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IntroductionLesions of the quadriceps or patellar tendon after total knee arthroplasty (TKA) are a rare but serious complication which, if left untreated, can lead to loss of function of the knee joint. While acute and subacute extensor mechanism disruptions may have several causes, chronic deficiencies are often related to multiple prior revision surgeries for joint infection or aseptic TKA failure. Up to date, biological allograft reconstruction showed unsatisfying results. The use of a monofilament polypropylene mesh is a promising approach for this pathological condition. The aim of the present study was to evaluate clinical, functional and patient reported outcomes of this procedure in patients with chronic extensor mechanism deficiency.Materials and MethodsTwenty-eight patients with chronic extensor mechanism deficiency (quadriceps tendon rupture n = 9, patellar tendon rupture n = 19) after TKA were included in this retrospective study. None of the patients were lost to follow-up. Surgical reconstruction was performed at one institution between 2014 and 2020 with a monofilament polypropylene mesh (Marlex Mesh, Bard, Murray Hill, USA). The mean age at the time of surgery was 69 years. Patients presented with a mean BMI of 33 kg/m2. The mean follow-up period was 23 months.ResultsThe 2-year survivorship free of mesh revision was 89% [95% confidence interval (CI): 75% to 100%]. Three patients (11%) had to undergo revision because of mechanical mesh failure and received another polypropylene mesh. No further revisions were performed thereafter. Flexion was 87° (range, 30–120°) on average. The majority of patients (75%, 21/28) had a full active extension. The mean active extension lag after surgery was 4 degrees (range, 0–30°).DiscussionWe observed a substantial improvement of extensor mechanism function. The majority of patients had full extension and showed good clinical results. A failure rate of over 50% has been published for alternative procedures. Thus, the use of the described augmentation technique represents a reasonable treatment option for chronic extensor mechanism disruptions of the patellar tendon as well as the quadriceps tendon after total knee arthroplasty. However, there might be a potentially higher risk for infection persistence in periprosthetic joint infection cases due to the presence of a foreign material.

X-ray free-electron lasers can generate radiation pulses with extreme peak intensities at short wavelengths. This enables the investigation of laser–matter interactions in a regime of high fields, yet at a non-relativistic ponderomotive potential, where ordinary rules of light–matter interaction may no longer apply and nonlinear processes are starting to become observable. Despite small cross-sections, first nonlinear effects in the hard x-ray regime have recently been observed in solid targets, including x-ray-optical sum-frequency generation (XSFG), x-ray second harmonic generation (XSHG) and two-photon Compton scattering (2PCS). Nonlinear interactions of bound electrons in the x-ray range are fundamentally different from those dominating at optical frequencies. Whereas in the optical regime nonlinearities are predominantly caused by anharmonicities of the atomic potential in the chemical bonds, x-ray nonlinearities far above atomic resonances are expected to be due to nonlinear oscillations of quasi-free electrons, including inner-shell atomic electrons. While the quasi-free-electron model agrees reasonably well with the experimental data for XSFG and XSHG, 2PCS measurements have led to unexpected results: the energy of the nonlinearly scattered photons from non-relativistic electrons shows a substantial unexpected red shift in addition to the Compton shift that is well beyond that predicted by a nonlinear quantum electrodynamics model for free electrons. A potential explanation for the spectral broadening is based on a previously unexplored scattering process that involves the whole atom rather than just quasi-free electrons. A first simulation that includes the atomic binding potential was successful in describing a broadening of the spectrum of the nonlinearly scattered photons to longer wavelengths for soft x-rays. However, the same model does not show any broadening at hard x-ray wavelengths, which is in agreement with other simulation approaches. To this point no calculation has been able to reproduce the experimentally observed broadening. Here we present further experimental data of 2PCS for an extended parameter range using additional diagnostics. In particular, we present measurements of the electron momentum distribution during the interaction that strongly suggest that the spectral broadening is not caused by an increased plasma temperature. We extend our measurement of the magnitude of the red shift in beryllium to $ > 1.9\enspace \mathrm{k}\mathrm{e}\mathrm{V}$ in addition to the Compton shift expected for free electrons and expand the measurement of the angular distribution to include forward scattering angles. We also present first measurements of 2PCS from diamond.

Abstract Phages play an essential role in controlling bacterial populations. Those infecting Pelagibacterales (SAR11), the dominant bacteria in surface oceans, have been studied in silico and by cultivation attempts. However, little is known about the quantity of phage-infected cells in the environment. Using fluorescence in situ hybridization techniques, we here show pelagiphage-infected SAR11 cells across multiple global ecosystems and present evidence for tight community control of pelagiphages on the SAR11 hosts in a case study. Up to 19% of SAR11 cells were phage-infected during a phytoplankton bloom, coinciding with a ~90% reduction in SAR11 cell abundance within 5 days. Frequently, a fraction of the infected SAR11 cells were devoid of detectable ribosomes, which appear to be a yet undescribed possible stage during pelagiphage infection. We dubbed such cells zombies and propose, among other possible explanations, a mechanism in which ribosomal RNA is used as a resource for the synthesis of new phage genomes. On a global scale, we detected phage-infected SAR11 and zombie cells in the Atlantic, Pacific, and Southern Oceans. Our findings illuminate the important impact of pelagiphages on SAR11 populations and unveil the presence of ribosome-deprived zombie cells as part of the infection cycle.

Abstract In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp1–140 interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63–94 residues. Longer RNCs (apoHmp1–189) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.

In order to define the source of cholesterol for bile acid synthesis and biliary cholesterol, hamsters with an extracorporeal bile duct received an intraperitoneal bolus of [3H]water labeling newly synthesized cholesterol. Thereafter the enterohepatic circulation was interrupted and a nutrient solution was infused during the experimental period of 78 h. In a separate group, pravastatin was administered (54-78 h) to allow discrimination of 3H-labeled cholesterol recycling from plasma and newly synthesized hepatic cholesterol late during the experiment. In controls, newly synthesized biliary cholesterol and primary bile acids derived from cholesterol newly synthesized during the experiment amounted to 5% and 12% immediately after depletion of the bile acid pool (6-9 h), respectively. After longterm bile diversion these proportions increased to 56-63%, whereas 71% of plasma cholesterol was labeled. Pravastatin inhibited the secretion of biliary cholesterol, cholate, and chenodeoxycholate by 30, 50, and 44%, respectively. In contrast, the preinfusion tritium label was suppressed by a maximum of 16%, 14%, and 26%, respectively, reflecting the contribution of cholesterol newly synthesized in the hepatocyte as opposed to labeled cholesterol recycling from the plasma. It is concluded that in the hamster newly synthesized cholesterol is of minor importance as substrate for bile acid synthesis as well as biliary cholesterol, both under near physiologic conditions and after long-term bile diversion. Moreover, the hepatic cholesterol pools subserving the synthesis of the primary bile acids are identical but appear to be different from that of biliary cholesterol directly after the depletion of the enterohepatic bile acids.

The present study describes a novel technique for investigations of the enterohepatic circulation in the hamster with an extracorporeal bile duct that allows long-term bile collection in the free-moving animal. The animals recovered for 7 days after the operation before the external loop was cut and bile was collected over a period of 78 h. Under these optimal conditions, initial bile flow (651 +/- 89 microliters per 100 g.h-1) and the secretion rates of biliary lipids were several-fold higher than reported in an earlier study using the acute fistula hamster. Biliary cholesterol secretion amounted to 369 +/- 32 nmol per 100 g.h-1, phospholipid secretion was 2.6 +/- 0.3 mumol per 100 g.h-1, and total bile acid secretion was 31.9 +/- 2.2 mumol per 100 g.h-1. A clearcut diurnal rhythm was demonstrated for bile flow and all biliary constituents. After 9 h the depletion of the bile acid pool was complete and cholic acid synthesis derepressed 1.4-fold from a basal rate of 818 nmol per 100 g.h-1, whereas the derepression of chenodeoxycholic acid synthesis was even less pronounced. Biliary cholesterol output increased 2.2-fold, but the phospholipid secretion was constant during the full experiment. It may be concluded that the technique of an extracorporeal bile duct in the free-moving animal allows studies of bile secretion under optimal conditions. Most likely the bile secretion rates given above approach the physiological rates in the hamster.

The permeability of rock fractures is a crucial parameter for flow processes in the subsurface. In the last few decades, different methods were developed to investigate on permeability in fractures, such as flow-through experiments, numerical flow simulations, or empirical equations. In recent years, the topological method of persistent homology was also used to estimate the permeability of fracture networks and porous rocks but not for rough single fractures yet. Hence, we apply persistent homology analysis on a decimetre-scale, rough sandstone bedding joint. To investigate the influence of roughness, three different data sets are created to perform the analysis: (1) 200 µm, (2) 100 µm, and (3) 50 µm resolutions. All estimated permeabilities were then compared to values derived by experimental air permeameter measurements and numerical flow simulation. The results reveal that persistent homology analysis is able to estimate the permeability of a single fracture, even if it tends to slightly overestimate permeabilities compared to conventional methods. Previous studies using porous media showed the same overestimation trend. Furthermore, the expenditure of time for persistent homology analysis, as well as air permeameter measurements and numerical flow simulation, was compared, which showed that persistent homology analysis can be also an acceptable alternative method.

Abstract Background Marine microalgae (phytoplankton) mediate almost half of the worldwide photosynthetic carbon dioxide fixation and therefore play a pivotal role in global carbon cycling, most prominently during massive phytoplankton blooms. Phytoplankton biomass consists of considerable proportions of polysaccharides, substantial parts of which are rapidly remineralized by heterotrophic bacteria. We analyzed the diversity, activity, and functional potential of such polysaccharide-degrading bacteria in different size fractions during a diverse spring phytoplankton bloom at Helgoland Roads (southern North Sea) at high temporal resolution using microscopic, physicochemical, biodiversity, metagenome, and metaproteome analyses. Results Prominent active 0.2–3 µm free-living clades comprised Aurantivirga, “Formosa”, Cd. Prosiliicoccus, NS4, NS5, Amylibacter, Planktomarina, SAR11 Ia, SAR92, and SAR86, whereas BD1-7, Stappiaceae, Nitrincolaceae, Methylophagaceae, Sulfitobacter, NS9, Polaribacter, Lentimonas, CL500-3, Algibacter, and Glaciecola dominated 3–10 µm and > 10 µm particles. Particle-attached bacteria were more diverse and exhibited more dynamic adaptive shifts over time in terms of taxonomic composition and repertoires of encoded polysaccharide-targeting enzymes. In total, 305 species-level metagenome-assembled genomes were obtained, including 152 particle-attached bacteria, 100 of which were novel for the sampling site with 76 representing new species. Compared to free-living bacteria, they featured on average larger metagenome-assembled genomes with higher proportions of polysaccharide utilization loci. The latter were predicted to target a broader spectrum of polysaccharide substrates, ranging from readily soluble, simple structured storage polysaccharides (e.g., laminarin, α-glucans) to less soluble, complex structural, or secreted polysaccharides (e.g., xylans, cellulose, pectins). In particular, the potential to target poorly soluble or complex polysaccharides was more widespread among abundant and active particle-attached bacteria. Conclusions Particle-attached bacteria represented only 1% of all bloom-associated bacteria, yet our data suggest that many abundant active clades played a pivotal gatekeeping role in the solubilization and subsequent degradation of numerous important classes of algal glycans. The high diversity of polysaccharide niches among the most active particle-attached clades therefore is a determining factor for the proportion of algal polysaccharides that can be rapidly remineralized during generally short-lived phytoplankton bloom events. Video Abstract

Abstract Forests and their provision of ecosystem services are endangered by climate change. Tree-species diversification has been identified as a key adaptation strategy to balance economic risks and returns in forest stands. Yet, whether this synergy between ecology and economics persists under large-scale extreme weather events remains unanswered. Our model accounts for both, small-scale disturbances in individual stands and extreme weather events that cause spatio-temporally correlated disturbances in a large number of neighboring stands. It economically optimizes stand-type allocations in a large forest enterprise with multiple planning units. Novel components are: spatially explicit site heterogeneity and a comparison of economic diversification strategies under local and regionally coordinated planning by simplified measures for $$\alpha$$ α , $$\beta$$ β , and $$\gamma$$ γ -diversity of stand types. $$\alpha$$ α -diversity refers to the number and evenness of stand types in local planning units, $$\beta$$ β -diversity to the dissimilarity of the species composition across planning units, and $$\gamma$$ γ -diversity to the number and evenness of stand types in the entire enterprise. Local planning led to stand-type diversification within planning units ( $$\alpha$$ α -diversity), while regionally coordinated planning led to diversification across planning units ( $$\beta$$ β -diversity). We observed a trend towards homogenization of stand-type composition likely selected under economic objectives with increasing extreme weather events. No diversification strategy fully buffered the adverse economic consequences. This led to fatalistic decisions, i.e., selecting stand types with low investment risks but also low resistance to disturbances. The resulting forest structures indicate potential adverse consequences for other ecosystem services. We conclude that high tree-species diversity may not necessarily buffer economic consequences of extreme weather events. Forest policies reducing forest owners’ investment risks are needed to establish stable forests that provide multiple ecosystem services.

ABSTRACTOcean microorganisms constitute ~70% of the marine biomass, contribute to ~50% of the Earth’s primary production, and play a vital role in global biogeochemical cycles. The marine heterotrophic and mixotrophic protistan and fungal communities have often been overlooked mainly due to limitations in morphological species identification. Despite the accumulation of studies on biogeographic patterns observed in microbial communities, our understanding of the abundance and distribution patterns within the microbial community of the largest subtropical gyre, the South Pacific Gyre (SPG), remains incomplete. Here, we investigated the diversity and vertical composition of protistan and fungal communities in the water column of the ultra-oligotrophic SPG. Our results showed apparent differences in protistan community diversity in the photic and aphotic regions. The entire protistan community diversity was significantly affected by temperature, salinity, oxygen, and nutrient concentrations, while the parasitic community diversity was also affected by chlorophyll a concentration. The parasitic protists were assigned to the class Syndiniales accounting for over 98% of the total parasitic protists, exhibiting higher relative sequence abundance along the water depth and displaying consistent patterns among different sampling stations. In contrast to the protistan community, the fungal community along the SPG primarily clustered based on the sampling station and pelagic zones. In particular, our study reveals a significant presence of parasitic protists and functionally diverse fungi in SPG and their potential impact on carbon cycling in the gyre.IMPORTANCEOur findings carry important implications for understanding the distribution patterns of the previously unrecognized occurrence of parasitic protists and functionally diverse fungi in the nutrient-limited South Pacific Gyre. In particular, our study reveals a significant presence of parasitic Syndiniales, predominantly abundant in the upper 300 m of the aphotic zone in the gyre, and a distinct presence of fungal communities in the aphotic zone at the central part of the gyre. These findings strongly suggest that these communities play a substantial role in yet insufficiently described microbial food web. Moreover, our research enhances our understanding of their contribution to the dynamics of the food webs in oligotrophic gyres and is valuable for projecting the ecological consequences of future climate warming.

ABSTRACT The metabolic island GEI4417/4436 of Salmonella enterica serovar Typhimurium (S. Typhimurium) enables the degradation of myo-inositol (MI) as the sole carbon and energy source. The island encodes two regulatory factors, the autoregulated repressor IolR that inhibits the transcription of most iol genes in the absence of MI, and the activator ReiD that induces the expression of an iol gene operon that is not controlled by IolR. In this study, we investigated the putative role of global regulators in the control of MI utilization by S. Typhimurium. The histone-like nucleoid structuring protein H-NS is demonstrated here to interact with 16 regions of GEI4417/4436 and to silence the transcriptional activity of the promoters P reiD and P iolE , thus controlling the expression of genes initial for MI degradation. The cAMP-binding regulatory protein (CRP) is shown to bind numerous promoters in GEI4417/4436 and is required for the growth of S. Typhimurium strain 14028 in a minimal medium with MI. The binding kinetics of H-NS and CRP toward promoters of GEI4417/4436 were quantified by surface resonance spectroscopy, showing that H-NS weakly binds to promoters of initial genes and that CRP has a high affinity to promoters of all genes essential for MI utilization. Furthermore, three promoters of the metabolic island were identified here to belong to the virulon of the two-component system SsrA/SsrB of salmonellae as demonstrated by electrophoretic mobility shift assays and the use of chromosomal luciferase reporter fusions. IMPORTANCE The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen S. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by S. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments.

The purpose of this work is to explore the potential of deep reinforcement learning (DRL) as a black-box optimizer for turbulence model identification. For this, we consider a Reynolds-averaged Navier–Stokes (RANS) closure model of a round turbulent jet flow at a Reynolds number of 10,000. For this purpose, we augment the widely utilized Spalart–Allmaras turbulence model by introducing a source term that is identified by DRL. The algorithm is trained to maximize the alignment of the augmented RANS model velocity fields and time-averaged large eddy simulation (LES) reference data. It is shown that the alignment between the reference data and the results of the RANS simulation is improved by 48% using the Spalart–Allmaras model augmented with DRL compared to the standard model. The velocity field, jet spreading rate, and axial velocity decay exhibit substantially improved agreement with both the LES reference and literature data. In addition, we applied the trained model to a jet flow with a Reynolds number of 15,000, which improved the mean field alignment by 35%, demonstrating that the framework is applicable to unseen data of the same configuration at a higher Reynolds number. Overall, this work demonstrates that DRL is a promising method for RANS closure model identification. Hurdles and challenges associated with the presented methodology, such as high numerical cost, numerical stability, and sensitivity of hyperparameters are discussed in the study.

The μDose system is a recently developed analytical instrument applying a combined α- and β-sensitive scintillation technique for determining the radioactivity arising from the decay chains of 235U, 238U and 232Th as well as from the decay of 40K. The device was designed to meet the particular requirements of trapped charge dating methods and allows the assessment of environmental (i.e. low) levels of natural radionuclides. The μDose system was developed as a piece of low-cost laboratory equipment, but a systematic test of its performance is still pending. For the first time, we present results from a comprehensive performance test based on an inter-laboratory comparison. We compare the results obtained with μDose measurements with those from thick source alpha counting (TSAC), inductively coupled plasma optical emission spectrometry (ICP-OES) and low-level high-resolution gamma spectrometry (HRGS) applied in five participating laboratories. In addition, the reproducibility and accuracy of μDose measurements were tested on certified reference materials distributed by the International Atomic Energy Agency (IAEA; RGU-1, RGTh-1 and RGK-1) and on two loess standards (Nussy and Volkegem) frequently used in trapped charge dating studies. We compare μDose-based results for a total of 47 sediment samples with results previously obtained for these materials by well-established methods of dose rate determination. The investigated natural samples cover a great variety of environments, including fluvial, aeolian, littoral, colluvial and (geo-)archaeological sites originating from high and low mountain regions as well as from lowlands in tropical areas, drylands and mid-latitude zones of Europe, Africa, Australia, Central Asia and the Americas. Our results suggest the μDose system's capability of assessing low-level radionuclide contents with very good accuracy and precision comparable to well-established dosimetry methods. Based on the results of our comparative study and with respect to the practical experiences gained so far, the μDose system appears to be a promising tool for trapped charge dating studies.

Background Women with cardiomyopathy (CM) are often advised against pregnancy due to risk for major adverse cardiovascular events (MACE). However, the impact of CM subtype on maternal MACE is not understood, and so we sought to evaluate the influence of CM phenotype on maternal outcomes, as well as the effect on immediate and late left ventricular function.Methods We evaluated all pregnant women in our high-risk maternal cardiovascular programme (2009–2019). Composite maternal MACE included: death, inotrope use, left ventricular assist device, orthotopic heart transplant and/or escalation in transplant listing status, acute decompensated heart failure and sustained ventricular arrhythmia.Results Among 875 women followed, 32 had CM (29±7 years old, left ventricular ejection fraction (LVEF) 41%±12%): 3 ischaemic CM (ICM), 10 peripartum CM (PPCM) and 19 non-ICM (NICM). MACE events occurred in 6 (18%) women (PPCM: 2 (33%), NICM: 4 (67%)). There was no difference in LVEF at baseline, however, women with MACE had significantly lower LVEF both early (LVEF: 27±5% vs . 41±2%, p

The impacts of climate change on the Arctic Ocean are manifesting throughout the ecosystem at an unprecedented rate. Of global importance are the impacts on heat and freshwater exchange between the Arctic and North Atlantic Oceans. An expanding Atlantic influence in the Arctic has accelerated sea-ice decline, weakened water column stability and supported the northward shift of temperate species. The only deep-water gateway connecting the Arctic and North Atlantic and thus, fundamental for these exchange processes is the Fram Strait. Previous research in this region is extensive, however, data on the ecology of microbial communities is limited, reflecting the wider bias towards temperate and tropical latitudes. Therefore, we present 14 metagenomes, 11 short-read from Illumina and three long-read from PacBio Sequel II, of the 0.2–3 µm fraction to help alleviate such biases and support future analyses on changing ecological patterns. Additionally, we provide 136 species-representative, manually refined metagenome-assembled genomes which can be used for comparative genomics analyses and addressing questions regarding functionality or distribution of taxa.

Across eukaryotes, homopolymeric repeats of amino acids are enriched in regulatory proteins such as transcription factors and chromatin remodelers. These domains play important roles in signaling, binding, prion formation, and functional phase separation. Azf1p is a prion-forming yeast transcription factor that contains two homorepeat domains, a polyglutamine and a polyasparagine domain. In this work, we report a new phenotype for Azf1p and identify a large set of genes that are regulated by Azf1p during growth in glucose. We show that the polyasparagine (polyN) domain plays a subtle role in transcription but is dispensable for Azf1p localization and prion formation. Genes upregulated upon deletion of the polyN domain are enriched in functions related to carbon metabolism and storage. This domain may therefore be a useful target for engineering yeast strains for fermentation applications and small molecule production. We also report that both the polyasparagine and polyglutamine domains vary in length across strains of S. cerevisiae and propose a model for how this variation may impact protein function.

As yeast are starved of nutrients, they enter G0, a quiescent state. Quiescent yeast (Q) cells retain viability for extended periods of time and resume growth following supplementation of missing nutrients. As such, Q cells have become a valuable model for studying longevity and self-renewal of chronologically aged cells. Traditional isolation of Q cells involves a relatively long centrifugation time through a continuous density gradient. Here, we describe a rapid and cost-effective Q-cell isolation technique that uses a single-density, one-step gradient prepared from media containing iodixanol.