analysis, sample sharing, and coordinated research between more than 50 groups from 18 countries simultaneously.

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development.

SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2.

Outcomes and Risk Factors in Microsurgical Forefoot Reconstruction.

Background:  Defects at the forefoot frequently require microsurgical reconstruction; however, reconstructive failure can lead to results inferior to primary amputation. The purpose of this study was to identify independent factors affecting surgical outcomes and hospitalization time in these patients.

Methods:  All patients that underwent free flap reconstruction of the forefoot between 2008 and 2019 were reviewed retrospectively.

Photosynthetic activity in both algae and cyanobacteria changes in response to cues of predation.

A plethora of adaptive responses to predation has been described in microscopic aquatic producers. Although the energetic costs of these responses are expected, with their consequences going far beyond an individual, their underlying molecular and metabolic mechanisms are not fully known. One, so far hardly considered, is if and how the photosynthetic efficiency of phytoplankton might change in response to the predation cues.

A sterol-mediated gleaner-opportunist trade-off underlies the evolution of grazer resistance to cyanobacteria.

The human-caused proliferation of cyanobacteria severely impacts consumers in freshwater ecosystems. Toxicity is often singled out as the sole trait to which consumers can adapt, even though cyanobacteria are not necessarily toxic and the lack of nutritionally critical sterols in cyanobacteria is known to impair consumers. We studied the relative significance of toxicity and dietary sterol deficiency in driving the evolution of grazer resistance to cyanobacteria in a large lake with a well-documented history of eutrophication and oligotrophication.