Insulin-like peptides (ILPs) play highly conserved roles in development and physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms for how the forty Caenorhabditis elegans ILPs coordinate diverse processes, including development, reproduction, longevity and several specific stress responses. Our systematic studies identify an ILP-based combinatorial code for these phenotypes characterized by substantial functional specificity and diversity rather than global redundancy. Notably, we show that ILPs regulate each other transcriptionally, uncovering an ILP-to-ILP regulatory network that underlies the combinatorial phenotypic coding by the ILP family. Extensive analyses of genetic interactions among ILPs reveal how their signals are integrated. A combined analysis of these functional and regulatory ILP interactions identifies local genetic circuits that act in parallel and interact by crosstalk, feedback and compensation. This organization provides emergent mechanisms for phenotypic specificity and graded regulation for the combinatorial phenotypic coding we observe. Our findings also provide insights into how large hormonal networks regulate diverse traits.

A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.

A new automated microfluidic platform can deliver a wide range of mechanical stimuli for functional neural imaging in C. elegans.

IntroductionCameroon is classified by the World Health Organization (WHO) as having a critical shortage of health personnel. This is further complicated by the geographic distributional inequalities of the national health workforce. This shortfall impedes Cameroons’ progress of improving the human resources for health (HRH) to meet up with the Millennium Development Goals (MDGs) by 2015. However, it is unknown whether the health workforce of Cameroon is distributed equally across geographic regions. Additionally, indicators other than population levels have not been used to measure health care needs. This study aimed to assess the adequacy, evenness of distribution and challenges faced by the health workforce across the different regions of Cameroon.MethodsNational health personnel availability and distribution were assessed by use of end-of-year census data for 2011 obtained from the MoPH data base. The inequalities and distribution of the workforce were estimated using Gini coefficient and Lorenz curve and linear regression was used to determine the relation between health personnel density and selected health outcomes. Alternative indicators to determine health care needs were illustrated using concentration curves.ResultsSignificant geographic inequalities in the availability of health workforce exist in Cameroon. Some regions have a higher number of physicians (per person) than others leading to poor health outcomes across the regions. 70 % of regions have a density of health personnel-to-population per 1,000 that is less than 1.5, implying acute shortage of health personnel. Poor working and living conditions, coupled with limited opportunities for career progress accounted for some documented 232 physicians and 205 nurses that migrated from the public sector. Significant distributional inequality was noticed when under-five infant mortality and malaria prevalence rate were used as indicators to measure health care needs.ConclusionOur results show an absolute shortage of public health personnel in Cameroon that is further complicated by the geographic distributional inequalities across the regions of the nation. Cameroon aims to achieve universal health coverage by 2035; to realize this objective, policies targeting training, recruitment, retention and effective deployment of motivated and supported health workforce as well as the development and improvement of health infrastructures remain the major challenge.