A computational model of limb impedance control based on principles of internal model uncertainty

Efficient human motor control is characterized by an extensive use of joint impedance modulation, which is achieved by co-contracting antagonistic muscles in a way that is beneficial to the specific task. While there is much experimental evidence available that the nervous system employs such strategies, no generally-valid computational model of impedance control derived from first principles has been proposed so far. Here we develop a new impedance control model for antagonistic limb systems which is based on a minimization of uncertainties in the internal model predictions. In contrast to previously proposed models, our framework predicts a wide range of impedance control patterns, during stationary and adaptive tasks. This indicates that many well-known impedance control phenomena naturally emerge from the first principles of a stochastic optimization process that minimizes for internal model prediction uncertainties, along with energy and accuracy demands. The insights from this computational model could be used to interpret existing experimental impedance control data from the viewpoint of optimality or could even govern the design of future experiments based on principles of internal model uncertainty.     

Mesozoic origin and ‘out-of-India’ radiation of ricefishes (Adrianichthyidae)

The Indian subcontinent has an origin geologically different from Eurasia, but many terrestrial animal and plant species on it have congeneric or sister species in other parts of Asia, especially in the Southeast. This faunal and floral similarity between India and Southeast Asia is explained by either of the two biogeographic scenarios, ‘into-India’ or ‘out-of-India’. Phylogenies based on complete mitochondrial genomes and five nuclear genes were undertaken for ricefishes (Adrianichthyidae) to examine which of these two biogeographic scenarios fits better. We found that Oryzias setnai, the only adrianichthyid distributed in and endemic to the Western Ghats, a mountain range running parallel to the western coast of the Indian subcontinent, is sister to all other adrianichthyids from eastern India and Southeast–East Asia. Divergence time estimates and ancestral area reconstructions reveal that this western Indian species diverged in the late Mesozoic during the northward drift of the Indian subcontinent. These findings indicate that adrianichthyids dispersed eastward ‘out-of-India’ after the collision of the Indian subcontinent with Eurasia, and subsequently diversified in Southeast–East Asia. A review of geographic distributions of ‘out-of-India’ taxa reveals that they may have largely fuelled or modified the biodiversity of Eurasia.     

Vertical distribution of female adults and larval offspring of the white grub <Emphasis Type="Italic">Dasylepida ishigakiensis</Emphasis> (Coleoptera: Scarabaeidae) in the soil of a sugarcane field on Miyako Island,Okinawa

To determine the depth of soil at which mated females of the white grub beetle Dasylepida ishigakiensis Niijima et Kinoshita oviposited and their larval offspring stayed in the soil in different seasons, 847 mated female and male adults were released into a caged sugarcane field on Miyako Island. We then excavated this field systematically to collect adults and their larval offspring in the soil once or twice per month from 24 April 2002 to 31 March 2003. Dead females were found between 10 and 50 cm deep in the soil (N = 91), but most frequently in the layer 30–40 cm deep (N = 42; 46.2%). They were recovered more frequently in the soil at the plant foot (N = 73; 80.2%) than in the furrows (N = 18; 19.8%). On the other hand, no male carcass was discovered either in the soil or on the ground surface. The number of larvae discovered in the soil per row was large on 30 April (N = 52.5) and on 5 June (N = 58.3), when they were at the first instar. It decreased rapidly thereafter until 21 August (N = 9.5), when they molted to the second instar, and remained at similar levels through to the following 31 March (N = 8.0), during which they were mostly at the third instar. The larvae were found at various soil depths ranging from 0 to 70 cm, but the majority were found between 10 and 30 cm deep. The last sampling on 31 March indicated that mature larvae moved to a deeper layer for estivation. These results suggested that physical control through rotary tillage before they move to the deeper layer may be effective.     

Characterization of sarcoplasmic reticulum Ca ATPase nucleotide binding domain mutants using NMR spectroscopy

Sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) is essential for muscle function by transporting Ca²⁺ from the cytosol into the sarcoplasmic reticulum through ATP hydrolysis. In this report, the effects of substitution mutations on the isolated SERCA-nucleotide binding domain (SERCA-N) were studied using NMR. ¹⁵N–¹H HSQC spectra of substitution mutants at the nucleotide binding site, T441A, R560V, and C561A, showed chemical shift changes, primarily in residues adjacent to the mutation sites, indicating only local effects. Further, the patterns of chemical shift changes upon AMP–PNP binding to these mutants were similar to that of the wild type SERCA-N (WT). In contrast to these nucleotide binding site mutants, a mutant found in patients with Darier’s disease, E412G, showed small but significant chemical shift changes throughout the protein and rapid precipitation. However, the AMP–PNP dissociation constant (∼2.5 mM) was similar to that of WT (∼3.8 mM). These results indicate that the E412G mutant retains its catalytic activity but most likely reduces its stability. Our findings provide molecular insight into previous clinical, physiological, and biochemical observations.     

Genetic suppression analysis in novel vacuolar processing enzymes reveals their roles in controlling sugar accumulation in tomato fruits

In plant cells, many vacuolar proteins are synthesized as precursors in the endoplasmic reticulum and are subsequently transported to the vacuole. These precursors are subject to post-translational modifications to allow the active mature forms to be produced. Vacuolar processing enzyme (VPE) has been identified as a family of cysteine proteases involved in protein maturation in the vacuole. In this study, novel VPE genes were isolated from tomato (Solanum lycopersicum), and they were designated SlVPE1-SlVPE5. Phylogenic analysis suggested that SlVPE1 and SlVPE2 were categorized as the seed coat type, SlVPE4 was categorized as the seed type, and both SlVPE3 and SlVPE5 were categorized as the vegetative type. Expression analysis demonstrated that these genes were expressed during fruit development, and that their expression profiles agreed with this classification. High VPE enzyme activity was observed during tomato fruit development; the enzyme activity was correlated with the SlVPE mRNA levels, indicating that the SlVPE encoded active VPE proteins. The total sugar content was higher in RNA interference (RNAi) lines compared with the control plants, suggesting negative roles for SlVPE in sugar accumulation. The quantitative expression analysis of each SlVPE gene in the RNAi lines suggested that the suppression of SlVPE5 probably had the strongest effect on the sugar accumulation observed. The suppression of SlVPE did not influence the total amino acid content, suggesting that the molecular targets of SlVPE were mainly involved in sugar accumulation.     

A Conditional Knockout Toolkit for Caenorhabditis elegans Based on the Cre/loxP Recombination

Conditional knockout (cKO) based on site-specific recombination (SSR) technology is a powerful approach for estimating gene functions in a spatially and temporally specific manner in many model animals. In Caenorhabditis elegans (C. elegans), spatial- and temporal-specific gene functions have been largely determined by mosaic analyses, rescue experiments and feeding RNAi methods. To develop a systematic and stable cKO system in C. elegans, we generated Cre recombinase expression vectors that are driven by various tissue-specific or heat-shock promoters. Validation using Cre-mediated fluorescence protein inactivation or activation systems demonstrated successful Cre-dependent loxP excision. We established a collection of multi-copy Cre transgenic strains for each evaluated vector. To evaluate our Cre/loxP-based cKO system, we generated sid-1 deletion mutants harboring floxed sid-1 single-copy integration (SCI) using ultraviolet trimethylpsoralen (UV/TMP) methods. sid-1 mutants that were rescued by the floxed sid-1 SCI were then crossed with the Pdpy-7::Cre strain for cKO in the hypodermis. The sid-1 cKO animals were resistant to bli-3 RNAi, which causes the Bli-phenotyple in the hypodermis, but they were sensitive to unc-22 RNAi, which leads to twitching of the body wall muscle. Our system, which is based on the combination of a transgenic Cre collection, pre-existing deletion mutants, and UV/TMP SCI methods, provided a systematic approach for cKO in C. elegans.     

Identification of asymptomatic Entamoeba histolytica infection by a serological screening test: A cross-sectional study of an HIV-negative men who have sex with men cohort in Japan

BackgroundAmebiasis, caused by Entamoeba histolytica, is spreading in developing countries and in many developed countries as a sexually transmitted infection. Here, we evaluated the efficacy of serological screening to identify asymptomatic E. histolytica infection as a potential epidemiological control measure to limit its spread.Methodology/Principal findingsThis cross-sectional study was carried out between January and March 2021 in an HIV-negative men who have sex with men (MSM) cohort at the National Center for Global Health and Medicine. Serological screening was performed using a commercially available ELISA kit. For seropositive individuals, we performed stool polymerase chain reaction (PCR) to determine current E. histolytica infection. We performed E. histolytica serological screening of 312 participants. None had a history of E. histolytica infection prior to the study. The overall E. histolytica seropositivity was 6.7% (21/312), which was similar to that found by the rapid plasma reagin test (17/312). We identified current infection in 8 of 20 seropositive participants (40.0%) by stool PCR.Conclusions/SignificanceOur serological screening approach constitutes a potentially practical epidemiological strategy. Active epidemiological surveys, in combination with an effective screening strategy for asymptomatically infected individuals, should be applied to help reduce sexually transmitted E. histolytica infections.     

A new gain‐of‐function mouse line to study the role of Wnt3a in development and disease

Wnt/β‐catenin signals are important regulators of embryonic and adult stem cell self‐renewal and differentiation and play causative roles in tumorigenesis. Purified recombinant Wnt3a protein, or Wnt3a‐conditioned culture medium, has been widely used to study canonical Wnt signaling in vitro or ex vivo. To study the role of Wnt3a in embryogenesis and cancer models, we developed a Cre recombinase activatable Rosa26^Wnt3a allele, in which a Wnt3a cDNA was inserted into the Rosa26 locus to allow for conditional, spatiotemporally defined expression of Wnt3a ligand for gain‐of‐function (GOF) studies in mice. To validate this reagent, we ectopically overexpressed Wnt3a in early embryonic progenitors using the T‐Cre transgene. This resulted in up‐regulated expression of a β‐catenin/Tcf‐Lef reporter and of the universal Wnt/β‐catenin pathway target genes, Axin2 and Sp5. Importantly, T‐Cre; Rosa26^Wnt3a mutants have expanded presomitic mesoderm (PSM) and compromised somitogenesis and closely resemble previously studied T‐Cre; Ctnnb1^ex3 (β‐catenin^GOF) mutants. These data indicate that the exogenously expressed Wnt3a stimulates the Wnt/β‐catenin signaling pathway, as expected. The Rosa26^Wnt3a mouse line should prove to be an invaluable tool to study the function of Wnt3a in vivo.     

Efficacy of agar-plate culture in detection of Strongyloides stercoralis infection

Agar-plate culture of feces using a modified petri dish proved to be highly efficient in the detection of Strongyloides stercoralis infection. Furrows left by S. stercoralis on the agar plate were distinguished readily in size from those left by Necator americanus.     

Identification of the N-terminal residue of the heavy chain of both native and recombinant human hepatocyte growth factor.

The N-terminal amino acid of the heavy chain of native (purified from human plasma) and recombinant human hepatocyte growth factor (hHGF) was determined by analyses of amino acid composition and sequence of peptide fragments derived by enzymatic cleavage, peptide mapping, and fast atom bombardment mass spectrometry. Our results indicate that the N-terminal amino acid of the heavy chain of hHGF, both native and recombinant, is pyroglutamate, derived from glutamine at the 32nd residue from the initiation methionine.