Odor-driven face-like categorization in the human infant brain.

Understanding how the young infant brain starts to categorize the flurry of ambiguous sensory inputs coming in from its complex environment is of primary scientific interest. Here, we test the hypothesis that senses other than vision play a key role in initiating complex visual categorizations in 20 4-mo-old infants exposed either to a baseline odor or to their mother's odor while their electroencephalogram (EEG) is recorded. Various natural images of objects are presented at a 6-Hz rate (six images/second), with face-like object configurations of the same object categories (i.e., eliciting face pareidolia in adults) interleaved every sixth stimulus (i.e., 1 Hz). In the baseline odor context, a weak neural categorization response to face-like stimuli appears at 1 Hz in the EEG frequency spectrum over bilateral occipitotemporal regions. Critically, this face-like-selective response is magnified and becomes right lateralized in the presence of maternal body odor. This reveals that nonvisual cues systematically associated with human faces in the infant's experience shape the interpretation of face-like configurations as faces in the right hemisphere, dominant for face categorization. At the individual level, this intersensory influence is particularly effective when there is no trace of face-like categorization in the baseline odor context. These observations provide evidence for the early tuning of face-(like)-selective activity from multisensory inputs in the developing brain, suggesting that perceptual development integrates information across the senses for efficient category acquisition, with early maturing systems such as olfaction driving the acquisition of categories in later-developing systems such as vision.

Testing detectability, attractivity, hedonic specificity, extractability, and robustness of colostrum odor-Toward an olfactory bioassay for human neonates.

Human milk odor is attractive and appetitive for human newborns. Here, we studied behavioral and heart-rate (HR) responses of 2-day-old neonates to the odor of human colostrum. To evaluate detection in two conditions of stimulus delivery, we first presented the odor of total colostrum against water. Second, the hedonic specificity of total colostrum odor was tested against vanilla odor. Third, we delivered only the fresh effluvium of colostrum separated from the colostrum matrix; the stability of this colostrum effluvium was then tested after deep congelation; finally, after sorptive extraction of fresh colostrum headspace, we assessed the activity of colostrum volatiles eluting from the gas chromatograph (GC). Regardless of the stimulus-delivery method, neonates displayed attraction reactions (HR decrease) as well as appetitive oral responses to the odor of total colostrum but not to vanilla odor. The effluvium separated from the fresh colostrum matrix remained appetitive but appeared labile under deep freezing. Finally, volatiles from fresh colostrum effluvium remained behaviorally active after GC elution, although at lower magnitude. In sum, fresh colostrum effluvium and its eluate elicited a consistent increase in newborns' oral activity (relative to water or vanilla), and they induced shallow HR decrease. Newborns' appetitive oral behavior was the most reproducible response criterion to the effluvium of colostrum. In conclusion, a set of unidentified volatile compounds from human colostrum is robust enough after extraction from the original matrix and chromatographic processing to continue eliciting appetitive responses in neonates, thus opening new directions to isolate and assay specific volatile molecules of colostrum.

Smell what you hardly see: Odors assist visual categorization in the human brain.

Visual categorization is the brain ability to rapidly and automatically respond to a certain category of inputs. Whether category-selective neural responses are purely visual or can be influenced by other sensory modalities remains unclear. Here, we test whether odors modulate visual categorization, expecting that odors facilitate the neural categorization of congruent visual objects, especially when the visual category is ambiguous. Scalp electroencephalogram (EEG) was recorded while natural images depicting various objects were displayed in rapid 12-Hz streams (i.e., 12 images / second) and variable exemplars of a target category (either human faces, cars, or facelike objects in dedicated sequences) were interleaved every 9th stimulus to tag category-selective responses at 12/9 = 1.33 Hz in the EEG frequency spectrum. During visual stimulation, participants (N = 26) were implicitly exposed to odor contexts (either body, gasoline or baseline odors) and performed an orthogonal cross-detection task. We identify clear category-selective responses to every category over the occipito-temporal cortex, with the largest response for human faces and the lowest for facelike objects. Critically, body odor boosts the response to the ambiguous facelike objects (i.e., either perceived as nonface objects or faces) over the right hemisphere, especially for participants reporting their presence post-stimulation. By contrast, odors do not significantly modulate other category-selective responses, nor the general visual response recorded at 12 Hz, revealing a specific influence on the categorization of congruent ambiguous stimuli. Overall, these findings support the view that the brain actively uses cues from the different senses to readily categorize visual inputs, and that olfaction, which has long been considered as poorly functional in humans, is well placed to disambiguate visual information.

CovCopCan: An efficient tool to detect Copy Number Variation from amplicon sequencing data in inherited diseases and cancer.

Molecular diagnosis is an essential step of patient care. An increasing number of Copy Number Variations (CNVs) have been identified that are involved in inherited and somatic diseases. However, there are few existing tools to identify them among amplicon sequencing data generated by Next Generation Sequencing (NGS). We present here a new tool, CovCopCan, that allows the rapid and easy detection of CNVs in inherited diseases, as well as somatic data of patients with cancer, even with a low ratio of cancer cells to healthy cells. This tool could be very useful for molecular geneticists to rapidly identify CNVs in an interactive and user-friendly way.

Newborn crawling and rooting in response to maternal breast odor.

A growing literature shows that perception and action are already tightly coupled in the newborn. The current study aimed to examine the nature of the coupling between olfactory stimuli from the mother and the newborn's crawling and rooting (exploratory movements of the head). To examine the coupling, the crawling and rooting behavior of 28 2-day-old newborns were studied while they were supported prone on a mobility device shaped like a mini skateboard, the Crawliskate®, their head positioned directly on top of a pad infused with either their mother's breast odor (Maternal) or the odor of water (Control). Video and 3D kinematic analyses of the number and types of limb movements and quantification of displacement across the surface revealed that newborns are significantly more efficient crawlers when they smell the maternal odor, moving greater distances although performing fewer locomotor movements. In addition, the newborns made significantly more head rooting movements in the presence of the maternal odor. These findings suggest that the circuitry underlying quadrupedal locomotion and exploratory movements of the head is already adaptable to olfactory information via higher brain processing. Moreover, the coupling between olfaction and the two action systems, locomotion and rooting, is already differentiated. As crawling enables the newborn to move toward the mother's breast immediately after birth and facilitates mother-infant interaction, the results of this study highlight the potential value of using maternal odors to stimulate mobility in infants at risk of motor delay and/or deprived of this odor when born prematurely.

Human neonates prefer colostrum to mature milk: Evidence for an olfactory bias toward the "initial milk"?

OBJECTIVES: Colostrum is the initial milk secretion which ingestion by neonates warrants their adaptive start in life. Colostrum is accordingly expected to be attractive to newborns. The present study aims to assess whether colostrum is olfactorily attractive for 2-day-old newborns when presented against mature milk or a control. METHODS: The head-orientation of waking newborns was videotaped in three experiments pairing the odors of: (a) colostrum (sampled on postpartum day 2, not from own mother) and mature milk (sampled on average on postpartum day 32, not from own mother) (n tested newborns = 15); (b) Colostrum and control (water; n = 9); and (c) Mature milk and control (n = 13). RESULTS: When facing the odors of colostrum and mature milk, the infants turned their nose significantly longer toward former (32.8 vs 17.7% of a 120-s test). When exposed to colostrum against the control, they responded in favor of colostrum (32.9 vs 16.6%). Finally, when the odor of mature milk was presented against the control, their response appeared undifferentiated (26.7 vs 28.6%). CONCLUSIONS: These results indicate that human newborns can olfactorily differentiate conspecific lacteal fluids sampled at different lactation stages. They prefer the odor of the mammary secretion - colostrum - collected at the lactation stage that best matches the postpartum age of their own mother. These results are discussed in the context of the earliest mother-infant chemo-communication. Coinciding maternal emission and offspring reception of chemosignals conveyed in colostrum may be part of the sensory precursors of attunement between mothers and infants.

The role of papillary skin glands in guiding mouse pups to the nipple.

The nipple odor of lactating mice (Mus musculus) plays a crucial role in attracting newborn pups and motivating them to suck milk. The characteristic odor of a lactating murine nipple is assumed to be a mixture of multiple odorous substrates, that is, milk, dam's and pups' saliva, skin glands' secretions, and amniotic fluid. The present study aimed to characterize the behavioral activity of the original odor mixture that develops over the nipples in the first 2 days postpartum. We extracted this odor mixture in water and evaluated its attractive and appetitive potencies using two behavioral assays (viz., relative attraction and oral activation assays). It resulted that the so-called nipple wash was as appetitive as fresh milk, and even more attractive than it. The behavioral potency of the nipples was shown to be specific to lactating nipples (relative to nulliparous nipples) and to be preserved for 2 weeks when stored at -80°C. Finally, we perfected a nipple deodorization procedure by inactivating the nipples' behavioral potency. We observed that such altered appetitive potency was fully restored 30 min after its washing, but without any maternal self-licking and pups' sucking, indicating that the secretions of the nipple skin glands' were sufficient to explain the success of neonatal guidance to the nipple.

Maternal odor shapes rapid face categorization in the infant brain.

To successfully interact with a rich and ambiguous visual environment, the human brain learns to differentiate visual stimuli and to produce the same response to subsets of these stimuli despite their physical difference. Although this visual categorization function is traditionally investigated from a unisensory perspective, its early development is inherently constrained by multisensory inputs. In particular, an early-maturing sensory system such as olfaction is ideally suited to support the immature visual system in infancy by providing stability and familiarity to a rapidly changing visual environment. Here, we test the hypothesis that rapid visual categorization of salient visual signals for the young infant brain, human faces, is shaped by another highly relevant human-related input from the olfactory system, the mother's body odor. We observe that a right-hemispheric neural signature of single-glance face categorization from natural images is significantly enhanced in the maternal versus a control odor context in individual 4-month-old infant brains. A lack of difference between odor conditions for the common brain response elicited by both face and non-face images rules out a mere enhancement of arousal or visual attention in the maternal odor context. These observations show that face-selective neural activity in infancy is mediated by the presence of a (maternal) body odor, providing strong support for multisensory inputs driving category acquisition in the developing human brain and having important implications for our understanding of human perceptual development.

Does any mother's body odor stimulate interest in mother's face in 4-month-old infants?

Little is known about the effects of olfaction on visual processing during infancy. We investigated whether and how an infant's own mother's body odor or another mother's body odor affects 4-month-old infants' looking at their mother's face when it is paired with a stranger's face. In Experiment 1, infants were exposed to their mother's body odor or to a control odor, while in Experiment 2, infants were exposed to a stranger mother's body odor while their visual preferences were recorded. Results revealed that infants looked more at the stranger's female face in presence of the control odor but that they looked more at their mother's face in the context of any mother's body odors. This effect was due to a reduction of looking at the stranger's face. These findings suggest that infants react similarly to the body odor of any mother and add to the growing body of evidence indicating that olfactory stimulation represents a pervasive aspect of infant multisensory perception.

Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma.

PURPOSE: Assessment of the risk of recurrence is essential to determine the therapeutic strategy of meningioma treatment. Many relapsing or aggressive meningiomas show elevated mitotic and/or Ki67 indices, reflecting cell cycle deregulation. As CDKN2A is a key tumor suppressor gene involved in cell cycle control, we investigated whether CDKN2A alterations may be involved in tumor recurrence. METHODS: We carried out a comparative analysis of 17 recurrent and 13 non-recurrent meningiomas. CDKN2A single nucleotide variations (SNVs), deletions, methylation status of the promotor, and p16 expression were investigated. Results were correlated with the recurrent or non-recurrent status and clinicopathological data. RESULTS: We identified a CDKN2A SNV (NM_000077, exon2, c.G442A, p.Ala148Thr) in five meningiomas that was significantly associated with recurrence (p = 0.03). This mutation, confirmed by Sanger sequencing and referenced in the COSMIC database in various cancers, has not been reported in meningioma. The presence of one of the three following CDKN2A alterations-p.(Ala148Thr) mutation, whole homozygous or heterozygous gene loss, or promotor methylation > 8%-was observed in 13 of the 17 relapsing meningiomas and was strongly associated with recurrence (p < 0.0001) and a Ki67 labeling index > 7% (p = 0.004). CONCLUSION: We report an undescribed p.(Ala148Thr) CDKN2A mutation in meningioma that was only present in relapsing tumors. In our series, CDKN2A gene alterations were only found in recurrent meningiomas. However, our results need to be evaluated on a larger series to ensure that these CDKN2A alterations can be used as biomarkers of recurrence in meningioma.

Tuning functions for automatic detection of brief changes of facial expression in the human brain.

Efficient decoding of even brief and slight intensity facial expression changes is important for social interactions. However, robust evidence for the human brain ability to automatically detect brief and subtle changes of facial expression remains limited. Here we built on a recently developed paradigm in human electrophysiology with full-blown expressions (Dzhelyova et al., 2017), to isolate and quantify a neural marker for the detection of brief and subtle changes of facial expression. Scalp electroencephalogram (EEG) was recorded from 18 participants during stimulation of a neutral face changing randomly in size at a rapid rate of 6 Hz. Brief changes of expression appeared every five stimulation cycle (i.e., at 1.2 Hz) and expression intensity increased parametrically every 20 s in 20% steps during sweep sequences of 100 s. A significant 1.2 Hz response emerged in the EEG spectrum already at 40% of facial expression-change intensity for most of the 5 emotions tested (anger, disgust, fear, happiness, or sadness in different sequences), and increased with intensity steps, predominantly over right occipito-temporal regions. Given the high signal-to-noise ratio of the approach, thresholds for automatic detection of brief changes of facial expression could be determined for every single individual brain. A time-domain analysis revealed three components, the two first increasing linearly with increasing intensity as early as 100 ms after a change of expression, suggesting gradual low-level image-change detection prior to visual coding of facial movements. In contrast, the third component showed abrupt sensitivity to increasing expression intensity beyond 300 ms post expression-change, suggesting categorical emotion perception. Overall, this characterization of the detection of subtle changes of facial expression and its temporal dynamics open promising tracks for precise assessment of social perception ability during development and in clinical populations.

Seeing odors in color: Cross-modal associations in children and adults from two cultural environments.

We investigated the occurrence and underlying processes of odor-color associations in French and American 6- to 10-year-old children (n = 386) and adults (n = 137). Nine odorants were chosen according to their familiarity to either cultural group. Participants matched each odor with a color, gave hedonic and familiarity judgments, and identified each odor. By 6 years of age, children displayed culture-specific odor-color associations, but age differences were noted in the type of associations. Children and adults in both cultural groups shared common associations and formed associations that were unique to their environment, underscoring the importance of exposure learning in odor-color associations.

Mimicking emotions: how 3-12-month-old infants use the facial expressions and eyes of a model.

While there is an extensive literature on the tendency to mimic emotional expressions in adults, it is unclear how this skill emerges and develops over time. Specifically, it is unclear whether infants mimic discrete emotion-related facial actions, whether their facial displays are moderated by contextual cues and whether infants' emotional mimicry is constrained by developmental changes in the ability to discriminate emotions. We therefore investigate these questions using Baby-FACS to code infants' facial displays and eye-movement tracking to examine infants' looking times at facial expressions. Three-, 7-, and 12-month-old participants were exposed to dynamic facial expressions (joy, anger, fear, disgust, sadness) of a virtual model which either looked at the infant or had an averted gaze. Infants did not match emotion-specific facial actions shown by the model, but they produced valence-congruent facial responses to the distinct expressions. Furthermore, only the 7- and 12-month-olds displayed negative responses to the model's negative expressions and they looked more at areas of the face recruiting facial actions involved in specific expressions. Our results suggest that valence-congruent expressions emerge in infancy during a period where the decoding of facial expressions becomes increasingly sensitive to the social signal value of emotions.

Autophagy and TrkC/NT-3 signaling joined forces boost the hypoxic glioblastoma cell survival.

Glioblastoma multiform (GBM), the most common and aggressive primary brain tumor, is characterized by a high degree of hypoxia and resistance to therapy because of its adaptation capacities, including autophagy and growth factors signaling. In this study, we show an efficient hypoxia-induced survival autophagy in four different GBM cell lines (U87MG, M059K, M059J and LN-18) and an activation of a particular neurotrophin signaling pathway. Indeed, the enhancement of both TrkC and NT-3 was followed by downstream p38MAPK phosphorylation, suggesting the occurrence of a survival autocrine loop. Autophagy inhibition increased the hypoxia-induced expression of TrkC and its phosphorylated form as well as the phosphorylation of p38, suggesting a complementary effect of the two processes, leading to cell survival. Alone, autophagy inhibition reduced cellular growth without inducing cell death. However, the double inhibition of autophagy and TrkC signaling was necessary to bring cells to death as shown by PARP cleavage, particularly important in hypoxia. Moreover, a very high expression of TrkC and NT-3 was found in tumor sections from GBM patients, highlighting the importance of neurotrophic signaling in GBM tumor cell survival. These data suggest that a combined treatment targeting these two pathways could be considered in order to induce the death of GBM cells.

KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness.

Glioblastoma is the most lethal brain tumour with a poor prognosis. Cancer stem cells (CSC) were proposed to be the most aggressive cells allowing brain tumour recurrence and aggressiveness. Current challenge is to determine CSC signature to characterize these cells and to develop new therapeutics. In a previous work, we achieved a screening of glycosylation-related genes to characterize specific genes involved in CSC maintenance. Three genes named CHI3L1, KLRC3 and PRUNE2 were found overexpressed in glioblastoma undifferentiated cells (related to CSC) compared to the differentiated ones. The comparison of their roles suggest that KLRC3 gene coding for NKG2E, a protein initially identified in NK cells, is more important than both two other genes in glioblastomas aggressiveness. Indeed, KLRC3 silencing decreased self-renewal capacity, invasion, proliferation, radioresistance and tumourigenicity of U87-MG glioblastoma cell line. For the first time we report that KLRC3 gene expression is linked to glioblastoma aggressiveness and could be a new potential therapeutic target to attenuate glioblastoma.

Responses of Human Neonates to Highly Diluted Odorants from Sweat.

Conjugated forms of odorants contributing to sweat odor occur not only in human sweat but also in amniotic fluid, colostrum, and milk. However, it is unclear whether the released odorants are detected and hedonically discriminated by human newborns. To investigate this issue, we administered highly diluted solutions of (R)/(S)-3-methyl-3-sulfanylhexan-1-ol (MSH), (R)/(S)-3-sulfanylhexan-1-ol (SH), (E)/(Z)-3-methylhex-2-enoic acid (3M2H), and (R)/(S)-3-hydroxy-3-methylhexanoic acid (HMHA) to 3-d-old infants while their respiratory rate and oro-facial movements were recorded. Adult sensitivity to these odorants was assessed via triangle tests. Whereas no neonatal stimulus-specific response was found for respiratory rate, oro-facial reactivity indicated orthonasal detection of MSH and SH by male neonates, and of HMHA by the whole group of neonates. Dependent on the dilution of odorants, newborns evinced neutral responses or longer negative oro-facial expressions compared with the reference stimuli. Finally, newborns appeared to be more sensitive to the target odorants than did adults.

Affective matching of odors and facial expressions in infants: shifting patterns between 3 and 7 months.

Recognition of emotional facial expressions is a crucial skill for adaptive behavior. Past research suggests that at 5 to 7 months of age, infants look longer to an unfamiliar dynamic angry/happy face which emotionally matches a vocal expression. This suggests that they can match stimulations of distinct modalities on their emotional content. In the present study, olfaction-vision matching abilities were assessed across different age groups (3, 5 and 7 months) using dynamic expressive faces (happy vs. disgusted) and distinct hedonic odor contexts (pleasant, unpleasant and control) in a visual-preference paradigm. At all ages the infants were biased toward the disgust faces. This visual bias reversed into a bias for smiling faces in the context of the pleasant odor context in the 3-month-old infants. In infants aged 5 and 7 months, no effect of the odor context appeared in the present conditions. This study highlights the role of the olfactory context in the modulation of visual behavior toward expressive faces in infants. The influence of olfaction took the form of a contingency effect in 3-month-old infants, but later evolved to vanish or to take another form that could not be evidenced in the present study.

Three-month-old infants' sensitivity to horizontal information within faces.

Horizontal information is crucial to face processing in adults. Yet the ontogeny of this preferential type of processing remains unknown. To clarify this issue, we tested 3-month-old infants' sensitivity to horizontal information within faces. Specifically, infants were exposed to the simultaneous presentation of a face and a car presented in upright or inverted orientation while their looking behavior was recorded. Face and car images were either broadband (UNF) or filtered to only reveal horizontal (H), vertical (V) or this combined information (HV). As expected, infants looked longer at upright faces than at upright cars, but critically, only when horizontal information was preserved in the stimulus (UNF, HV, H). These results first indicate that horizontal information already drives upright face processing at 3 months of age. They also recall the importance, for infants, of some facial features, arranged in a top-heavy configuration, particularly revealed by this band of information. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 536-542, 2016.

New Coffee Plant-Infecting Xylella fastidiosa Variants Derived via Homologous Recombination.

Xylella fastidiosa is a xylem-limited phytopathogenic bacterium endemic to the Americas that has recently emerged in Asia and Europe. Although this bacterium is classified as a quarantine organism in the European Union, importation of plant material from contaminated areas and latent infection in asymptomatic plants have engendered its inevitable introduction. In 2012, four coffee plants (Coffea arabica and Coffea canephora) with leaf scorch symptoms growing in a confined greenhouse were detected and intercepted in France. After identification of the causal agent, this outbreak was eradicated. Three X. fastidiosa strains were isolated from these plants, confirming a preliminary identification based on immunology. The strains were characterized by multiplex PCR and by multilocus sequence analysis/typing (MLSA-MLST) based on seven housekeeping genes. One strain, CFBP 8073, isolated from C. canephora imported from Mexico, was assigned to X. fastidiosa subsp. fastidiosa/X. fastidiosa subsp. sandyi. This strain harbors a novel sequence type (ST) with novel alleles at two loci. The two other strains, CFBP 8072 and CFBP 8074, isolated from Coffea arabica imported from Ecuador, were allocated to X. fastidiosa subsp. pauca. These two strains shared a novel ST with novel alleles at two loci. These MLST profiles showed evidence of recombination events. We provide genome sequences for CFBP 8072 and CFBP 8073 strains. Comparative genomic analyses of these two genome sequences with publicly available X. fastidiosa genomes, including the Italian strain CoDiRO, confirmed these phylogenetic positions and provided candidate alleles for coffee plant adaptation. This study demonstrates the global diversity of X. fastidiosa and highlights the diversity of strains isolated from coffee plants.

Responsiveness of human neonates to the odor of 5α-androst-16-en-3-one: a behavioral paradox?

The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother's skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discussed.