Individuality of distress and discomfort calls in neonates with bass voices: Wild‐living goitred gazelles (Gazella subgutturosa) and saiga antelopes (Saiga tatarica)

Neonate ruminants produce distress calls when captured by a predator and discomfort milk begging calls when hungry. In many neonate ruminants, the distress and discomfort calls are high‐frequency vocalizations, in which the fundamental frequency is the key variable for recognition of their emotional arousal by caregivers. In contrast, in this study, we examine the low‐frequency open‐mouth distress and discomfort calls in the neonates of two species of wild‐living ungulates, which clearly highlight vocal tract resonances (formants). In the goitred gazelle (Gazella subgutturosa), the distress calls were higher in fundamental frequency (f0) and in the first and third formants than the discomfort calls. The accuracy of classifying individuals by variables of distress calls with discriminant function analysis (67%) was significantly lower than that of discomfort calls (85%). In the saiga (Saiga tatarica), only the third formant was higher in the distress calls than in the discomfort calls. The accuracy of classifying individuals by variables of distress calls (89%) did not differ significantly from that of discomfort calls (94%). Thus, the use of acoustic cues to vocal identity and to the degree of arousal differs between the two species. Calls were significantly more individualistic in the saiga, probably because this species lives in large herds and neonates use a ‘following’ antipredatory strategy, in which vocal individuality is crucial for mother–offspring communication. In contrast, goitred gazelles live in smaller groups and neonates use a ‘hiding’ antipredatory strategy. Accordingly, mothers can rely on additional environmental cues for spotting their young and this may decrease the necessity for individualization of the calls of neonates.     

Discomfort-related changes in pup ultrasonic calls of fat-tailed gerbils Pachyuromys duprasi

Rodent pups vocalize when placed in social isolation. We apply a method of “joint calls” for examining discomfort in rodent pup ultrasonic (>20 kHz) calls. Previously, this method has been developed for audible calls of fur farm mammals. Using a repeated measures design to exclude effects of individual identity and age on the analysed variables, we compared the ultrasonic call variables produced by 8–40-day pups of fat-tailed gerbils Pachyuromys duprasi during two subsequent experimental stages, the Isolation Stage and the Handling Stage. We considered that discomfort-related negative emotional arousal increased towards the Handling Stage compared to the Isolation Stage because of cumulative effects of handling and time of pup isolation from the nest. At the Isolation Stage, the call rate (calls/s) was higher from 10 to 18 days of age, whereas both the maximum amplitude frequency and power quartiles of joint calls were lower than at the Handling Stage from 20 to 32 days of age. At the same time, in audible (<20 kHz) vocalizations of a wide range of mammalian species, both the higher call rate and the upward shift of the maximum amplitude frequency and power quartiles indicate the discomfort-related increase of negative emotional arousal. We discuss the advantages of the method of joint calls for express-analyses of power variables for large sequences of ultrasonic vocalizations of complex acoustic structure during experimental trials.     

Prescribed “Breaks” as a Means to Disrupt Weight Control Efforts

Objective: Research on long‐term maintenance of weight loss is hampered by the fact that relapse typically does not occur until after 6 months. We sought to determine whether relapses could be induced earlier by intentionally interrupting the momentum of weight loss during a treatment program and thus provide a model for weight maintenance research. Research Methods and Procedures: Subjects (N = 142) were recruited at two centers and randomly assigned to a control group, a long break group (LB), or a short break group (SB). The control group received a standard behavioral weight loss program with 14 weekly sessions; the LB and SB groups received the same. However, the LB group took a 6‐week break after lesson 7, and the SB group took a 2‐week break after lessons 3, 6, and 9. Participants were instructed to stop all weight loss efforts during breaks. Results: Participants seemed to take breaks as prescribed, with interruptions in self‐monitoring, dietary adherence, and self‐weighing (but not in exercise). However, participants quickly resumed these behaviors after the break. Breaks produced a slowing of weight loss or slight regain, but weight losses during the breaks were not significantly different from the control group. Importantly, overall weight losses (0 to 5 months or 0 to 11 months) did not differ between conditions. Discussion: This study was not successful in developing a method to experimentally produce weight loss relapses. However, the finding that prescribed breaks do not have adverse effects may have clinical application.     

Using Attachment Theory and Social Support Theory to Examine and Measure Pets as Sources of Social Support and Attachment Figures

Companion animals are increasingly being recognized by society as beneficial to our health and considered by many owners as authentic and affectional family members. Human relationship theories help us to understand the emotional and supportive aspect of the human– companion animal bond. This study uses attachment theory, social support theory, and the concept of the hierarchical nature of attachment relationships to further understand and measure human–animal attachment. In study 1,161 university-student pet owners completed a modified multidimensional scale of perceived social support (MSPSS) that included pets as a source of support, and we pre-tested a 60-item pet attachment measure. Results showed that students perceived their pets as distinctive sources of social support, at similar levels to their significant others, family, and friends. Principal components analysis of the 60-item measure reduced it to 31 items, and revealed four pet attachment components: (a) Proximity maintenance and interaction, (b) Emotional attachment behaviors, (c) Emotional support given and received, and (d) Emotional and monetary value. The scale was named the Emotional and Supportive Attachment to Companion Animals Scale (ESACA) (Cronbach’s α = 0.96). In study 2, 83 university students completed an attachment hierarchy scale and the ESACA. Companion animals were included in pet owners’ attachment hierarchies and ranked higher than siblings but lower than romantic partners, parents, and close friends. Those who indicated higher attachment to their companion animals ranked them higher in their attachment hierarchy than those less attached. This study supports and extends previous research that has used aspects of attachment theory and social support theory when exploring the human–animal bond. Many companion animal owners perceive their pets as additional sources of emotional support, fulfilling the four features of an attachment relationship and including them in their hierarchy of important attachment relationships.     

Positive emotional priming of facial affect perception in females is diminished by chemosensory anxiety signals

Chemosensory communication of anxiety is a common phenomenon in vertebrates and improves perceptual and responsive behaviour in the perceiver in order to optimize ontogenetic survival. A few rating studies reported a similar phenomenon in humans. Here, we investigated whether subliminal face perception changes in the context of chemosensory anxiety signals. Axillary sweat samples were taken from 12 males while they were waiting for an academic examination and while exercising ergometric training some days later. 16 subjects (eight females) participated in an emotional priming study, using happy, fearful and sad facial expressions as primes (11.7 ms) and neutral faces as targets (47 ms). The pooled chemosensory samples were presented before and during picture presentation (920 ms). In the context of chemosensory stimuli derived from sweat samples taken during the sport condition, subjects judged the targets significantly more positive when they were primed by a happy face than when they were primed by the negative facial expressions (P = 0.02). In the context of the chemosensory anxiety signals, the priming effect of the happy faces was diminished in females (P = 0.02), but not in males. It is discussed whether, in socially relevant ambiguous perceptual conditions, chemosensory signals have a processing advantage and dominate visual signals or whether fear signals in general have a stronger behavioural impact than positive signals.     

雌激素对情绪的影响：心理、神经、内分泌研究

雌激素通过复杂的生理和心理学机制对中枢神经系统施加影响.生理学方面包括：雌激素在杏仁核、海马和前额叶等这些与情绪认知相关的重要脑区内影响神经递质的产生和效能;雌激素可以作用于下丘脑-垂体-肾上腺轴,改变情绪性行为;雌激素受体的基因转录也可以调节情绪性行为的变化.雌激素也通过神经心理学的因素影响情绪加工：雌激素可以提高情绪编码技能,提升表情识别的准确性;雌激素能够影响情绪的唤醒,改变个体情绪体验的强度.未来的研究要融合心理、神经和内分泌等各种因素,以解决女性情绪障碍这一难题.     

GPC3-targeted CAR-T cells secreting B7H3-targeted BiTE exhibit potent cytotoxicity activity against hepatocellular carcinoma cell in the in vitro assay

Hepatocellular carcinoma (HCC), the most common primary liver cancer has a high mortality in China, and it is usually diagnosed at a late stage, thereby leaving patients with few effective treatment options. Chimeric antigen receptor-T (CAR-T) cell therapy, a novel immunotherapy that has shown promising results in leukemia, lymphoma and multiple myeloma, is also expected to work well in solid tumors, including HCC. However, the ideal therapeutic efficacy has not yet been achieved, in part due to tumor antigen escape caused by antigen heterogeneity. To overcome such challenge, we screened a panel of biomarkers in HCC cell lines and found that GPC3 and B7H3 were highly expressed on HCC with expression heterogeneity. Then we developed a novel bispecific T cell engagers CAR-T (CAR.T-BiTEs) that drives the expression of a CAR specific for GPC3 and BiTEs against CD3 and B7H3, herein referred to as “GPC3-BiTE CAR.” We found that BiTEs promoted the increased activation of untransduced T cells and IFN-γ release. Moreover, BiTEs secreted by GPC3-BiTE CAR-HEK293T cells promoted increased cytotoxicity activity of untransduced T cells against GPC3+/B7H3+ (GPC3 positive/B7H3 positive) and GPC3-/B7H3+(GPC3 negative/B7H3 positive) HCC cell lines. In vitro function assays showed that GPC3-BiTE CAR-T cells exhibited greater cytotoxicity activity against GPC3+/B7H3+ HCC cell lines than GPC3 CAR-T cells (GPC3-targeted CAR-T cells) and B7H3 CAR-T cells (B7H3-targeted CAR-T cells). Furthermore, GPC3-BiTE CAR-T cells exhibited superior cytotoxicity against GPC3 negative HCC cell lines compared with GPC3 CAR T cells. In conclusion, our study showed that GPC3-BiTE CAR T cells exhibited superior antitumor activity than single-target CAR-T cells and can overcome tumor escape induced by antigen heterogeneity, suggesting that this could be a promising therapeutic strategy for HCC.     

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma

Understanding tumor clonality is critical to understanding the mechanisms involved in tumorigenesis and disease progression. In addition, understanding the clonal composition changes that occur within a tumor in response to certain micro-environment or treatments may lead to the design of more sophisticated and effective approaches to eradicate tumor cells. However, tracking tumor clonal sub-populations has been challenging due to the lack of distinguishable markers. To address this problem, a VDJ-seq protocol was created to trace the clonal evolution patterns of diffuse large B cell lymphoma (DLBCL) relapse by exploiting VDJ recombination and somatic hypermutation (SHM), two unique features of B cell lymphomas.In this protocol, Next-Generation sequencing (NGS) libraries with indexing potential were constructed from amplified rearranged immunoglobulin heavy chain (IgH) VDJ region from pairs of primary diagnosis and relapse DLBCL samples. On average more than half million VDJ sequences per sample were obtained after sequencing, which contain both VDJ rearrangement and SHM information. In addition, customized bioinformatics pipelines were developed to fully utilize sequence information for the characterization of IgH-VDJ repertoire within these samples. Furthermore, the pipeline allows the reconstruction and comparison of the clonal architecture of individual tumors, which enables the examination of the clonal heterogeneity within the diagnosis tumors and deduction of clonal evolution patterns between diagnosis and relapse tumor pairs. When applying this analysis to several diagnosis-relapse pairs, we uncovered key evidence that multiple distinctive tumor evolutionary patterns could lead to DLBCL relapse. Additionally, this approach can be expanded into other clinical aspects, such as identification of minimal residual disease, monitoring relapse progress and treatment response, and investigation of immune repertoires in non-lymphoma contexts.     

Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry

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Bridging the Divide: Drinking among Street Drug Users

In this research report, we present findings on drinking among drug users from a larger multimethod study of the public health consequences of emergent, changing, and understudied drug-related behavioral patterns among street drug users in Hartford, CT. Although drinking and illicit drug use traditionally have been studied in anthropology as separate cultural domains, this conceptual division has hindered examination of the significant level of drinking among street drug users, the motivations for heavy drinking in this population, and the public health consequences of mixing alcohol and other drugs, including drug relapse.