Effect of low dose honey on the apoptosis and inflammation gene expression in corneal limbal stem cells and keratocytes and its efficacy as an ophthalmic formulation in the treatment of dry eye: in-vitro and clinical study.

Background: The use of honey as an eye treatment encounters challenges due to its high osmolarity, low pH, and difficulties in sterilization. This study addresses these issues by employing a low concentration of honey, focusing on both in-vitro experiments and clinical trials for treating dry eye disease in corneal cells. Methods: In the in-vitro experiment, we investigated the impact of a 1% honey-supplemented medium (HSM) on limbal stem cells (LSCs) and keratocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and real-time polymerase chain reaction (PCR) for BCL-2, BAX, and IL-1ß gene expression. Simultaneously, in the clinical trial, 80 participants were divided into two groups, receiving either a 1% w/v honey ophthalmic formulation or a placebo for 3 months. Study outcomes included subjective improvement in dry eye symptoms, tear break-up time (TBUT), and Schirmer's test results. Results: MTT results indicated that 1% HSM did not compromise the survival of corneal cells and significantly reduced the expression of the IL-1ß gene. Additionally, participants in the honey group demonstrated a higher rate of improvement in dry eye symptoms and a significant enhancement in TBUT values at the three-month follow-up. However, there was no significant difference between the study groups in terms of Schirmer's test values. No adverse events were observed or reported. Conclusion: In conclusion, 1% honey exhibits anti-inflammatory and anti-infective properties, proving effective in ameliorating dry eye symptoms and enhancing tear film stability in patients with dry eye disease.Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/63800.

Intraspecific diversity of Meriones persicus (Rodentia; Gerbillinae), the main plague reservoir in Iran, and its connection to enzootic plague in Iran.

Plague, a lethal zoonotic disease, primarily circulates within rodent populations and their fleas. In Iran, the widely distributed jird, Meriones persicus, serves as the principal reservoir for plague, with a belief in the existence of five out of its six recognized subspecies within the country. However, these subspecies are classified into four mitochondrial cytochrome b sub-lineages (IA, IB, IIA, IIB). This discrepancy, combined with the presence of an unnamed sub-lineage in central Iran awaiting taxonomic clarification, has left intraspecific taxonomy unsettled and obscured the true alignment between mtDNA sub-lineages and nominal subspecies. In this study, we investigated the intraspecific variation in the cytb gene across populations sampled throughout Iran, focusing on underexplored regions between the Zagros and Alborz Mountains and central Iran. While our genetic data generally support reported subspecies validity in Iran, we raise questions about M. p. baptistae, emphasizing the need for further data from its type territory in Pakistan. Two main lineages of M. persicus (I and II) exhibit geographical isolation, with limited overlap in the central Zagros Mts., where three subspecies (M. p. ambrosius, M. p. rossicus, and M. p. persicus) coexist. Superimposing infected rodents' geographic coordinates onto updated sub-lineages' distribution revealed a potential association between sub-lineage IA (M. p. rossicus) and all enzootic plague cases from 1946 to 2023. M. persicus rossicus extends into the Caucasus (where plague infections are common), Eastern Turkey, and Iraq. Consequently, interpreting this finding in the context of plague surveillance in Iran and neighboring areas requires caution.

The Epidemiological Investigation of Yersinia pestis, Francisella tularensis, and Arenavirus Infections in Small Mammals in Northwestern Iran.

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis, Yersinia pestis, and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis, Y. pestis, and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y. pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata, Paraceras melis, Ctenophthalmus rettigi smiti, Rhadinopsylla bivirgis, Paradoxopsyllus grenieri, and Nosopsyllus iranus. Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis. The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis. Conclusions: F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas.

The surveillance of plague among rodents and dogs in Western Iran.

BACKGROUND: The causative agent of plague, Yersinia pestis, is maintained in nature via a flea-rodent cycle. Western Iran is an old focus for plague, and recent data indicate that rodents and dogs in this region have serological evidence of Y. pestis infection. The purpose of this study was to conduct a large-scale investigation of Y. pestis infection in shepherd dogs, rodents, and their fleas in old foci for plague in Western Iran. MATERIALS AND METHODS: This study was conducted in Hamadan province from 2014 to 2020. Rodents and fleas were collected from various locations throughout this region. Y. pestis was investigated in rodent spleen samples and fleas using culture, serology, and real-time PCR methods. Additionally, sera samples were collected from carnivores and hares in this region, and the IgG antibody against the Y. pestis F1 antigen was assessed using an ELISA. RESULTS: In this study, 927 rodents were captured, with Meriones spp. (91.8%) and Microtus qazvinensis (2.6%) being the most prevalent. A total of 6051 fleas were collected from rodents and carnivores, most of which were isolated from Meriones persicus. None of the rodents or fleas examined tested positive for Y. pestis using real-time PCR and culture methods. Meanwhile, IgG antibodies were detected in 0.32% of rodents. All serologically positive rodents belonged to M. persicus. Furthermore, none of the sera from the 138 carnivores (129 sheepdogs, five Vulpes vulpes, four Canis aureus), and nine hares tested positive in the ELISA test. CONCLUSION: This primary survey of rodent reservoirs shows serological evidence of Y. pestis infection. Western Iran is an endemic plague focus, and as such, it requires ongoing surveillance.

Molecular investigation of Coxiella burnetii and Francisella tularensis infection in ticks in northern, western, and northwestern Iran.

Tularemia and Q fever are endemic diseases in Iran; however, little information is available on the prevalence of the causative agents, Coxiella burnetii and Francisella tularensis, in Iranian ticks. This study investigated C. burnetii and F. tularensis among hard ticks in this country. We collected ticks from livestock and other mammals in Guilan, Mazandaran, Golestan (northern Iran), Kurdistan (western Iran), and West Azerbaijan (northwestern Iran) provinces. Genomic DNA from collected ticks was extracted and screened for C. burnetii and F. tularensis using Real-time PCR. A total of 4,197 ticks (belonging to 12 different species) were collected, and Ixodes ricinus (46.4%), Rhipicephalus turanicus (25%), and Rhipicephalus sanguineus sensu lato (19.1%) were the most collected species. Of 708 pooled tick samples, 11.3% and 7.20% were positive for C. burnetii and F. tularensis, respectively. The genus of Rhipicephalus had the highest (18.3%) C. burnetii infection among the collected tick pools (P<0.001). Furthermore, the most positive pools for F. tularensis belonged to Haemaphysalis spp. (44.4%). Kurdistan had the most significant percentage of C. burnetii-infected ticks (92.5%), and there was a meaningful relationship between the provinces and the infection (P< 0.001). The ticks from Golestan exhibited the highest F. tularensis infection rate (10. 9%), and the infection showed no significant relationship with the provinces (P = 0.19). Ticks collected from grasslands had a higher Coxiella burnetii infection rate than those collected from animals (39.4% vs. 7.9%; p<0.01). However, ticks collected from animal surfaces had a slightly higher rate of Francisella tularensis infection than those collected from grasslands (7.6% vs. 3.9%; p = 0.24). Here, we demonstrated the presence of both pathogens in the north (Guilan, Mazandaran, and Golestan provinces), the west (Kurdistan province), and the northwest (West Azerbaijan province) of Iran. The public health system should pay particular attention to tick bites in veterinary medicine and humans.

Discovery of a novel marker for human granulocytes and tissue macrophages: RTL1 revisited.

Here, retrotransposon-like 1 (RTL1) is introduced as a marker for circulating and tissue neutrophils, tissue macrophages, and tumor-associated macrophages (TAM) and neutrophils (TAN). Anti-RTL1 polyclonal and monoclonal antibodies were produced, and their reactivity was examined by Western blotting (WB), ELISA, and immunostaining of human normal and cancer tissues. The reactivity of the anti-RTL1 antibodies with peripheral blood leukocytes and a panel of hematopoietic cell lines was examined. The generated antibodies specifically detected RTL1 in the WB of the placenta and U937 cells. The polyclonal antibody showed excellent reactivity with tissue-resident macrophages, Hofbauer cells, alveolar and splenic macrophages, Kupffer cells, and inflammatory cells in the tonsil, appendix, and gallbladder. In vitro GM-CSF-differentiated macrophages also showed a high level of intracellular RTL1 expression. TAM and TAN also showed excellent reactivity with this antibody. Almost all circulating granulocytes but not lymphocytes or monocytes expressed RTL1 at their surface. Serial sections of the appendix stained with CD15 and RTL1 and placenta stained with CD68 and RTL1 showed a considerable overlap in RTL1 expression in CD15+ granulocytes and CD68+ macrophages. A small percentage of myelomonocytic cell lines was positive for surface RTL1, while promyelocytic, monocytic, megaloblastic, and lymphoblastic cell lines were negative. Endothelial cells of normal and cancer tissues highly expressed RTL1. RTL1 could be considered a new marker for different normal tissue macrophages, TAM, circulating and tissue neutrophils, and TAN.

Serological evidence of Yersinia pestis infection in rodents and carnivores in Northwestern Iran.

BACKGROUND: Plague may recur after several decades in its endemic regions; therefore, the continuous monitoring of wildlife is essential, even when no human cases are reported in the old foci. The present study was conducted to monitor rodents and their ectoparasites as well as carnivores to learn about the epidemiology of plague infection in an old focus of Iran. METHODOLOGY: The present study was conducted from 2019 to 2020 in Takestan county of Qazvin Province in northwestern Iran. Rodents were caught using live traps, and their fleas were separated. Blood and spleen specimens were taken from the captured rodents. Serum samples were also collected from sheepdogs and wild carnivores. The collected samples were tested by culture, serology (ELISA), and molecular methods to detect Yersinia pestis infection. FINDINGS: A total of 399 small mammals were caught, of which 68.6% were Meriones persicus. A total of 2438 fleas were collected from the rodents, 95.3% of which were Xenopsylla buxtoni. Overall, 23 out of 377 tested rodents (5.7%, CI 95%, 3.9-9.0) had IgG antibodies against the F1 antigen of Y. pestis, and all the positive samples belonged to M. persicus. Nine (4.8%) out of 186 collected sera from the sheepdogs' serum and one serum from the Canis aureus had specific IgG antibodies against the F1 antigen of Y. pestis. There were no positive cases of Y. pestis in the rodents and fleas based on the culture and real-time PCR. CONCLUSION: Serological evidence of Y. pestis circulation was observed in rodents and carnivores (sheepdogs and C. aureus). The presence of potential plague vectors and serological evidence of Y. pestis infection in the surveyed animals could probably raise the risk of infection and clinical cases of plague in the studied region. Training health personnel is therefore essential to encourage their detection of possible human cases of the disease.

Case report: A novel mutation in the EYA1 gene in a child with branchiootic syndrome with secretory otitis media and bilateral vestibular hypofunction.

Branchiootic syndrome (BOS) is a rare, autosomal dominant syndrome characterized by malformations of the ear associated with hearing loss, second branchial arch anomalies, and the absence of renal anomalies. Herein, we report the case of an 8-year-old male patient with BOS. The proband also experiences mixed conductive and sensorineural hearing loss in the right ear, and severe-to-profound sensorineural hearing loss in the left ear. Preauricular pits, branchial fistulae, and cochlear hypoplasia were present bilaterally. Type III cup-shaped ear, and external auditory canal stenosis were detected in the right ear. Lateral semicircular canal-vestibule dysplasia was detected in the left ear. Moreover, the patient had unilateral secretory otitis media (SOM) in the right ear and bilateral vestibular hypofunction (VH), which has not been reported in previous studies. The patient's hearing on the right side was restored to nearly normal after myringotomy. Whole exome sequencing identified a novel frameshift mutation in EYA1 (NM_000503.6): c.1697_1698delinT [p.(Lys566IlefsTer73)] in the proband, which was defined a "pathogenic" mutation according to American College of Medical Genetics and Genomics guidelines. This is the first report of a child presenting with BOS, SOM and VH, which expands the known clinical manifestations of this syndrome. We also observed a novel EYA1 gene mutation in this patient with BOS, which enriches the mutation map and provides a reference for genetic diagnosis of this syndrome.

A Review on the Application of Stem Cell Secretome in the Protection and Regeneration of Retinal Ganglion Cells; a Clinical Prospect in the Treatment of Optic Neuropathies.

PURPOSE: Retinal ganglion cells (RGCs) are one the most specialized neural tissues in the body. They transmit (and further process) chemoelectrical information originating in outer retinal layers to the central nervous system. In fact, the optic nerve is composed of RGC axons. Like other neural cells, RGCs will not completely heal after the injury, leading to irreversible vision loss from disorders such as glaucoma that primarily affect these cells. Several methods have been developed to protect or regenerate RGCs during or after the insult has occurred. This study aims to review the most recent clinical, animal and laboratory experiments designed for the regeneration of RGC that apply the stem cell-derived secretome. METHODS: We extracted the studies from Web of Science (ISI), Medline (PubMed), Scopus, Embase, and Google scholar from the first record to the last report registered in 2022, using the following keywords; "secretome" OR "conditioned medium" OR "exosome" OR "extracellular vesicle" AND "stem cell" AND "RGC" OR "optic neuropathy". Any registered clinical trials related to the subject were also extracted from clinicaltrial.gov. All published original studies that express the effect of stem cell secretome on RGC cells in optic neuropathy, whether in vitro, in animal studies, or in clinical trials were included in this survey. RESULTS: In this review, we provided an update on the existing reports, and a brief description of the details applied in the procedure. Compared to cell transplant, applying stem cell-derived secretome has the advantage of minimized immunogenicity yet preserving efficacy via its rich content of growth factors. CONCLUSIONS: Different sources of stem cell secretomes have distinct implications in the management of RGC injury, which is the main subject of the present article.

Effect of Aerobic, Resistance, and Combined Exercise Training on Depressive Symptoms, Quality of Life, and Muscle Strength in Healthy Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aerobic training, resistance training, or combined training are interventions that can be modified to suit the needs of aged people. OBJECTIVE: This meta-analysis aimed to investigate the impact of exercise training on depression symptoms, quality of life, and muscle strength in healthy people aged 60 or more. DATA SOURCES: Searches were conducted in PubMed, Web of Science, Medline, Google Scholar, and Scopus databases from inception to February 2022. RESULTS: Eighteen studies, totaling 1354 participants, were included in the meta-analysis. Overall, exercise training significantly declined depressive symptoms (standard mean difference (SMD): -.52, 95% confidence interval (CI): -.76 to -.28; p < .001). Moreover, there was a significant reduction in bodily pain (p < .05) and body mass (p < .01), and a significant increase in mental health (p < .001), physical functioning (p < .01), and general health (p < .001) subscales of quality of life as well as upper- (p < .001) and lower-limb strength (p < .001). Subgroup analysis revealed that depression decreased significantly when aerobic training (p = .000) and resistance training (p = .003) were applied, and for studies including both genders (p = .000) or men subjects (p = .002). Moreover, subgroup analysis demonstrated that depression reduced following both medium- (p = .006) and long-term (p = .002) interventions. CONCLUSION: These findings demonstrate that exercise interventions may produce improvements in depressive symptoms, some components of quality of life, muscle strength, and body mass. Additional research is required to define the optimal dose of exercise training interventions.

Green and four-component cyclocondensation synthesis and in silico docking of new polyfunctionalized pyrrole derivatives as the potential anticholinesterase agents.

Synthesis of new substituted pyrrole scaffolds containing substituted thiadiazol-2-amine moiety was successfully developed through one-pot and multi-component tandem condensation reaction utilizing of triethyl ammonium hydrogen sulfate ([Et3NH][HSO4]) ionic liquid as a green media under solvent-free conditions. The chemical structures of all newly synthesized compounds were fully characterized by spectroscopic methods (IR, 1H NMR, 13C NMR) and elemental analyzes. The molecular docking studies were also performed to predict the possible binding sites of the derivatives on the active site gorge of cholinesterase enzymes (AChE and BuChE). The results showed that all the seventeen derivatives interact with the enzymes with high affinity and among them 7d and 7f possess the greatest ability to bind to AChE and BuChE, respectively.

Phylogenetic relations and range history of jerboas of the Allactaginae subfamily (Dipodidae, Rodentia).

Five-toed jerboas of the subfamily Allactaginae comprise several complex taxa occurring over a wide distribution range covering a large part of the Eurasian arid belt. In this study, we employed current methods of molecular phylogenetics based on 15 nuclear genes and the mitochondrial gene cytb to revise relations and systematics within Allactaginae. We also applied species distribution modelling projected on paleo-environmental data to reconstruct the geographic patterns of speciation in Allactaginae. We elucidated the intergeneric relationships within this subfamily and clarified interspecies relations within the genus Scarturus. Moreover, our results demonstrate the species status of S. caprimulga; outline the currently understudied diversity within Orientallactaga, Allactaga, and Pygeretmus; and improve the divergence estimates of these taxa. Based on our results from modelling of geographic range fragmentation in allactagines, we suggest the dating and location of speciation events and present hypotheses regarding general habitat niche conservatism in small mammals.

Borrelia duttonii-like spirochetes parasitize Meriones persicus in East Azerbaijan Province of Iran.

In Iran, Borrelia persica and Borrelia microti/microti-like borreliae have been established as causative agents of tickborne relapsing fever (TBRF). However, the epidemiology of two previously described species, Borrelia balthazardi and Borrelia latyschewii (latychevi), has remained elusive for many years. We investigated Borrelia infection in various rodents and small mammals in the TBRF endemic East Azerbaijan Province, northwestern Iran, where B. perisca and B. balthazardi might coexist. Among trapped animals (n=210), a 16S real-time PCR detected Borrelia DNA in 11 Meriones persicus. Multilocus sequence analysis (MLSA) using six different loci, including four coding regions (flaB, glpQ, groEL, p66) and two non-coding (rrs, IGS) followed by phylogeny revealed considerable sequence identity between the borreliae detected, B. microti, and East African Borrelia duttonii, and Borrelia recurrentis. Our results indicate that B. microti and microti-like borreliae, including the specimens previously characterized in the south of Iran and the present study, are different ecotypes of B. duttonii, i.e., exhibiting a single species/entity or descendants of a recent common ancestor. Our findings also suggest that the species we had long coined as B. balthazardi and the microti-like borreliae detected herein might be the same.

Morphometric Study of Mus musculus, Rattus norvegicus, and Rattus rattus in Qatar.

The current study was undertaken to estimate the morphometric pattern of three commensal rodents, i.e., Mus musculus, Rattus norvegicus, and Rattus rattus in Qatar. One hundred forty-eight rodents were captured from different facilities throughout Qatar. The captured rodents were used to identify the external body and cranio-mandibular morphometry. The study found that R. norvregicus was the most prevalent (n = 120, 81%, 95% CI: 73.83-87.05). Most of the rodents were collected from Al Rayan municipality (n = 92, 62%), were adults (n = 138, 93.2%, 95% CI: 87.92-96.71), and were from livestock farms (n = 79, 49%, 95% CI: 41.02-57.65). The rodents' average body weights were 18.8 ± 2.2 gm, 264.3 ± 87.5 gm, and 130 ± 71.3 gm for M. musculus, R. norvegicus, and R. rattus, respectively. The research found that the studied rodents are smaller than those of other countries such as Turkey, Tunisia, and Iran. The study of morphometry is a useful tool for the traditional identification of small mammal species, including rodents. The average morphometric measurements of the external body and skull were normally distributed and can be used as a reference of R. norvegicus and R. rattus for Qatar. A further comprehensive study is required to investigate the rodent population index, eco-friendly control program, and public health importance in Qatar.

New Data on Comparative Cytogenetics of the Mouse-Like Hamsters (Calomyscus Thomas, 1905) from Iran and Turkmenistan.

The taxonomy of the genus Calomyscus remains controversial. According to the latest systematics the genus includes eight species with great karyotypic variation. Here, we studied karyotypes of 14 Calomyscus individuals from different regions of Iran and Turkmenistan using a new set of chromosome painting probes from a Calomyscus sp. male (2n = 46, XY; Shahr-e-Kord-Soreshjan-Cheshme Maiak Province). We showed the retention of large syntenic blocks in karyotypes of individuals with identical chromosome numbers. The only rearrangement (fusion 2/21) differentiated Calomyscus elburzensis, Calomyscus mystax mystax, and Calomyscus sp. from Isfahan Province with 2n = 44 from karyotypes of C. bailwardi, Calomyscus sp. from Shahr-e-Kord, Chahar Mahal and Bakhtiari-Aloni, and Khuzestan-Izeh Provinces with 2n = 46. The individuals from Shahdad tunnel, Kerman Province with 2n = 51-52 demonstrated non-centric fissions of chromosomes 4, 5, and 6 of the 46-chromosomal form with the formation of separate small acrocentrics. A heteromorphic pair of chromosomes in a specimen with 2n = 51 resulted from a fusion of two autosomes. C-banding and chromomycin A3-DAPI staining after G-banding showed extensive heterochromatin variation between individuals.

Rodent-Related Zoonotic Pathogens at the Human-Animal-Environment Interface in Qatar: A Systematic Review and Meta-Analysis.

Rodents are one of the most diversified terrestrial mammals, and they perform several beneficial activities in nature. These animals are also important as carriers of many pathogens with public health importance. The current systematic review was conducted to formulate a true depiction of rodent-related zoonoses in Qatar. Following systematic searches on PubMed, Scopus, Science Direct, and Web of Science and a screening process, a total of 94 published articles were selected and studied. The studied articles reported 23 rodent-related zoonotic pathogens that include nine bacterial, eleven parasitic, and three viral pathogens, from which the frequently reported pathogens were Mycobacterium tuberculosis (32 reports), Escherichia coli (23), and Salmonella spp. (16). The possible pathway of entry of the rodent-borne pathogens can be the land port, seaports, and airport of Qatar through carrier humans and animals, contaminated food, and agricultural products. The pathogens can be conserved internally by rodents, pets, and livestock; by agricultural production systems; and by food marketing chains. The overall estimated pooled prevalence of the pathogens among the human population was 4.27% (95%CI: 4.03-4.51%; p < 0.001) with significant heterogeneity (I2 = 99.50%). The top three highest prevalent pathogens were M.tuberculosis (30.90%; 22.75-39.04%; p < 0.001; I2 = 99.70%) followed by Toxoplasmagondii (21.93%; 6.23-37.61%; p < 0.001; I2 = 99.30%) and hepatitis E virus (18.29%; 11.72-24.86%; p < 0.001; I2 = 96.70%). However, there is a knowledge gap about the listed pathogens regarding the occurrence, transmission pathways, and rodent role in transmission dynamics at the human-animal-environment interface in Qatar. Further studies are required to explore the role of rodents in spreading zoonotic pathogens through the One Health framework, consisting of zoologists, ecologists, microbiologists, entomologists, veterinarians, and public health experts in this country.

Expression profiling of RTL1 in human breast cancer tissues and cell lines.

Breast cancer (BC) is the most common cancer in females. In this regard, the identification of molecular alterations driving BC is an immediate need for developing effective immunotherapeutic tools. Here we investigated the expression of a placenta-specific protein, Retrotransposon-like 1 (RTL1) in a series of BC tissues and cell lines. RTL1-specific polyclonal antibody was generated and characterized. Using tissue microarray immunohistochemistry, expression of RTL1 in a total of 147 BC and 36 non-malignant breast tissues was investigated and the association of patient's clinicopathological parameters with RTL1 expression was then examined. Expression of RTL1 in four BC cells was assessed by flow cytometry, immunofluorescent staining and Western blotting. We observed a mixture pattern of nuclear and cytoplasmic RTL1 expression in most tissues examined, however nuclear expression was found to be dominant pattern of expression. The level of nuclear RTL1 expression was significantly higher in BC tissues (P < 0.001). A statistically significant association between nuclear RTL1 expression and histological grade and vascular invasion was found (P < 0.001 and P < 0.05). All cell lines expressed RTL1 with varying degrees at their surface. The most invasive BC cell line MDA-MB-231, compared to T-47D, SKBR3 and MCF7 expressed higher levels of RTL1 at their surface. Cells with a low level of surface expression, expressed high levels of intracellular RTL1 expression. Our antibody reacted with a specific band of about 125 KD in normal human placenta and all cell lines examined. In contrast to placenta, two additional bands were also observed in cancer cell lines. Our results showed for the first time that RTL1 is differentially expressed in BC compared to non-malignant breast tissues and is associated with a higher grade and vascular invasion. In BC cells with high metastatic and invasive potential, this antigen is mostly confined to cell surface compartment indicating the possibility of using antibody-based immunotherapy for advanced metastatic BC patients.

Reproductive Isolation Between Taxonomically Controversial Forms of the Gray Voles (Microtus, Rodentia; Arvicolinae): Cytological Mechanisms and Taxonomical Implications.

The formation of hybrid sterility is an important stage of speciation. The voles of the genus Microtus, which is the most speciose genus of rodents, provide a good model for studying the cytological mechanisms of hybrid sterility. The voles of the "mystacinus" group of the subgenus Microtus (2n = 54) comprising several recently diverged forms with unclear taxonomic status are especially interesting. To resolve the taxonomic status of Microtus mystacinus and Microtus kermanensis, we crossed both with Microtus rossiaemeridionalis, and M. kermanensis alone with Microtus arvalis "obscurus" and M. transcaspicus and examined the reproductive performance of their F1 hybrids. All interspecies male hybrids were sterile. Female M. kermanensis × M. arvalis and M. kermanensis × M. transcaspicus hybrids were sterile as well. Therefore, M. mystacinus, M. kermanensis, and M. rossiaemeridionalis could be considered valid species. To gain an insight into the cytological mechanisms of male hybrid sterility, we carried out a histological analysis of spermatogenesis and a cytological analysis of chromosome synapsis, recombination, and epigenetic chromatin modifications in the germ cells of the hybrids using immunolocalization of key meiotic proteins. The hybrids showed wide variation in the onset of spermatogenesis arrest stage, from mature (although abnormal) spermatozoa to spermatogonia only. Chromosome asynapsis was apparently the main cause of meiotic arrest. The degree of asynapsis varied widely across cells, individuals, and the crosses-from partial asynapsis of several small bivalents to complete asynapsis of all chromosomes. The asynapsis was accompanied by a delayed repair of DNA double-strand breaks marked by RAD51 antibodies and silencing of unpaired chromatin marked by γH2A.X antibodies. Overall, the severity of disturbances in spermatogenesis in general and in chromosome synapsis in particular increased in the hybrids with an increase in the phylogenetic distance between their parental species.

Francisella tularensis human infections in a village of northwest Iran.

BACKGROUND: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran. METHODS: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture. RESULTS: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area. CONCLUSIONS: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

Plague reservoir species throughout the world.

Plague has been known since ancient times as a re-emerging infectious disease, causing considerable socioeconomic burden in regional hotspots. To better understand the epidemiological cycle of the causative agent of the plague, its potential occurrence, and possible future dispersion, one must carefully consider the taxonomy, distribution, and ecological requirements of reservoir-species in relation either to natural or human-driven changes (e.g. climate change or urbanization). In recent years, the depth of knowledge on species taxonomy and species composition in different landscapes has undergone a dramatic expansion, driven by modern taxonomic methods such as synthetic surveys that take into consideration morphology, genetics, and the ecological setting of captured animals to establish their species identities. Here, we consider the recent taxonomic changes of the rodent species in known plague reservoirs and detail their distribution across the world, with a particular focus on those rodents considered to be keystone host species. A complete checklist of all known plague-infectable vertebrates living in plague foci is provided as a Supporting Information table.