Undetected leprosy in an endemic area: A case report

Leprosy is an infectious disease causing irreversible disability if unnoticed. A 69-year-old man with undetected leprosy from 30 years ago referred to us with claw hand and Madrosis (Milphosis). The patient complained of non-healing and painless ulcers on the extremities as well as numbness in the right leg. He told the medical team that he could not feel his feet in his shoes. The patient had blurred vision and lacrimation two weeks before admission. He had a history of recurrent foot ulcers from 25 years ago although he referred to medical staff about 5 years ago with infected wound on the hands and multiple scars of pervious ulcers. The disabilities were mainly in consequence of late visit to healthcare centers, misdiagnosis, difficult access to medical centers and patient's unawareness. The case showed the significance of medical education and public awareness for signs and symptoms of leprosy to be recognized and treated on time. In conclusion detecting leprosy should not be delayed just because of a decrease in the number of cases especially in an endemic area like Kurdistan, Iran

sy680 is a novel allele of pkd-2

A new allele of pkd-2 was isolated in a behavioral genetic screen for male mating defects, and found to result in a substitution of Arginine for Glycine in the equivalent of human PKD2 alanine 615. The C. elegans ortholog of polcystin-2 is encoded by pkd-2 (Barr et al., 2001). From an EMS screen of a plg-1; him-5 strain for male mating defective mutants and a secondary behavioral screen for defects in discrete steps of male mating behavior, namely response to contact to hermaphrodites and vulval location (described in Schindelman et al., 2006), we identified a new allele of pkd-2 based on mapping and complementation. sy680 fails to complement pkd-2(sy606) for defects in response to contact with hermaphrodite and vulval location. Here we report the sequence of this allele. PCR amplification and sequencing of pkd-2 exons indicated that there was a c-->t transition in the transcribed DNA strand (g-->a in the pkd-2 sense strand; Figure 1A). This change leads to an altered codon, a Glycine to Arginine substitution the PKD-2 protein. This position corresponds to A615 of the human protein (Figure 1B)

A new mutation with a polycystin phenotypic spectrum in Caenorhabditis elegans

lov-1 and pkd-2, which encode the C. elegans orthologs of human polycystin-1 and -2, are necessary for three particular aspects of male mating behavior. In a screen for male mating defective mutants with similar spectrum of mating defects, we identified a mutation that apparently defines a new locus, lov-3. We isolated the sy682 mutation in an ethyl-methane sulphonate (EMS)-screen of Caenorhabditis elegans strain PS1395 [genotype: plg-1(e2001d); him-5(e1490)] for mutant males that do not mate efficiently and hence do not form plugs on hermaphrodites (Liu et al, 2017). sy682 is defective in the males’ response to contact with hermaphrodite and in vulval location (Table 1). The vulval location defect is failing to stop at the vulva. These two phenotypes are associated with lov-1 (Barr, 1999) and pkd-2 loss-of-function mutations (Barr et al. 2001; Whittaker et al., 2017). sy682 maps to the X chromosome and thus is distinct from lov-1 and pkd-2, so it defines a likely new locus, lov-3

Caenorhabditis elegans Gα_q Regulates Egg-Laying Behavior via a PLCβ-Independent and Serotonin-Dependent Signaling Pathway and Likely Functions Both in the Nervous System and in Muscle

egl-30 encodes the single C. elegans ortholog of vertebrate Gα_q family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the nervous system and in pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as intragenic revertants of an egl-30reduction-of-function mutation. Using these gain-of-function mutants and existing reduction-of-function mutants, we examined the site and mode of action of EGL-30. On the basis of pharmacological analysis, it has been determined that egl-30 functions both in the nervous system and in the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that eliminate detectable levels of serotonin reveals that egl-30requires serotonin to regulate egg laying. Furthermore, pharmacological response assays strongly suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg laying. We also examined genetic interactions with mutations in the gene that encodes the single C. elegans homolog of PLCβ and mutations in genes that encode signaling molecules downstream of PLCβ. We conclude that PLCβ functions in parallel with egl-30 with respect to egg laying or is not the major effector of EGL-30. In contrast, PLCβ-mediated signaling is likely downstream of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors

Extrasynaptic acetylcholine signaling through a muscarinic receptor regulates cell migration

Acetylcholine (ACh) promotes various cell migrations in vitro, but there are few investigations into this nonsynaptic role of ACh signaling in vivo. Here we investigate the function of a muscarinic receptor on an epithelial cell migration in Caenorhabditis elegans. We show that the migratory gonad leader cell, the linker cell (LC), uses an M1/M3/M5-like muscarinic ACh receptor GAR-3 to receive extrasynaptic ACh signaling from cholinergic neurons for its migration. Either the loss of the GAR-3 receptor in the LC or the inhibition of ACh release from cholinergic neurons resulted in migratory path defects. The overactivation of the GAR-3 muscarinic receptor caused the LC to reverse its orientation through its downstream effectors Gαq/egl-30, PLCβ/egl-8, and TRIO/unc-73. This reversal response only occurred in the fourth larval stage, which corresponds to the developmental time when the GAR-3::yellow fluorescent protein receptor in the membrane relocalizes from a uniform to an asymmetric distribution. These findings suggest a role for the GAR-3 muscarinic receptor in determining the direction of LC migration

DVC interneuron cGAL driver in Caenorhabditis elegans

cGAL, a recently developed temperature-robust bipartite GAL4-UAS system in C. elegans, consists of two components: a cGAL “driver” that expresses the cGAL protein in specific cells using a promoter (i.e. neuron-specific or tissue-specific), and an “effector” that carries a gene of interest downstream of UAS (Wang et al., 2017). Crossing or combining a driver with an effector leads to the expression of the gene of interest in a cell-specific or tissue-specific manner. Here we report a new cGAL driver for the DVC interneuron. The ceh-63 promoter was chosen due to its restricted expression in the DVC neuron (Feng et al. 2012). The DVC interneuron driver construct containing the ceh-63 promoter (646 bp upstream of ATG translation start site) was injected into N2 and an integrated DVC driver line was generated. When crossed with the UAS-GFP effector strain (PS6843), the ceh-63 cGAL driver dictated GFP expression in the single DVC neuron (Figure 1), in addition to GFP in the coelomocyte from Punc-122::gfp co-injection marker. We did not observe GFP expression in uterus as reported by Feng et al., 2012

DVC interneuron cGAL driver in Caenorhabditis elegans

cGAL, a recently developed temperature-robust bipartite GAL4-UAS system in C. elegans, consists of two components: a cGAL “driver” that expresses the cGAL protein in specific cells using a promoter (i.e. neuron-specific or tissue-specific), and an “effector” that carries a gene of interest downstream of UAS (Wang et al., 2017). Crossing or combining a driver with an effector leads to the expression of the gene of interest in a cell-specific or tissue-specific manner. Here we report a new cGAL driver for the DVC interneuron. The ceh-63 promoter was chosen due to its restricted expression in the DVC neuron (Feng et al. 2012). The DVC interneuron driver construct containing the ceh-63 promoter (646 bp upstream of ATG translation start site) was injected into N2 and an integrated DVC driver line was generated. When crossed with the UAS-GFP effector strain (PS6843), the ceh-63 cGAL driver dictated GFP expression in the single DVC neuron (Figure 1), in addition to GFP in the coelomocyte from Punc-122::gfp co-injection marker. We did not observe GFP expression in uterus as reported by Feng et al., 2012

Initiation of male sperm-transfer behavior in Caenorhabditis elegans requires input from the ventral nerve cord

BACKGROUND: The Caenorhabditis elegans male exhibits a stereotypic behavioral pattern when attempting to mate. This behavior has been divided into the following steps: response, backing, turning, vulva location, spicule insertion, and sperm transfer. We and others have begun in-depth analyses of all these steps in order to understand how complex behaviors are generated. Here we extend our understanding of the sperm-transfer step of male mating behavior. RESULTS: Based on observation of wild-type males and on genetic analysis, we have divided the sperm-transfer step of mating behavior into four sub-steps: initiation, release, continued transfer, and cessation. To begin to understand how these sub-steps of sperm transfer are regulated, we screened for ethylmethanesulfonate (EMS)-induced mutations that cause males to transfer sperm aberrantly. We isolated an allele of unc-18, a previously reported member of the Sec1/Munc-18 (SM) family of proteins that is necessary for regulated exocytosis in C. elegans motor neurons. Our allele, sy671, is defective in two distinct sub-steps of sperm transfer: initiation and continued transfer. By a series of transgenic site-of-action experiments, we found that motor neurons in the ventral nerve cord require UNC-18 for the initiation of sperm transfer, and that UNC-18 acts downstream or in parallel to the SPV sensory neurons in this process. In addition to this neuronal requirement, we found that non-neuronal expression of UNC-18, in the male gonad, is necessary for the continuation of sperm transfer. CONCLUSION: Our division of sperm-transfer behavior into sub-steps has provided a framework for the further detailed analysis of sperm transfer and its integration with other aspects of mating behavior. By determining the site of action of UNC-18 in sperm-transfer behavior, and its relation to the SPV sensory neurons, we have further defined the cells and tissues involved in the generation of this behavior. We have shown both a neuronal and non-neuronal requirement for UNC-18 in distinct sub-steps of sperm-transfer behavior. The definition of circuit components is a crucial first step toward understanding how genes specify the neural circuit and hence the behavior

Pancytopenia as a rare complication of acute Brucellosis: A case report

Human Brucellosis still challenges many physicians, especially in developing countries where it is still a very common, but sometimes ignored disease. Its reemergence in developed countries and its status as a class B bioterrorist agent has recently attracted much interest. Having over 500,000 new cases annually, Brucellosis is known as one of the most common zoonotic infections in the world and “the great imitator” because of many clinical and hematological manifestations. Brucellosis is still endemic in many developing countries and remains under-diagnosed and sometimes missed reported. Although this province (Kurdistan, Iran) is a Brucella endemic area with a very high prevalence and incidence rate, except for very few and negligible case reports, we did not find any reports or epidemiological study regarding this zoonotic infection. This is the first reported case of Brucellosis with pancytopenia from this western province of Iran which has been neglected. Our case was a 16-year-old girl referred with protracted fever during the last month and undetermined diagnosis. She also suffered from generalized pain, pale skin, sweating, anorexia, and weight loss. After clinical surveying, taking history, and physical examination, Brucella infection was suspected. Diagnosis confirmed by standard tube agglutination test (STA), 1/640. The patient was successfully treated with doxycycline, rifampicin, and ceftriaxone

Conserved missense variant in ALDH1A3 ortholog impairs fecundity in C. elegans

Accumulating evidence demonstrates that mutations in ALDH1A3 (the aldehyde dehydrogenase 1 family, member A3) are associated with developmental defects. The ALDH1A3 enzyme catalyzes retinoic acid biosynthesis and is essential to patterning and neuronal differentiation in the development of embryonic nervous system. Several missense mutations in ALDH1A3 have been identified in family studies of autosomal recessive microphthalmia, autism spectrum disorder, and other neurological disorders. However, there has been no evidence from animal models that verify the functional consequence of missense mutations in ALDH1A3. Here, we introduced the equivalent of the ALDH1A3 C174Y variant into the Caenorhabditis elegans ortholog, alh-1, at the corresponding locus. Mutant animals with this missense mutation exhibited decreased fecundity by 50% compared to wild-type animals, indicating disrupted protein function. To our knowledge, this is the first ALDH1A3 C174Y missense model, which might be used to elucidate the effects of ALDH1A3 C174Y missense mutation in the retinoic acid signaling pathway during development