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Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.Survival depends on the ability to adaptively react or execute actions based on previous aversive salient experiences. Although lateral habenula (LHb) activity has been broadly implicated in the regulation of aversively motivated responses, it is not clear under which conditions this brain structure is necessary to regulate defensive responses to a threat. To address this issue, we combined pharmacological inactivations with behavioral tasks that involve aversive and appetitive events and evaluated defensive responses in rats. We found that LHb pharmacological inactivation did not affect cued threat conditioning (fear) and extinction (safety) learning and memory, anxiety-like or reward-seeking behaviors. Surprisingly, we found that LHb inactivation abolished reactive defensive responses (tone-elicited freezing) only when threat (conditioning) and safety memories (extinction and latent inhibition) compete during retrieval. Consistently, we found that LHb inactivation impaired active defensive responses [platform-mediated avoidance (PMA)], thereby biasing choice behavior (between avoiding a threat or approaching food) toward reward-seeking responses. Together, our findings suggest that LHb activity mediates defensive responses only when guided by competing threat and safety memories, consequently revealing a previously uncharacterized role for LHb in experience-dependent emotional conflict.The perception of our surrounding environment is an amalgamation of stimuli detected by sensory neurons. In Caenorhabditis elegans, olfaction is an essential behavior that determines various behavioral functions such as locomotion, feeding and development. Sensory olfactory cues also initiate downstream neuroendocrine signaling that controls aging, learning, development and reproduction. Innate sensory preferences toward odors (food, pathogens) and reproductive pheromones are modulated by 11 pairs of amphid chemosensory neurons in the head region of C. elegans Amongst these sensory neurons, the ASI neuron has neuroendocrine functions and secretes neuropeptides, insulin-like peptide (DAF-28) and the TGF-β protein, DAF-7. Its expression levels are modulated by the presence of food (increased levels) and population density (decreased levels). A recent study has shown that EXP-1, an excitatory GABA receptor regulates DAF-7/TGF-β levels and participates in DAF-7/TGF-β-mediated behaviors such as aggregation and bordering. Here, we show that exp-1 mutants show defective responses toward AWC-sensed attractive odors in a non-autonomous manner through ASI neurons. Our dauer experiments reveal that in daf-7 mutants, ASI expressed EXP-1 and STR-2 (a G-protein-coupled receptor; GPCR) that partially maintained reproductive growth of animals. Further, studies suggest that neuronal connections between ASI and AWC neurons are allowed at least partially through ASI secreted DAF-7 or through alternate TGF- β pathway/s regulated by EXP-1 and STR-2. Together, our behavioral, genetic and imaging experiments propose that EXP-1 and STR-2 integrate food cues and allow the animals to display DAF-7/TGF-β neuroendocrine dependent or independent behavioral responses contributing to chemosensensory and developmental plasticity. We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520. The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured. All patients had 28.9-30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of -1.7 and -3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with 10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL. MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable. NCT02065336.NCT02065336. Ruptured ovarian cysts are common gynaecological presentation to health institutions with abdominal pain. While this phenomenon is generally self-limiting, surgery may be necessary in cases of haemodynamic compromise or association with torsion. The aim of this audit is to identify the trend of hospital presentations, as well as the review the management of modern gynaecology practice. A retrospective audit of all women who presented to the emergency department with an imaging diagnosis of ruptured ovarian cysts was conducted over a 5-year period at St Vincent's Hospital, Sydney. During the study period, 408 women were identified. There was a trend towards conservative management, as observed in 84.7% of women, while the remaining 15.4% underwent surgery. Haemorrhagic or ruptured corpus luteum was the most common diagnoses. As expected, women who had surgical intervention were more likely to have larger cysts (20 vs 50%; p<0.05), and larger free fluid findings on imaging (1.4 vs 23.8%; p<0.05) compared with those managed conservatively. There were no statistically significant differences in location of ovarian cysts (right or left) or antecedent to hospital presentation (vaginal intercourse or trauma). Ruptured ovarian cysts of both functional and non-functional types remained a common clinical presentation of acute pain for women to the emergency department. Majority of women were managed conservatively in our cohort, and indications for surgery were large ovarian cysts and large free fluid seen on imaging findings. Surgery was largely feasible with minimal complications.Ruptured ovarian cysts of both functional and non-functional types remained a common clinical presentation of acute pain for women to the emergency department. Majority of women were managed conservatively in our cohort, and indications for surgery were large ovarian cysts and large free fluid seen on imaging findings. https://www.selleckchem.com/peptide/gsmtx4.html Surgery was largely feasible with minimal complications.Escherichia coli [2Fe-2S]-ferredoxin and other ISC proteins encoded by the iscRSUA-hscBA-fdx-iscX (isc) operon are responsible for the assembly of iron-sulfur clusters. It is proposed that ferredoxin (Fdx) donates electrons from its reduced [2Fe-2S] center to iron-sulfur cluster biogenesis reactions. However, the underlying mechanisms of the [2Fe-2S] cluster assembly in Fdx remain elusive. Here, we report that Fdx preferentially binds iron, but not the [2Fe-2S] cluster, under cold stress conditions (≤16°C). The iron binding in Fdx is characterized by a unique absorption peak at 320 nm based on UV-visible spectroscopy. In addition, the iron-binding form of Fdx could be converted to the [2Fe-2S] cluster-bound form after transferring cold-stressed cells to normal cultivation temperatures above 25°C. In vitro experiments also revealed that Fdx could utilize bound iron to assemble the [2Fe-2S] cluster by itself. Furthermore, inactivation of the genes encoding IscS, IscU, and IscA did not limit [2Fe-2S] cluster ass single Fe atom at the cluster binding site. link2 Moreover, when temperatures increase, Fdx can assemble clusters by itself from its iron-only binding form in E. coli cells. The possibility remains that Fdx can effectively accept clusters from multiple sources. Nevertheless, our results suggest that Fdx has a strong iron binding activity that contributes to the assembly of its own [2Fe-2S] cluster and that Fdx acts as a temperature sensor to regulate Isc system-mediated iron-sulfur cluster biogenesis.Enterococci are ubiquitous opportunistic pathogens that have become a major public health issue globally. The increasing prevalence of antimicrobial resistance in hospital-adapted enterococci had been thought to originate from livestock. However, this association between livestock and hospital-adapted enterococci is currently unclear. This study investigates the antimicrobial susceptibilities of enterococci isolated from pig cecal samples and compares the genomic characteristics of Enterococcus faecium from pigs to those of isolates from meat chickens and from human sepsis cases. From 200 cecal samples, antimicrobial susceptibility testing was performed for E. faecium (n = 84), E. hirae (n = 36), and E. faecalis (n = 17). Whole-genome sequencing was performed for all E. faecium isolates, and the sequences were compared to those of previously studied isolates from meat chickens and human sepsis cases through bioinformatics analysis. Resistance (non-wild type) to erythromycin, gentamicin, tetracycline, ampicillal resistance was observed. In particular, resistance to quinupristin-dalfopristin, a combination of two streptogramin class antimicrobials, was identified despite the absence of streptogramin use Australia-wide since 2005. Other observed resistance among enterococci from pigs include chloramphenicol, erythromycin, and tetracycline resistance. Genomic comparison of E. faecium from Australian pigs to isolates collected from previous studies on chickens and humans indicate that E. faecium from pigs are genetically more similar to those of humans than those from chickens. Despite the increased genetic similarities, E. link3 faecium strains from pigs are phylogenetically distinct and did not belong to the dominant sequence types found in hospital-adapted strains causing sepsis in humans. Therefore, the results indicate that Australian finisher pigs are not a source of hospital-adapted E. faecium in Australia.
