Humans recognize affective cues in primate vocalizations: acoustic and phylogenetic perspectives.

Humans are adept at extracting affective information from vocalizations of humans and other animals. However, the extent to which human recognition of vocal affective cues of other species is due to cross-taxa similarities in acoustic parameters or the phylogenetic closeness between species is currently unclear. To address this, we first analyzed acoustic variation in 96 affective vocalizations, taken from agonistic and affiliative contexts, of humans and three other primates-rhesus macaques (Macaca mulatta), chimpanzees and bonobos (Pan troglodytes and Pan paniscus). Acoustic analyses revealed that agonistic chimpanzee and bonobo vocalizations were similarly distant from agonistic human voices, but chimpanzee affiliative vocalizations were significantly closer to human affiliative vocalizations, than those of bonobos, indicating a potential derived vocal evolution in the bonobo lineage. Second, we asked 68 human participants to categorize and also discriminate vocalizations based on their presumed affective content. Results showed that participants reliably categorized human and chimpanzee vocalizations according to affective content, but not bonobo threat vocalizations nor any macaque vocalizations. Participants discriminated all species calls above chance level except for threat calls by bonobos and macaques. Our results highlight the importance of both phylogenetic and acoustic parameter level explanations in cross-species affective perception, drawing a more complex picture to the origin of vocal emotions.

Female genital mutilation/cutting incidence, diagnostic capacities, and obstetric outcomes among migrant women: a single-center retrospective analysis in a 10-year birth cohort in Austria.

INTRODUCTION: Practical experience in the care of women with female genital mutilation/cutting (FGM/C) is uncommon in Austria. However, affected women require specialized gynecological and obstetric care. In our region, there is currently neither an official counseling center nor specially trained medical personnel to address the special needs of women after FGM/C. The aim of this study was to determine the potential need for obstetric care for women who have undergone FGM/C in our region. METHODS: We retrospectively reviewed women presenting for delivery at the LKH University Hospital Graz from 1.1.2010 until 31.12.2020 regarding the place of birth and/or the nationality of the mother to filter out women from a country with known FGM/C prevalence according to the UNICEF Global Database. Data on the documentation of FGM/C as well as demographic maternal data and peripartal parameters were gathered. Periods before and after the European refugee crisis in 2015 were compared. RESULTS: During the study period, a total of 35,628 deliveries took place at our hospital. 856 (2.4%) deliveries of 539 women were included due to nationality or birthplace in a country with known FGM/C prevalence. We found only 17/539 (3.2%) documented FGM/C cases. The estimated FGM/C prevalence among those patients was, however, 208/539 (38,6%). Women affected by FGM/C in our collective were most frequently from Nigeria, Egypt, Iraq, Ghana, and Somalia. No statistically significant increase in deliveries during the study period in the overall study cohort was observed, with the exception of deliveries of Somali women (p = 0.000). DISCUSSION: The discrepancy between documented and expected FGM/C rates (3,2% vs. 38,6%) in our collective suggests that most cases of FGM/C go undetected among women delivering in Austria. These data show the great need for special training for obstetricians and targeted contact points for affected women.

Efficiency fosters cumulative culture across species.

Recent studies in several taxa have demonstrated that animal culture can evolve to become more efficient in various contexts ranging from tool use to route learning and migration. Under recent definitions, such increases in efficiency might satisfy the core criteria of cumulative cultural evolution (CCE). However, there is not yet a satisfying consensus on the precise definition of efficiency, CCE or the link between efficiency and more complex, extended forms of CCE considered uniquely human. To bring clarity to this wider discussion of CCE, we develop the concept of efficiency by (i) reviewing recent potential evidence for CCE in animals, and (ii) clarifying a useful definition of efficiency by synthesizing perspectives found within the literature, including animal studies and the wider iterated learning literature. Finally, (iii) we discuss what factors might impinge on the informational bottleneck of social transmission, and argue that this provides pressure for learnable behaviours across species. We conclude that framing CCE in terms of efficiency casts complexity in a new light, as learnable behaviours are a requirement for the evolution of complexity. Understanding how efficiency greases the ratchet of cumulative culture provides a better appreciation of how similar cultural evolution can be between taxonomically diverse species-a case for continuity across the animal kingdom. This article is part of a discussion meeting issue 'The emergence of collective knowledge and cumulative culture in animals, humans and machines'.

AMKL chimeric transcription factors are potent inducers of leukemia.

Acute megakaryoblastic leukemia in patients without Down syndrome is a rare malignancy with a poor prognosis. RNA sequencing of fourteen pediatric cases previously identified novel fusion transcripts that are predicted to be pathological including CBFA2T3-GLIS2, GATA2-HOXA9, MN1-FLI and NIPBL-HOXB9. In contrast to CBFA2T3-GLIS2, which is insufficient to induce leukemia, we demonstrate that the introduction of GATA2-HOXA9, MN1-FLI1 or NIPBL-HOXB9 into murine bone marrow induces overt disease in syngeneic transplant models. With the exception of MN1, full penetrance was not achieved through the introduction of fusion partner genes alone, suggesting that the chimeric transcripts possess a unique gain-of-function phenotype. Leukemias were found to exhibit elements of the megakaryocyte erythroid progenitor gene expression program, as well as unique leukemia-specific signatures that contribute to transformation. Comprehensive genomic analyses of resultant murine tumors revealed few cooperating mutations confirming the strength of the fusion genes and their role as pathological drivers. These models are critical for both the understanding of the biology of disease as well as providing a tool for the identification of effective therapeutic agents in preclinical studies.

Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy.

To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ⩾1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.

Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia.

Somatic mutations that lead to constitutive activation of NRAS and KRAS proto-oncogenes are among the most common in human cancer and frequently occur in acute myeloid leukemia (AML). An inducible NRAS(V12)-driven AML mouse model has established a critical role for continued NRAS(V12) expression in leukemia maintenance. In this model genetic suppression of NRAS(V12) expression results in rapid leukemia remission, but some mice undergo spontaneous relapse with NRAS(V12)-independent (NRI) AMLs providing an opportunity to identify mechanisms that bypass the requirement for Ras oncogene activity and drive leukemia relapse. We found that relapsed NRI AMLs are devoid of NRAS(V12) expression and signaling through the major oncogenic Ras effector pathways, phosphatidylinositol-3-kinase and mitogen-activated protein kinase, but express higher levels of an alternate Ras effector, Ralb, and exhibit NRI phosphorylation of the RALB effector TBK1, implicating RALB signaling in AML relapse. Functional studies confirmed that inhibiting CDK5-mediated RALB activation with a clinically relevant experimental drug, dinaciclib, led to potent RALB-dependent antileukemic effects in human AML cell lines, induced apoptosis in patient-derived AML samples in vitro and led to a 2-log reduction in the leukemic burden in patient-derived xenograft mice. Furthermore, dinaciclib potently suppressed the clonogenic potential of relapsed NRI AMLs in vitro and prevented the development of relapsed AML in vivo. Our findings demonstrate that Ras oncogene-independent activation of RALB signaling is a therapeutically targetable mechanism of escape from NRAS oncogene addiction in AML.

Transient binding accounts for apparent violation of the generalized Stokes-Einstein relation in crowded protein solutions.

The effect of high concentration, also referred to as crowding conditions, on Brownian motion is of central relevance for the understanding of the physical, chemical and biological properties of proteins in their native environment. Specifically, the simple inverse relationship between the translational diffusion coefficient and the macroscopic solution viscosity as predicted by the generalized Stokes-Einstein (GSE) relation has been the subject of many studies, yet a consensus on its applicability has not been reached. Here, we use isotope-filtered pulsed-field gradient NMR to separately assess the µm-scale diffusivity of two proteins, BSA and an SH3 domain, in mixtures as well as single-protein solutions, and demonstrate that transient binding can account for an apparent violation of the GSE relation. Whereas GSE behavior applies for the single-protein solutions, it does not hold for the protein mixtures. Transient binding behavior in the concentrated mixtures is evidenced by calorimetric experiments and by a significantly increased apparent activation energy of diffusion. In contrast, the temperature dependence of the viscosity, as well as of the diffusivity in single-component solutions, is always dominated by the flow activation energy of pure water. As a practically relevant second result, we further show that, for high protein concentrations, the diffusion of small molecules such as dioxane or water is not generally a suitable probe for the viscosity experienced by the diffusing proteins.

Synthesis of macrocyclic receptors with intrinsic fluorescence featuring quinizarin moieties.

An unprecedented class of macrocycles with intrinsic fluorescence consisting of phenolic trimers and quinizarin is developed. Though they are lacking strong hydrogen bonds as observed in calixarenes, the two examples introduced here each adopt a vase-like conformation with all four aromatic units pointing in one direction (syn orientation). This "cone" conformation has been confirmed by NMR spectroscopy, molecular modeling, and X-ray crystallography. The laminar, electron-rich fluorophore as part of the macrocycle allows additional contacts to enclosed guest molecules.

A revised definition for cure of childhood acute lymphoblastic leukemia.

With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).

Use of sodium polyphosphates with different linear lengths in the production of spreadable processed cheese.

The objective of this study was to describe the dependence of textural properties (hardness, cohesiveness, and relative adhesiveness) of processed cheese spreads on the proportion of disodium phosphate (DSP), tetrasodium diphosphate (TSPP), and sodium salts of polyphosphate in ternary mixtures of emulsifying salts. Sodium salts of polyphosphate with different mean lengths (n ≈ 5, 9, 13, 20, and 28) were used. Pentasodium triphosphate (PSTP) was used instead of TSPP in the second part of the study. Products with and without pH adjustment were tested (the target pH value was 5.60-5.80). Textural properties of the processed cheese were observed after 2, 9, and 30 d of storage at 6°C. Hardness of the processed cheese with a low content of polyphosphate increased at a specific DSP:TSPP ratio (~1:1 to 3:4). This trend was the same for all the polyphosphates used; only the absolute values of texture parameters were different. The same trends were observed in the ternary mixtures with PSTP, showing lower final values of hardness compared with samples containing TSPP. Hardness and cohesiveness decreased and relative adhesiveness increased in the samples with increased pH values and vice versa; the main trend remained unchanged.

Sources of synchronized induced Gamma-Band responses during a simple object recognition task: a replication study in human MEG.

Natural stimuli are compiled of numerous features, which are cortically represented in dispersed structures. Synchronized oscillations in the Gamma-Band (>30 Hz; induced Gamma-Band Responses, iGBRs), are regarded as a plausible mechanism to re-integrate these regions into a meaningful cortical object representation. Using electroencephalography (EEG) it was demonstrated that the generators of iGBRs can be localized to temporal, parietal, posterior, and frontal areas. The present magnetoencephalogram (MEG) study intended to replicate these findings in order contribute to the ongoing debate regarding the possible functional difference of high-frequency signals as measured by both techniques. During a standard object recognition task we found an augmentation of the iGBR after the presentation of meaningful as opposed to meaningless stimuli at approximately 160-440 ms after stimulus onset. This peak was localized to inferior temporal gyri, superior parietal lobules and the right middle frontal gyrus. Importantly, most of these brain structures were significantly phase-locked to each other. The implications of these results are twofold: (1) they present further evidence for the view that iGBRs signify neuronal activity in a broadly distributed network during object recognition. (2) MEG is well suited to detect induced high-frequency oscillations with a very similar morphology as revealed by EEG recordings, thereby eliminating known problems with electroencephalographical methods (e.g. reference confounds). In contrast to the iGBR, the localization of event-related fields (ERFs) and evoked Gamma-Band Response (eGBRs) revealed generators in focal visual areas, and thus, seem to mirror early sensory processing.

Sustained spatial attention to vibration is mediated in primary somatosensory cortex.

Focusing attention to a specific body location has been shown to improve processing of events presented at this body location. One important debate concerns the stage in the somatosensory pathway at which the neural response is modulated when one attends to a tactile stimulus. Previous studies focused on components of the somatosensory evoked potential to transient stimuli, and demonstrated an early cortical attentional modulation. The neural basis of sustained spatial stimulus processing with continuous stimulation remains, however, largely unexplored. A way to approach this topic is to present vibrating stimuli with different frequencies for several seconds simultaneously to different body locations while subjects have to attend to the one or the other location. The amplitude of the somatosensory steady-state evoked potential (SSSEP) elicited by these vibrating stimuli increases with attention. On the basis of 128 electrode recordings, we investigated the topographical distribution and the underlying cortical sources by means of a VARETA approach of this attentional amplitude modulation of the SSSEP. Sustained spatial attention was found to be mediated in primary somatosensory cortex with no differences in SSSEP amplitude topographies between attended and unattended body locations. These result patterns were seen as evidence for a low-level sensory gain control mechanism in tactile spatial attention.

Sustained division of the attentional spotlight.

By voluntarily directing attention to a specific region of a visual scene, we can improve our perception of stimuli at that location. This ability to focus attention upon specific zones of the visual field has been described metaphorically as a moveable spotlight or zoom lens that facilitates the processing of stimuli within its 'beam'. A long-standing controversy has centred on the question of whether the spotlight of spatial attention has a unitary beam or whether it can be divided flexibly to disparate locations. Evidence supporting the unitary spotlight view has come from numerous behavioural and electrophysiological studies. Recent experiments, however, indicate that the spotlight of spatial attention may be divided between non-contiguous zones of the visual field for very brief stimulus exposures (&<100 ms). Here we use an electrophysiological measure of attentional allocation (the steady-state visual evoked potential) to show that the spotlight may be divided between spatially separated locations (excluding interposed locations) over more extended time periods. This spotlight division appears to be accomplished at an early stage of visual-cortical processing.

Human large-scale oscillatory brain activity during an operant shaping procedure.

The present study aimed at examining the oscillatory brain-electric correlates of human operant learning using high-density electroencephalography (EEG). Induced gamma-band activity (GBA) was studied using a fixed-interval reinforcement schedule with a variable limited hold period, which was decreased depending on response accuracy. Thus, participants' behavior was shaped during the course of the learning session. After each response, numbers indicating the money value of that response served as reinforcing stimuli. Random reinforcement and self-paced button pressing without reinforcement were added as control conditions. GBA around 40 Hz was enhanced at posterior electrodes in response to visual feedback stimuli during shaping and random reward compared to the self-paced pressing condition where no visual feedback was provided. Furthermore, shaping was associated with a pronounced left frontal lower gamma (20-30 Hz) increase in response to feedback stimuli, whereas this pattern was not observed in the random reinforcement and self-paced pressing conditions. The present findings are in line with the notion that macroscopic high-frequency dynamics of neuronal cell assemblies may be regarded as a mechanism involved in learning and memory formation.

Modulation of induced gamma band responses and phase synchrony in a paired associate learning task in the human EEG.

It has been proposed that associative learning is accomplished by the formation of cell assemblies and synchronous activity among the neurons of such an assembly. Induced gamma band responses (GBRs) and phase synchrony between electrode sites are discussed as a signature of activity within a cell assembly. To examine the activation of this network due to memory recall, a paired associate learning paradigm was used. EEG was analyzed in the frequency domain. Results showed a significant increase of induced GBRs at posterior and anterior electrode sites in the recall sequence of the learning condition. Furthermore, phase synchrony revealed a broad distribution pattern of phase synchrony between posterior and frontal electrode sites.

Effects of emotional arousal in the cerebral hemispheres: a study of oscillatory brain activity and event-related potentials.

OBJECTIVE: The present study aimed at examining the time course and topography of oscillatory brain activity and event-related potentials (ERPs) in response to laterally presented affective pictures. METHODS: Electroencephalography was recorded from 129 electrodes in 10 healthy university students during presentation of pictures from the international affective picture system. Frequency measures and ERPs were obtained for pleasant, neutral, and unpleasant pictures. RESULTS: In accordance with previous reports, a modulation of the late positive ERP wave at parietal recording sites was found as a function of emotional arousal. Early mid gamma band activity (GBA; 30-45 Hz) at 80 ms post-stimulus was enhanced in response to aversive stimuli only, whereas the higher GBA (46-65 Hz) at 500 ms showed an enhancement of arousing, compared to neutral pictures. ERP and late gamma effects showed a pronounced right-hemisphere preponderance, but differed in terms of topographical distribution. CONCLUSIONS: Late gamma activity may represent a correlate of widespread cortical networks processing different aspects of emotionally arousing visual objects. In contrast, differences between affective categories in early gamma activity might reflect fast detection of aversive stimulus features.

Functional correlates of macroscopic high-frequency brain activity in the human visual system.

The present article reviews empirical findings of large-scale gamma oscillations in the human brain, in the context of their functional correlates. Evidence supporting the fact that high-frequency neuronal oscillations are involved in several aspects of visual processing is presented, with a focus on bottom-up and top-down visual feature processing, selective attention, and emotional evaluation. This evidence suggests that visual processing involves the integrated activity of wide spread neuronal assemblies that can be studied with respect to time course and topography, employing frequency-domain analyses. Possible mechanisms underlying these phenomena are considered. Furthermore, the effects of attention and motivation, as well as characteristics of experimental paradigms are discussed as determinants of reliability and validity of measures of high-frequency oscillations.

Binding of the initiation factor sigma(70) to core RNA polymerase is a multistep process.

The interaction of RNA polymerase and its initiation factors is central to the process of transcription initiation. To dissect the role of this interface, we undertook the identification of the contact sites between RNA polymerase and sigma(70), the Escherichia coli initiation factor. We identified nine mutationally verified interaction sites between sigma(70) and specific domains of RNA polymerase and provide evidence that sigma(70) and RNA polymerase interact in at least a two-step process. We propose that a cycle of changes in the interface of sigma(70) with core RNA polymerase is associated with progression through the process of transcription initiation.

A coiled-coil from the RNA polymerase beta' subunit allosterically induces selective nontemplate strand binding by sigma(70).

For transcription to initiate, RNA polymerase must recognize and melt promoters. Selective binding to the nontemplate strand of the -10 region of the promoter is central to this process. We show that a 48 amino acid (aa) coiled-coil from the beta' subunit (aa 262--309) induces sigma(70) to perform this function almost as efficiently as core RNA polymerase itself. We provide evidence that interaction between the beta' coiled-coil and region 2.2 of sigma(70) promotes an allosteric transition that allows sigma(70) to selectively recognize the nontemplate strand. As the beta' 262--309 peptide can function with the previously crystallized portion of sigma(70), nontemplate recognition can be reconstituted with only 47 kDa, or 1/10 of holoenzyme.