Threshold dissociation and molecular modeling of transition metal complexes of flavonoids

The relative threshold dissociation energies of a series of flavonoid/transition metal/auxiliary ligand complexes of the type [MII (flavonoid − H) auxiliary ligand]+ formed by electrospray ionization (ESI) were measured by energy-variable collisionally activated dissociation (CAD) in a quadrupole ion trap (QIT). For each of the isomeric flavonoid diglycoside pairs, the rutinoside (with a 1–6 inter-saccharide linkage) requires a greater CAD energy and thus has a higher dissociation threshold than its neohesperidoside (with a 1–2 inter-saccharide linkage) isomer. Likewise, the threshold energies of complexes containing flavones are higher than those containing flavanones. The monoglycoside isomers also have characteristic threshold energies. The flavonoids that are glycosylated at the 3-O- position tend to have lower threshold energies than those glycosylated at the 7-O- or 4′-O- position, and those that are C- bonded have lower threshold energies than the O- bonded isomers. The structural features that substantially influence the threshold energies include the aglycon type (flavanone versus flavone), the type of disaccharide (rutinose versus neohesperidose), and the linkage type (O- bonded versus C- bonded). Various computational means were applied to probe the structures and conformations of the complexes and to rationalize the differences in threshold energies of isomeric flavonoids. The most favorable coordination geometry of the complexes has a plane-angle of about 62°, which means that the deprotonated flavonoid and 2,2′-bipyridine within a complex do not reside on the same plane. Stable conformations of five cobalt complexes and five deprotonated flavonoids were identified. The conformations were combined with the point charges and helium accessible surface areas to explain qualitatively the differences in threshold energies for isomeric flavonoids

Goal-Focused Emotion-Regulation Therapy (GET) for young adult survivors of testicular cancer: a pilot randomized controlled trial of a biobehavioral intervention protocol.

BackgroundTesticular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients.MethodsParticipants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2.DiscussionGET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors.Trial registrationClinicaltrials.gov, NCT04150848. Registered on 28 October 2019

Functional anatomy of the masking level difference, an fMRI study

Introduction: Masking level differences (MLDs) are differences in the hearing threshold for the detection of a signal presented in a noise background, where either the phase of the signal or noise is reversed between ears. We use N0/Nπ to denote noise presented in-phase/out-of-phase between ears and S0/Sπ to denote a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the noise/signal combinations N0Sπ and NπS0 is typically 10-20 dB better than for N0S0. All combinations have the same spectrum, level, and duration of both the signal and the noise. Methods: Ten participants (5 female), age: 22-43, with N0Sπ-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400-600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle) were used to create the stimuli. Brain maps of statistically significant regions were formed from a second-level analysis using SPM5. Results: The contrast NπS0- N0Sπ had significant regions of activation in the right pulvinar, corpus callosum, and insula bilaterally. The left inferior frontal gyrus had significant activation for contrasts N0Sπ-N0S0 and NπS0-N0S0. The contrast N0S0-N0Sπ revealed a region in the right insula, and the contrast N0S0-NπS0 had a region of significance in the left insula. Conclusion: Our results extend the view that the thalamus acts as a gating mechanism to enable dichotic listening, and suggest that MLD processing is accomplished through thalamic communication with the insula, which communicate across the corpus callosum to either enhance or diminish the binaural signal (depending on the MLD condition). The audibility improvement of the signal with both MLD conditions is likely reflected by activation in the left inferior frontal gyrus, a late stage in the what/where model of auditory processing. © 2012 Wack et al

Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

ATP-sensitive potassium channels (K(ATP) channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, K(ATP) channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism–secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional K(ATP) channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts. We further show that pharmacological activation of native zebrafish K(ATP) using diazoxide, a specific K(ATP) channel opener, is sufficient to disturb glucose tolerance in adult zebrafish. That β-cell K(ATP) channel expression and function are conserved between zebrafish and mammals illustrates the evolutionary conservation of islet metabolic sensing from fish to humans, and lends relevance to the use of zebrafish to model islet glucose sensing and diseases of membrane excitability such as neonatal diabetes

Superparasitism and Population Regulation of the Mosquito-Parasitic Mermithid Nematodes Romanomermis iyengari and Strelkovimermis spiculatus

Superparasitism is a common phenomenon in mosquito-parasitic mermithid nematodes. Multiple nematodes are needed in a single host to produce males. Host selection behavior and intraspecific competition among Romanomermis iyengari and Strelkovimermis spiculatus were investigated against their host, Culex pipiens pipiens in laboratory experiments. In a choice assay between previously infected and uninfected host larvae, infectious preparasites of both nematode species could distinguish not only between infected and uninfected hosts, but even between different parasite loads in showing a strong preference for uninfected hosts or hosts with a low parasite load. Host heart rate declined briefly immediately after parasitism. Superparasitism resulted in increased parasite mortality. Scramble competition within mosquito larvae for limited host nutrients, coupled with a skewed sex ratio favoring males, is assumed to lead to parasite population decline and subsequently toward host-parasite population equilibrium. The ability of mermithid preparasites to accurately assess parasite load likely plays an important role in host population dynamics and regulation

Stingless bees in Miocene amber of southeastern China (Hymenoptera: Apidae)

Among the many inclusions from the exceptionally rich fossiliferous amber of Zhangpu, China (Middle Miocene: Langhian), stingless bees (Apinae: Meliponini) are particularly common, analogous to the merely slightly older amber sites of Mexico and the Dominican Republic. While there is a large number of workers in Zhangpu amber, only two species are represented. The systematics and morphology of the tribe Meliponini is outlined, including a revision to terms of orientation and direction when discussing surfaces and features of appendages, all in order to better discuss the traits of the fossils as well as place them into a broader context in the global systematics of stingless bees. The two amber species are representative of two Old World genera of Meliponini: Tetragonula Moure and Austroplebeia Moure. While the former is widespread across southern Asia, Malesia, Papuasia, and Australia, the latter is today known only from New Guinea and Australia. Neither genus occurs in the environs of Zhangpu today. Tetragonula (Tetragonula) florilega Engel, new species, is a generally typical species of the subgenus although it intermingles traits otherwise found in two large species groups of non-Australian Tetragonula s.str. The species of Austroplebeia from Zhangpu is sufficiently distinct to place in a new subgenus, Anteplebeina Engel. Austroplebeia (Anteplebeina) fujianica Engel, new species, shares a long list of character states with Austroplebeia s.str., including the presence of yellow maculation on the face, mesoscutum, mesoscutellum, and metepisternum, found only in this clade among Asiatic Meliponini. Nonetheless, the species differs in the length of the malar space and various features of wing venation. Keys are provided to the genera in Zhangpu amber and the subgenera of both genera. The diversity of stingless bees in amber is discussed, as well as the presence of these two fossils in the Middle Miocene of mainland Asia in relation to prior divergence time estimates, phylogenetic relationships, as well as the paleogeography of the region and potential biogeographic hypotheses. The biological association of stingless bees with resins, particularly the collection of dipterocarp resins, is discussed as Zhangpu amber is a Class II resin likely produced by an extinct species of Dipterocarpaceae (Malvales). Also discussed are the ecological preferences of modern Tetragonula and Austroplebeia relative to the reconstructed paleoenvironment of the Zhangpu amber rainforest. Emendations to the classification of Meliponini are appended, with the following new taxa proposed: Atrichotrigona Engel, new subgenus of Axestotrigona Moure; Lispotrigona V.H. Gonzalez & Engel, new subgenus of Nannotrigona Cockerell; Asperplebeia Engel, new genus; Nanoplebeia Engel, new subgenus of Plebeia Schwarz; Aphaneuropsis Engel, Koilotrigona Engel, Necrotrigona Engel, Dichrotrigona Engel, Nostotrigona Engel, Ktinotrofia Engel, all new subgenera of Trigona Jurine; Chapadapis Engel, new subgenus of Schwarziana Moure. The following higher groups are also established: Hypotrigonina Engel, new sutribe; Heterotrigonitae Engel, new infratribe; Trigoniscitae Engel, new infratribe

Microbiome Influencers of Checkpoint Blockade-Associated Toxicity

Immunotherapy has greatly improved cancer outcomes, yet variability in response and off-target tissue damage can occur with these treatments, including immune checkpoint inhibitors (ICIs). Multiple lines of evidence indicate the host microbiome influences ICI response and risk of immune-related adverse events (irAEs). As the microbiome is modifiable, these advances indicate the potential to manipulate microbiome components to increase ICI success. We discuss microbiome features associated with ICI response, with focus on bacterial taxa and potential immune mechanisms involved in irAEs, and the overall goal of driving novel approaches to manipulate the microbiome to improve ICI efficacy while avoiding irAE risk