Severe Bottleneck Impacted the Genomic Structure of Egg-Eating Cichlids in Lake Victoria.

Within 15,000 years, the explosive adaptive radiation of haplochromine cichlids in Lake Victoria, East Africa, generated 500 endemic species. In the 1980s, the upsurge of Nile perch, a carnivorous fish artificially introduced to the lake, drove the extinction of more than 200 endemic cichlids. The Nile perch predation particularly harmed piscivorous cichlids, including paedophages, cichlids eat eggs and fries, which is an example of the unique trophic adaptation seen in African cichlids. Here, aiming to investigate past demographic events possibly triggered by the invasion of Nile perch and the subsequent impacts on the genetic structure of cichlids, we conducted large-scale comparative genomics. We discovered evidence of recent bottleneck events in 4 species, including 2 paedophages, which began during the 1970s to 1980s, and population size rebounded during the 1990s to 2000s. The timing of the bottleneck corresponded to the historical records of endemic haplochromines" disappearance and later resurgence, which is likely associated with the introduction of Nile perch by commercial demand to Lake Victoria in the 1950s. Interestingly, among the 4 species that likely experienced bottleneck, Haplochromis sp. "matumbi hunter," a paedophagous cichlid, showed the most severe bottleneck signatures. The components of shared ancestry inferred by ADMIXTURE suggested a high genetic differentiation between matumbi hunter and other species. In contrast, our phylogenetic analyses highly supported the monophyly of the 5 paedophages, consistent with the results of previous studies. We conclude that high genetic differentiation of matumbi hunter occurred due to the loss of shared genetic components among haplochromines in Lake Victoria caused by the recent severe bottleneck.

Electronic Structure of Isolated Graphene Nanoribbons in Solution Revealed by Two-Dimensional Electronic Spectroscopy.

Structurally well-defined graphene nanoribbons (GNRs) are nanostructures with unique optoelectronic properties. In the liquid phase, strong aggregation typically hampers the assessment of their intrinsic properties. Recently we reported a novel type of GNRs, decorated with aliphatic side chains, yielding dispersions consisting mostly of isolated GNRs. Here we employ two-dimensional electronic spectroscopy to unravel the optical properties of isolated GNRs and disentangle the transitions underlying their broad and rather featureless absorption band. We observe that vibronic coupling, typically neglected in modeling, plays a dominant role in the optical properties of GNRs. Moreover, a strong environmental effect is revealed by a large inhomogeneous broadening of the electronic transitions. Finally, we also show that the photoexcited bright state decays, on the 150 fs time scale, to a dark state which is in thermal equilibrium with the bright state, that remains responsible for the emission on nanosecond time scales.

Non-Degenerate Two-Photon Absorption of Fluorescent Protein Chromophores.

Two-photon absorption (2PA), where a pair of photons are absorbed simultaneously, is recognized as a potent bioimaging technique, which depends on the quantified 2PA probability, defined as cross-section (σ2PA). The absorbed photons either have equivalent (ω1 = ω2) or different frequencies (ω1 ≠ ω2), where the former is degenerate 2PA (D-2PA) and the latter is nondegenerate 2PA (ND-2PA). ND-2PA is of particular interest since it is a promising imaging technology with flexibility of photon frequencies and enhanced cross sections, however, it remains a relatively unexplored area compared to D-2PA. This work utilizes time-dependent density functional theory (TD-DFT) and second-order approximate coupled-cluster with the resolution-of-identity approximation (RI-CC2), for the excitation from S0 to S1, to investigate σD-2PA and σND-2PA of FP chromophore models. Interestingly, comparing CAM-B3LYP with the RI-CC2 computations shows qualitative and, in fact, near quantitative agreement in the computed improvements of σND-2PA for comparable (relative) frequency detunings, despite the known underestimations of 2PA cross sections, for TD-DFT results relative to RI-CC2 values. As expected from the 2-state model, the computed values of σND-2PA are quantitatively larger than σD-2PA, where chromophores with the largest values of σD-2PA show greater potential for σND-2PA improvement. Anionic chromophores demonstrated improvements up to 14%, while substantial enhancements were observed in neutral chromophores with some achieving a 30% increase. This work investigates the ND-2PA photophysical characteristics of FP chromophores and identifies qualitative patterns in the computed properties of ND-2PA relative to D-2PA.

Development of inorganic and mixed matrix membranes for application in toxic dyes-contaminated industrial effluents with in-situ treatments.

Dyes are the most ubiquitous organic pollutants in industrial effluents. They are highly toxic to both plants and animals; thus, their removal is paramount to the sustainability of ecosystem. However, they have shown resistance to photolysis and various biological, physical, and chemical wastewater remediation processes. Membrane removal technology has been vital for the filtration/separation of the dyes. In comparison to polymeric membranes, inorganic and mixed matrix (MM) membranes have shown potentials to the removal of dyes. The inorganic and MM membranes are particularly effective due to their high porosity, enhanced stability, improved permeability, higher enhanced selectivity and good stability and resistance to harsh chemical and thermal conditions. They have shown prospects in filtration/separation, adsorption, and catalytic degradation of the dyes. This review highlighted the advantages of the inorganic and MM membranes for the various removal techniques for the treatments of the dyes. Methods for the membranes production have been reviewed. Their application for the filtration/separation and adsorption have been critically analyzed. Their application as support for advanced oxidation processes such as persulfate, photo-Fenton and photocatalytic degradations have been highlighted. The mechanisms underscoring the efficiency of the processes have been cited. Lastly, comments were given on the prospects and challenges of both inorganic and MM membranes towards removal of the dyes from industrial effluents.

Vibrational coherences in half-broadband 2D electronic spectroscopy: Spectral filtering to identify excited state displacements.

Vibrational coherences in ultrafast pump-probe (PP) and 2D electronic spectroscopy (2DES) provide insights into the excited state dynamics of molecules. Femtosecond coherence spectra and 2D beat maps yield information about displacements of excited state surfaces for key vibrational modes. Half-broadband 2DES uses a PP configuration with a white light continuum probe to extend the detection range and resolve vibrational coherences in the excited state absorption (ESA). However, the interpretation of these spectra is difficult as they are strongly dependent on the spectrum of the pump laser and the relative displacement of the excited states along the vibrational coordinates. We demonstrate the impact of these convoluting factors for a model based upon cresyl violet. A careful consideration of the position of the pump spectrum can be a powerful tool in resolving the ESA coherences to gain insights into excited state displacements. This paper also highlights the need for caution in considering the spectral window of the pulse when interpreting these spectra.

A review on carbon-based biowaste and organic polymer materials for sustainable treatment of sulfonamides from pharmaceutical wastewater.

Frequent detection of sulfonamides (SAs) pharmaceuticals in wastewater has necessitated the discovery of suitable technology for their sustainable remediation. Adsorption has been widely investigated due to its effectiveness, simplicity, and availability of various adsorbent materials from natural and artificial sources. This review highlighted the potentials of carbon-based adsorbents derived from agricultural wastes such as lignocellulose, biochar, activated carbon, carbon nanotubes graphene materials as well as organic polymers such as chitosan, molecularly imprinted polymers, metal, and covalent frameworks for SAs removal from wastewater. The promising features of these materials including higher porosity, rich carbon-content, robustness, good stability as well as ease of modification have been emphasized. Thus, the materials have demonstrated excellent performance towards the SAs removal, attributed to their porous nature that provided sufficient active sites for the adsorption of SAs molecules. The modification of physico-chemical features of the materials have been discussed as efficient means for enhancing their adsorption and reusable performance. The article also proposed various interactive mechanisms for the SAs adsorption. Lastly, the prospects and challenges have been highlighted to expand the knowledge gap on the application of the materials for the sustainable removal of the SAs.

Ultrafast and Coherent Dynamics in a Solvent Switchable "Pink Box" Perylene Diimide Dimer.

Perylene diimide (PDI) dimers and higher aggregates are key components in organic molecular photonics and photovoltaic devices, supporting singlet fission and symmetry breaking charge separation. Detailed understanding of their excited states is thus important. This has proven challenging because interchromophoric coupling is a strong function of dimer architecture. Recently, a macrocyclic PDI dimer was reported in which excitonic coupling could be turned on and off simply by changing the solvent. This presents a useful case where coupling is modified without synthetic changes to tune supramolecular structure. Here we present a detailed study of solvent dependent excited state dynamics in this dimer by means of coherent multidimensional spectroscopy. Spectral analysis resolves the different coupling strengths, which are consistent with solvent dependent changes in dimer conformation. The strongly coupled conformer forms an excimer within 300 fs. The low-frequency Raman active modes recovered from two-dimensional electronic spectra reveal frequencies characteristic of exciton coupling. These are assigned to modes modulating the coupling from the corresponding DFT calculations. Further analysis reveals a time dependent frequency during excimer formation. Analysis of two-dimensional "beatmaps" reveals features in the coupled dimer which are not predicted by the displaced harmonic oscillator model and are assigned to vibronic coupling.

Genomic Profiling of Metastatic Basal cell Carcinoma Reveals Candidate Drivers of Disease and Therapeutic Targets.

Basal cell carcinomas (BCCs) are human beings' most common malignant tumors. Most are easily managed by surgery or topical therapies, and metastasis is rare. Although BCCs can become locally advanced, metastatic BCCs are very uncommon and may be biologically distinct. We assessed the clinicopathologic characteristics of 17 patients with metastatic BCC and pursued whole-exome sequencing of tumor and germline DNA from 8 patients. Genomic profiling revealed aberrant activation of Hedgehog signaling and alterations in GLI transcriptional regulators and Notch and Hippo signaling. Matched local recurrences of primary BCCs and metastases from 3 patients provided evidence of a clonal origin in all cases. Mutations associated with YAP inhibition were found exclusively in 2 hematogenously-spread lung metastases, and metastatic BCCs were enriched for mutations in the YAP/TAZ-binding domain of TEAD genes. Accordingly, YAP/TAZ nuclear localization was associated with metastatic types and Hippo mutations, suggesting an enhanced oncogenic role in hematogenously-spread metastases. Mutations in RET, HGF, and phosphatidylinositol 3­kinase (PI3K)/protein kinase B (AKT) signaling were enriched compared with a cohort of low clinical-risk BCCs. Our results implicate Hippo and PI3K/AKT dysregulation in metastatic progression of BCCs, making these potential therapeutic targets in metastatic disease. The common clonal origin of matched recurrent and metastatic BCCs suggests that molecular profiling can assist in determining the nature/origin of poorly differentiated metastatic tumors of uncertain type. Genes and pathways enriched for mutations in this cohort are candidate drivers of metastasis and can be used to identify patients at high risk of metastasis who may benefit from aggressive local treatment and careful clinical follow-up.

Half-broadband two-dimensional electronic spectroscopy with active noise reduction.

Two-dimensional electronic spectroscopy (2DES) provides detailed insight into coherent ultrafast molecular dynamics in the condensed phase. Here we report a referenced broadband pump-compressed continuum probe half-broadband (HB) 2DES spectrometer in a partially collinear geometry. To optimize signal-to-noise ratio (SNR) we implement active noise reduction referencing, which has not previously been applied in 2DES. The method is calibrated against the well characterized 2DES response of the oxazine dye cresyl violet and demonstrated at visible wavelengths on the photochromic photoswitch 1,2-Bis(2-methyl-5-phenyl-3-thienyl) perfluorocyclopentene (DAE). The SNR is improved by a factor of ∼2 through active referencing. This is illustrated in an application to resolve a low frequency mode in the excited electronic state of DAE, yielding new data on the reaction coordinate. We show that the active noise reduction referencing, coupled with the rapid data collection, allows the extraction of weak vibronic features, most notably a low frequency mode in the excited electronic state of DAE.

Degenerate and non-degenerate two-photon absorption of coumarin dyes.

Two-photon absorption (2PA) spectroscopy is a robust bioimaging tool that depends on the determined cross-sections (σ2PA). The absorption of both photons occurs simultaneously with equivalent (degenerate) or different (non-degenerate) photon energies, D-2PA and ND-2PA, respectively. The former has been investigated experimentally and computationally for many systems, while the latter remains relatively unexplored computationally and limited experimentally. In this study, response theory using time-dependent density functional theory (TD-DFT) and the 2-state model (2SM) have been utilized to investigate σD-2PA and σND-2PA for the excitation to the lowest energy singlet state (S1) of coumarin, coumarin 6, coumarin 120, coumarin 307, and coumarin 343. Solvents involved were methanol (MeOH), chloroform (ClForm), and dimethylsulfoxide (DMSO), where the latter leads to the largest σ2PA. Values of σ2PA are largest for coumarin 6 and lowest for coumarin, which illustrates the effect of substituents. The 2SM clarifies how the largest cross-sections correspond to molecules with the largest transition dipole moments, µ01. In general, σD-2SM computations agree with σD-2PA. Moreover, σND-2SM are in qualitative agreement with σND-2PA with comparable enhancement relative to σD-2PA. Overall, σND-2PA are larger than σD-2PA where the increase is in the range of 22% to 49%, depending on the coumarin as well as the relative energies of the two photons. This work aids in future investigations into various fluorophores to understand their photophysical properties for ND-2PA.

The use of veno-arterial extracorporeal membrane oxygenation in the octogenarian population: A single-center experience.

INTRODUCTION: Advanced age is a known risk factor for poor outcomes after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac support. The use of ECMO support in patients over the age of 80 is controversial, and sometimes its use is contraindicated. We aimed to assess the use of ECMO in octogenarian patients to determine survival and complication rates. METHODS: A single-center, retrospective analysis was completed at a large, urban academic medical center. Patients requiring V-A ECMO support between December of 2012 and November of 2019 were included as long as the patient was at least 80 years of age at the time of cannulation. Post cardiotomy shock patients were excluded. RESULTS: A total of 46 patients met eligibility criteria; all received V-A ECMO support. Overall, the majority of patients (71.7%; 33/46) survived to decannulation, and 43.5% (20/46) survived to discharge. Patients who were previously rescued from percutaneous interventions tend to have a better survival than other patients (p = .06). The most common complications were renal and hemorrhagic. CONCLUSIONS: We demonstrated that advanced age alone should not disqualify patients from cannulating and supporting with V-A ECMO.

Emergence of Dalbavancin, Vancomycin, and Daptomycin Nonsusceptible Staphylococcus aureus in a Patient Treated With Dalbavancin: Case Report and Isolate Characterization.

A patient with end-stage renal disease received 2 doses of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) arteriovenous fistula infection and presented 5 weeks later with infective endocarditis secondary to vancomycin, daptomycin, and dalbavancin nonsusceptible MRSA. Resistance was associated with walK and scrA mutations, reduced long-chain lipid content, and reduced membrane fluidity.

A global agenda for advancing freshwater biodiversity research.

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.

Genetic drivers of non-cutaneous melanomas: Challenges and opportunities in a heterogeneous landscape.

Non-cutaneous melanomas most frequently involve the uveal tract and mucosal membranes, including the conjunctiva. In contrast to cutaneous melanoma, they often present at an advanced clinical stage, are associated with worse clinical outcomes and show poorer responses to immunotherapy. The mutational load within most non-cutaneous melanomas reflects their lower ultraviolet light (UV) exposure. The genetic drivers within non-cutaneous melanomas are heterogeneous. Within ocular melanomas, posterior uveal tract melanomas typically harbour one of two distinct, sets of driver mutations and alterations of clinical and biological significance. In contrast to posterior uveal tract melanomas, anterior uveal tract melanomas of the iris and conjunctival melanomas frequently carry both a higher mutational burden and specific mutations linked with UV exposure. The genetic drivers in iris melanomas more closely resemble those of the posterior uveal tract, whereas conjunctival melanomas harbour similar genetic driver mutations to cutaneous melanomas. Mucosal melanomas occur in sun-shielded sites including sinonasal and oral cavities, nasopharynx, oesophagus, genitalia, anus and rectum, and their mutational landscape is frequently associated with a dominant process of spontaneous deamination and infrequent presence of UV mutation signatures. Genetic drivers of mucosal melanomas are diverse and vary with anatomic location. Further understanding of the causes of already identified recurrent molecular events in non-cutaneous melanomas, identification of additional drivers in specific subtypes, integrative multi-omics analyses and analysis of the tumor immune microenvironment will expand knowledge in this field. Furthermore, such data will likely uncover new therapeutic strategies which will lead to improved clinical outcomes in non-cutaneous melanoma patients.

The Genetic Population Structure of Lake Tanganyika's Lates Species Flock, an Endemic Radiation of Pelagic Top Predators.

Understanding genetic connectivity plays a crucial role in species conservation decisions, and genetic connectivity is an important component of modern fisheries management. In this study, we investigated the population genetics of four endemic Lates species of Lake Tanganyika (Lates stappersii, L. microlepis, L. mariae, and L. angustifrons) using reduced-representation genomic sequencing methods. We find the four species to be strongly differentiated from one another (mean interspecific FST = 0.665), with no evidence for contemporary admixture. We also find evidence for strong genetic structure within L. mariae, with the majority of individuals from the most southern sampling site forming a genetic group that is distinct from the individuals at other sampling sites. We find evidence for much weaker structure within the other three species (L. stappersii, L. microlepis, and L. angustifrons). Our ability to detect this weak structure despite small and unbalanced sample sizes and imprecise geographic sampling locations suggests the possibility for further structure undetected in our study. We call for further research into the origins of the genetic differentiation in these four species-particularly that of L. mariae-which may be important for conservation and management of this culturally and economically important clade of fishes.

ΔNO and the complexities of electron correlation in simple hydrogen clusters.

The Δ natural orbital (ΔNO) two-electron density matrix (2-RDM) and energy expression are derived from a multideterminantal wave function. The approximate ΔNO 2-RDM is combined with an on-top density functional and a double-counting correction to capture electron correlation. A trust-region Newton's method optimization algorithm for the simultaneous optimization of ΔNO orbitals and occupancies is introduced and compared to the previous iterative diagonalization algorithm. The combination of ΔNO and two different on-top density functionals, Colle-Salvetti (CS) and Opposite-spin exponential cusp and Fermi-hole correction (OF), is assessed on small hydrogen clusters and compared to density functional, single-reference coupled-cluster, and multireference perturbation theory (MRMP2) methods. The ΔNO-CS and ΔNO-OF methods outperform the single-reference methods and are comparable to MRMP2. However, there is a distinct qualitative error in the ΔNO potential energy surface for H4 compared to the exact. This discrepancy is explained through analysis of the ΔNO orbitals, occupancies, and the two-electron density.

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are currently in clinical development in melanoma, a tumor that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib and demonstrate that the activity of PRMT5, a protein arginine methyltransferase and indirect target of CDK4, is essential for CDK4/6 inhibitor sensitivity. By indirectly suppressing PRMT5 activity, palbociclib alters the pre-mRNA splicing of MDM4, a negative regulator of p53, leading to decreased MDM4 protein expression and subsequent p53 activation. In turn, p53 induces p21, leading to inhibition of CDK2, the main kinase substituting for CDK4/6 and a key driver of resistance to palbociclib. Loss of the ability of palbociclib to regulate the PRMT5-MDM4 axis leads to resistance. Importantly, combining palbociclib with the PRMT5 inhibitor GSK3326595 enhances the efficacy of palbociclib in treating naive and resistant models and also delays the emergence of resistance. Our studies have uncovered a mechanism of action of CDK4/6 inhibitors in regulating the MDM4 oncogene and the tumor suppressor, p53. Furthermore, we have established that palbociclib inhibition of the PRMT5-MDM4 axis is essential for robust melanoma cell sensitivity and provide preclinical evidence that coinhibition of CDK4/6 and PRMT5 is an effective and well-tolerated therapeutic strategy. Overall, our data provide a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma.

Altered relaxation dynamics of excited state reactions by confinement in reverse micelles probed by ultrafast fluorescence up-conversion.

Chemical reactions in confined environments are important in areas as diverse as heterogenous catalysis, environmental chemistry and biochemistry, yet they are much less well understood than the equivalent reactions in either the gas phase or in free solution. The understanding of chemical reactions in solution was greatly enhanced by real time studies of model reactions, through ultrafast spectroscopy (especially when supported by molecular dynamics simulation). Here we review some of the efforts that have been made to adapt this approach to the investigation of reactions in confined media. Specifically, we review the application of ultrafast fluorescence spectroscopy to measure reaction dynamics in the nanoconfined water phase of reverse micelles, as a function of the droplet radius and the charge on the interface. Methods of measurement and modelling of the reactions are outlined. In all of the cases studied (which are focused on ultrafast intramolecular reactions) the effect of confinement was to suppress the reaction. Even in the largest micelles the result in the bulk aqueous phase was not usually recovered, suggesting an important role for specific interactions between reactant and environment, for example at the interface. There was no simple one-to-one correspondence with direct measures of the dynamics of the confined phase. Thus, understanding the effect of confinement on reaction rate appears to require not only knowledge of the dynamics of the reaction in solutions and the effect of confinement on the medium, but also of the interaction between reactant and confining medium.

Traumatic respiratory failure and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation. STUDY DESIGN: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed. RESULTS: Fifteen patients from a large Level I trauma center met the criteria. The median PaO2/FiO2 ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%). CONCLUSIONS: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

Accumulation characteristics and ecological implications of heavy metals in surface sediments of the Mwanza Gulf, Lake Victoria.

The distribution of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn and their fraction characteristics (except Hg) were investigated in surface sediments of the Mwanza Gulf, Lake Victoria. The ecological risks, bioavailability, and mobility of the metals were also evaluated by using enrichment factor (EF), contamination factor (Cf), geo-accumulation index (Igeo), potential ecological risk index (RI), risk assessment code (RAC), individual contamination factor (ICF), and global contamination factor (GCF). Results showed that there were moderate accumulations of heavy metals in sediments from the southern part of the gulf. The mean Cf of heavy metals ranged from 1.19 (Ni) to 2.85 (Hg) suggesting moderate contamination of heavy metals in the sediments while Igeo results showed that the sediments are mainly contaminated by As, Cr, and Hg. The average potential ecological risk of heavy metals in sediments of the Mwanza Gulf is at moderate level (RI 205.49). Hg and Cd posed considerable or moderated risks with mean ecological risk of 114.18 and 44.16, which accounted for 51.08% and 21.54% of the total RI, respectively. High bioavailability and mobility of heavy metals were found in sediments near Mwanza city, particularly Zn and Cd, of which the bioavailability risks were at medium to high levels. Given the biological and environmental importance of the Mwanza Gulf and Lake Victoria, emission paths and bioaccumulation of heavy metals through food webs should be studied carefully to ensure the safety of food and the health and well-being of humans.