Single-Cell Analysis of Rohon-Beard Neurons Implicates Fgf Signaling in Axon Maintenance and Cell Survival.

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons. Previous studies provided evidence that RBs fall into multiple subclasses; however, the number and molecular makeup of these potential RB subtypes have not been well defined. Using a single-cell RNA sequencing (scRNA-seq) approach, we demonstrate that larval RBs in zebrafish fall into three, largely nonoverlapping classes of neurons. We also show that RBs are molecularly distinct from trigeminal neurons in zebrafish. Cross-species transcriptional analysis indicates that one RB subclass is similar to a mammalian group of A-fiber sensory neurons. Another RB subclass is predicted to sense multiple modalities, including mechanical stimulation and chemical irritants. We leveraged our scRNA-seq data to determine that the fibroblast growth factor (Fgf) pathway is active in RBs. Pharmacological and genetic inhibition of this pathway led to defects in axon maintenance and RB cell death. Moreover, this can be phenocopied by treatment with dovitinib, an FDA-approved Fgf inhibitor with a common side effect of peripheral neuropathy. Importantly, dovitinib-mediated axon loss can be suppressed by loss of Sarm1, a positive regulator of neuronal cell death and axonal injury. This offers a molecular target for future clinical intervention to fight neurotoxic effects of this drug.

Rohon-beard neurons do not succumb to programmed cell death during zebrafish development.

During neural development, sculpting of early formed circuits by cell death and synaptic pruning is necessary to generate a functional and efficient nervous system. This allows for the establishment of rudimentary circuits which necessitate early organism survival to later undergo subsequent refinement. These changes facilitate additional specificity to stimuli which can lead to increased behavioral complexity. In multiple species, Rohon-Beard neurons (RBs) are the earliest mechanosensory neurons specified and are critical in establishing a rudimentary motor response circuit. Sensory input from RBs gradually becomes redundant as dorsal root ganglion (DRG) neurons develop and integrate into motor circuits. Previous studies demonstrate that RBs undergo a dramatic wave of cell death concurrent with development of the DRG. However, contrary to these studies, we show that neurogenin1+ (ngn1) RBs do not undergo a widespread wave of programmed cell death during early zebrafish development and instead persist until at least 15 days post fertilization (dpf). Starting at 2 dpf, we also observed a dramatic medialization and shrinkage of ngn1+ RB somas along with a gradual downregulation of ngn1 in RBs. This alters a fundamental premise of early zebrafish neural development and opens new avenues to explore mechanisms of RB function, persistence, and circuit refinement.

Efficacy of topical minoxidil in enhancing beard growth in a group of transgender assigned female at birth individuals on gender affirming hormone therapy.

PURPOSE: Testosterone therapy represents the cornerstone of gender affirming hormone therapy (GAHT) among t-AFAB (transgender Assigned Female At Birth) people. Minoxidil is a vasodilator drug approved for topical use for the treatment of androgenetic alopecia. The aim of the present study was to evaluate the efficacy of topical minoxidil in enhancing beard growth in a group of t-AFAB people on GAHT. METHODS: Sixteen t-AFAB individuals with an incomplete beard development, on GAHT for at least 6 months, were enrolled. Topical minoxidil was applied to the interested facial areas. Before starting (T0), after 3 (T3) and 6 (T6) months, we evaluated facial hair growth using the Ferriman-Gallwey modified score (FGm). RESULTS: Subjects were 26 (2.7) years old and on GAHT for 18.5 [15-54] months; using a paired match evaluation, a statistically significant facial hair growth was observed over time, in particular at T6 (median upper lip FGm 3.5 [3-4] vs 2 [1-2] at T0 and chin FGm 4 [3.25-4] vs 1 [1-2] at T0; p ≤ 0.002). Comparing the minoxidil group with a control group (n = 16) matched for age and BMI who developed a full-grown beard only with GAHT, a logistic multivariable analysis identified hirsutism before GAHT was independently positively associated with the development of a full beard [OR 15.22 (95% CI 1.46-158.82); p = 0.023]. CONCLUSIONS: This is the first study demonstrating the efficacy of topical minoxidil in enhancing facial hair growth among t-AFAB people on GAHT. Further studies will be necessary to assess whether the obtained improvements will persist after discontinuing the medication.

Convenient Frailty: Medical Contestations of Asthma and Hay Fever in African Americans in Late Nineteenth-Century America.

Post-Emancipation medical and social science scholars extensively theorized Black susceptibility to illness, disease, and death. Most studies of late nineteenth-century medical ideas about the relationship between race and disease have highlighted the construction of medical beliefs that associated Black physical weakness with a proclivity to ill health. This study presents an alternate narrative, one where certain diseases - asthma and hay fever - reflected an opposing racialized understanding of disease that instead centered on White frailty. Based on an examination of turn-of-the-century asthma and hay fever medical literature produced by George Miller Beard, the professionalization of the United States Hay Fever Association, and the publication and dismissal of the first recorded case of asthma in an African American man in 1884, this article argues that late nineteenth-century asthma and hay fever physicians, who themselves often suffered from the conditions, defined the typical asthma patient along racial lines to protect the exclusivity of their own professional and social identities. As a result, asthma and hay fever in Black communities, particularly in the North, where asthma and hay fever scholars primarily lived and worked, remained obscured and untreated until the mid-twentieth century.

Facial Scar Management by Hair Transplant: A Case Report.

Facial scars in hair-bearing areas are a difficult problem to deal with owing to the nature of the scar tissue and the poor survivability of the grafts. A 26-year-old male presented with a scar on the right cheek area. The patient complained of recurrence and widening of scar and resultant facial asymmetry after serial excision in another hospital. The scar was the result of a burn injury sustained 15 years back. The scar was managed by using 2,642 hair grafts harvested from the scalp area. The patient had excellent hair growth at the end of 1 year with a high satisfaction level. There was a visible improvement in the lip deviation. Restoration of hair in the hair-bearing region of the face may be considered a permanent single-stage solution in such patients.

Long-lived zebrafish Rohon-Beard cells.

During normal development of the nervous system, extensive neuronal proliferation as well as death occurs. The extent of development death varies considerably between neuronal populations from little to almost 100%. Early born somatosensory neurons, known as Rohon-Beard cells, have served as an example of neurons that disappear during early developmental stages, presumably as their function is taken over by later developing dorsal root ganglion neurons. However, recent studies have raised questions about the extent to which zebrafish Rohon-Beard cells die during embryogenesis. While Rohon-Beard cells have distinguishing morphological features during embryonic stages development, they subsequently undergo substantial changes in their shape, size and position that hinder their unambiguous identification at later stages. To overcome this obstacle, we identify Rohon-Beard cells at one day, and using a combination of mosaic and stable transgenic labeling and repeated observation, follow them for 13-16 days post fertilization. We find that about 40% survive to late larval stages. Our studies also reveal that Rohon-Beard cells display an unusual repertoire of cell death properties. At one day, about 25% Rohon-Beard cells expose phosphatidyl serine at the surface membrane, but less than one Rohon-Beard cell/embryo expresses activated-caspase-3. Further, the temporal delay between detection of cell death markers and loss of the soma ranges from

Are Beards Honest Signals of Male Dominance and Testosterone?

The male beard is one of the most visually salient and sexually dimorphic traits and a hypothesized potential marker of other traits, such as dominance, masculinity, social status, and self-confidence. However, as men can easily alter their facial hair, beards may provide unreliable information about the beard owner's characteristics. Here, we examined whether beards are honest signals of biological (testosterone levels) and psychological (self-reported dominance) traits. Young (M = 21.29, SD = 1.54) and healthy men (N = 97) participated in the study. Their beards were measured directly (using digital calipers) and by self-report. Participants provided saliva samples before and after acute exercise (to assess their testosterone and cortisol levels) and reported their dominance on a 5-item scale. The results showed that beard length (directly measured and self-reported) was not related to testosterone levels or dominance; thus, no evidence was found to support the hypothesis that beards are honest (or dishonest) signals of the beard owners' testosterone levels and dominance.

The red-beard evolutionary explanation of human sociality.

Recent evolutionary studies on cooperation devote specific attention to non-verbal expressions of emotions. In this paper, I examine Robert Frank's popular attempt to explain emotions, non-verbal markers and social behaviours. Following this line of work, I focus on the green-beard explanation of social behaviours. In response to the criticisms raised against this controversial ultimate explanation, based on resources found in Frank's work, I propose an alternative red-beard explanation of human sociality. The red-beard explanation explains the emergence and evolution of emotions, a proximate cause, rather than patterns of behaviour. In contrast to simple evolutionary models that invoke a green-beard mechanism, I demonstrate that the red-beard explanation can be evolutionary stable. Social emotions are a common cause of a social behaviour and a phenotypic marker and therefore cooperative behaviour cannot be suppressed without also changing the marker.

Beard and Moustache Reconstruction.

Beard and moustache reconstruction has gained more popularity and acceptance over the last decade. The procedure is done for the correction of facial areas with hair density deficit and also for the cosmetic enhancement of pre-existing facial hair. The surgical technique includes the harvesting of grafts from the scalp by the follicular unit excision (FUE) or follicular unit transplantation (FUT) technique and then placing them in either premade slits or by stick and place method. The advancement and refinement of procedure over the years has aided in achieving the optimal aesthetic results, with minimal side effects.

Using Nonscalp Hair in Scalp Hair Restoration-Theory and Execution.

Harvesting of beard and body hair follicles for transplantation can be an effective form of treatment for appropriate patients. These patients may have had prior scalp transplantation and require repair but do not have sufficient scalp donor follicles remaining. Other patients will have these hairs mixed with scalp hairs to produce a greater density of hair on the bald scalp. Follicular unit excision (FUE) is preferred for body and beard follicle harvesting. Not all body hair is suitable for transplantation. Only hairs that are similar in appearance and behavior to scalp hair are suitable for transplantation to the scalp. The best nonscalp sources are the beard and anterior torso. Hairs from other body sites may be used for transplantation to the eyebrows. The standard techniques of FUE harvesting and anesthesia must be modified from those used in scalp harvesting to be safe and effective. With proper patient selection and technique, a significant cosmetic benefit can be achieved from these procedures.

Antagonistic interactions subdue inter-species green-beard cooperation in bacteria.

Cooperation can be favoured through the green-beard mechanism, where a set of linked genes encodes both a cooperative trait and a phenotypic marker (green beard), which allows carriers of the trait to selectively direct cooperative acts to other carriers. In theory, the green-beard mechanism should favour cooperation even when interacting partners are totally unrelated at the genome level. Here, we explore such an extreme green-beard scenario between two unrelated bacterial species-Pseudomonas aeruginosa and Burkholderia cenocepacia, which share a cooperative locus encoding the public good pyochelin (an iron-scavenging siderophore) and its cognate receptor (green beard) required for iron-pyochelin uptake. We show that pyochelin, when provided in cell-free supernatants, can be mutually exchanged between species and provide fitness benefits under iron limitation. However, in co-culture we observed that these cooperative benefits vanished and communities were dominated by P. aeruginosa, regardless of strain background and species starting frequencies. Our results further suggest that P. aeruginosa engages in interference competition to suppress B. cenocepacia, indicating that inter-species conflict arising from dissimilarities at the genome level overrule the aligned cooperative interests at the pyochelin locus. Thus, green-beard cooperation is subdued by competition, indicating that interspecific siderophore cooperation is difficult to evolve and to be maintained.

Copy number variation in HOXB7 and HOXB8 involves in the formation of beard trait in chickens.

The derived feathering phenotype beard in domestic birds is an ideal resource to investigate the genetic mechanisms controlling feather development and differentiation. In the present study, we performed a GWAS and QTL linkage analysis on the trait of beard in Beijing fatty chicken. One major QTL (1.2-1.9 Mb) was identified that could explain 34% of the phenotypic variation. The copy number variation that was copied from the region (GGA27:3 578 409-3 592 890 bp) containing homebox B7 (HOXB7) and homebox B8 (HOXB8) was validated to be only exhibited in the genome of bearded chickens. Protein-protein interaction analysis indicated that HOXB7 and HOXB8 proteins could highly interact with the HOXB family members, including HOXB4, HOXB5 and HOXB6, whose genomic locations near HOXB7 and HOXB8 suggested that they may regulate their family members to involve in the formation of the beard trait in chickens. Overall, our work provides basic data for understanding the mechanisms regulating beard development and differentiation.

THE (A)SYMMETRY OF THE MALE GRAYING BEARD HAIRS AS AN INDICATION OF THE PROGRAMMED AGING PROCESS.

Aging interventions will be ineffective if we do not understand the basic principles of aging. Currently, there is no consensus on the issue whether aging is programmed or not. The hypothesis presented in this article indicates that aging (at least graying of male hairs) is programmed. This hypothesis is supported by the symmetry of the graying of male beard hairs. According to stochastic theories of aging, aging is a passive non-programmed process where random dispersion of graying hairs should result. On the contrary, programmed theories of aging would predict that there should be symmetry on the left and right parts of the face showing the same proportion, pattern and time of appearance of graying hairs.

Discrimination Experiments in Entamoeba and Evidence from Other Protists Suggest Pathogenic Amebas Cooperate with Kin to Colonize Hosts and Deter Rivals.

Entamoeba histolytica is one of the least understood protists in terms of taxa, clone, and kin discrimination/recognition ability. However, the capacity to tell apart same or self (clone/kin) from different or nonself (nonclone/nonkin) has long been demonstrated in pathogenic eukaryotes like Trypanosoma and Plasmodium, free-living social amebas (Dictyostelium, Polysphondylium), budding yeast (Saccharomyces), and in numerous bacteria and archaea (prokaryotes). Kin discrimination/recognition is explained under inclusive fitness theory; that is, the reproductive advantage that genetically closely related organisms (kin) can gain by cooperating preferably with one another (rather than with distantly related or unrelated individuals), minimizing antagonism and competition with kin, and excluding genetic strangers (or cheaters = noncooperators that benefit from others' investments in altruistic cooperation). In this review, we rely on the outcomes of in vitro pairwise discrimination/recognition encounters between seven Entamoeba lineages to discuss the biological significance of taxa, clone, and kin discrimination/recognition in a range of generalist and specialist species (close or distantly related phylogenetically). We then focus our discussion on the importance of these laboratory observations for E. histolytica's life cycle, host infestation, and implications of these features of the amebas' natural history for human health (including mitigation of amebiasis).

The 'over-the-top' modified Cutler-Beard procedure for complete upper eyelid defect reconstruction.

PURPOSE: To describe the 'Over-the-Top' Modified Cutler Beard Procedure (OTTMCB) for complete upper eyelid defect reconstruction Methods: This is retrospective case note review of four patients that underwent the OTTMCB procedure. This two-stage procedure comprises the replacement of the posterior lamella with a free tarsal graft from the contralateral upper eyelid, and the anterior lamella with a lower lid skin flap over the lower eyelid margin which is divided 2-4 weeks later. RESULTS: The procedure was undertaken for four patients with 75-90% upper eyelid defects from tumour excision surgery. One patient had post-operative dehiscence requiring debridement and resuturing and further reconstructive surgery 18 months later to improve the cosmesis and lagophthalmos. The other three patients had good functional and cosmetic outcomes. CONCLUSIONS: The OTTMCB procedure replaces the anterior and posterior lamellae of the upper eyelid with 'like-for-like' tissues. It avoids some of the drawbacks of the original and other variations of the Cutler-Beard procedure and achieves a good cosmetic outcome.

A case series of Merkel cell carcinoma of the eyelid: a rare entity often misdiagnosed.

Merkel cell carcinoma (MCC) is one of the rarest eyelid tumors, with high mortality rate due to lymphatic and metastatic spread. We hereby report six cases of patients with histological diagnosis of MCC referred to our Orbit Unit between 2012 and 2018, focusing on diagnosis, treatment, and subsequent follow up. All patients underwent surgical excision and systemic work-up. Both MCC TNM and eyelid MCC TNM were used to stage lesions. MCC of the eyelid is usually misdiagnosed as benign or other malignant lesions. A prompt examination and a wide local excision are mandatory. A close follow-up of these patients is advised due to high recurrence rate and lymphatic spread.

Influence of facial hair length, coarseness, and areal density on seal leakage of a tight-fitting half-face respirator.

BACKGROUND: OSHA regulations state that an employer shall not permit tight-fitting respirators to be worn by employees who have facial hair that comes between the skin and facepiece seal. Studies have shown that facial hair in the face seal zone can increase penetration and decrease the fit factor (FF), although the relationship between the amount and characteristics of facial hair and the increase in penetration is not well quantified. This article examines the influence of facial hair length, areal density, and coarseness on FF for one model of half-face elastomeric negative-pressure air purifying respirator. APPROACH: Quantitative fit tests (QNFT) were performed on 19 subjects with beards initially 0.500-in long and subsequently trimmed to 0.250, 0.125, and 0.063 in, then after a razor shave. Three fit tests were performed at each of the 5 lengths, for 285 total tests. The average diameter and areal density of cheek and chin hair were measured. Penetration was modeled as a function of hair length category, beard areal density, and hair coarseness. RESULTS: FF decreased with beard length, especially beyond 0.125 in. However, passing FF scores were achieved on all tests by all subjects at the smooth shave and 0.063 in conditions, and 98% of tests were passed at 0.125 in; seven subjects passed all tests at all conditions. Chin and cheek areal densities were significantly different and were only weakly correlated. Beard hair diameters were normally distributed across subjects (mean 76 µm, standard deviation 7.4 µm). Beard length and areal density, but not coarseness, were statistically significant predictors of fit using an arcsine transformed penetration model. FF decreased with increasing beard length, especially beyond 0.125 in, although FF with a "stubble" beard did not differ significantly from a smooth shave. FF also decreased with increasing areal beard hair density. CONCLUSION: Beard length and areal density negatively influence FF. However, tight-fitting half-face negative-pressure respirator fit tests can achieve adequate fit factor scores even with substantial facial hair in the face seal area.