bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2008 Law “On Gender Equality in Society” and Some of its Effects on Equal Representation.
Authors: Marko Gjinko Juliana
Published: December 2023

Since the fall of their socialist centralized systems, the countries of Central and Eastern Europe have experienced considerable changes to their socioeconomic policies. The Republic of Albania has encountered several noteworthy challenges since 1992, and initially, eradicating gender inequality was not given much emphasis. Gender equality is an essential element that needs to be incorporated into the legal frameworks of all candidate countries aspiring to join the EU, in addition to being a fundamental right and a shared vision of EU institutions. In developing nations, social exclusion can be either active or passive. Because females are excluded from many facets of society, such as the workforce, education, access to the legal system, the realization of their property rights, and so forth, women’s demands and interests are frequently disregarded. Following the UN Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW), the Republic of Albania has developed a number of laws, policies, and action plans pertaining to gender equality, in addition to measures addressing issues such as human trafficking, domestic abuse, closing the representational gap in politics and the economy, and other matters. This essay looks at Albania’s methodology for evaluating European standards and, where necessary, adapts them to regional political and cultural norms. Ensuring that the body of legislation is in accord with the culture in which it functions is a better strategy to enforce laws than merely making models, rules, and regulations. This is a comprehensive effort to assess and contrast specific in pursuing full EU integration. This is an overall attempt to evaluate and compare some of the strategies and actions Albanian representatives and society have taken to address the gender factor in the democratization process and institution-building while pursuing full EU integration.
Empirical Study on the Currency Exchange Market. Determinants on the Exchange Rate of the U.S. Dollars and the Japanese Yen by the Regression Analysis.
Authors: (Tony) Komiya Tokuichi
Published: December 2023

It is widely known that in the exchange rate market there are three factors influential to determine the currency exchange rate between the related countries in theory; i.e., the interest rate, inflation, and expectation on the exchange rate. This paper aims to find how the exchange rate between U.S. dollar and Japanese Yen, both of which are widely recognized as major currencies in the international financial market, are affected by the four key variables selected here in this paper related to these three factors under the recent inflationary economic environment; i.e., interest rate yield of the two year treasury bond, inflation rate, and the two moving average of the exchange rate to be considered as rational expectation on the movement of the exchange rate. As result it is our discovery that the selected predicator variables have been influential to the daily volatility and monthly movement of the exchange rate of the Japanese Yen /US $ with evidence the two different models of the regression analysis are able to show the exchange rate are significantly correlated with these four key variables and strongly affected by them. Also, over 30-month study period, the interest rate parity or the purchasing power parity did not hold because of the strong US dollar and the continuous increase in interest rate yield during the rapid inflation in the US economy.
Courtship behaviour reveals temporal regularity is a critical social cue in mouse communication
Authors: Perrodin Catherine , Verzat Colombine , Bendor Daniel
Published: December 2023

While animals navigating the real world face a barrage of sensory input, their brains evolved to perceptually compress multidimensional information by selectively extracting the features relevant for survival. Notably, communication signals supporting social interactions in several mammalian species consist of acoustically complex sequences of vocalisations. However, little is known about what information listeners extract from such time-varying sensory streams. Here, we utilise female mice’s natural behavioural response to male courtship songs to identify the relevant acoustic dimensions used in their social decisions. We found that females were highly sensitive to disruptions of song temporal regularity and preferentially approached playbacks of intact over rhythmically irregular versions of male songs. In contrast, female behaviour was invariant to manipulations affecting the songs’ sequential organisation or the spectro-temporal structure of individual syllables. The results reveal temporal regularity as a key acoustic cue extracted by mammalian listeners from complex vocal sequences during goal-directed social behaviour.
Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis
Authors: Watanuki Shintaro , Kobayashi Hiroshi , Sugiura Yuki , Yamamoto Masamichi , Karigane Daiki , Shiroshita Kohei , Sorimachi Yuriko , Fujita Shinya , Morikawa Takayuki , Koide Shuhei , Oshima Motohiko , Nishiyama Akira , Murakami Koichi , Haraguchi Miho , Tamaki Shinpei , Yamamoto Takehiro , Yabushita Tomohiro , Tanaka Yosuke , Nagamatsu Go , Honda Hiroaki , Okamoto Shinichiro , Goda Nobuhito , Tamura Tomohiko , Nakamura-Ishizu Ayako , Suematsu Makoto , Iwama Atsushi , Suda Toshio , Takubo Keiyo
Published: December 2023

Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in HSCs and elucidate their regulatory mechanisms. Through quantitative
13
C metabolic flux analysis of glucose metabolism using high-sensitivity glucose tracing and mathematical modeling, we found that HSCs activate the glycolytic rate-limiting enzyme phosphofructokinase (PFK) during proliferation and oxidative phosphorylation (OXPHOS) inhibition. Real-time measurement of adenosine triphosphate (ATP) levels in single HSCs demonstrated that proliferative stress or OXPHOS inhibition led to accelerated glycolysis via increased activity of PFKFB3, the enzyme regulating an allosteric PFK activator, within seconds to meet ATP requirements. Furthermore, varying stresses differentially activated PFKFB3 via PRMT1-dependent methylation during proliferative stress and via AMPK-dependent phosphorylation during OXPHOS inhibition. Overexpression of
Pfkfb3
induced HSC proliferation and promoted differentiated cell production, whereas inhibition or loss of
Pfkfb3
suppressed them. This study reveals the flexible and multilayered regulation of HSC glycolytic metabolism to sustain hematopoiesis under stress and provides techniques to better understand the physiological metabolism of rare hematopoietic cells.Combined isotope tracing, mathematical modeling, and single cell ATP analysis enable high-resolution evaluation of blood cell metabolism.Under stress, HSCs quickly accelerate glycolysis to meet ATP demands and maintain hematopoiesis via context-dependent PFKFB3 activation.
Sensory neurons couple arousal and foraging decisions in Caenorhabditis elegans
Authors: Scheer Elias , Bargmann Cornelia I
Published: December 2023

Foraging animals optimize feeding decisions by adjusting both common and rare behavioral patterns. Here, we characterize the relationship between an animal’s arousal state and a rare decision to leave a patch of bacterial food. Using long-term tracking and behavioral state classification, we find that food leaving decisions in Caenorhabditis elegans are coupled to arousal states across multiple timescales. Leaving emerges probabilistically over minutes from the high arousal roaming state, but is suppressed during the low arousal dwelling state. Immediately before leaving, animals have a brief acceleration in speed that appears as a characteristic signature of this behavioral motif. Neuromodulatory mutants and optogenetic manipulations that increase roaming have a coupled increase in leaving rates, and similarly acute manipulations that inhibit feeding induce both roaming and leaving. By contrast, inactivating a set of chemosensory neurons that depend on the cGMP-gated transduction channel TAX-4 uncouples roaming and leaving dynamics. In addition, tax-4-expressing sensory neurons promote lawn-leaving behaviors that are elicited by feeding inhibition. Our results indicate that sensory neurons responsive to both internal and external cues play an integrative role in arousal and foraging decisions.
Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells
Authors: Verdikt Roxane , Armstrong Abigail A , Cheng Jenny , Hwang Young Sun , Clark Amander T , Yang Xia , Allard Patrick
Published: December 2023

Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures the early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naive mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs’ metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.
Unveiling the domain-specific and RAS isoform-specific details of BRAF kinase regulation
Authors: Trebino Tarah Elizabeth , Markusic Borna , Nan Haihan , Banerjee Shrhea , Wang Zhihong
Published: December 2023

BRAF is a key member in the MAPK signaling pathway essential for cell growth, proliferation, and differentiation. Mutant BRAF is often the underlying cause of various types of cancer and mutant RAS, the upstream regulator of BRAF, is a driver of up to one-third of all cancers. BRAF interacts with RAS and undergoes a conformational change from an inactive, autoinhibited monomer to an active dimer, which propagates downstream signaling. Because of BRAF’s complex regulation mechanism, the exact order and magnitude of its activation steps have yet to be confirmed experimentally. By studying the inter- and intramolecular interactions of BRAF, we unveil the domain-specific and isoform-specific details of BRAF regulation through pulldown assays, open surface plasmon resonance (OpenSPR), and hydrogen-deuterium exchange mass spectrometry (HDX-MS). We demonstrate that the BRAF specific region (BSR) and cysteine rich domain (CRD) play a crucial role in regulating the activation of BRAF in a RAS isoform-specific manner. Moreover, we quantified the binding affinities between BRAF N-terminal and kinase domains (KD) to reveal their individual roles in autoinhibition. Our findings also indicate that oncogenic BRAF-KDD594G mutant has a lower affinity for the N-terminal domains, implicating that pathogenic BRAF acts through decreased propensity for autoinhibition. Collectively, our study provides valuable insight into the activation mechanism of BRAF kinase to guide the development of new therapeutic strategies for cancer treatment.
Mechanical coupling coordinates microtubule growth
Authors: Leeds Bonnibelle K , Kostello Katelyn F , Liu Yuna Y , Nelson Christian R , Biggins Sue , Asbury Charles L
Published: December 2023

During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes.
Complete suspension culture of human induced pluripotent stem cells supplemented with suppressors of spontaneous differentiation
Authors: Matsuo-Takasaki Mami , Kambayashi Sho , Hemmi Yasuko , Wakabayashi Tamami , Shimizu Tomoya , An Yuri , Ito Hidenori , Takeuchi Kazuhiro , Ibuki Masato , Kawashima Terasu , Masayasu Rio , Suzuki Manami , Kawai Yoshikazu , Umekage Masafumi , Kato Tomoaki M , Noguchi Michiya , Nakade Koji , Nakamura Yukio , Nakaishi Tomoyuki , Nishishita Naoki , Tsukahara Masayoshi , Hayashi Yohei
Published: December 2023

Human induced pluripotent stem cells (hiPSCs) are promising resources for producing various types of tissues in regenerative medicine; however, the improvement in a scalable culture system that can precisely control the cellular status of hiPSCs is needed. Utilizing suspension culture without microcarriers or special materials allows for massive production, automation, cost-effectiveness, and safety assurance in industrialized regenerative medicine. Here, we found that hiPSCs cultured in suspension conditions with continuous agitation without microcarriers or extracellular matrix components were more prone to spontaneous differentiation than those cultured in conventional adherent conditions. Adding PKCβ and Wnt signaling pathway inhibitors in the suspension conditions suppressed the spontaneous differentiation of hiPSCs into ectoderm and mesendoderm, respectively. In these conditions, we successfully completed the culture processes of hiPSCs, including the generation of hiPSCs from peripheral blood mononuclear cells with the expansion of bulk population and single-cell sorted clones, long-term culture with robust self-renewal characteristics, single-cell cloning, direct cryopreservation from suspension culture and their successful recovery, and efficient mass production of a clinical-grade hiPSC line. Our results demonstrate that precise control of the cellular status in suspension culture conditions paves the way for their stable and automated clinical application.
Complete suspension culture of human induced pluripotent stem cells supplemented with suppressors of spontaneous differentiation
Authors: Matsuo-Takasaki Mami , Kambayashi Sho , Hemmi Yasuko , Wakabayashi Tamami , Shimizu Tomoya , An Yuri , Takeuchi Kazuhiro , Ibuki Masato , Kawai Yoshikazu , Umekage Masafumi , Kato Tomoaki M , Noguchi Michiya , Nakade Koji , Nakamura Yukio , Nakaishi Tomoyuki , Tsukahara Masayoshi , Hayashi Yohei
Published: December 2023

Human induced pluripotent stem cells (hiPSCs) are promising resources for producing various type of tissues in regenerative medicine; however, a scalable culture system that can precisely control the cell status for hiPSCs is not developed yet. Utilizing suspension culture without microcarriers or special materials allows for massive production, automation, cost effectiveness, and safety assurance in industrialized regenerative medicine. Here, we found that hiPSCs cultured in suspension conditions with continuous agitation without any microcarriers or extracellular matrix components were more prone to spontaneous differentiation than those cultured in conventional adherent conditions. Adding PKCβ and Wnt signaling pathway inhibitors in the suspension conditions suppressed the spontaneous differentiation of hiPSCs into ectoderm and mesendoderm, respectively. In these conditions, we successfully completed culture processes of hiPSCs including the generation of hiPSCs from peripheral blood mononuclear cells with the expansion of bulk population and single-cell sorted clones, long-term culture with robust self-renewal characteristics, single cell cloning, direct cryopreservation from suspension culture and their successful recovery, and efficient mass production of a clinical-grade hiPSC line. Our results demonstrate that precise control of hiPSC status in suspension culture conditions paves the way for their stable and automated clinical application.
Identification of key yeast species and microbe–microbe interactions impacting larval growth of Drosophila in the wild
Authors: Mure Ayumi , Sugiura Yuki , Maeda Rae , Honda Kohei , Sakurai Nozomu , Takahashi Yuuki , Watada Masayoshi , Katoh Toshihiko , Gotoh Aina , Gotoh Yasuhiro , Taniguchi Itsuki , Nakamura Keiji , Hayashi Tetsuya , Katayama Takane , Uemura Tadashi , Hattori Yukako
Published: December 2023

Microbiota consisting of various fungi and bacteria have a significant impact on the physiological functions of the host. However, it is unclear which species are essential to this impact and how they affect the host. This study analyzed and isolated microbes from natural food sources of Drosophila larvae, and investigated their functions. Hanseniaspora uvarum is the predominant yeast responsible for larval growth in the earlier stage of fermentation. As fermentation progresses, Acetobacter orientalis emerges as the key bacterium responsible for larval growth, although yeasts and lactic acid bacteria must coexist along with the bacterium to stabilize this host–bacterial association. By providing nutrients to the larvae in an accessible form, the microbiota contributes to the upregulation of various genes that function in larval cell growth and metabolism. Thus, this study elucidates the key microbial species that support animal growth under microbial transition.
Heterogeneous presynaptic receptive fields contribute to directional tuning in starburst amacrine cells
Authors: Gaynes John A , Budoff Samuel A , Grybko Michael J , Poleg-Polsky Alon
Published: December 2023

The processing of visual information by retinal starburst amacrine cells (SACs) involves transforming excitatory input from bipolar cells (BCs) into directional calcium output. While previous studies have suggested that an asymmetry in the kinetic properties of BCs along the soma-dendritic axes of the postsynaptic cell could enhance directional tuning at the level of individual branches, it remains unclear whether biologically relevant presynaptic kinetics contribute to direction selectivity (DS) when visual stimulation engages the entire dendritic tree. To address this question, we built multicompartmental models of the bipolar–SAC circuit and trained them to boost directional tuning. We report that despite significant dendritic crosstalk and dissimilar directional preferences along the dendrites that occur during whole-cell stimulation, the rules that guide BC kinetics leading to optimal DS are similar to the single-dendrite condition. To correlate model predictions to empirical findings, we utilized two-photon glutamate imaging to study the dynamics of bipolar release onto ON- and OFF-starburst dendrites in the murine retina. We reveal diverse presynaptic dynamics in response to motion in both BC populations; algorithms trained on the experimental data suggested that the differences in the temporal release kinetics are likely to correspond to heterogeneous receptive field properties among the different BC types, including the spatial extent of the center and surround components. In addition, we demonstrate that circuit architecture composed of presynaptic units with experimentally recorded dynamics could enhance directional drive but not to levels that replicate empirical findings, suggesting other DS mechanisms are required to explain SAC function. Our study provides new insights into the complex mechanisms underlying DS in retinal processing and highlights the potential contribution of presynaptic kinetics to the computation of visual information by SACs.
Efficient estimation for large-scale linkage disequilibrium patterns of the human genome
Authors: Huang Xin , Zhu Tian-Neng , Liu Ying-Chao , Qi Guo-An , Zhang Jian-Nan , Chen Guo-Bo
Published: December 2023

In this study, we proposed an efficient algorithm (X-LD) for estimating linkage disequilibrium (LD) patterns for a genomic grid, which can be of inter-chromosomal scale or of small segments. Compared with conventional methods, the proposed method was significantly faster, dropped from O(nm2) to O(n2m)—n the sample size and m the number of SNPs, and consequently we were permitted to explore in depth unknown or reveal long-anticipated LD features of the human genome. Having applied the algorithm for 1000 Genome Project (1KG), we found (1) the extended LD, driven by population structure, universally existed, and the strength of inter-chromosomal LD was about 10% of their respective intra-chromosomal LD in relatively homogeneous cohorts, such as FIN, and to nearly 56% in admixed cohort, such as ASW. (2) After splitting each chromosome into upmost of more than a half million grids, we elucidated the LD of the HLA region was nearly 42 folders higher than chromosome 6 in CEU and 11.58 in ASW; on chromosome 11, we observed that the LD of its centromere was nearly 94.05 folders higher than chromosome 11 in YRI and 42.73 in ASW. (3) We uncovered the long-anticipated inversely proportional linear relationship between the length of a chromosome and the strength of chromosomal LD, and their Pearson’s correlation was on average over 0.80 for 26 1KG cohorts. However, this linear norm was so far perturbed by chromosome 11 given its more completely sequenced centromere region. Uniquely chromosome 8 of ASW was found most deviated from the linear norm than any other autosomes. The proposed algorithm has been realized in C++ (called X-LD) and is available at https://github.com/gc5k/gear2, and can be applied to explore LD features in any sequenced populations.
Extramacrochaetae regulates Notch signaling in the Drosophila eye through non-apoptotic caspase activity
Authors: Nair Sudershana , Baker Nicholas E
Published: December 2023

Many cell fate decisions are determined transcriptionally. Accordingly, some fate specification is prevented by Inhibitor of DNA-binding (Id) proteins that interfere with DNA binding by master regulatory transcription factors. We show that the Drosophila Id protein Extra macrochaetae (Emc) also affects developmental decisions by regulating caspase activity. Emc, which prevents proneural bHLH transcription factors from specifying neural cell fate, also prevents homodimerization of another bHLH protein, Daughterless (Da), and thereby maintains expression of the Death-Associated Inhibitor of Apoptosis (diap1) gene. Accordingly, we found that multiple effects of emc mutations on cell growth and on eye development were all caused by activation of caspases. These effects included acceleration of the morphogenetic furrow, failure of R7 photoreceptor cell specification, and delayed differentiation of non-neuronal cone cells. Within emc mutant clones, Notch signaling was elevated in the morphogenetic furrow, increasing morphogenetic furrow speed. This was associated with caspase-dependent increase in levels of Delta protein, the transmembrane ligand for Notch. Posterior to the morphogenetic furrow, elevated Delta cis-inhibited Notch signaling that was required for R7 specification and cone cell differentiation. Growth inhibition of emc mutant clones in wing imaginal discs also depended on caspases. Thus, emc mutations reveal the importance of restraining caspase activity even in non-apoptotic cells to prevent abnormal development, in the Drosophila eye through effects on Notch signaling.
Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury
Authors: Varadharajan Venkateshwari , Ramachandiran Iyappan , Massey William J , Jain Raghav , Banerjee Rakhee , Horak Anthony J , McMullen Megan R , Huang Emily , Bellar Annette , Lorkowski Shuhui W , Gulshan Kailash , Helsley Robert N , James Isabella , Pathak Vai , Dasarathy Jaividhya , Welch Nicole , Dasarathy Srinivasan , Streem David , Reizes Ofer , Allende Daniela S , Smith Jonathan D , Simcox Judith , Nagy Laura E , Brown J Mark
Published: December 2023

Recent genome-wide association studies (GWAS) have identified a link between single-nucleotide polymorphisms (SNPs) near the MBOAT7 gene and advanced liver diseases. Specifically, the common MBOAT7 variant (rs641738) associated with reduced MBOAT7 expression is implicated in non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and liver fibrosis. However, the precise mechanism underlying MBOAT7-driven liver disease progression remains elusive. Previously, we identified MBOAT7-driven acylation of lysophosphatidylinositol lipids as key mechanism suppressing the progression of NAFLD (Gwag et al., 2019). Here, we show that MBOAT7 loss of function promotes ALD via reorganization of lysosomal lipid homeostasis. Circulating levels of MBOAT7 metabolic products are significantly reduced in heavy drinkers compared to healthy controls. Hepatocyte- (Mboat7-HSKO), but not myeloid-specific (Mboat7-MSKO), deletion of Mboat7 exacerbates ethanol-induced liver injury. Lipidomic profiling reveals a reorganization of the hepatic lipidome in Mboat7-HSKO mice, characterized by increased endosomal/lysosomal lipids. Ethanol-exposed Mboat7-HSKO mice exhibit dysregulated autophagic flux and lysosomal biogenesis, associated with impaired transcription factor EB-mediated lysosomal biogenesis and autophagosome accumulation. This study provides mechanistic insights into how MBOAT7 influences ALD progression through dysregulation of lysosomal biogenesis and autophagic flux, highlighting hepatocyte-specific MBOAT7 loss as a key driver of ethanol-induced liver injury.
Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications
Authors: Schuster Jens , Lu Xi , Dang Yonglong , Klar Joakim , Wenz Amelie , Dahl Niklas , Chen Xingqi
Published: December 2023

Dravet syndrome (DS) is a devastating early-onset refractory epilepsy syndrome caused by variants in the SCN1A gene. A disturbed GABAergic interneuron function is implicated in the progression to DS but the underlying developmental and pathophysiological mechanisms remain elusive, in particularly at the chromatin level. Induced pluripotent stem cells (iPSCs) derived from DS cases and healthy donors were used to model disease-associated epigenetic abnormalities of GABAergic development. Chromatin accessibility was assessed at multiple time points (Day 0, Day 19, Day 35, and Day 65) of GABAergic differentiation. Additionally, the effects of the commonly used anti-seizure drug valproic acid (VPA) on chromatin accessibility were elucidated in GABAergic cells. The distinct dynamics in the chromatin profile of DS iPSC predicted accelerated early GABAergic development, evident at D19, and diverged further from the pattern in control iPSC with continued differentiation, indicating a disrupted GABAergic maturation. Exposure to VPA at D65 reshaped the chromatin landscape at a variable extent in different iPSC-lines and rescued the observed dysfunctional development of some DS iPSC-GABA. The comprehensive investigation on the chromatin landscape of GABAergic differentiation in DS-patient iPSC offers valuable insights into the epigenetic dysregulations associated with interneuronal dysfunction in DS. Moreover, the detailed analysis of the chromatin changes induced by VPA in iPSC-GABA holds the potential to improve the development of personalized and targeted anti-epileptic therapies.
BMP signalling facilitates transit amplification in the developing chick and human cerebellum
Authors: Rook V , Haldipur P , Millen K , Wingate RJ , Butts T
Published: December 2023

The external granule layer (EGL) is a transient proliferative layer that gives rise to cerebellar granule cell neurons. Extensive EGL proliferation characterises the foliated structure of amniote cerebella, but the factors that regulate EGL formation, amplification within it, and differentiation from it, are incompletely understood. Here, we characterise bone morphogenic protein (BMP) signalling during cerebellar development in chick and human and show that while in chick BMP signalling correlates with external granule layer formation, in humans BMP signalling is maintained throughout the external granule layer after the onset of foliation. We also show via Immunohistochemical labelling of phosphorylated Smad1/5/9, that the spatiotemporal activity of BMP signalling is conserved between chick and human. Using
in ovo
electroporation in chick, we demonstrate that BMP signalling is necessary for subpial migration of granule cell precursors and hence the formation of the external granule layer (EGL) prior to transit amplification. However, altering BMP signalling does not block the formation of mature granule neurons but significantly disrupts that pattern of morphological transitions that accompany transit amplification. Our results elucidate two key, temporally distinct roles for BMP signalling
in vivo
in organising first the assembly of the EGL from the rhombic lip and subsequently the tempo of granule neuron production within the EGL.Improper development of cerebellar granule neurons can manifest in a plethora of neurodevelopmental disorders, including but not limited to medulloblastoma and autism. Medulloblastoma can be a consequence of uncontrolled proliferation of granule cell progenitors, with BMP overexpression being a potential therapeutic avenue to inhibit this proliferation. Many studies have sought to understand the role of developmental signalling pathways in granule cell neurogenesis, using genetic manipulation in transgenic mice. To complement these insights, we have used comparative assessment of BMP signalling during development in chick and human embryos and
in vivo
manipulation of the chick to understand and segregate the spatiotemporal roles of BMP signalling, yielding important insights on evolution and in consideration of future therapeutic avenues that target BMP signalling.
A single pair of pharyngeal neurons functions as a commander to reject high salt in Drosophila melanogaster
Authors: Sang Jiun , Dhakal Subash , Shrestha Bhanu , Nath Dharmendra Kumar , Kim Yunjung , Ganguly Anindya , Montell Craig , Lee Youngseok
Published: December 2023

Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster, internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b, is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.
An Assessment of Influence of Industrial Training Learning Outcomes on the Decision of Students to Leave or Stay in Hotel Management Courses
Authors: Chauhan Suresh , Bakshi Ishan , Khatkar Pardeep
Published: December 2023

The benefits of the training experience in terms of education and job development are commonly acknowledged.  Skill mismatch is currently common among young people who are unemployed. This is mostly due to the wide disparity between the professional abilities of job searchers and the needs of businesses, which is primarily caused by the disrupted connection between training, educational background and the workplace for young people across different countries. In order to determine the impact of these learning outcomes on students' decisions to leave or remain in the hotel management courses, the current study used a cross-sectional study design to examine changes in personality traits and skills among 432 undergraduate hotel management students based on hotel Industrial Training learning outcomes. Based on learning outcomes following the completion of their industrial training, it was discovered that students studying hotel management had a considerable positive boost in their personality traits and competencies. Additionally, it was also discovered that the most important hotel industrial training learning outcomes such as Extended and refined knowledge, Positive attitude and perception, Self-motivation, Enhancing Interpersonal Skills, and Self-improvement had a significant positive influence on students' decisions to leave or remain in the hotel management courses.
Estimation of Glomerular Filtration Rate Using the New Ekfc Equation in Healthy and Chronic Kidney Disease Adult Subjects from Sub-Saharan Africa
Authors: Yao-Yapo Carine Mireille , Yayo Eric Sagou , Koné-Dakouri Yékayo Bénédicte , Kouacou Kadio Morel , Konan Jean Louis , Koffi Akissi Joelle , Yao Hubert , Hauhouot-Attoungbré Marie Laure , Monnet Dagui
Published: December 2023

Introduction: Since the publication of the first equation for estimate creatinine clearance in 1957, several other equations estimating glomerular filtration rate have followed in succession. To date, a new equation has been published by the European Kidney Function Consortium (EKFC) in 2021, which would have the advantage of being adaptable to any type of population. In this study, we aimed to evaluate the performance of this new equation in our black African population of healthy subjects and subjects with chronic kidney disease.

Material and Methods: This was a cross-sectional study involving 192 healthy subjects and 183 subjects with chronic kidney disease. Plasma iohexol clearance (mGFR) constituted́ the reference method used to measure glomerular filtration rate and allowed evaluation of all equation variants (EKFC crea, EKFC cys, EKFC crea-cys). Equation performance was studied by calculating the 95% CI bias, the interquartile range (25% percentile, 75% percentile) and the 30% accuracy (P30) compared with the reference method.

Results: All EKFC variants in both populations (healthy subjects and chronic kidney disease subjects) had biases below 5 ml/min/1.73 m2. Biases were therefore acceptable. On the other hand, P30s were less good in subjects with chronic kidney disease.

Conclusion: Thus, the EKFC equation performs well in the healthy population, but its evaluation in the chronic kidney disease population needs to be strengthened on the basis of larger cohorts.
Agroforestry and Its Potential for Sustainable Land Management and Climate Action: A Review
Authors: Kumar Raj , Veeraragavan M. , Baral Kirttiranjan , Saikanth D. R. K. , Singh Veerendra , Upadhyay Lalit , Raj Sumit
Published: December 2023

Agroforestry, the integration of trees and shrubs with crops and/or livestock, stands as a pivotal strategy in sustainable land management and climate action. This review synthesizes current knowledge and practices of agroforestry, focusing on its diverse systems, contributions to sustainable land management, role in climate change mitigation and adaptation, and the challenges and future prospects, with a special emphasis on the Indian context. Agroforestry systems, classified into silvopastoral, agrosilvicultural, and silvoarable, along with specialized practices like alley cropping and forest farming, demonstrate significant adaptability across various climatic and geographical regions. These systems have shown promising results globally, evident in case studies highlighting their effectiveness in different environmental settings. In the realm of sustainable land management, agroforestry is instrumental in soil conservation, enhancing soil fertility, and nutrient cycling. It also plays a critical role in biodiversity conservation and the enhancement of ecosystem services, such as water regulation and pollination. Socioeconomically, agroforestry contributes to improving livelihoods and economic resilience, as demonstrated in various local community case studies. In addressing climate change, agroforestry systems are notable for their carbon sequestration capabilities. Compared to traditional agricultural practices, these systems exhibit a higher potential for carbon storage, both above and below ground. They also enhance resilience to climate extremes, offering adaptive strategies for farmers and communities facing climatic variability. Policy and global initiatives increasingly recognize agroforestry's role in climate action, with international agreements and organizations fostering its integration into national policies. The implementation of agroforestry is not without challenges. Technical complexities, the need for site-specific knowledge, economic and policy barriers, and sociocultural factors pose significant hurdles. For India, a country with diverse agro-ecological zones, these challenges are coupled with opportunities for research, technological innovation, policy improvement, and global-local collaborations. The future prospects for agroforestry are vast, particularly in the Indian context, where it can significantly contribute to sustainable agriculture and rural development. Continued research, policy support, and collaborative efforts are essential to fully realize the potential of agroforestry in environmental conservation, climate change mitigation, and socioeconomic development.
Papyrology
Authors: Cromwell Jennifer
Published: December 2023

Taking its name from the writing medium produced from the papyrus plant, papyrology is the study and use of texts written on papyrus and other portable materials (potsherds, limestone flakes, leather, bone). Deriving mainly from Egypt, papyrological materials also survive from elsewhere in Africa, western Asia, and the northern Mediterranean, and preserve a diverse range of textual types, including documentary, literary, and semi‐literary works. The study of these sources is essential for reconstructing the history of the ancient to early medieval world, from the life of individual men and women to the pivotal moments of social, religious, and political change.
Face‐on Orientation Matches Vertical Organic Electrochemical Transistors for High Transconductance and Superior Non‐Volatility
Authors: Wang Bingjun , Kong Yuxin , Zhang Sen , Wu Ziang , Wang Shijie , Ren Jiaqi , Woo Han Young , Li Yuxiang , Ma Wei
Published: December 2023

The recently developed vertical structure of organic electrochemical transistors (OECTs) can integrate volatile and non‐volatile functions into one reconfigurable device, making it highly promising. However, comparing with the conventional planar OECT (c‐OECT), the understanding of vertical OECT (v‐OECT) working principles and device engineering strategies is still lacking, impeding rational optimization. Since a major difference between c‐ and v‐OECTs is their charge transport directionality, which is highly influenced by crystallite orientations, the orientation–device structure match thus becomes an important yet outstanding topic for OECTs. Herein, using an n‐type small molecule IDIC‐MEG, investigate how much impact such match can have on OECT performance. The IDIC‐MEG c‐OECT fails to work due to the seriously hindered in‐plane electron transport by face‐on orientation. Surprisingly, simply changing the device structure from planar to vertical allows the resultant v‐OECT to exhibit the highest reported transconductance (46.3 mS) among all small‐molecule OECTs, thanks to the match between face‐on orientation and the vertical structure. Such match also leads to excellent non‐volatility, including highly predictable programmability and good operational stability. This work, for the first time, explicitly demonstrates the significance of orientation–device structure match for OECT optimization, establishing new guidelines for achieving high‐performance volatile and non‐volatile OECTs.
Pom Functionalized Ionogels with Tunable Optical, Mechanical, Electrical, and Sensory Properties
Authors: Mu Chenglong , Chen Yulin , Dai Zhang , Li Wei , Wang Jiefei , Jiao Xiuling , Chen Dairong , Wang Ting
Published: December 2023

Ionogels, with wide applications in tissue engineering, soft robotics, and flexible iontronic devices, require tunable optical, mechanical, and electrical properties for advanced functionality applications. Here, a facile strategy is reported to tune a set of properties of ionogels via tuning the redox states of the added polyoxometalate (POM) clusters. Upon external electrical stimuli, the POM clusters in the ionogels can be reversibly tuned from a transparent, oxidized state to a blue, reduced state. The redox states of the POM anions influence the POM‐polymer interactions, which promotes the in situ modulation of the ionogel properties reversibly over a large window: optical transparency from 91% to 7%, dissipated energy from 0.9 to 3.1 MJ m−3, elastic modulus from 1.5 to 2 MPa, conductivity from 1.6 × 10−4 to 2.2 × 10−4 S cm−1. Meanwhile, the sensory properties of the ionogels can be modulated simultaneously. For strain sensing and pressure sensing, the GF can be tuned from 2.3 to 7.2, and the sensitivity can be tuned from 0.8 to 1.2 kPa−1. Such an ionogel with tunable optical, mechanical, and electrical properties may find a variety of applications meeting specific demands. The POM functionalization strategy may also bring new insights into the design of the stimuli‐responsive ionogels.
A High‐Q Electric‐Mechano‐Magnetic Coupled Resonator for ELF/SLF Cross‐Medium Magnetic Communication
Authors: Chang Jianglei , He Zhuangzhuang , Xu Shupeng , Zheng Xinyi , Peng Wei , Ci Penghong , Wang Bin , Zhang Chunli , Dong Shuxiang
Published: December 2023

Extremely/super low frequency (ELF/SLF) electromagnetic wave can effectively propagate in the harsh cross‐medium environment where a high‐frequency electromagnetic wave cannot pass due to the fast decay. For efficiently transmitting a strong ELF/SLF radiation signal, the traditional electromagnetic antenna requires a super‐large loop (>10 km). To address this issue, in this work, a piezoelectric ceramic/ferromagnetic heterogeneous structured, cantilever beam‐type electric‐mechano‐magnetic coupled resonator at only centimeter scale for ELF/SLF cross‐medium magnetic communication is reported. Through designing hard‐soft hybrid step‐stiffness elastic beam, the resonator exhibits a much higher quality factor Q (≈240) for ELF/SLF magnetic field transmitting, which is one to five orders of magnitude higher than those of previously reported mechanical antennas and loop coil antennas. Moreover, the resonator exhibits a 5000 times higher magnetic field emitting efficiency compared to a conventional loop coil antenna in ELF/SLF band. It also demonstrates a 200% increase in magnetic field emitting capacity compared to existing piezoelectric‐driven antennas. In addition, an ASK+PSK modulation method is proposed for suppressing relaxation time of the resonator, and a reduction in the relaxation time by 80% is observed. Furthermore, an air–seawater cross‐medium magnetic field communication is successful demonstrated, indicating its potential as portable, high‐efficient antenna for underwater and underground communications.
A Customizable Proteinic Bioadhesive Patch with Water‐Switchable Underwater Adhesiveness, Adjustable Biodegradability, and Modifiable Stretchability for Healing Diverse Internal Wounds
Authors: Yang Jang Woo , Song Kang‐Il , Lee Jaeyun , Park Sungho , Huh Hyungkyu , Choi Geunho , Shin Hwa Hui , Cha Hyung Joon
Published: December 2023

Customizable bioadhesives for individual organ requirements, including tissue type and motion, are essential, especially given the rise in implantable medical device applications demanding adequate underwater adhesion. While synthetic bioadhesives are widely used, their toxicity upon degradation shifts focus to biocompatible natural biomaterials. However, enhancing the adhesive strengths of these biomaterials presents ongoing challenges while accommodating the unique properties of specific organs. To address these issues, three types of customized underwater bioadhesive patches (CUBAPs) with strong, water‐responsive adhesion and controllable biodegradability and stretchability based on bioengineered mussel adhesive proteins conjugated with acrylic acid and/or methacrylic acid are proposed. The CUBAP system, although initially nonadhesive, shows strong underwater adhesion upon hydration, adjustable biodegradation, and adequate physical properties by adjusting the ratio of poly(acrylic acid) and poly(methacrylic acid). Through ex vivo and in vivo evaluations using defective organs and the implantation of electronic devices, the suitability of using CUBAPs for effective wound healing in diverse internal organs is demonstrated. Thus, this innovative CUBAP system offers strong underwater adhesiveness with tailored biodegradation timing and physical properties, giving it great potential in various biomedical applications.
Alpha‐Synuclein Oligomers Driven T1–T2 Switchable Nanoprobes for Early and Accurate Diagnosis of Parkinson's Disease
Authors: Chen Ying , Liang Zeyu , Wang Qiyue , Xiao Lin , Xie Shangzhi , Yang Shengfei , Liu Xun , Ling Daishun , Li Fangyuan
Published: December 2023

The alpha‐synuclein (α‐syn) oligomers hold a central role in the pathology of Parkinson's disease (PD). Achieving accurate detection of α‐syn oligomers in vivo presents a promising avenue for early and accurate diagnosis of PD. Magnetic resonance imaging (MRI), with non‐invasion and exceptional tissue penetration, offers a potent tool for visualizing α‐syn oligomers in vivo. Nonetheless, ensuring diagnostic specificity remains a formidable challenge. Herein, a novel MRI probe (ASOSN) is introduced, which encompasses highly sensitive antiferromagnetic nanoparticles functionalized with single‐chain fragment variable antibodies, endowing it with the capacity for discerning recognition and binding to α‐syn oligomers and triggering a switchable T1–T2 MRI signal. Significantly, ASOSN possesses the unique capability to accurately discriminate α‐syn oligomers from neuroinflammation in vivo. Moreover, ASOSN facilitates the non‐invasive and precise visualizing of endogenous α‐syn oligomers in living systems. This innovative design heralds the development of a non‐invasive visualization strategy for α‐syn oligomers, marking a pivotal advancement for early and accurate diagnosis of PD.