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Abstract The morphological transformation of the pectoral/shoulder girdle is fundamental to the water-to-land transition in vertebrate evolution. Although previous studies have resolved the embryonic origins of tetrapod shoulder girdles, those of fish pectoral girdles remain uncharacterized, creating a gap in the understanding of girdle transformation mechanisms from fish to tetrapods. Here, we identify the embryonic origins of the zebrafish pectoral girdle, including the cleithrum as an ancestral girdle element lost in extant tetrapods. Our combinatorial approach of photoconversion and genetic lineage tracing demonstrates that cleithrum development combines four adjoining embryonic populations. A comparison of these pectoral girdle progenitors with extinct and extant vertebrates highlights that cleithrum loss, indispensable for neck evolution, is associated with the disappearance of its unique developmental environment at the head/trunk interface. Overall, our study establishes an embryological framework for pectoral/shoulder girdle formation and provides evolutionary trajectories from their origin in water to diversification on land.

Abstract Background The gold standard treatment for locally advanced colon cancer is curative surgery followed by adjuvant chemotherapy, although this approach is associated with serious concerns, such as high recurrence rates and occasionally unnecessary oversurgery. Neoadjuvant chemotherapy may be a promising strategy for overcoming these issues. This study reports a case of a recurrence-free patient who underwent curative resection without significant organ dysfunction after preoperative chemotherapy for locally advanced sigmoid colon cancer. The tumor coexisted with a large intra-abdominal abscess, and the patient was quite frail at the first visit. We performed percutaneous drainage followed by preoperative panitumumab monotherapy, which yielded favorable outcomes. Case presentation A 78-year-old frail woman was emergently transferred to our hospital with fever and abdominal pain. The diagnosis was locally advanced sigmoid colon cancer stage IIIC (T4bN2aM0) with a large intra-abdominal abscess. Immediate curative surgery was inappropriate, considering both tumor progression and the patient’s frailty. We performed percutaneous drainage and colostomy construction, which was followed by seven cycles of preoperative panitumumab monotherapy without significant adverse events. After these treatments, inflammation was well controlled, and the tumor shrank remarkably. Furthermore, the patient recovered well from frailty; therefore, curative sigmoidectomy combined with resection of the left ovary and stoma closure was possible without any postoperative complications. The final pathological finding was T3N0M0, stage IIA disease. The patient was recurrence-free and had no significant organ dysfunction 21 months after the curative surgery. Conclusions The management of intra-abdominal abscesses and tailor-made preoperative chemotherapy based on the patient’s frailty may have been the key factors responsible for the favorable course of this patient. Although further research is needed on the appropriateness of percutaneous drainage for malignancies related to intra-abdominal abscesses and preoperative panitumumab use for locally advanced colon cancer, the study findings can serve as reference for managing similar cases in an aging society.

Abstract Deep-water (DW) management in rice fields is a promising technique for efficient control of paddy weeds with reduced herbicide use. Maintaining a water depth of 10–20 cm for several weeks can largely suppress the weed growth, though it also inhibits rice growth because the DW management is usually initiated immediately after transplanting. Improving the DW resistance of rice during the initial growth stage is essential to avoid suppressing growth. In this study, we demonstrate a large genetic variation in the above-ground biomass (AGB) after the end of DW management among 165 temperate japonica varieties developed in Japan. Because the AGB closely correlated with plant length (PL) and tiller number (TN) at the early growth stage, we analyzed genomic regions associated with PL and TN by conducting a genome-wide association study. For PL, a major peak was detected on chromosome 3 (qPL3), which includes a gene encoding gibberellin biosynthesis, OsGA20ox1. The rice varieties with increased PL had a higher expression level of OsGA20ox1 as reported previously. For TN, a major peak was detected on chromosome 4 (qTN4), which includes NAL1 gene associated with leaf morphological development and panicle number. Although there was less difference in the expression level of NAL1 between genotypes, our findings suggest that an amino acid substitution in the exon region is responsible for the phenotypic changes. We also found that the rice varieties having alternative alleles of qPL3 and qTN4 showed significantly higher AGB than the varieties with the reference alleles. Our results suggest that OsGA20ox1 and NAL1 are promising genes for improving DW resistance in rice.

Abstract Background Dysregulation of the terminal differentiation of bladder urothelium is associated with the pathogenesis of urinary tract disorders. Fibroblast growth factor (Fgf)7 and Fgf10 stimulate urothelial proliferation; however, their roles in cellular differentiation remain unclear. In this study, we used an organoid system to investigate the roles of these Fgfs in regulating bladder urothelium differentiation and identify their distribution patterns in the mouse bladder. Methods Adult bladder epithelia (AdBE) isolated from adult mouse bladder tissues (AdBTs) were used to culture adult bladder organoids (AdBOs) in the presence of Fgf7 and Fgf10. The differentiation status of the cells in AdBTs, AdBEs, AdBOs, and neonatal bladder tissues (NeoBTs) was analyzed via quantitative real-time-PCR for the presence of undifferentiated cell markers (Krt5, Trp63, and Krt14) and differentiated cell markers (Krt20, Upk1a, Upk2, and Upk3a). Organoid cell proliferation was assessed by counting cell numbers using the trypan blue method. The effects of Fgf7 and Fgf10 on organoid differentiation were assessed using different doses of Fgfs, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) signaling in these processes was tested by introducing a PPARγ agonist (Rosiglitazone) and antagonist (T0070907) to the culture. The expression patterns of Fgf7 and Fgf10 were examined via in situ hybridization of AdBTs. Results AdBOs showed higher expression of undifferentiated cell markers and lower expression of differentiated cell markers than AdBTs, NeoBTs, and AdBEs, indicating the relatively immature state of AdBOs. Differentiation of AdBOs was enhanced by Rosiglitazone and Fgf7, suggesting an interplay of intracellular signals between Fgf7 and PPARγ. Co-addition of T0070907 suppressed Fgf7-mediated differentiation, demonstrating that PPARγ is activated downstream of Fgf7 to promote cellular differentiation into umbrella cells. Furthermore, we found that Fgf7 is predominantly expressed in the umbrella cells of the urothelium, whereas Fgf10 is predominantly expressed in the urothelium and stroma of AdBTs. Conclusions We demonstrated that unlike Fgf10, Fgf7 induces cellular differentiation via PPARγ activity and has a unique tissue distribution pattern in the adult bladder. Further studies on the Fgf7-PPARγ signaling axis would provide insights into the differentiation mechanisms toward functional umbrella cells and the pathogenesis of several urinary tract diseases.

Abstract Nd-Fe-B-based permanent magnets are widely used for energy conversion applications. However, their usage at elevated temperatures is difficult due to the relatively low coercivity (H c) with respect to the anisotropy field (H A) of the Nd2Fe14B compound, which is typically 0.2H A. In this work, we found that the coercivity of an (Nd0.8Dy0.2)-Fe-B sintered magnet could reach 0.4H A, which was twice as high as the H c/H A of its Dy-free counterpart. Detailed microstructural characterizations, density functional theory and micromagnetic simulations showed that the large value of coercivity, H c = 0.4H A, originated not only from the enhanced H A of the main phase (intrinsic factor) but also from the reduced magnetization of the thin intergranular phase (extrinsic factor). The latter was attributed to the dissolution of 4 at.% Dy in the intergranular phase that anti-ferromagnetically coupled with Fe. The reduction in the magnetization of the intergranular phase resulted in a change in the angular dependence of coercivity from the Kondorsky type for the Dy-free magnet to the Stoner–Wohlfarth-like shape for the Dy-containing magnet, indicating that the typical pinning-controlled coercivity mechanism began to show nucleation features as the magnetization of the intergranular phase was reduced by Dy substitution.

The year 2023 marks the 12th anniversary of the Great East Japan Earthquake (GEJE). Immediately after the disaster, the number of evacuees reached approximately 470,000, but by November 2022, the number had decreased to approximately 31,000. The reconstruction of housing, disposal of debris, public infrastructure development, and overall restoration and reconstruction has progressed steadily. However, a re-examination of the status of industrial restoration and reconstruction reveals that restoration and reconstruction have not progressed in some areas. This research statistically analyzes how the Japanese public perceives the issues around the recovery process and what memories and records they would like to learn from regarding the GEJE. The purpose of this study is to ask about reconstruction issues and lessons learned from the GEJE by conducting a web-based survey with 2000 respondents in Japan. The method of estimation is the use of ordinal logistic regression analysis to statistically estimate whether there are differences in recovery issues and lessons learned depending on individual attributes. The results suggest that those who are interested in, remember, and express anxiety about the recovery issues and lessons learned tend to be men, do not have children, are highly educated, and have a higher income. In sum, many of Japan’s citizens are highly interested in the reconstruction of agriculture, forestry, fisheries, housing, urban development, living environment, industry, and livelihood in the affected areas. In the future, they will play a central role in modernizing, scaling up, and integrating the agriculture, forestry, and fisheries industries, as well as in rebuilding towns and livelihoods. In the affected areas, it will be necessary to draw on the lessons learned from the GEJE and create reconstruction plans for the future, and then, policymakers will need to formulate reconstruction policies that reflect the concerns of the Japanese people.

Objective: To examine the relationship between the cognitive assessment of stress (cognitive appraisal) caused in a scenario requiring basic life support (BLS) and the roles during BLS/personality traits in nursing students. Methods: We conducted an anonymous self-administered questionnaire survey for 264 freshman and senior nursing students. The study period was one month from June 2019. The questionnaire included characteristics, roles (active involvement group/passive involvement group/no involvement group), Cognitive Appraisal Rating Scale (CARS), and Maudsley Personality Inventory (MPI). We only included data for female students (107 people) in the analysis because very little data is available for male students. The Mann-Whitney test was used for the comparison between two groups and the Kruskal-Wallis test was used for the comparison between three groups. The significance level was set at p

Abstract Spin current, converted from charge current via spin Hall or Rashba effects, can transfer its angular momentum to local moments in a ferromagnetic layer. In this regard, the high charge‐to‐spin conversion efficiency is required for magnetization manipulation for developing future memory or logic devices including magnetic random‐access memory. Here, the bulk Rashba‐type charge‐to‐spin conversion is demonstrated in an artificial superlattice without centrosymmetry. The charge‐to‐spin conversion in [Pt/Co/W] superlattice with sub‐nm scale thickness shows strong W thickness dependence. When the W thickness becomes 0.6 nm, the observed field‐like torque efficiency is about 0.6, which is an order larger than other metallic heterostructures. First‐principles calculation suggests that such large field‐like torque arises from bulk‐type Rashba effect due to the vertically broken inversion symmetry inherent from W layers. The result implies that the spin splitting in a band of such an ABC‐type artificial SL can be an additional degree of freedom for the large charge‐to‐spin conversion.

The gill skeleton of cartilaginous fishes (sharks, skates, rays, and holocephalans) exhibits a striking anterior–posterior polarity, with a series of fine appendages called branchial rays projecting from the posterior margin of the gill arch cartilages. We previously demonstrated in the skate (Leucoraja erinacea) that branchial rays derive from a posterior domain of pharyngeal arch mesenchyme that is responsive to Sonic hedgehog (Shh) signaling from a distal gill arch epithelial ridge (GAER) signaling centre. However, how branchial ray progenitors are specified exclusively within posterior gill arch mesenchyme is not known. Here, we show that genes encoding several Wnt ligands are expressed in the ectoderm immediately adjacent to the skate GAER, and that these Wnt signals are transduced largely in the anterior arch environment. Using pharmacological manipulation, we show that inhibition of Wnt signalling results in an anterior expansion of Shh signal transduction in developing skate gill arches, and in the formation of ectopic anterior branchial ray cartilages. Our findings demonstrate that ectodermal Wnt signalling contributes to gill arch skeletal polarity in skate by restricting Shh signal transduction and chondrogenesis to the posterior arch environment and highlights the importance of signalling interactions at embryonic tissue boundaries for cell fate determination in vertebrate pharyngeal arches.

Abstract Background Frailty is a clinical condition characterized by increased vulnerability to adverse health outcomes. Elderly people are screened for frailty as part of preventative care. However, the risk factors for frailty among older adults who undergo Ningen Dock, a comprehensive medical checkup, remain unclear. Thus, this cross-sectional study aims to identify the risk factors for frailty in older adults who received Ningen Dock. The study included 372 participants over 65 years of age who underwent Ningen Dock at the Health Care Center of Gunma Chuo Hospital between April 2019 and March 2020. Frailty was defined using the Kihon Checklist, a basic checklist. Clinical variables were obtained from Ningen Dock records, a vascular function test, and a questionnaire on medication, among others. Multivariate ordinal logistic regression models were used to assess risk factors. Results Prevalence for frailty and pre-frailty was 12.6% and 26.6%, respectively. The mean age of participants was 72.0 ± 5.1 years old, and 43.5% were female. Compared with systolic blood pressure (SBP) ≥ 130 mmHg, the odds ratios for the 100–129 mmHg and < 100 mmHg groups were 2.43 (P = 0.020) and 8.95 (P 0.6 mg/dL. Compared with an exercise habit of ≥ 4 metabolic equivalents (METs), the odds ratio for < 2 METs/week was 2.45 (P < 0.001). The odds ratio for the cardio-ankle vascular index (CAVI) ≥ 9 group was 1.84 (P = 0.020) compared to < 9. Conclusions In older adults who received Ningen Dock, SBP < 100 mmHg, medications ≥ 7, serum iron ≤ 85 μg/dL, total bilirubin ≤ 0.6 mg/dL, exercise habits < 2 METs, and CAVI ≥ 9 were associated with frailty.

Abstract Odontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentin covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have reacquired dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages. De novo transcriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as expression of paired like homeodomain 2 (pitx2), previously known as an early regulator of oGRN in teeth but not in other dermal odontodes, in developing dermal denticles. The early onset of pitx2 expression in cranial dermal denticle placodes implies its function as one of the inducing factors of the cranial dermal denticles. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes might have evolved and diverged in distinct teleost lineages via redeployment of oGRN.

Multiple-input-multiple-output (MIMO) optical wireless communication systems are potential candidates for high-speed data transmission in indoor environments. In this work, we present an experimental evaluation of two different MIMO systems, i.e., conventional-MIMO (c-MIMO) and imaging-MIMO (i-MIMO) in terms of design considerations. Both systems use the same transmitter configuration featuring a one-dimensional (light-emitting diode) LED transmitting array. On the receiver side, the c-MIMO system employs a similar one-dimensional receiving avalanche photodetector (APD)-based array, whereas the i-MIMO system uses a customized imaging camera-based receiver design. To assess the performance of the two systems, the channel matrix and the bit-error rate are calculated based on the experimental data. At distances shorter than 50 m, the proposed c-MIMO system demonstrates a good transmission performance, particularly when the maximum likelihood detection (MLD) technique is applied. Whereas, at long distances ranging from 40 m to 65 m, the proposed i-MIMO system can ensure an error-free transmission due to the efficient spatial separation between the emitted optical beams. Furthermore, the experimental results confirm that our systems have the potential for high data rates over longer distances in indoor environments.

The X-ray magnetic circular dichroism detection of magnetic octupole moment has not been experimentally demonstrated so far. Here, the authors observe ferroic order of magnetic octupole in Mn3Sn, finding the exotic material functionalities related to the multipole order.

Abstract This study investigates the effect of strain on the compensation temperature of ferrimagnetic Tb–Fe films formed on a flexible substrate. The compensation temperature is determined by the anomalous Hall measurement, and an application of 1.2% tensile strain reduces the compensation temperature by 12 K. X-ray magnetic circular dichroism reveals that approximately 5% of Fe magnetic moment and approximately 1% of Tb magnetic moment are reduced by an application of 0.9% tensile strain at the room temperature. To understand the greater reduction in Fe magnetization compared with that in Tb and the compensation temperature reduction simultaneously, a model applying molecular field theory is analyzed. Changes in three types of exchange coupling between Fe and Tb atoms are speculated to be caused by the strain.

In this article, we investigate the performance of the newly designed 4 × 4 optical wireless multiple-input-multiple-output (MIMO-OWC) system based on a linearly-shaped arrangement of transmitters and receivers, to achieve long-distance and high data rate transmission. To highlight the importance of selecting an appropriate arrangement for the optical elements, we carried on a comparative study, considering both the conventional square and the proposed horizontal linear constellation of optical modems. The performance of the bit error rate (BER) is experimentally evaluated at distances up to 65 m, using two important metrics inherent to the MIMO transmission channel matrix, i.e., the Frobenius norm and the condition number. The results show that the channel matrix shape characterized by the condition number dominates the BER if the Frobenius norm is smaller than 1. Furthermore, the proposed MIMO-OWC system employing a linearly-shaped arrangement of transmitters and receivers, shows to be more immune to the calibration error rather than the conventional square constellation optical modems. Moreover, the transmission of 100 Mbps data-rate and a BER lower than 10-4 could be successfully achieved at a 65 m communication range.

Background & Aims: The reason why small intestinal cancer is rarer than colorectal cancer is not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the small intestine, are the closest immune cells to epithelial cells, exclude tumor cells via cell-to-cell contact. Methods: We developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple intestinal neoplasia (APCmin ) mice, which is a T-cell–reporter mouse with spontaneous intestinal tumors. We visualized the dynamics of IELs in the intestinal tumor microenvironment and the interaction between IELs and epithelial cells, and the roles of cell-to-cell contact in anti-intestinal tumor immunity using a novel in vivo live-imaging system and a novel in vitro co-culture system. Results: In the small intestinal tumor microenvironment, T-cell movement was restricted around blood vessels and the frequency of interaction between IELs and epithelial cells was reduced. Genetic deletion of CD103 decreased the frequency of interaction between IELs and epithelial cells, and increased the number of small intestinal tumors. In the co-culture system, wild-type IELs expanded and infiltrated to intestinal tumor organoids from APCmin mice and reduced the viability of them, which was cell-to-cell contact and CD103 dependent. Conclusions: The abundance of IELs in the small intestine may contribute to a low number of tumors, although this system may not work in the colon because of the sparseness of IELs. Strategies to increase the number of IELs in the colon or enhance cell-to-cell contact between IELs and epithelial cells may be effective for the prevention of intestinal tumors in patients with a high cancer risk.

Objectives: The microsurgical approach is considered the most reliable procedure in varicocelectomy. However, as there are difficulties in identifying the spermatic artery at the peripheral level, we had introduced intraoperative indocyanine green angiography (ICGA) for identification of arteries. In this study, we further investigated the usefulness of intraoperative ICGA in combination with an ordinary Doppler detector in microsurgical subinguinal varicocelectomy. Methods: A total of 140 men who underwent microsurgical subinguinal varicocelectomy at Gunma University Hospital were included. An operating microscope equipped with a near-infrared charge-coupled device was used for intraoperative ICGA. After exposing the vessels, arteries were identified using endoscopic vision only or with assistance of Doppler detector or ICGA, or of both. The number of preserved arteries was compared among the groups. Results: ICGA clearly visualized the internal spermatic arteries in all cases, allowing the surgeon to perform real-time identification and isolation of the spermatic artery intraoperatively. The use of ICGA or Doppler detector significantly increased the number of preserved arteries compared to the microscope-only operation from 1.11 to 1.75 (p

Objectives: Current evidence regarding metabolic surgery suggests that different types of digestive tract reconstruction can result in differences in postoperative glucose tolerance. This study evaluated the impact of Billroth I (B-I), Billroth II (B-II), and Roux-en-Y (R-Y) procedures on peri-operative glucose tolerance in patients with gastric carcinoma who had diabetes mellitus. Methods: A single-institution, retrospective cohort study was conducted using data from patients who underwent totally laparoscopic distal gastrectomy. These patients were grouped according to the type of reconstruction (B-I, B-II, or R-Y). After the operation, we addressed the changes in glucose tolerance—including changes in HbA1c levels, remission of diabetes, and overall effects of the treatment. Results: We studied 57 patients (B-I, n=32; B-II, n=17; R-Y, n=8). B-II and R-Y reconstruction improved HbA1c levels more than B-I. Notably, R-Y improved tolerance the most (B-I vs. B-II, p

We investigated the structural influence of Nd2Fe14B phase magnetostriction on the Nd-rich secondary phases of hcp-Nd2O3, fcc-NdOx, dhcp-Nd, and fcc-Nd, in Nd-Fe-B bulk-sintered magnets. The temperature dependence of the secondary phase lattice constants was evaluated by synchrotron X-ray diffraction using rod-shaped isotropic (randomly oriented) and anisotropic (c-axis oriented) Nd-Fe-B-Cu sintered magnets. The lattice constants of each secondary phase in the rod-shaped isotropic and anisotropic samples exhibited an invar-type expansion below the Nd2Fe14B phase Curie temperature (TC), despite the phases not showing ferromagnetic ordering at TC—and peak broadening was seen for the secondary phases below TC. Since such volume expansion has not been seen in powdered sintered magnets, we viewed it as a phenomenon particular to rod-shaped sintered magnets. These results indicated that the Nd2Fe14B phase spontaneous volume expansion induced the volume expansion observed in all the constituent phases of the bulk sintered magnets.

Dzyaloshinskii–Moriya interaction (DMI) is one of the key factors to control the chiral spin textures in spintronic applications. Here the authors demonstrate the correlation of the DMI with the anisotropy of the orbital magnetic moment and magnetic dipole moment in Pt/Co/MgO ultrathin trilayers.

With the emergence of technologies to culture intestinal epithelial cells in vitro as various forms of intestinal organoids, there is growing interest in using such cultured intestinal cells as a source for tissue engineering and regenerative medicine. One such approach would be to combine the organoid technology with methodologies to engineer the culture environment, particularly the three-dimensional scaffold materials, to generate intestines that exquisitely recapitulate their original structures and functions. Another approach to use organoids for regenerative medicine would be to urge them to mature into functional intestines by implanting them into hosts. This process includes the tissue-engineered small intestine that uses synthetic scaffolds for tissue regeneration and direct organoid transplantation that takes advantage of submucosal tissues in the native intestines as a scaffold. Further study in these subfields could lead to the development of therapeutic options to use different types of organoids with various cell types in regenerative medicine for intestinal diseases in humans.

Summary: ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1+ secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1+ cell-lineage tracing, we show here that a definite number of ATOH1+ IECs retain stem cell properties and can form ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) under completely homeostatic conditions. Interestingly, colonic ATOH1+ IECs appeared to exhibit their stem cell function more frequently compared with those of the small intestine. Consistently, the formation of ATOH1+ICRs was significantly enhanced upon dextran sodium sulfate colitis-induced mucosal damage. In addition, colonic ATOH1+ IECs acquired tumor stem cell-like properties in the azoxymethane-DSS tumor model. Our results reveal an unexpected contribution of colonic ATOH1+ IECs to maintaining the stem cell population under both homeostatic and pathologic conditions and further illustrate the high plasticity of the crypt-intrinsic stem cell hierarchy.

The current process of meat production using livestock has significant effects on the global environment, including high emissions of greenhouse gases. In recent years, cultured meat has attracted attention as a way to acquire animal proteins. However, the lack of markers that isolate proliferating cells from bovine tissues and the complex structure of the meat make it difficult to culture meat in a dish. In this study, we screened 246 cell-surface antibodies by fluorescence-activated cell sorting for their capacity to form colonies and their suitability to construct spheroid “meat buds”. CD29+ cells (Ha2/5 clone) have a high potency to form colonies and efficiently proliferate on fibronectin-coated dishes. Furthermore, the meat buds created from CD29+ cells could differentiate into muscle and adipose cells in a three-dimensional structure. The meat buds embedded in the collagen gel proliferated in the matrix and formed large aggregates. Approximately 10 trillion cells can theoretically be obtained from 100 g of bovine tissue by culturing and amplifying them using these methods. The CD29+ cell characteristics of bovine tissue provide insights into the production of meat alternatives in vitro.

Objectives: Neoadjuvant chemotherapy is a widely-accepted potential treatment for locally-advanced gastric carcinoma. Laparoscopic gastrectomy is performed for advanced gastric carcinoma because it is minimally invasive, which could lead to accessibility to combined chemotherapies. We evaluated the feasibility of performing laparoscopic gastrectomy in patients with or without neoadjuvant chemotherapy. Methods: We performed a retrospective cohort study that was conducted from 2005–2013. We assessed 49 and 35 patients with clinical stage III disease who underwent laparoscopic gastrectomy with and without neoadjuvant chemotherapy, respectively, using a two-cycle regimen of S-1 plus cisplatin. We evaluated patients’ background data, efficacy and adverse events of chemotherapy, and perioperative factors, including the postoperative complication rate, reoperation rate, and length of hospital stay. Results: Adverse events of grade 3 or higher during neoadjuvant chemotherapy were observed in five (10.2%) patients. The response and disease control rates were 61.2% and 93.9%, respectively. There were no significant differences in the postoperative complication rate, reoperation rate, and length of hospital stay between the groups. There were no conversions to laparotomy and no in-hospital deaths. Multivariate analyses showed that total gastrectomy was the only significant independent risk factor for determining postoperative complications, and neoadjuvant chemotherapy was not a risk factor. Conclusions: Our protocol of laparoscopic gastrectomy for locally-advanced gastric carcinoma following neoadjuvant chemotherapy resulted in a considerable response to the chemotherapy and sufficient feasibility in the selected patients. Our strategy is a promising therapeutic option for patients with locally-advanced gastric carcinoma.

Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans.

Objectives: Microsurgical subinguinal varicocelectomy is one of the best treatment modalities for varicoceles related to male infertility and scrotal pain. However, the difficulty in identifying testicular arteries, which should be spared, is a limitation of this technique. To visualize and identify the testicular arteries in spermatic cord during the operation, we examined the efficacy of intraoperative indocyanine green angiography (ICGA), which is regularly used in microsurgical neurosurgery. Methods: After the exposure of the spermatic cord blood vessels, ICG was injected intravenously under a surgical microscope for observing infrared fluorescence in patients to identify and isolate the testicular artery. Results: The testicular artery was clearly identified by ICGA and was able to separate under ICGA view. Thereafter, the varicose veins were repeatedly ligated, while preserving a few lymphatic vessels and the spermatic duct. The preserved arteries were confirmed by repeated ICGA at the end of microsurgical operation. The number of arteries identified by ICGA was greater than the number detected by preoperative computed tomography angiogram. Conclusions: Microsurgical subinguinal varicocelectomy using intraoperative ICGA facilitated safe and quick surgery by enabling the visualization of the spermatic cord blood vessels. This is the first report to indicate the usefulness of vessel visualization by ICGA during microsurgical subinguinal varicocelectomy.

Electric field control of magnetization is usually weak and this hampers its application for the ultralow-power-consumption spintronic devices. Here, the authors demonstrate a mechanism to enhance the control of magnetic anisotropy by voltage-induced electric quadrupole in a metal–dielectric interface.

Abstract Tandem solar cells are suited for space applications due to their high performance, but also have to be designed in such a way to minimize influence of degradation by the high energy particle flux in space. The analysis of the subcell performance is crucial to understand the device physics and achieve optimized designs of tandem solar cells. Here, the radiation-induced damage of inverted grown InGaP/GaAs/InGaAs triple-junction solar cells for various electron fluences are characterized using conventional current-voltage (I–V) measurements and time-resolved photoluminescence (PL). The conversion efficiencies of the entire device before and after damage are measured with I–V curves and compared with the efficiencies predicted from the time-resolved method. Using the time-resolved data the change in the carrier dynamics in the subcells can be discussed. Our optical method allows to predict the absolute electrical conversion efficiency of the device with an accuracy of better than 5%. While both InGaP and GaAs subcells suffered from significant material degradation, the performance loss of the total device can be completely ascribed to the damage in the GaAs subcell. This points out the importance of high internal electric fields at the operating point.

The efficacy and safety of botulinum toxin B (BTX-B) for treatment of Raynaud’s phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud’s phenomenon were blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numbness visual analogue scale scores and Raynaud’s score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numbers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud’s phenomenon and digital ulcers in patients with SSc without serious adverse events.

The data on the immunohistochemical analysis of conditional Notch ligand knockout mice is presented. Targeted deletion of Jag1, Dll1, Dll4, or Dll1 plus Dll4 in Lgr5+ve cells was induced by a Cre-mediated gene recombination, and differentiation or proliferation of the intestinal epithelial cells was examined by immunohistochemistry. These data are the extension of the data presented and discussed in the paper entitled “Indispensable role of non-canonical Notch signaling in the proliferation of Apc-deficient intestinal tumors“ (Nakata et al., Submitted for publication) [1].

The aim of the present study is to evaluate the association of serum uric acid (UA) levels with the risk of incident hypertension among different age groups in men and women using a single large Japanese general cohort. The present study is based on annual health check-up program in Gunma, Japan. We studied 12,029 participants (mean age, 48 ​± ​9 years old; 31% women) free of prevalent cardiovascular disease and hypertension at baseline (2009). Hypertension was defined by self-report, hypertensive medication use, or measured BP ​> ​140/90 ​mmHg ​at each visit. Discrete proportional hazards regression model was used to evaluate the association of UA level at baseline with incident hypertension through 2012 adjusted for age, gender, baseline blood pressure, and other CVD risk factors among different age decade groups in men and women. During follow-up of 3 years, 12% of the cohort (n ​= ​1457) developed hypertension. UA was strongly associated with incident hypertension in the multivariable model in all participants. In age-stratified analysis, participants below 50 years of age in men had the significant association of UA with incident hypertension, whereas participants above 50 years did not. In women, participants above 40 years had the significant association, whereas participants below 40 years did not. The present data suggest that UA level is an independent predictor for incident hypertension among middle aged men below 50 years old and middle aged and the elderly women above 40 years.

Spin–orbit torque facilitates efficient magnetisation switching via an in-plane current in perpendicularly magnetised heavy-metal/ferromagnet heterostructures. The efficiency of spin–orbit-torque-induced switching is determined by the charge-to-spin conversion arising from either bulk or interfacial spin–orbit interactions or both. Here, we demonstrate that the spin–orbit torque and the resultant switching efficiency in Pt/CoFeB systems are significantly enhanced by an interfacial modification involving Ti insertion between the Pt and CoFeB layers. Spin pumping and X-ray magnetic circular dichroism experiments reveal that this enhancement is due to an additional interface-generated spin current of the non-magnetic interface and/or improved spin transparency achieved by suppressing the proximity-induced moment in the Pt layer. Our results demonstrate that interface engineering affords an effective approach to improve spin–orbit torque and thereby magnetisation switching efficiency.

We observed the magnetoelectric induced domain wall propagation in a Pt/Co/Au/Cr2O3/Pt stacked thin film based on magnetic domain observations using scanning soft X-ray magnetic circular dichroism microscopy. The antiferromagnetic (Cr2O3) domain wall velocity was estimated by a quasi-static approach using a pulsed voltage. At a pulse voltage amplitude of −12 V, corresponding to an electric field of −8.0 × 102 kV/cm, the domain wall velocity was very low, at 0.3 m/s. The domain wall velocity increased with increasing voltage amplitude, reaching 22 m/s at −20 V (−1.3 × 103 kV/cm). The change in the domain wall velocity with the applied voltage amplitude indicates the creep motion of the domain wall. Using a phenomenological model, we estimated the domain wall depinning energy, and found that the bulk and interface terms of the magnetic anisotropy affect the effective magnetic field to the same degree, suggesting that the magnetic domain wall motion may be controllable by the antiferromagnetic layer thickness.

Vertical indoor farming under artificial lighting has gained attention as a novel means of food production. However, consumer acceptance of vegetable crops grown under artificial conditions is not well understood. Our nationwide online survey of 289 Russians gathered attitudes and opinions toward vertically farmed vegetables. Employing an ordered logit model and a two-mode co-occurrence network analysis, we show how respondents’ attitudes relate to their key demographic characteristics and opinions about the vegetables. Results indicate that respondents’ attitudes are heterogeneous and related to their region of residence, income level, and opinions regarding nutrients, safety, and taste. Respondents in the Central and Volga districts exhibited less favorable attitudes. Less favorably inclined respondents viewed the produce as unnatural, less nutritious, bad-tasting, and even dangerous, presumably because of misconceptions or lack of knowledge. On the other hand, respondents with monthly income above RUB 60,001 (1018 USD, 867 EURO) had relatively positive attitudes toward such vegetables. Respondents having positive attitudes saw the vegetables as safe, tasty, and of good quality. We discuss the political and commercial implications of these findings.

Therapeutic applications of coenzyme Q10 (CoQ10) are greatly limited by its lack of solubility in aqueous media. In this study, polyethylene glycol monostearate (stPEG) was used to construct micelles containing CoQ10 as a new formulation. The micellar formulations (stPEG/CoQ10) were prepared using five types of stPEG with 10, 25, 40, 55, and 140 PEG repeat units, respectively. The micellar preparation was simple, consisting of only stPEG and CoQ10. Next, we compared the physical properties and blood circulation of these micelles. The CoQ10 load of this formulation was approximately 15 w/w%. Based on the dynamic light scattering method, the average molecular size of the stPEG/CoQ10 micelles was approximately 15 to 60 nm. The zeta potentials of these micelles were approximately −10 to −25 mV. The micelles using stPEG25, 40, and 55 demonstrated high solubility in water. Furthermore, these micelles had in vitro antioxidant activity. On comparing the blood circulation of micelles using stPEG25, 40, 55, and 140, micelles using stPEG55 had a significantly higher circulation in blood. The stPEG55/CoQ10 micelle demonstrated a protective effect against acetaminophen-induced liver injury in mice. In conclusion, these data indicate that the intravenous administration of the stPEG/CoQ10 micellar aqueous formulation is of great value against oxidant stress.

The electric field effect on the magnetism in a MgO/Pd/Co system, in which a magnetic moment is induced in the Pd layer owing to the ferromagnetic proximity effect, has been investigated using various experimental methods. An electric field was applied to the surface of the Pd layer through a solid-state HfO2/MgO dielectric bilayer by applying a gate voltage with a back-gating configuration. Changes in the magnetic properties of the system as a result of gate voltage application were detected using magnetization and polar-Kerr effect measurements as well as X-ray absorption and X-ray magnetic circular dichroism (XMCD) spectroscopies. A systematic change in the magnetic moment of the system by the application of a gate voltage is observed. The magnetic hysteresis loops obtained by the polar-Kerr effect measurement and the element-specific XMCD signal at the Co L3-edge clearly show a reproducible change in the coercivity that is dependent on the gate voltage.

The fish-to-tetrapod transition is one of the fundamental problems in evolutionary biology. A significant amount of paleontological data has revealed the morphological trajectories of skeletons, such as those of the skull, vertebrae, and appendages in vertebrate history. Shifts in bone differentiation, from dermal to endochondral bones, are key to explaining skeletal transformations during the transition from water to land. However, the genetic underpinnings underlying the evolution of dermal and endochondral bones are largely missing. Recent genetic approaches utilizing model organisms—zebrafish, frogs, chickens, and mice—reveal the molecular mechanisms underlying vertebrate skeletal development and provide new insights for how the skeletal system has evolved. Currently, our experimental horizons to test evolutionary hypotheses are being expanded to non-model organisms with state-of-the-art techniques in molecular biology and imaging. An integration of functional genomics, developmental genetics, and high-resolution CT scanning into evolutionary inquiries allows us to reevaluate our understanding of old specimens. Here, we summarize the current perspectives in genetic programs underlying the development and evolution of the dermal skull roof, shoulder girdle, and appendages. The ratio shifts of dermal and endochondral bones, and its underlying mechanisms, during the fish-to-tetrapod transition are particularly emphasized. Recent studies have suggested the novel cell origins of dermal bones, and the interchangeability between dermal and endochondral bones, obscuring the ontogenetic distinction of these two types of bones. Assimilation of ontogenetic knowledge of dermal and endochondral bones from different structures demands revisions of the prevalent consensus in the evolutionary mechanisms of vertebrate skeletal shifts.

In order to understand the coercivity mechanism in Nd-Fe-B sintered magnets, the angular dependence of the coercivity of an isotropically aligned Nd15Co1.0B6Febal. sintered magnet was investigated through magnetization measurements using a vibrating sample magnetometer. These results are compared with the angular dependence calculated under the assumption that the magnetization reversal of each grain follows the Kondorskii law or, in other words, the 1/cos θ law for isotropic alignment distributions. The calculated angular dependence of the coercivity agrees very well with the experiment for magnetic fields applied between angles of 0 and 60°, and it is expected that the magnetization reversal occurs in each grain individually followed the 1/cos θ law. In contrast, this agreement between calculation and experiment is not found for anisotropic Nd-Fe-B samples. This implies that the coercivity of the aligned magnets depends upon the de-pinning of the domain walls from pinning sites. When the de-pinning occurs, it is expected that the domain walls are displaced through several grains at once.

Experimental results of the alignment dependence of the coercivity in Nd-Fe-B sintered magnets showed that the angle of magnetization reversal for anisotropically aligned magnets was bigger than that obtained from the theoretical results calculated using the postulation that every grain independently reverses its magnetization direction following the 1/cos θ law. The angles of reversed magnetization (θ1) for Nd13.48Co0.55B5.76Febal. with alignment α=0.95 and for Nd12.75Dy0.84B5.81Co0.55Febal. with α=0.96 were 30° and 36°, respectively, which were very similar to that of an ideal magnet with a Gaussian distribution (σ=31° and 44°, respectively) of the grain alignment. In this model, we postulated that every grain independently reversed according to the 1/cos θ law. The calculation results for the angular dependence of the coercivity using the values θ1=ω1(0°)=30°, σ=31° and θ1=ω1(0°)=36°, σ=44° could qualitatively and convincingly explain the observed angular dependence of the coercivity of Nd14.2B6.2Co1.0Febal. and Nd14.2Dy0.3B6.2Co1.0Febal.. It is speculated that the magnetic domain wall is pinned at grains tilted away from the easy magnetization direction, and when the magnetic domain wall de-pins from the tilted grains, the magnetic domain wall jumps through several grains. We suggest that the coercive force of the aligned magnet behaves like a low-aligned magnet owing to the magnetization reversal of the crust of the grains induced by the pinning and subsequent jumping of the magnetic domain wall.

By using focused soft X-rays, magnetic domain imaging based on X-ray magnetic circular dichroism (XMCD) measurements was performed on a Pt/Co/Cr2O3/Pt film that exhibits both perpendicular magnetic anisotropy and perpendicular exchange anisotropy. In the AC-demagnetized state, spatial distributions of the XMCD corresponding to the magnetic domains were clearly observed. In particular, ferromagnetic and antiferromagnetic magnetic domains were separately observed by tuning the photon energy to either the ferromagnetic Co L3 edge or the antiferromagnetic Cr L3 edge. The ferromagnetic domain pattern is similar to the ones previously reported for Co/Pt multilayers, and the ferromagnetic and antiferromagnetic domains are spatially coupled. The magnetization curve measured after cooling the sample, while maintaining the demagnetized state, exhibited positive and negative exchange biases simultaneously, which suggests that the exchange bias is determined on a domain-by-domain basis.

The cubic Heusler compound Mn1.5FeV0.5Al with the L21 Heusler structure is the first fully compensated half-metallic ferrimagnet with 24 valence electrons. The ferrimagnetic state can be tuned by changing the composition such that the compensation point appears at finite temperatures ranging from 0 K up to 226 K, while retaining half-metallicity in the system. In this paper, the structural, magnetic and transport properties of the Mn-Fe-V-Al system are discussed. Magnetic reversal and a change of sign of the anomalous Hall effect were observed at the compensation point, which gives rise to a sublattice spin-crossing. These materials present new possibilities for potential spintronic devices because of their advantageous properties such as imperceptibility to external fields, lower power consumption and ultrafast switching in the THz region.

Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance.

Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes-all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome.

Effects of a new lipophilic L-type calcium channel blocker, azelnidipine, on the expression of molecular components of the renin-angiotensin-aldosterone system (RAAS) were assessed. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of diabetes with hypertension, and their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats, were treated with azelnidipine for 2 weeks. The renal cortical mineralocorticoid receptor mRNA in OLETF was higher than in LETO, but was suppressed (P

Reports have suggested that the two Notch ligands, Dll1 and Dll4, are indispensable to maintain the homeostasis of the intestinal epithelium. However, within the intestinal epithelium, the precise distribution of the cells that express those ligands at the protein level remains largely unknown. Here, we show a series of immunohistochemical analysis through which we successfully identified mice intestinal epithelial cells (IECs) that endogenously express Dll1 or Dll4. Results showed that Dll1-positive (Dll1+ve) IECs reside exclusively within the crypt, whereas Dll4-positive (Dll4+ve) IECs can locate both in the crypt and in the villus of the small intestine. Also in the colon, Dll1+ve IECs resided at the lower part of the crypt, whereas Dll4+ve IECs resided at both upper and lower part of the crypt, including the surface epithelium. Both Dll1+ve and Dll4+ve IECs were ATOH1-positive, but Hes1-negative cells, and located adjacent to Hes1-positive cells within the crypts. A sub-population of both Dll1+ve and Dll4+ve IECs appeared to co-express Muc2, but rarely co-expressed other secretory lineage markers. However, as compared to Dll1+ve IECs, Dll4+ve IECs included larger number of Muc2-postive IECs, suggesting that Dll4 is more preferentially expressed by goblet cells. Also, we identified that Dll4 is expressed in the Paneth cells of the small intestine, whereas Dll1 and Dll4 is expressed in the c-kit-positive IECs of the colon, indicating that Dll1+ve and Dll4+ve IECs may contribute to constitute the intestinal stem cell niche. Compared to the normal colon, analysis of DSS-colitis showed that number of Dll1+ve IECs significantly decrease in the elongated crypts of the inflamed colonic mucosa. In sharp contrast, number of Dll4+ve IECs showed a significant increase in those crypts, which was accompanied by the increase in number of Hes1-positive IECs. Those Dll4+ve IECs were mostly found adjacent to the Hes1-positive IECs, suggesting that Dll4 may act as a major Notch ligand in the crypts of the inflamed colonic mucosa. Our results illustrate distinct expression patterns of Dll1 and Dll4 within the intestinal epithelium, and suggest that these two ligands may have different roles in normal and inflamed mucosa.

It has been suggested that prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). We previously observed that the NF-κB activation in colonic epithelial cells is associated with increased tumor necrosis factor receptor 2 (TNFR2) expression in CAC development. However, the mechanism by which epithelial NF-κB activation leading to CAC is still unclear. Myosin light chain kinase (MLCK) has been reported to be responsible for the epithelial permeability associated with TNF signaling. Therefore we focused on the role of MLCK expression via TNFR2 signaling on CAC development. Pro-tumorigenic cytokines such as IL-1β, IL-6 and MIP-2 production as well as INF-γ and TNF production at the lamina propria were increased in the setting of colitis, and further in tumor tissues in associations with up-regulated TNFR2 and MLCK expressions in the epithelial cells of a CAC model. The up-regulated MLCK expression was observed in TNF-stimulated colonic epithelial cells in a dose-dependent fashion in association with up-regulation of TNFR2. Silencing TNFR2, but not TNFR1, resulted in restoration of epithelial tight junction (TJ) associated with decreased MLCK expression. Antibody-mediated blockade of TNF signaling also resulted in restoration of TJ in association with suppressed MLCK expression, and interestingly, similar results were observed with suppressing TNFR2 and MLCK expressions by inhibiting MLCK in the epithelial cells. Silencing of MLCK also resulted in suppressed TNFR2, but not TNFR1, expression, suggesting that the restored TJ leads to reduced TNFR2 signaling. Such suppression of MLCK as well as blockade of TNFR2 signaling resulted in restored TJ, decreased pro-tumorigenic cytokines and reduced CAC development. These results suggest that MLCK may be a potential target for the prevention of IBD-associated tumor development.

The determination of left-right body asymmetry in mouse embryos depends on the interplay of molecules in a highly sensitive structure, the node. Here, we show that the localization of Cerl2 protein does not correlate to its mRNA expression pattern, from 3-somite stage onwards. Instead, Cerl2 protein displays a nodal flow-dependent dynamic behavior that controls the activity of Nodal in the node, and the transmission of the laterality information to the left lateral plate mesoderm (LPM). Our results indicate that Cerl2 initially localizes and prevents the activation of Nodal genetic circuitry on the right side of the embryo, and later its right-to-left translocation shutdowns Nodal activity in the node. The consequent prolonged Nodal activity in the node by the absence of Cerl2 affects local Nodal expression and prolongs its expression in the LPM. Simultaneous genetic removal of both Nodal node inhibitors, Cerl2 and Lefty1, sustains even longer and bilateral this LPM expression.

Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

This study examines the results of an online survey on the impact of the global food crisis on Germany's food aid measures. The global food crisis has left Germans food insecure, leading them to seek additional financial support to increase food production, including lower sales tax and aid for vulnerable groups. Perception of the causes of the food crisis differ across socio-economic groups, such as age, education, and income. Older participants were dissatisfied with the measures taken by the government and European Union to secure the functioning of the food security system. This group was also supportive of reduced consumption tax on food and increased charitable assistance for vulnerable groups. In Germany, where the birthrate is steadily declining and the population is aging, social security system reform is underway, with hope for stable and sustainable food assistance supported by older generations. [ABSTRACT FROM AUTHOR]