Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression.

We describe here the molecular mechanisms by which juvenile experience defines patterns of sexually dimorphic synaptic connectivity in the adult nervous system of the nematode C. elegans. We show that starvation of juvenile males disrupts serotonin-dependent activation of the CREB transcription factor in a nociceptive sensory neuron, PHB. CREB acts through a cascade of transcription factors to control expression of an atypical cadherin protein, FMI-1/Flamingo. During postembryonic development, FMI-1/Flamingo has the capacity to promote and maintain synaptic connectivity of the PHB nociceptive sensory to a command interneuron, AVA, in both sexes, but the serotonin transcriptional regulatory cassette antagonizes FMI-1/Flamingo expression in males, thereby establishing sexually dimorphic connectivity between PHB and AVA. A critical regulatory node in this process is the CREB-target LIN-29, a Zn finger transcription factor which integrates four different layers of information - sexual specificity, past feeding status, time and cell-type specificity. Our findings provide the mechanistic details of how an early juvenile experience defines sexually dimorphic synaptic connectivity.

Toolkits for detailed and high-throughput interrogation of synapses in C. elegans.

Visualizing synaptic connectivity has traditionally relied on time-consuming electron microscopy-based imaging approaches. To scale the analysis of synaptic connectivity, fluorescent protein-based techniques have been established, ranging from the labeling of specific pre- or post-synaptic components of chemical or electrical synapses to transsynaptic proximity labeling technology such as GRASP and iBLINC. In this paper, we describe WormPsyQi, a generalizable image analysis pipeline that automatically quantifies synaptically localized fluorescent signals in a high-throughput and robust manner, with reduced human bias. We also present a resource of 30 transgenic strains that label chemical or electrical synapses throughout the nervous system of the nematode Caenorhabditis elegans, using CLA-1, RAB-3, GRASP (chemical synapses), or innexin (electrical synapse) reporters. We show that WormPsyQi captures synaptic structures in spite of substantial heterogeneity in neurite morphology, fluorescence signal, and imaging parameters. We use these toolkits to quantify multiple obvious and subtle features of synapses - such as number, size, intensity, and spatial distribution of synapses - in datasets spanning various regions of the nervous system, developmental stages, and sexes. Although the pipeline is described in the context of synapses, it may be utilized for other 'punctate' signals, such as fluorescently tagged neurotransmitter receptors and cell adhesion molecules, as well as proteins in other subcellular contexts. By overcoming constraints on time, sample size, cell morphology, and phenotypic space, this work represents a powerful resource for further analysis of synapse biology in C. elegans.

Dietary replacement of soybean meal with black soldier fly larvae meal in juvenile Labeo rohita and Catla catla: Effects on growth, nutritional quality, oxidative stress biomarkers and disease resistance.

This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0

Marine life as a source for breast cancer treatment: A comprehensive review.

Breast cancer, one of the most significant tumors among all cancer cells, still has deficiencies for effective treatment. Moreover, substitute treatments employing natural products as bioactive metabolites has been seriously considered. The source of bioactive metabolites are not only the most numerous but also represent the richest source. A unique source is from the oceans or marine species which demonstrated intriguing chemical and biological diversity which represents an astonishing reserve for discovering novel anticancer drugs. Notably, marine sponges produce the largest amount of diverse bioactive peptides, alkaloids, terpenoids, polyketides along with many secondary metabolites whose potential is mostly therapeutic. In this review, our main focus is on the marine derived secondary metabolites which demonstrated cytotoxic effects towards numerous breast cancer cells and have been isolated from the marine sources such as marine sponges, cyanobacteria, fungi, algae, tunicates, actinomycetes, ascidians, and other sources of marine organisms.

Microswimmer Combing: Controlling Interfacial Dynamics for Open-Surface Multifunctional Screening of Small Animals.

Image-based screening of multicellular model organisms is critical for both investigating fundamental biology and drug development. Current microfluidic techniques for high-throughput manipulation of small model organisms, although useful, are generally complicated to operate, which impedes their widespread adoption by biology laboratories. To address this challenge, this paper presents an ultrasimple and yet effective approach, "microswimmer combing," to rapidly isolate live small animals on an open-surface array. This approach exploits a dynamic contact line-combing mechanism designed to handle highly active microswimmers. The isolation method is robust, and the device operation is simple for users without a priori experience. The versatile open-surface device enables multiple screening applications, including high-resolution imaging of multicellular organisms, on-demand mutant selection, and multiplexed chemical screening. The simplicity and versatility of this method provide broad access to high-throughput experimentation for biologists and open up new opportunities to study active microswimmers by different scientific communities.

Incidence, Predictors, and Prognosis of Acute Kidney Injury Among Cardiac Arrest Survivors.

BACKGROUND: Acute kidney injury (AKI) is common among cardiac arrest survivors. However, the outcomes and predictors are not well studied. METHODS: This is a cohort study of cardiac arrest patients enrolled from January 2012 to December 2016 who were able to survive for 24 hours post-cardiopulmonary resuscitation. Patients with anuria, chronic kidney disease (stage 5), and end-stage renal disease were excluded. Acute kidney injury (stage 1) or higher was defined using Kidney Disease: Improving Global Outcomes classification. Multivariable adjusted regression models were used to compute hazard ratio (HR) for association of AKI with risk of mortality and odds ratio (OR) with risk of poor neurological outcomes after adjusting for demographics, comorbidities, and medical therapy. Multivariable logistic regression model was used to compute OR for association of various predictors with AKI. RESULTS: Of 842 cardiac arrest survivors, 588 (69.8%) developed AKI. Among AKI patients, 69.4% died compared with 52.0% among non-AKI patients. In multivariable adjusted Cox proportional hazard model, development of AKI post-cardiac arrest was significantly associated with mortality (HR: 1.35; 95% confidence interval [CI]: 1.07-1.71, P = .01) and poor neurological outcomes defined as cerebral performance category >2 (OR: 2.27; 95% CI: 1.45-3.57, P < .001) and modified Rankin scale >3 (OR: 2.22; 95% CI: 1.43-3.45, P < .001). Postdischarge dialysis was also associated with increased risk of mortality (HR: 2.57; 95% CI: 1.57-4.23, P < .001). Use of vasopressors was strongly associated with development of AKI and continued need for postdischarge dialysis. CONCLUSIONS: Acute kidney injury was associated with increased risk of mortality and poor neurological outcomes. There is need for further studies to prevent AKI in cardiac arrest survivors.

Psychometric Assessment of the Urdu Version of the Index of Dental Anxiety and Fear.

BACKGROUND: The objective of the current study was to adapt the Index of Dental Anxiety and Fear (IDAF-4C) in the Urdu language and measure its validity and reliability. METHODS: Original English questionnaire of IDAF-4C was translated into Urdu language by a panel of dentists and language experts (Urdu and English) followed by critical evaluation, modification and back translation into English language. A final Urdu questionnaire was distributed among 250 patients visiting the Endodontics section at Margalla Institute of Health Sciences (MIHS), Rawalpindi, Pakistan. Cronbach's alpha was used to determine the reliability of the Index whereas validity was assessed by exploratory factor analysis (EFA). Mean rank scores of IDAF-4C for male and female participants were evaluated using Mann-Whitney U tests (P < 0.05). RESULTS: Of 250 questionnaires, 209 were returned with a response rate of 84%. Cronbach's alpha for the Urdu version of IDAF-4C was 0.88. Exploratory factor analysis of the IDAF-4C revealed one factor explaining 55.55% of the common variance (Eigenvalue = 4.5). The mean rank scores of all eight items of IDAF-4C were greater for female participants as compared to male participants with a statistically significant association (P < 0.05). CONCLUSION: The psychometric analysis of the Urdu version of IDAF-4C showed good reliability and consistency compared to the original version as well as other translated versions.

A study of 99mTc/Re-tricarbonyl complexes of 4-amino-1,8-naphthalimides.

Three 4-amino-1,8-naphthalimide analogues were synthesized, consisting of the tridentate chelators di-2-picolylamine, (pyridin-2-ylmethyl)glycinate, and iminodiacetate conjugated to the naphthalimide scaffold. Coordination with fac-99mTc/Re(CO)3 resulted in metal complexes with overall charges of -1, 0, or +1. Upon coordination of Re(i), the initial naphthalimide-based fluorescence is largely maintained for both negative and neutral complexes compared to their free ligand forms, while an increase in fluorescence quantum yield was observed for the positively charged complex. OVCAR-8 ovarian cancer cells were stained with each of the complexes, demonstrating that the positive complex is more lipophilic and cell membrane permeable than the neutral and negative complexes. Each of the three technetium-99m labelled naphthalimide complexes were successfully produced from fac-[99mTc(CO)3(H2O)3]+ in 15 minutes at 70 °C and isolated in radiochemical yields ranging from 60-95% with radiochemical purities greater than 95%. These fluorescent metal complexes of various charges can be used to tune pharmacokinetic and cellular uptake properties of 99mTc/Re-naphthalimide-bioconjugates, while still maintaining desirable fluorescence properties.

Proteomic Profiling and the Predicted Interactome of Host Proteins in Compatible and Incompatible Interactions Between Soybean and Fusarium virguliforme.

Sudden death syndrome (SDS) is a complex of two diseases of soybean (Glycine max), caused by the soil borne pathogenic fungus Fusarium virguliforme. The root rot and leaf scorch diseases both result in significant yield losses worldwide. Partial SDS resistance has been demonstrated in multiple soybean cultivars. This study aimed to highlight proteomic changes in soybean roots by identifying proteins which are differentially expressed in near isogenic lines (NILs) contrasting at the Rhg1/Rfs2 locus for partial resistance or susceptibility to SDS. Two-dimensional gel electrophoresis resolved approximately 1000 spots on each gel; 12 spots with a significant (P < 0.05) difference in abundance of 1.5-fold or more were picked, trypsin-digested, and analyzed using quadruple time-of-flight tandem mass spectrometry. Several spots contained more than one protein, so that 18 distinct proteins were identified overall. A functional analysis performed to categorize the proteins depicted that the major pathways altered by fungal infection include disease resistance, stress tolerance, and metabolism. This is the first report which identifies proteins whose abundances are altered in response to fungal infection leading to SDS. The results provide valuable information about SDS resistance in soybean plants, and plant partial resistance responses in general. More importantly, several of the identified proteins could be good candidates for the development of SDS-resistant soybean plants.