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Olfaction is fundamental for sensing environmental chemicals and has obvious adaptive advantages. In fish, the peripheral olfactory organ is composed of lamellae in which the olfactory mucosa contains three main categories of olfactory sensory neurons (OSNs) as follows: ciliated (cOSNs), microvillous (mOSNs), and crypt cells. We studied the appearance of these different OSNs during development of Poecilia reticulata, given its growing use as animal model system. We performed immunohistochemical detection of molecular markers specific for the different OSNs, carrying out image analyses for marked-cell counting and measuring optical density. The P. reticulata olfactory organ did not show change in size during the first weeks of life. The proliferative activity increased at the onset of secondary sexual characters, remaining high until sexual maturity. Then, it decreased in both sexes, but with a recovery in females, probably in relation to their almost double body growth, compared to males. The density of both cOSNs and mOSNs remained constant throughout development, probably due to conserved functions already active in the fry, independently of the sex. The density of calretinin-positive crypt cells decreased progressively until sexual maturity, whereas the increased density of calretinin-negative crypt cell fraction, prevailing in later developmental stages, indicated their probable involvement in reproductive activities., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alström syndrome (AS) is a rare genetic disease caused by ALMS1 mutations, characterized by short stature, and vision and hearing loss. Patients with AS develop the metabolic syndrome, long-term organ complications, and die prematurely. We explored the association between AS and a shortage of hematopoietic stem/progenitor cells (HSPCs), which is linked to metabolic diseases and predicts diabetic complications. We included patients with AS at a national referral center. We measured HSPCs with flow cytometry at baseline and follow-up. We followed patients up to January 2022 for metabolic worsening and end-organ damage. We evaluated HSPC levels and mobilization as well as bone marrow histology in a murine model of AS. In 23 patients with AS, we found significantly lower circulating HSPCs than in healthy blood donors (-40%; P = .002) and age/sex-matched patients (-25%; P = .022). Longitudinally, HSPCs significantly declined by a further 20% in patients with AS over a median of 36 months (interquartile range 30-44). Patients with AS who displayed metabolic deterioration over 5.3 years had lower levels of HSPCs, both at baseline and at last observation, than those who did not deteriorate. Alms1-mutated mice were obese and insulin resistant and displayed significantly reduced circulating HSPCs, despite no overt hematological abnormality. Contrary to what was observed in diabetic mice, HSPC mobilization and bone marrow structure were unaffected. We found depletion of HSPCs in patients with AS, which was recapitulated in Alms1-mutated mice. Larger and longer studies will be needed to establish HSPCs shortage as a driver of metabolic deterioration leading to end-organ damage in AS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Resting energy expenditure (REE) decreases after weight loss more than expected according to body composition changes. Metabolic adaptation (MA) or metabolic slowing represents the difference between measured (m) and predicted (p) REE, and it is not clear whether it persists in the long-term. The aim of this study is to evaluate MA occurring 1 year (V1) and 5 years (V5) after laparoscopic sleeve gastrectomy (LSG) in patients with obesity and normal glucose tolerance, prediabetes (preDM) and type 2 diabetes (T2DM)., Methods: We reassessed 37 patients (14 males/23 females) of 44.8 ± 10 years old, since they registered all the biochemical, body composition, and REE assessments at baseline (V0), V1, and V5. Physical activity (PA) was assessed by interview and questionnaire., Results: Patients displayed a percentage of weight loss of 31.5 ± 7.4% at V1 and a weight regain of 8.9 ± 7.5% at V5. Comparing V1 and V5, fat mass showed a slight increase (P = 0.011), while free fat mass remained unchanged (P = 0.304). PA improved at V1 (P < 0.001), remaining stable at V5 (P = 0.9). Measured REE (mREE) displayed a 31.2% reduction with a corresponding decrease of predicted REE (pREE) of 21.4% at V1, compared with V0 (P = 0.005), confirming a significant MA at V1. Conversely, no difference between mREE and pREE was observed at V5 (P = 0.112)., Conclusion: Our results suggested that only patients with preDM and T2DM displayed MA at V1, which vanished 5 years after LSG. Patients who practiced more PA prevent MA after surgery-induced wight loss., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Olfactory sensory neurons (OSNs) of fish belong to three main types: ciliated olfactory sensory neurons (cOSNs), microvillous olfactory sensory neurons (mOSNs), and crypt cells. Mercury is a toxic metal harmful for olfaction. We exposed the olfactory epithelium of zebrafish to three sublethal Hg2+ concentrations. Molecular markers specific for the different types of OSNs were immunohistochemically detected. Image analysis of treated sections enabled counting of marked cells and measurement of staining optical density indicative of the response of OSNs to Hg2+ exposure. The three types of OSNs reacted to mercury in a different way. Image analysis revealed that mOSNs are more susceptible to Hg2+ exposure than cOSNs and crypt cell density decreases. Moreover, while the ratio between sensory/nonsensory epithelium areas is unchanged, epithelium thickness drops, and dividing cells increase in the basal layer of the olfactory epithelium. Cell death but also reduction of apical processes and marker expression could account for changes in OSN immunostaining. Also, the differential results between dorsal and ventral halves of the olfactory rosette could derive from different water flows inside the olfactory chamber or different subpopulations in OSNs.

Heteroplasmy is the presence of more than one type of mitochondrial genome within an individual, a condition commonly reported as unfavorable and affecting mitonuclear interactions. So far, no study has investigated heteroplasmy at protein level, and whether it occurs within tissues, cells, or even organelles. The only known evolutionarily stable and natural heteroplasmic system in Metazoa is the Doubly Uniparental Inheritance (DUI)-reported so far in ∼100 bivalve species-in which two mitochondrial lineages are present: one transmitted through eggs (F-type) and the other through sperm (M-type). Because of such segregation, mitochondrial oxidative phosphorylation proteins reach a high amino acid sequence divergence (up to 52%) between the two lineages in the same species. Natural heteroplasmy coupled with high sequence divergence between F- and M-type proteins provides a unique opportunity to study their expression and assess the level and extent of heteroplasmy. Here, for the first time, we immunolocalized F- and M-type variants of three mitochondrially-encoded proteins in the DUI species Ruditapes philippinarum, in germline and somatic tissues at different developmental stages. We found heteroplasmy at organelle level in undifferentiated germ cells of both sexes, and in male soma, whereas gametes were homoplasmic: eggs for the F-type and sperm for the M-type. Thus, during gametogenesis, only the sex-specific mitochondrial variant is maintained, likely due to a process of meiotic drive. We examine the implications of our results for DUI proposing a revised model, and we discuss interactions of mitochondria with germ plasm and their role in germline development. Molecular and phylogenetic evidence suggests that DUI evolved from the common Strictly Maternal Inheritance, so the two systems likely share the same underlying molecular mechanism, making DUI a useful system for studying mitochondrial biology., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

We used immunodeficient mice, whose dorsomedial olfactory region was permanently damaged by dichlobenil inoculation, to test the neuroregenerative properties of transplanted human adipose tissue-derived stem cells after 30 and 60 days. Analysis of polymerase chain reaction bands revealed that stem cells preferentially engrafted in the lesioned olfactory epithelium compared with undamaged mucosa of untreated transplanted mice. Although basal cell proliferation in untransplanted lesioned mice did not give rise to neuronal cells in the olfactory mucosa, we observed clusters of differentiating olfactory cells in transplanted mice. After 30 days, and even more at 60 days, epithelial thickness was partially recovered to normal values, as also the immunohistochemical properties. Functional reactivity to odorant stimulation was also confirmed through electro-olfactogram recording in the dorsomedial epithelium. Furthermore, we demonstrated that engrafted stem cells fused with mouse cells in the olfactory organ, even if heterokaryons detected were too rare to hypothesize they directly repopulated the lesioned epithelium. The data reported prove that the migrating transplanted stem cells were able to induce a neuroregenerative process in a specific lesioned sensory area, enforcing the perspective that they could become an available tool for stem cell therapy., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The herbicide dichlobenil selectively causes necrosis of the dorsomedial part of olfactory neuroepithelium (NE) with permanent damage to the underlying mucosa, whereas the lateral part of the olfactory region and the nasal respiratory mucosa remain undamaged. We investigated here whether human umbilical cord blood CD133(+) stem cells (HSC) injected intravenously to nod-scid mice pretreated with dichlobenil may engraft the olfactory mucosa and contribute to the regeneration of the damaged NE. We tested HLA-DQalpha1 DNA and three human microsatellites (Combined DNA Index System) as indicators of engrafted cells, finding polymerase chain reaction evidence of chimaerism in various tissues of the host, including the olfactory mucosa and bulb, at 7 and 31 days following HSC transplantation. Histology, immunohistochemistry, and lectin staining revealed the morphological recovery of the dorsomedial region of the NE in dichlobenil-treated mice that received HSC, contrasting with the lack of regeneration in similarly injured areas as these remained damaged in control nontransplanted mice. FISH analysis, to detect human genomic sequences from different chromosomes, confirmed persistent engraftment of the regenerating olfactory area with chimeric cells. Electro-olfactograms in response to odorants, to test the functionality of the olfactory NE, confirmed the functional damage of the dorsomedial area in dichlobenil-treated mice and the functional recovery of the same area in transplanted mice. These findings support the concept that transplanted HSC migrating to the damaged olfactory area provide conditions facilitating the recovery from olfactory receptor cell loss.

About half (640 subjects) of the population of Soleminis, a canine leishmaniasis focus 15 km north of Cagliari, Sardinia, was subjected to the leishmanin skin test. The total positive rate was 9.7%, and that of males was 15.5%. The age trend in the positive rate resembled a hyperbolic curve, with the 0-5 years age group rate being zero and the highest rate (39.3%) occurring in the 55-65 years age group. The Soleminis focus was classified as hypoendemic, with a prevalence of canine leishmaniasis of about 3%. Dog surveillance, land reclamation and changes in population habits during the last few decades are considered to be responsible for the reduction of transmission to man.

The recent finding that four Leishmania isolates from Rattus rattus are enzymologically identical to L. infantum, aetiological agent of human and canine visceral leishmaniasis in the Mediterranean area, has stimulated further research on the role of R. rattus in the epidemiology of visceral leishmaniasis in Tuscany, Italy. The present work has led to the following results: (a) R. rattus experimentally infected with L. infantum displayed a general resistance to the parasite, even though it appeared that a very low number of amastigotes persisted in the animal for a long period; (b) Phlebotomus perniciosus and P. perfiliewi induced to feed on rats, with either a massive visceral infection or a subpatent immunodepressed infection, became infected, though in different proportions; (c) P. perniciosus and P. perfiliewi were readily attracted to, and fed on, the black rat in nature. These findings, together with those obtained earlier, strongly suggest that the black rat may be one of the wild reservoirs of L. infantum in the areas under study.

Recent investigations on the distribution of human and canine leishmaniasis, and on the vectors and wild reservoirs of the disease in foci in Tuscany have stimulated a retrospective evaluation of human leishmaniasis of the whole region. From a study of the literature, of statistical reports (ISTAT) and of unpublished information, 77 cases of visceral leishmaniasis and 97 of cutaneous leishmaniasis have been analysed. From the case reports of both forms it appears that: (a) a higher incidence of cases occurred in restricted areas; (b) visceral and cutaneous leishmaniasis have been hypoendemic in Tuscany since the years of the earlier reports (1933 and 1936, respectively); (c) the number of infantile visceral cases was much higher in the period from 1933 to 1955 (84.5% of subjects in the 0-10 years age group) than in the subsequent years, 1956-75 (50.0%). The possible significance of the infantile and adult forms of visceral leishmaniasis in Tuscany is discussed, and the local data are compared with those of other regions.

A survey of phlebotomines has been made in the area of the Province of Grosseto (Tuscany, Italy) where human cases of both visceral and cutaneous leishmaniasis have recently occurred. 12 collecting stations, placed around the leishmaniasis foci, were divided into three groups of localities, the Argentario Promontory, coastal plains territory and hilly inland territory. Sandflies were collected with lit and unlit oil traps, and by hand. A total of 11,032 specimens (57% males) were caught and identified. Of these, 86.6% were Phlebotomus perfiliewi, 10.8% P. perniciosus and 2.3% Sergentomyia minuta; only a few specimens were P. papatasi and P. mascittii. In the first group of localities, P. perniciosus was very abundant (87.8%) and S. minuta scarce (12.0%); in the second group, P. perfiliewi was the only species collected; in the third group, P. perfiliewi was very abundant (98.0%), S. minuta was vert scarce (1.1%) and P. perniciosus even more so (0.7%). P. perniciosus is thought to be the probable vector of visceral leishmaniasis in the area of the Monte Argentario and P. perfiliewi is strongly suspected of playing a role in transmission of the cutaneous form in the third group of localities. The species responsible for transmitting visceral leishmaniasis in some of the foci in this area is yet to be found.

Two promastigote-infected specimens of Phlebotomus perniciosus Newstead, 1911, were found in the province of Cagliari, Italy. The parasites from one specimen were successfully cultured in a hamster. The isolate was typed on 11 enzymes and shown to be identical with the reference strain of Leishmania infantum s.st. This is the first typing of a leishmanial organism from naturally infected P. perniciosus.

From April 1977 to February 1978, wild mammals were trapped in a focus of low leishmanial endemicity (Baccinello) in the Province of Grosseto (Tuscany, Italy). Spleen homogenates of the trapped animals were injected i.p. into hamsters, from which spleen biopsies were taken after 60 days and impression smears carefully observed for the presence of Leishmania. Positive spleens were subinoculated into hamsters. 404 animals of 12 species were trapped: 31 insectivores, 317 rodents and 56 carnivores. Black rats (Rattus rattus) and field mice (Apodemus sylvaticus) were the rodent species most frequently trapped--160 and 139 respectively--of which 143 and 134 respectively were tested in hamsters for Leishmania. 35 foxes (Vulpes vulpes) were caught, of which 16 were tested for Leishmania. Four hamsters were found infested with Leishmania. Three of them had been injected with spleen homogenates from R. rattus and one from V. vulpes although liver and spleen impression smears of all trapped animals were negative for Leishmania on direct microscopical examination. The significance of Leishmania infection in wild animals in the leishmanial focus of Baccinello is discussed.

Leishmanin skin testing was performed on 1,285 people in the Tuscany region of Italy. In a known endemic area for leishmaniasis there was an increasing positivity with age, while in another area the curve was bell-shaped suggesting an interruption of transmission in the recent past. In all areas the positivity rate for males was higher than for females, but it was not possible to distinguish between areas of cutaneous and visceral disease.