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The integration of theory and data drives progress in science, but a persistent barrier to such integration in ecology and evolutionary biology is that theory is often developed and expressed in the form of mathematical models that can feel daunting and inaccessible for students and empiricists with variable quantitative training and attitudes towards math. A promising way to make mathematical models more approachable is to embed them into interactive tools with which one can visually evaluate model structures and directly explore model outcomes through simulation. To promote such interactive learning of quantitative models, we developed EcoEvoApps, a collection of free, open‐source, and multilingual R/Shiny apps that include model overviews, interactive model simulations, and code to implement these models directly in R. The package currently focuses on canonical models of population dynamics, species interactions, and landscape ecology. These apps help illustrate fundamental results from theoretical ecology and can serve as valuable teaching tools in classroom settings. We present data from student surveys which show that students rate these apps as useful learning tools, and that using interactive apps leads to substantial gains in students' interest and confidence in working with mathematical models. This points to the potential for interactive activities to make theoretical models more accessible to a wider audience, and thus facilitate the feedback between theory and data across ecology and evolutionary biology. [ABSTRACT FROM AUTHOR]

The article presents a complete analysis of the different negative mutations and haploefficiency taking place in [alpha]-II spectrin, STXBP1. These mutations are shown to lead to the onset of west syndrome with severe cerebral hypomyelination, spastic quadriplegia and developmental delay in humans.

Key points: The mature functioning of the primary visual cortex depends on postnatal visual experience, while the orientation/direction preference is established just after eye‐opening, independently of visual experience.In this study, we find that visual experience is required for the normal development of spatial‐frequency (SF) preference in mouse primary visual cortex.We show that age‐ and experience‐dependent shifts in optimal SFs towards higher frequencies occurred similarly in excitatory neurons and parvalbumin‐positive interneurons.We also show that some excitatory and parvalbumin‐positive neurons preferentially responded to visual stimuli consisting of very high SFs and posterior directions, and that the preference was established at earlier developmental stages than the SF preference in the standard frequency range.These results suggest that early visual experience is required for the development of SF representation and shed light on the experience‐dependent developmental mechanisms underlying visual cortical functions. Early visual experience is crucial for the maturation of visual cortical functions. It has been demonstrated that the orientation and direction preferences in individual neurons of the primary visual cortex are well established immediately after eye‐opening. The postnatal development of spatial frequency (SF) tuning and its dependence on visual experience, however, has not been thoroughly quantified. In this study, macroscopic imaging with flavoprotein autofluorescence revealed that the optimal SFs shift towards higher frequency values during normal development in mouse primary visual cortex. This developmental shift was impaired by binocular deprivation during the sensitive period, postnatal 3 weeks (PW3) to PW6. Furthermore, two‐photon Ca2+ imaging revealed that the developmental shift of the optimal SFs, depending on visual experience, concurrently occurs in excitatory neurons and parvalbumin‐positive inhibitory interneurons (PV neurons). In addition, some excitatory and PV neurons exhibited a preference for visual stimuli consisting of particularly high SFs and posterior directions at relatively early developmental stages; this preference was not affected by binocular deprivation. Thus, there may be two distinct developmental mechanisms for the establishment of SF preference depending on the frequency values. After PW3, SF tuning for neurons tuned to standard frequency ranges was sharper in excitatory neurons and slightly broader in PV neurons, leading to considerably attenuated SF tuning in PV neurons compared to excitatory neurons by PW5. Our findings suggest that early visual experience is far more important than orientation/direction selectivity for the development of the neural representation of the diverse SFs. Key points: The mature functioning of the primary visual cortex depends on postnatal visual experience, while the orientation/direction preference is established just after eye‐opening, independently of visual experience.In this study, we find that visual experience is required for the normal development of spatial‐frequency (SF) preference in mouse primary visual cortex.We show that age‐ and experience‐dependent shifts in optimal SFs towards higher frequencies occurred similarly in excitatory neurons and parvalbumin‐positive interneurons.We also show that some excitatory and parvalbumin‐positive neurons preferentially responded to visual stimuli consisting of very high SFs and posterior directions, and that the preference was established at earlier developmental stages than the SF preference in the standard frequency range.These results suggest that early visual experience is required for the development of SF representation and shed light on the experience‐dependent developmental mechanisms underlying visual cortical functions. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the locations of lymph node recurrence and their association with irradiation fields used for radiotherapy after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma. Methods: Medical records of 96 consecutive patients with superficial esophageal squamous cell carcinoma who underwent adjuvant chemoradiotherapy following endoscopic resection were reviewed. Computed tomography was used to identify whether nodal recurrences were within the elective nodal irradiation field. The cumulative incidence of recurrence was calculated, accounting for death as a competing risk. Univariate and multivariate analyses identified factors predicting nodal recurrence. Results: The median follow‐up period was 61 months (range: 6‐137 months). Seven patients (7.3%) developed lymph node recurrence only; two patients (2.1%) developed nodal plus local recurrence. Six of the seven cases without local recurrence involved the elective nodal irradiation field, with five cases involving the recurrent nerve lymph nodes. The 5‐year cumulative incidence of lymph node recurrence was higher for T1b tumors with lymphovascular invasion than for T1a tumors with lymphovascular invasion (17.6% vs 6.2%, P = 0.086; HR: 3.74, 95% CI: 0.80‐17.52, P = 0.094) and T1b tumors without lymphovascular invasion (17.6% vs 3.3%, P = 0.031; HR: 6.78, 95% CI: 0.80‐57.63, P = 0.080). Conclusions: Lymph node recurrence frequently involved the elective nodal irradiation field, with recurrent nerve lymph nodes being common metastasis sites. The high incidence of nodal recurrence for T1b tumors with lymphovascular invasion highlights a need for new strategies for treating this subset of superficial esophageal squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

Compact phased-array antennas embedded in flip-chip ball grid array (BGA) packages are proposed to operate over the unlicensed 60 GHz frequency band. Radiation properties are enhanced by designing novel corrugated soft-surface structures and implementing them using the low-temperature co-fired ceramic process with no extra cost and fabrication complexity. This is achieved by adjusting via land diameters of periodic grounded vias in top four layers of the package, which in fact create perfect magnetic boundaries between the phased-array antenna elements to modify the electric near-field distributions and consequently improve far-field characteristics including gain, cross polarization, sidelobe level, and beam steering. Low-loss transitions from flip-chip IC to antenna elements are designed with less than 0.1 dB amplitude and 2° phase imbalance over 50–70 GHz. Prototypes with/without soft-surface structures are fabricated to work with flip-chip ICs with/without switches. A USB-interface adapter and a waveguide-interface module with a compact vertical power combiner are proposed for the first time to experimentally evaluate the phased-array antenna while connected to the flip-chip RF IC. Significant miniaturizations and improvements are achieved over the wide frequency range of 56–67 GHz, demonstrating up to 7 dB reduction in sidelobe level, up to 4 dB reduction in cross polarization, and up to 3 dB enhancement in gain at different directions. [ABSTRACT FROM AUTHOR]

The axon initial segment ( AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 ( MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells. Interestingly, during early postnatal development, colocalization of MTCL1 with these stable MT bundles was observed prominently in the axon hillock and proximal axon. These results indicate that MTCL1-mediated formation of stable MT bundles is crucial for maintenance of AnkG localization. We also demonstrate that Mtcl1 gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia. [ABSTRACT FROM AUTHOR]

Background: Higher daytime cortisol levels because of a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts.Aims: To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method.Method: The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement.Results: Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected).Conclusions: Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits. [ABSTRACT FROM AUTHOR]

The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects. [ABSTRACT FROM AUTHOR]

Background/Aims: We examined sex differences in prevalence, progression, and improvement in early-stage chronic kidney disease (CKD). Methods: We analyzed data from 533 participants who took 4 consecutive annual CKD detection tests. Results: Urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and hemoglobin (Hb) at baseline in men with and without CKD and in women with and without CKD were 8.3±6.1, 149.2±310.4, 10.2±5.8, and 96.7±246.8 mg/g Cr; 83.4±14.7, 63.8±18.8, 79.9±13.0, and 69.4±20.0 mL/min/1.73 m2; and 14.8±1.2, 14.3±1.4, 13.0±1.0, and 13.0±1.2 mg/dL, respectively. ACR levels decreased significantly over time in men and women with CKD and they increased significantly over time in men and women without CKD. eGFR levels in men and women with CKD did not significantly change over time, but they decreased significantly over time in men and women without CKD. CKD prevalence and progression rate were not significantly different between sexes. Among the CKD participants, significantly more women had a 'cured' status at 3 years (39.1% vs. 19.4%, P<0.01). Most whose eGFR increased to >60 mL/min/1.73 m2 at 3 years had values just below those at baseline. Regression analysis showed that change in eGFR correlated significantly with ACR in men with CKD (change in eGFR = -1.707+0.022×ACR, P<0.001, r2=0.201) and with Hb and ACR in women with CKD (change in eGFR = 48.870-3.803×Hb + 0.018×ACR, P<0.05, r2=0.134). Conclusions: These results suggest that the slight decrease of Hb within a normal range and mild anemia can be managed in women with early-stage CKD. The key baseline for eGFR is 60 mL/min/1.73 m2. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05). No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association between the COMT gene Val158Met and the white matter abnormalities found in the temporal lobe of patients with MDD. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to investigate the difference in white matter between smokers and nonsmokers. In addition, we examined relationships between white matter integrity and nicotine dependence parameters in smoking subjects. Nineteen male smokers were enrolled in this study. Eighteen age-matched non-smokers with no current or past psychiatric history were included as controls. Diffusion tensor imaging scans were performed, and the analysis was conducted using a tract-based special statistics approach. Compared with nonsmokers, smokers exhibited a significant decrease in fractional anisotropy (FA) throughout the whole corpus callosum. There were no significant differences in radial diffusivity or axial diffusivity between the two groups. There was a significant negative correlation between FA in the whole corpus callosum and the amount of tobacco use (cigarettes/day; R = − 0.580, p = 0.023). These results suggest that the corpus callosum may be one of the key areas influenced by chronic smoking. [ABSTRACT FROM AUTHOR]

Objective: Electroconvulsive therapy (ECT) has proven to be effective in treatment-resistant depression (TRD). In recent reports, 70% to 90% of patients with TRD responded to ECT. However, post-ECT relapse Is a significant problem. There are no studies investigating risk factors associated with reintroducing ECT in depressive patients after remission previously achieved with former ECT. The aim of the present study is to examine such risk factors using a sample of TRD patients. Methods: We conducted a chart review to examine patient outcomes and adverse events over short- and long-term periods. Forty-two patients met the criteria for major depressive disorder. Results: The response rate was 85.7% (36/42). There were no significant differences in the baseline characteristics of patients exhibiting remission, response or non-response. The rate of adverse events was 21.4% (9/42). Among 34 patients who were available for follow-up, 18 patients relapsed (relapse rate, 52.9%), and 6 patients were reintroduced to ECT. The patients' age and age of onset were significantly higher In the re-ECT group than non re-ECT group. Conclusion: Our results suggest that older age and older age of onset might be considered for requirement of re-ECT after remission previously achieved with former ECT. [ABSTRACT FROM AUTHOR]

Objective: To study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia. Participants: Sixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study. Methods: We used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results. Results: We found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration. Conclusion: Taking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways. [ABSTRACT FROM AUTHOR]

Dendritic spines are postsynaptic structures that receive excitatory synaptic input from presynaptic terminals. Actin and its regulatory proteins play a central role in morphogenesis of dendritic spines. In addition, recent studies have revealed that microtubules are indispensable for the maintenance of mature dendritic spine morphology by stochastically invading dendritic spines and regulating dendritic localization of p140Cap, which is required for actin reorganization. However, the regulatory mechanisms of microtubule dynamics remain poorly understood. Partitioning-defective 1b (PAR1b), a cell polarity-regulating serine/threonine protein kinase, is thought to regulate microtubule dynamics by inhibiting microtubule binding of microtubule-associated proteins. Results from the present study demonstrated that PAR1b participates in the maintenance of mature dendritic spine morphology in mouse hippocampal neurons. Immunofluorescent analysis revealed PAR1b localization in the dendrites, which was concentrated in dendritic spines of mature neurons. PAR1b knock-down cells exhibited decreased mushroom-like dendritic spines, as well as increased filopodia-like dendritic protrusions, with no effect on the number of protrusions. Live imaging of microtubule plus-end tracking proteins directly revealed decreases in distance and duration of microtubule growth following PAR1b knockdown in a neuroblastoma cell line and in dendrites of hippocampal neurons. In addition, reduced accumulation of GFP-p140Cap in dendritic protrusions was confirmed inPAR1b knock-down neurons. In conclusion, the present results suggested a novel function for PAR1b in the maintenance of mature dendritic spine morphology by regulating microtubule growth and the accumulation of p140Cap in dendritic spines. [ABSTRACT FROM AUTHOR]

Depletion of intracellular calcium (Ca2+) stores induces store-operated Ca2+ (SOC) entry across the plasma membrane (PM). STIM1, a putative Ca2+ sensor in the endoplasmic reticulum (ER), has been recently shown to be necessary for SOC channel activation. Here we show that STIM1 dynamically moves in tubulovesicular shape on the ER and its subcompartment in resting living cells, whereas, upon Ca2+ store depletion, it is rapidly redistributed into discrete puncta that are located underneath, but not inserted into the PM. Normal constitutive movement of STIM1 is mediated through the coiled-coil and Ser/Thr-rich C-terminal domains in the cytoplasmic region of STIM1, whereas subsequent inducible puncta formation further requires the sterile α motif domain protruding into the ER lumen. Each of these three domains (coiled-coil, Ser/Thr-rich, and sterile α motif) was essential for activating SOC channels. Hence, our findings based on structure-function experiments suggest that constitutive dynamic movement of STIM1 in the ER and its subcompartment is obligatory for subsequent depletion-dependent redistribution of STIM1 into puncta underneath the PM and activation of SOC channels. [ABSTRACT FROM AUTHOR]

Cells communicate with each other to form organized structures by cell–cell adhesion and cell–cell repulsion, but it remains to be clarified how cell–cell contact information is converted into intracellular signals. Here, we show that cells in contact with neighbouring cells generate local transient intracellular Ca2+ signals (Ca2+ lightning). Ca2+ lightning was observed near cell–cell contact regions and was not observed in the central regions of cells or in solitary cells that were not in contact with other cells. We also show that Ca2+ lightning is able to regulate cell–cell repulsion by means of PYK2, a Ca2+-activated protein tyrosine kinase, which induces focal adhesion disassembly in a Ca2+-dependent manner. These results show that cell–cell contact information might be transmitted by Ca2+ lightning to regulate intracellular events. [ABSTRACT FROM AUTHOR]

Restenosis is the major clinical problem of angioplasty. We have previously shown that neointima formation is strikingly suppressed in midkine (MK)-deficienL mice. Neointima formation is restored if MK protein is administrated to the deficient mice. MK is a heparin-binding growth factor and implicated in the migration of inflammatory cells and vascular smooth muscle cells. Consistently, the suppression of neointima formation in the deficient mice is accompanied by suppression of recruitment of inflammatory cells into the vascular wall. Here, we evaluated the potential of MK antisense oligodeoxyribonucleotide (ODN) for the prevention of restenosis. We cloned the cDNA of rabbit MK, which showed a strongly conserved sequence in mammals. The balloon injury induced MK expression, with the maximum level occurring 7–14 days after angioplasty, in the rabbit carotid artery. Two antisense ODNs suppressed the production of MK in a rabbit kidney cell line, RK13 cells, one of which was then transfected into the arterial wall by means of lipofection immediately after balloon treatment. The antisense ODN suppressed MK induction in vivo and consequently suppressed neointima formation to 60% of the control level. These results suggest that MK is a candidate molecular target for the therapy for vascular restenosis. [ABSTRACT FROM AUTHOR]

SUMMARY:The complete amino acid sequence of phospholipase A2 (PLA2) from the pyloric ceca of the starfish Asterina pectinifera was determined by automated Edman degradation. The A. pectinifera PLA2 (APLA2) consists of 137 amino acids with an unblocked N-terminus and its molecular weight is calculated to be 15 300.1. The enzyme contains 14 cysteine (Cys) residues at the corresponding positions of the same residues which have been shown to be involved in intramolecular disulfide bonds in mammalian pancreatic PLA2. The region involving an active site and a Ca2+-binding loop shows fairly high sequence homology (75%) between the APLA2 and porcine pancreatic PLA2. The APLA2 conserved the amino acid sequence of the loop portion of the porcine pancreatic PLA2 except for the deletion of two amino acids. These features indicate that the APLA2 can be classified into the group 1 type PLA2. In contrast, the homology between the APLA2 and porcine pancreatic PLA2 was calculated to be 47% in the whole region. Further, the insertion of sixteen residues and the deletion of three residues were required in the sequence of the APLA2 to align the corresponding region to the β-wing of porcine pancreatic PLA2. These differences in amino acid sequence of the APLA2 may account for its specific properties such as the higher activity and the characteristic substrate specificity. [ABSTRACT FROM AUTHOR]

Pea mutant E135 (sym15) forms ineffective (Fix−) nodules that lack nitrogen fixing activity. To determine the developmental step blocked in E135 nodules we studied the nitrogenase activities in isolated bacteroids and in cell-free extracts of bacteroids, and measured the two components of nitrogenase protein in bacteroids. Bacteroids prepared anaerobically from E135 nodules showed no acetylene reduction activity in the presence and absence of myoglobin. Furthermore, no acetylene reduction activity by cell-free extracts of E135 bacteroids was detected in the presence of ATP-generating system and dithionite. However, immuno-blotting analyses revealed the presence of nitrogenase components I and II in E135 nodule bacteroids. These results suggest that a host plant gene is involved in the expression of nitrogenase activity in symbiotic bacteria. [ABSTRACT FROM AUTHOR]