The guanine nucleotide exchange factor Arhgef7/beta Pix promotes axon formation upstream of TC10

The characteristic six layers of the mammalian neocortex develop sequentially as neurons are generated by neural progenitors and subsequently migrate past older neurons to their final position in the cortical plate. One of the earliest steps of neuronal differentiation is the formation of an axon. Small GTPases play essential roles during this process by regulating cytoskeletal dynamics and intracellular trafficking. While the function of GTPases has been studied extensively in cultured neurons and in vivo much less is known about their upstream regulators. Here we show that Arhgef7 (also called \u3b2Pix or Cool1) is essential for axon formation during cortical development. The loss of Arhgef7 results in an extensive loss of axons in cultured neurons and in the developing cortex. Arhgef7 is a guanine-nucleotide exchange factor (GEF) for Cdc42, a GTPase that has a central role in directing the formation of axons during brain development. However, active Cdc42 was not able to rescue the knockdown of Arhgef7. We show that Arhgef7 interacts with the GTPase TC10 that is closely related to Cdc42. Expression of active TC10 can restore the ability to extend axons in Arhgef7-deficient neurons. Our results identify an essential role of Arhgef7 during neuronal development that promotes axon formation upstream of TC10

A Standard Platform for Testing and Comparison of MDAO Architectures

The Multidisciplinary Design Analysis and Optimization (MDAO) community has developed a multitude of algorithms and techniques, called architectures, for performing optimizations on complex engineering systems which involve coupling between multiple discipline analyses. These architectures seek to efficiently handle optimizations with computationally expensive analyses including multiple disciplines. We propose a new testing procedure that can provide a quantitative and qualitative means of comparison among architectures. The proposed test procedure is implemented within the open source framework, OpenMDAO, and comparative results are presented for five well-known architectures: MDF, IDF, CO, BLISS, and BLISS-2000. We also demonstrate how using open source soft- ware development methods can allow the MDAO community to submit new problems and architectures to keep the test suite relevant

Rotational superradiant scattering in a vortex flow

When an incident wave scatters off of an obstacle, it is partially reflected and partially transmitted. In theory, if the obstacle is rotating, waves can be amplified in the process, extracting energy from the scatterer. Here we describe in detail the first laboratory detection of this phenomenon, known as superradiance 1, 2, 3, 4. We observed that waves propagating on the surface of water can be amplified after being scattered by a draining vortex. The maximum amplification measured was 14% ± 8%, obtained for 3.70 Hz waves, in a 6.25-cm-deep fluid, consistent with the superradiant scattering caused by rapid rotation. We expect our experimental findings to be relevant to black-hole physics, since shallow water waves scattering on a draining fluid constitute an analogue of a black hole 5, 6, 7, 8, 9, 10, as well as to hydrodynamics, due to the close relation to over-reflection instabilities 11, 12, 13

Control of Transcription by Cell Size

Cell size increases significantly with increasing ploidy. Differences in cell size and ploidy are associated with alterations in gene expression, although no direct connection has been made between cell size and transcription. Here we show that ploidy-associated changes in gene expression reflect transcriptional adjustment to a larger cell size, implicating cellular geometry as a key parameter in gene regulation. Using RNA-seq, we identified genes whose expression was altered in a tetraploid as compared with the isogenic haploid. A significant fraction of these genes encode cell surface proteins, suggesting an effect of the enlarged cell size on the differential regulation of these genes. To test this hypothesis, we examined expression of these genes in haploid mutants that also produce enlarged size. Surprisingly, many genes differentially regulated in the tetraploid are identically regulated in the enlarged haploids, and the magnitude of change in gene expression correlates with the degree of size enlargement. These results indicate a causal relationship between cell size and transcription, with a size-sensing mechanism that alters transcription in response to size. The genes responding to cell size are enriched for those regulated by two mitogen-activated protein kinase pathways, and components in those pathways were found to mediate size-dependent gene regulation. Transcriptional adjustment to enlarged cell size could underlie other cellular changes associated with polyploidy. The causal relationship between cell size and transcription suggests that cell size homeostasis serves a regulatory role in transcriptome maintenance.National Institutes of Health (U.S.) (grant GM035010)National Institutes of Health (U.S.) (grant GM040266

Using direct observations on multiple occasions to measure household food availability among low-income Mexicano residents in Texas colonias

BACKGROUND: It has been recognized that the availability of foods in the home are important to nutritional health, and may influence the dietary behavior of children, adolescents, and adults. It is therefore important to understand food choices in the context of the household setting. Considering their importance, the measurement of household food resources becomes critical.Because most studies use a single point of data collection to determine the types of foods that are present in the home, which can miss the change in availability within a month and when resources are not available, the primary objective of this pilot study was to examine the feasibility and value of conducting weekly in-home assessments of household food resources over the course of one month among low-income Mexicano families in Texas colonias. METHODS: We conducted five in-home household food inventories over a thirty-day period in a small convenience sample; determined the frequency that food items were present in the participating households; and compared a one-time measurement with multiple measurements.After the development and pre-testing of the 252-item culturally and linguistically- appropriate household food inventory instrument that used direct observation to determine the presence and amount of food and beverage items in the home (refrigerator, freezer, pantry, elsewhere), two trained promotoras recruited a convenience sample of 6 households; administered a baseline questionnaire (personal info, shopping habits, and food security); conducted 5 in-home assessments (7-day interval) over a 30-day period; and documented grocery shopping and other food-related activities within the previous week of each in-home assessment. All data were collected in Spanish. Descriptive statistics were calculated for mean and frequency of sample characteristics, food-related activities, food security, and the presence of individual food items. Due to the small sample size of the pilot data, the Friedman Test and Kendall's W were used to assess the consistency of household food supplies across multiple observations. RESULTS: Complete data were collected from all 6 Mexicano women (33.2y +/- 3.3; 6.5 +/- 1.5 adults/children in household (HH); 5 HH received weekly income; and all were food insecure. All households purchased groceries within a week of at least four of the five assessments. The weekly presence and amounts of fresh and processed fruits and vegetables, dairy, meats, breads, cereals, beverages, and oils and fats varied. Further, the results revealed the inadequacy of a one-time measurement of household food resources, compared with multiple measures. The first household food inventory as a one-time measure would have mistakenly identified at least one-half of the participant households without fresh fruit, canned vegetables, dairy, protein foods, grains, chips, and sugar-sweetened beverages. CONCLUSIONS: This study highlights the value of documenting weekly household food supplies, especially in households where income resources may be more volatile. Clearly, the data show that a single HFI may miss the changes in availability--presence and amount--that occur among low-income Mexicano households who face challenges that require frequent purchase of foods and beverages. Use of multiple household food inventories can inform the development and implementation of nutrition-related policies and culturally sensitive nutrition education programs

Neighbor Overlap Is Enriched in the Yeast Interaction Network: Analysis and Implications

The yeast protein-protein interaction network has been shown to have distinct topological features such as a scale free degree distribution and a high level of clustering. Here we analyze an additional feature which is called Neighbor Overlap. This feature reflects the number of shared neighbors between a pair of proteins. We show that Neighbor Overlap is enriched in the yeast protein-protein interaction network compared with control networks carefully designed to match the characteristics of the yeast network in terms of degree distribution and clustering coefficient. Our analysis also reveals that pairs of proteins with high Neighbor Overlap have higher sequence similarity, more similar GO annotations and stronger genetic interactions than pairs with low ones. Finally, we demonstrate that pairs of proteins with redundant functions tend to have high Neighbor Overlap. We suggest that a combination of three mechanisms is the basis for this feature: The abundance of protein complexes, selection for backup of function, and the need to allow functional variation

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function

\ua9 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF

Functional Expression of Spider Neurotoxic Peptide Huwentoxin-I in E. coli

The coding sequence of huwentoxin-I, a neurotoxic peptide isolated from the venom of the Chinese spider Ornithoctonus huwena, was amplified by PCR using the cDNA library constructed from the spider venom glands. The cloned fragment was inserted into the expression vector pET-40b and transformed into the E. coli strain BL21 (DE3). The expression of a soluble fusion protein, disulfide interchange protein (DsbC)-huwentoxin-I, was auto-induced in the periplasm of E. coli in the absence of IPTG. After partial purification using a Ni-NTA column, the expressed fusion protein was digested using enterokinase to release heteroexpressed huwentoxin-I and was further purified using RP-HPLC. The resulting peptide was subjected to gel electrophoresis and mass spectrometry analysis. The molecular weight of the heteroexpressed huwentoxin-I was 3750.69, which is identical to that of the natural form of the peptide isolated from spider venom. The physiological properties of the heteroexpressed huwentoxin-I were further analyzed using a whole-cell patch clamp assay. The heteroexpressed huwentoxin-I was able to block currents generated by human Nav1.7 at an IC50 of 640 nmole/L, similar to that of the natural huwentoxin-I, which is 630 nmole/L

Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon

SUMMARY Background Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans