bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive mapping of cell fates in microsatellite unstable cancer cells support dual targeting of WRN and ATR
Authors: Zong Dali , Koussa Natasha C. , Cornwell James A. , Pankajam Ajith V. , Kruhlak Michael J. , Wong Nancy , Chari Raj , Cappell Steven D. , Nussenzweig André
Published: July 2023

Addiction to the WRN helicase is a unique vulnerability of human cancers with high levels of microsatellite instability (MSI-H). However, while prolonged loss of WRN ultimately leads to cell death, little is known about how MSI-H cancers initially respond to acute loss of WRN, knowledge that would be helpful for informing clinical development of WRN-targeting therapy, predicting possible resistance mechanisms, and identifying useful biomarkers of successful WRN inhibition. Here, we report the construction of an inducible ligand-mediated degradation system wherein the stability of endogenous WRN protein can be rapidly and specifically tuned, enabling us to track the complete sequence of cellular events elicited by acute loss of WRN function. We find that WRN degradation leads to immediate accrual of DNA damage in a replication-dependent manner that curiously did not robustly engage checkpoint mechanisms to halt DNA synthesis. As a result, WRN-degraded MSI-H cancer cells accumulate DNA damage across multiple replicative cycles and undergo successive rounds of increasingly aberrant mitoses, ultimately triggering cell death. Of potential therapeutic importance, we find no evidence of any generalized mechanism by which MSI-H cancers could adapt to near-complete loss of WRN. However, under conditions of partial WRN degradation, addition of low dose ATR inhibitor significantly increased their combined efficacy to levels approaching full inactivation of WRN. Overall, our results provided the first comprehensive view of molecular events linking upstream inhibition of WRN to subsequent cell death and suggested a potential therapeutical rationale for dual targeting of WRN and ATR.
A systematic comparison of computational methods for expression forecasting
Authors: Kernfeld Eric , Yang Yunxiao , Weinstock Joshua S. , Battle Alexis , Cahan Patrick
Published: July 2023

Expression forecasting methods use machine learning models to predict how a cell will alter its transcriptome upon perturbation. Such methods are enticing because they promise to answer pressing questions in fields ranging from developmental genetics to cell fate engineering and because they are a fast, cheap, and accessible complement to the corresponding experiments. However, the absolute and relative accuracy of these methods is poorly characterized, limiting their informed use, their improvement, and the interpretation of their predictions. To address these issues, we created a benchmarking platform that combines a panel of 11 large-scale perturbation datasets with an expression forecasting software engine that encompasses or interfaces to a wide variety of methods. We used our platform to systematically assess methods, parameters, and sources of auxiliary data, finding that performance strongly depends on the choice of metric, and especially for simple metrics like mean squared error, it is uncommon for expression forecasting methods to out-perform simple baselines. Our platform will serve as a resource to improve methods and to identify contexts in which expression forecasting can succeed.
Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing
Authors: Ryu Jihye , Choi Jeong-woo , Niketeghad Soroush , Torres Elizabeth B. , Pouratian Nader
Published: July 2023

Background

Goal-directed movements involve integrating proprioceptive and visuo-motor information. Although the neural correlates of such information processing are known, the details of how sensory-motor integration occurs are still largely unknown.

Objective

The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization.

Approach

In this study, 8 essential tremor patients undergoing an awake deep brain stimulation (DBS) implantation surgery repetitively touched the clinician’s finger (forward visually-guided/FV movement) and then one’s own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic (ECoG) recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30-80Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: 1) correlation between the amplitude and its proceeding IEI, and 2) auto-information of the IEI time series. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods.

Results

Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest.

Significance

We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e., IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.
Heat stress induces a developmental shift from type-V to type-IV trichome dependent on jasmonate signaling in tomato
Authors: Säbel Robert , Brand Alejandro , Bergau Nick , Balcke Gerd U. , Syrowatka Frank , Püffeld-Raorane Mandy , Hause Bettina , Tissier Alain
Published: July 2023

Cultivated tomato (Solanum lycopersicum) and related wild species develop several types of trichomes, both glandular and non-glandular, on their aerial parts. Among these, type-IV trichomes are responsible for the synthesis and secretion of acylsugars, which act as defense compounds against herbivores. In contrast to related wild species such asS. pennellii, type-IV trichomes are present only in the juvenile stages of cultivated tomato plants and absent in later stages of development. By submitting tomato plants to high temperatures during the day (37 °C), we observe that non-glandular type-V trichomes are replaced by type-IV trichomes. This is accompanied by a massive increase in acylsugar production. On the other hand, heat treatment does not affect type VI-trichomes, which produce mono- and sesquiterpenes, but the production of monoterpenes is increased while that of sesquiterpenes is suppressed. Furthermore, tomatojai1mutants deficient in jasmonate (JA) perception do not exhibit this developmental switch from type-V to type-IV trichomes. The implication of JA signaling in this process was further supported by an increase in JA-isoleucine and in the expression of genes involved in JA-signalling within hours of heat stress application. These results establish a unique system to study how environmental factors affect developmental fate decisions in plants while opening opportunities to understand mechanisms controlling type-IV trichome initiation and development.
Hawkes process modeling quantifies complicated firing behaviors of cortical neurons during sleep and wakefulness
Authors: Kanda Takeshi , Aritake Toshimitsu , Ohyama Kaoru , Vogt Kaspar E. , Makino Yuichi , McHugh Thomas J. , Hino Hideitsu , Akaho Shotara , Murata Noboru
Published: July 2023

Despite the importance of sleep to the cerebral cortex, how much sleep changes cortical neuronal firing remains unclear due to complicated firing behaviors. Here we quantified firing of cortical neurons using Hawkes process modeling that can model sequential random events exhibiting temporal clusters. “Intensity” is a parameter of Hawkes process that defines the probability of an event occurring. We defined the appearance of repetitive firing as the firing intensity corresponding to “intensity” in Hawkes process. Firing patterns were quantified by the magnitude of firing intensity, the time constant of firing intensity, and the background firing intensity. The higher the magnitude of firing intensity, the higher the likelihood that the spike will continue. The larger the time constant of firing intensity, the longer the repetitive firing lasts. The higher the background firing intensity, the more likely neurons fire randomly. The magnitude of firing intensity was inversely proportional to the time constant of firing intensity, and non-REM sleep increased the magnitude of firing intensity and decreased the time constant of firing intensity. The background firing intensity was not affected by the sleep/wake state. Our findings suggest that the cortex is organized such that neurons with a higher probability of repetitive firing have shorter repetitive firing periods. In addition, our results suggest that repetitive firing is ordered to become high frequency and short term during non-REM sleep, while unregulated components of firing are independent of the sleep/wake state in the cortex. Hawkes process modeling of firing will reveal novel properties of the brain.
Murine GMP- and MDP-derived classical monocytes have distinct functions and fates
Authors: Trzebanski Sébastien , Kim Jung-Seok , Larossi Niss , Raanan Ayala , Kancheva Daliya , Bastos Jonathan , Haddad Montaser , Solomon Aryeh , Sivan Ehud , Aizik Dan , Kralova Jarmila , Gross-Vered Mor , Boura-Halfon Sigalit , Lapidot Tsvee , Alon Ronen , Movahedi Kiavash , Jung Steffen
Published: July 2023

Monocytes are short-lived myeloid immune cells that arise from adult hematopoiesis and circulate for a short time in the blood. They comprise two main subsets, in mice defined as classical Ly6Chighand non-classical Ly6Clowmonocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM in the BM and blood. Functional characterization, including fate definition following adoptive cell transfer, established that GMP-Mo and MDP-Mo could equal rise to homeostatic CM progeny, such as NCM in blood and gut macrophages, but differentially seeded selected other tissues. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, thus linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide comprehensive evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge. Our findings are indicative of impact of monocyte ontogeny onin situdifferentiation.
Acoustic wave-induced stroboscopic optical mechanotyping of adherent cells
Authors: Combriat Thomas , Olsen Petter Angell , Låstad Silja Borring , Malthe-Sørenssen Anders , Krauss Stefan , Dysthe Dag Kristian
Published: July 2023

In this study, we present a novel, high content technique using an innovative cylindrical acoustic transducer, stroboscopic fast imaging and homodyne detection to recover the mechanical properties (dynamic shear modulus) of living adherent cells at low ultrasonic frequencies. By analyzing the micro-oscillations of cells we were able to simultaneously mechanotype whole populations of cells with sub-cellular resolution. The technique can be combined with standard fluorescence imaging allowing to further cross-correlate biological and mechanical information. We demonstrate the potential of the technique by mechanotyping co-cultures of different cell types with significantly different mechanical properties.
Evaluation of a BE-inactivated whole virus preparation using an encephalomyocarditis virus strain that was isolated from fatal infection in orangutans
Authors: Tong Cathlyn , Tan Boon-Huan , Sugrue Richard
Published: July 2023

A novel Encephalomyocarditis virus (EMCV) of the group 3 cluster (EMCV-3) was first reported in 2002 to be responsible for the deaths of orang-utans in an outbreak in the Singapore Zoo. After this first outbreak, sporadic infections among the primate population caused by EMCV-3 continued to be reported, suggesting that the virus remains prevalent in Singapore. To prevent future infections, we constructed an experimental vaccine using binary ethylenimine (BE) to inactivate the EMCV-3 virus. The immunological performance of the BE-inactivated (BEI) virus was analysed in mice and the neutralising titre of the immune sera measured against the wild-type EMCV-3. The BEI virus showed a strong immunological response in BALB/c mice at 1: 40,960 titre, suggesting that it can be used as a promising experimental vaccine candidate to prevent EMCV-3 infections.
Brd4::Nutm1fusion gene initiates NUT carcinomain vivo
Authors: Zheng Dejin , Elnegiry Ahmed , Luo Chenxiang , Bendahou Mohammed Amine , Xie Liangqi , Bell Diana , Takahashi Yoko , Hanna Ehab , Mias George I. , Tsoi Mayra F. , Gu Bin
Published: July 2023

Nut carcinoma (NC) is an aggressive cancer with no effective treatment. The majority (70%) of NUT carcinoma is associated with chromosome translocation events that lead to the formation of aBRD4::NUTM1fusion gene. However, because theBRD4::NUTM1gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model (GEMM) for NUT carcinoma recapitulating the human mutation. By stochastically inducing a chromosome translocation mirroring the human event, we demonstrated that theBrd4::Nutm1fusion gene could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with an enrichment of undifferentiated cells. Similar to the reports of human NC incidence,Brd4::Nutm1can induce NC from a broad range of tissues, demonstrating that its oncogenic potential is not lineage-restricted. The consistent induction of tumors of squamous phenotypes, even from ductal epithelial and mesenchymal tissues, demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC and opens new opportunities for understanding the oncogenic mechanism and developing new therapies.
Upper Thermal Tolerance of the Endemic Freshwater StingrayPotamotrygon Magdalenaeand Inference on its Populations: An Endemic Potamotrygonid Resistant to High Temperatures Facing Thermal Changes
Authors: Gómez-Martínez Daniela , Londoño-Cruz Edgardo , Mejía-Falla Paola Andrea
Published: July 2023

Knowledge on thermal tolerance limits provide important clues to the capacity of a species to withstand acute thermal conditions. Climatic models predict the increase and intensification of events such as heat waves, therefore understanding the upper thermal limits that a species can tolerate, has become of utmost importance. We measure the upper thermal tolerance of the endemic freshwater stingrayPotamotrygon magdalenaeacclimated to experimental conditions, using the Critical Thermal Methodology (CTM). We also describe the behavior of individuals and infer the possible consequences of temperature increases in the habitats ofP. magdalenaepopulations. There were no significant differences between sexes in temperature tolerance or behavior. The Critical Thermal Maximum - CTMax (39ºC) was 5.9ºC above the maximum recorded temperature for the study area. AlthoughP. magdalenaewas tolerant to high temperature and currently is not living at its upper thermal limit, its survival in Guarinocito Pond will be threatened if the increasing trend in temperature conditions keeps growing over time.

SUMMARY STATEMENT

Potamotrygon magdalenaeshows tolerance to high temperatures regardless of sex and size; however, can be threatened in the future if the temperature in its habitat continues rising.
Elevator motion of chloride ion transporter SLC26A9 induced by STAS domain
Authors: Omori Satoshi , Hanazono Yuya , Nishi Hafumi , Kinoshita Kengo
Published: July 2023

The anion exchanger SLC26A9, consisting of the transmembrane (TM) domain and the cytoplasmic STAS domain, plays an essential role in regulating chloride transport across cell membranes. Recent studies have indicated that C-terminal helices block the entrance of the putative ion transport pathway. However, the precise functions of the STAS domain and C-terminal helix, as well as the underlying molecular mechanisms governing the transport process, remain poorly understood. In this study, we performed molecular dynamics simulations of three distinct models of human SLC26A9: full-length (FL), STAS domain removal (ΔSTAS), and C-terminus removal (ΔC), to investigate their conformational dynamics and ion binding properties. Stable binding of ions to the binding sites was exclusively observed in the ΔC model in these simulations. Comparing the FL and ΔC simulations, the ΔC model displayed enhanced motion of the STAS domain. Furthermore, comparing the ΔSTAS and ΔC simulations, the ΔSTAS simulation failed to exhibit stable ion bindings to the sites despite the absence of the C-terminus blocking the ion transmission pathway in both systems. These results suggest that the removal of the C-terminus not only unblocks the access of ions to the permeation pathway but also triggers STAS domain motion, gating the TM domain to promote ions’ entry into their binding site. Further analysis revealed that the asymmetric motion of STAS domain leads to the expansion of the ion permeation pathway within the TM domain, resulting in the stiffening of the flexible TM12 helix near the ion binding site. This structural change in the TM12 helix stabilizes chloride ion binding, which is essential for SLC26A9 elevator motion. Overall, our study provides new insights into the molecular mechanisms of SLC26A9 transport and may pave the way for the development of novel treatments for diseases associated with dysregulated ion transport.

SIGNIFICANCE

We explored the mechanism by which the human protein SLC26A9 transports chloride in the cell. SLC26A9 is a potential therapeutic target for patients with cystic fibrosis, as by targeting drugs to it, it may be possible to restore chloride ion transport in epithelial cells. To design therapeutic drugs, it is essential to understand how the protein works. Our findings support an elevator-type mechanism, in which chloride ions bind to SLC26A9 inside the cell and are then released by the protein to the extracellular environment. We find that the STAS domain of SLC26A9 has critical roles in binding chloride and induces conformational changes in the transmembrane domain that facilitate chloride transport.
Refined read-out: The hUHRF1 Tandem-Tudor domain prefers binding to histone H3 tails containing K4me1 in the context of H3K9me2/3
Authors: Choudalakis Michel , Kungulovski Goran , Mauser Rebekka , Bashtrykov Pavel , Jeltsch Albert
Published: July 2023

UHRF1 is an essential chromatin protein required for DNA methylation maintenance, mammalian development and gene regulation. We investigated the Tandem-Tudor domain (TTD) of human UHRF1 that is known to bind H3K9me2/3 histones and is a major driver of UHRF1 localization in cells. We verified binding to H3K9me2/3 but unexpectedly discovered stronger binding to H3 peptides and mononucleosomes containing K9me2/3 with additional K4me1. We investigated the combined binding of TTD to H3K4me1-K9me2/3vs. H3K9me2/3, engineered mutants with specific and differential changes of binding, and discovered a novel read-out mechanism for H3K4me1 in an H3K9me2/3 context that is based on the interaction of R207 with the H3K4me1 methyl group and on counting the H-bond capacity of H3K4. Individual TTD mutants showed up to 10,000-fold preference for the double modified peptides, suggesting that after a conformational change, WT TTD could exhibit similar effects. The frequent appearance of H3K4me1-K9me2 regions demonstrated in our TTD pulldown and ChIP-western blot data suggests that it has specific biological roles. Chromatin pull-down of TTD from HepG2 cells and ChIP-seq data of full-length murine UHRF1 correlate with H3K4me1 profiles indicating that the H3K4me1-K9me2/3 interaction of TTD influences chromatin binding of full-length UHRF1. We demonstrated the H3K4me1-K9me2/3 specific binding of UHRF1-TTD to enhancers and promoters of cell-type specific genes, at the flanks of cell-type specific transcription factor binding sites, and provided evidence supporting an H3K4me1-K9me2/3 dependent and TTD mediated down-regulation of these genes by UHRF1, illustrating the physiological function of UHRF1-TTD binding to H3K4me1-K9me2/3 double marks in a cellular context.
Mutual dependence of Osbp and PI4KII in the maturation of regulated secretory granules
Authors: Ma Cheng-I Jonathan , Brill Julie A.
Published: July 2023

Secretory granules (SGs) are crucial for normal animal physiology due to their role in regulated exocytosis of biologically active molecules. SG membranes are enriched in phosphatidylinositol 4-phosphate (PI4P) and cholesterol, and previous studies suggest lipid composition is important for SG biogenesis and function. Nonetheless, the molecular details of how lipids are regulated during SG biogenesis remain poorly understood. Here, we identify Oxysterol binding protein (Osbp) as a novel regulator of SG biogenesis in aDrosophilamodel. We show Osbp expression level positively correlates with SG size and that Osbp requires type II phosphatidylinositol 4-kinase (PI4KII) to increase SG size. Moreover, Osbp is needed for proper PI4KII and PI4P distribution, autophagic resolution and formation of cholesterol-rich endosomal tubules that are positive for PI4KII. Feeding larvae food supplemented with sterol leads to partial suppression of SG size and PI4P distribution defects inOsbpmutants. Our results indicate that reciprocal regulation of Osbp and PI4KII drives formation of membrane tubules that mediate SG maturation through elevating PI4P levels on SG membranes.

Graphical Abstract

Highlights

Osbp is needed for formation of PI4KII-positive endosomal tubules that enrich secretory granule membranes with PI4P and facilitate granule maturation.

Reciprocally, PI4KII is needed for Osbp-mediated secretory granule growth in salivary gland cells.

Changes in Osbp expression levels alter autophagy initiation and autophagosome resolution in salivary gland cells.

PI4KII-positive endosomal tubules are enriched in sterols, and sterol feeding suppresses defects caused by loss of Osbp.
A conserved graft formation process inPicea abiesandArabidopsis thalianaidentifies the PAT gene family as central regulators of wound healing
Authors: Feng Ming , Zhang Ai , Nguyen Van , Bisht Anchal , Almqvist Curt , Veylder Lieven De , Carlsbecker Annelie , Melnyk Charles W.
Published: July 2023

The widespread use of plant grafting has enabled eudicots and gymnosperms to join with closely related species and grow as one. Gymnosperms have dominated forests for over 200 million years and despite their economic and ecological relevance, we know little about how they graft. Here, we developed a micrografting method in conifers using young tissues that allowed efficient grafting between closely related species and distantly related genera. Conifer graft junctions rapidly connected vasculature and differentially expressed thousands of genes including auxin and cell wall-related genes. By comparing these genes to those induced duringArabidopsis thalianagraft formation, we found a common activation of cambium, cell division, phloem and xylem-related genes. A gene regulatory network analysis inPicea abies(Norway spruce) predicted thatPHYTOCHROME A SIGNAL TRANSDUCTION 1(PAT1) acted as a core regulator of graft healing. This gene was strongly upregulation during bothP. abiesandArabidopsisgrafting, andArabidopsismutants lackingPAT-genes failed to attach tissues or successfully graft. ComplementingArabidopsisPAT mutants with theP. abies PAT1homolog rescued tissue attachment and enhance callus formation. Together, our data demonstrate an ability for young tissues to facilitate grafting with distantly related species and identifies the PAT gene family as conserved regulators of graft healing and tissue regeneration.
Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals
Authors: Sinha Anjali K. , Lee Choongheon , Holt Joseph C.
Published: July 2023

The peripheral vestibular system detects head position and movement through activation of vestibular hair cells (HCs) in vestibular end organs. HCs transmit this information to the CNS by way of primary vestibular afferent neurons. The CNS, in turn, modulates HCs and afferents via the efferent vestibular system (EVS) through activation of cholinergic signaling mechanisms. In mice, we previously demonstrated that activation of muscarinic acetylcholine receptors (mAChRs), during EVS stimulation, gives rise to a slow excitation that takes seconds to peak and tens of seconds to decay back to baseline. This slow excitation is mimicked by muscarine and ablated by the non-selective mAChR blockers scopolamine, atropine, and glycopyrrolate. While five distinct mAChRs (M1-M5) exist, the subtype(s) driving EVS-mediated slow excitation remain unidentified and details on how these mAChRs alter vestibular function is not well understood. The objective of this study is to characterize which mAChR subtypes drive the EVS-mediated slow excitation, and how their activation impacts vestibular physiology and behavior. In C57Bl/6J mice, M3mAChR antagonists were more potent at blocking slow excitation than M1mAChR antagonists, while M2/M4 blockers were ineffective. While unchanged in M2/M4mAChR double KO mice, EVS-mediated slow excitation in M3 mAChR-KO animals were reduced or absent in irregular afferents but appeared unchanged in regular afferents. In agreement, vestibular sensory-evoked potentials (VsEP), known to be predominantly generated from irregular afferents, were significantly less enhanced by mAChR activation in M3mAChR-KO mice compared to controls. Finally, M3mAChR-KO mice display distinct behavioral phenotypes in open field activity, and thermal profiles, and balance beam and forced swim test. M3mAChRs mediate efferent-mediated slow excitation in irregular afferents, while M1mAChRs may drive the same process in regular afferents.
Mutual optical intensity propagation through non-ideal two-dimensional mirrors
Authors: Meng Xiangyu , Wang Yong , Shi Xianbo , Ren Junchao , Sun Weihong , Cao Jiefeng , Li Junqin , Tai Renzhong
Published: July 2023

The mutual optical intensity (MOI) model is a partially coherent radiation propagation tool that can sequentially simulate beamline optics and provide beam intensity, local degree of coherence and phase distribution at any location along a beamline. This paper extends the MOI model to non-ideal two-dimensional (2D) optical systems, such as ellipsoidal and toroidal mirrors with 2D figure errors. Simulation results show that one can tune the trade-off between calculation efficiency and accuracy by varying the number of wavefront elements. The focal spot size of an ellipsoidal mirror calculated with 100 × 100 elements gives less than 0.4% deviation from that with 250 × 250 elements, and the computation speed is nearly two orders of magnitude faster. Effects of figure errors on 2D focusing are also demonstrated for a non-ideal ellipsoidal mirror and by comparing the toroidal and ellipsoidal mirrors. Finally, the MOI model is benchmarked against the multi-electron Synchrotron Radiation Workshop (SRW) code showing the model's high accuracy.
Lakhpati Kisan programme: boosting the income of marginal farmers through women empowerment
Authors: Ajgaonkar Mihir , Mankodi Tanvi
Published: July 2023

Learning outcomes

This case will help students to analyse and develop insights into the concepts of servant leadership; to analyse and develop insights into women’s empowerment and a process to achieve such empowerment; and to explore the social business models for scaling up.

Case overview/synopsis

The Lakhpati Kisan programme under the aegis of Tata Trusts focussed on empowering women marginal farmers in the tribal belts in India to significantly increase their income from 2015. Ganesh Neelam, Executive Director, Collectives for Integrated Livelihood Initiatives (CInI), a nodal agency of Tata Trusts, advocated various livelihood options in agriculture, livestock, non-timber forest resources and water conversation. Initially, CInI faced the challenge of getting the farmers to sign up for the programme due to lack of trust. CInI facilitators educated the farmers about the purpose of the initiative and the benefits they would accrue and built trust. CInI created awareness through knowledge-sharing sessions on best practices in agriculture. They formed self-help groups of farmers for decision-making and for easy access to capital. CInI established farmer producer organisations (FPOs) to bring in a business perspective among farmers. The farmers as Board members and executives ran the FPOs like commercial organisations. CInI built capabilities to create a sustainable and autonomous ecosystem that looked impressive. But still the programme was falling short of the desired target. The farmers were so far reluctant to move forward independently. Ganesh felt that the social business model that CInI had evolved needed a re-look to achieve a significant and lasting impact on the majority of the marginal farmers in India.

Complexity academic level

The case can be used in the organisation behaviour, human resource management courses and courses on social enterprises as part of the MBA or post-graduate management programme or in executive education programmes.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 6: Human Resource Management.
Italy and Spain at a crossroads: the politics of active social policies in southern Europe under a gender perspective
Authors: Giuliani Giovanni Amerigo , Rizza Roberto
Published: July 2023

Purpose

The article explores to what extent party politics has influenced the different trajectories in Spain and Italy in terms of gendered active social policies (ASPs) (i.e. ALMPs and WLBPs). Second, it investigates how social and political modernization in the two countries has facilitated or hindered party competition on gendered ASPs.

Design/methodology/approach

To investigate to what extent parties support gendered ASPs, the article relies on an original content analysis of party manifestos issued during the 2010s national elections. A total of 1387 quasi-sentences have been coded. The results were then quantified to graphically show how positions differentiate across parties and countries.

Findings

The content analysis of party manifestos displays that party politics matters: gendered ASPs are backed in a very different way by the Spanish and Italian parties. While in Spain all political parties have strongly championed ALMPs and WLBPs, this is not the case for the Italian parties. The research has also stressed that the specific path of social and political modernization is an important intervening variable that alters positively or negatively parties' support for gendered ASPs.

Originality/value

The article contributes to widen theoretically and empirically the literature on ASPs in the Southern European countries. Theoretically, it questions the supposed homogeneity of the Southern social model and investigated the alleged bifurcation between Italy and Spain, focusing on those policies – ASPs – that constitute the foundations of the Southern model: familialism and dualization. Furthermore, this bifurcation was analyzed adopting a gender perspective, and exploring adherence to or departure from the Southern model. Third, the article focuses on the politics of ASPs demonstrating that inspecting the political arena can contribute to explain policy change.
Gender diversity and collaboration with universities: drivers of innovation in family firms
Authors: Rodríguez-Gulías María Jesús , Rodeiro-Pazos David , Calvo Nuria , Fernández-López Sara
Published: July 2023

Purpose

This paper provides empirical evidence for how gender diversity in top management teams (TMTs) and collaboration with university and technological centres lead to innovation outcomes. The authors review past research on these concepts and illustrate their individual and joint effects on process innovation specifically in the unique context of family firms (FFs).

Design/methodology/approach

The authors used a sample of 788 Spanish manufacturing family firms in 2016 and applied logistic regression models since the dependent variables are dummies.

Findings

The authors found a positive relationship between gender-diverse TMTs, process innovation and research and development (R&D)-based process innovation. Similarly, the collaboration with university technological centres is positively associated with higher innovation outcome of FFs. In addition, the authors also found that the presence of women in TMTs shapes the relationship between the collaboration with university technological centres and process innovation.

Originality/value

This paper contributes to the research on collaborative innovation in FFs by emphasizing the collaboration with university technological centres, an external partner often ignored by this stream of literature. This research also responds to the calls for further study of the effect of the heterogeneity of the TMTs on the innovation outcome of FFs, from the perspective of the resource-based view (RBV) of the firms.
How and when social media influencers' intimate self-disclosure fosters purchase intentions: the roles of congruency and parasocial relationships
Authors: Koay Kian Yeik , Lim Weng Marc , Kaur Simran , Soh Kimberly , Poon Wai Ching
Published: July 2023

Purpose

This study aims to explore the impact of social media influencers' (SMIs) intimate self-disclosure on consumers' purchase intentions, with a focus on the role of parasocial relationships and congruence among the influencer, product and consumer. The study finds its theoretical foundation in parasocial theory and self-congruency theory.

Design/methodology/approach

This study employs a quantitative approach, utilizing a sample of 232 collected survey responses. The proposed hypotheses are evaluated using partial least squares structural equation modeling (PLS-SEM).

Findings

Contrary to initial assumptions, the study reveals that parasocial relationships do not mediate the link between SMIs' intimate self-disclosure and purchase intentions. However, an interesting moderating effect was discovered: the congruence between the consumer and the influencer influences the relationship between SMIs' intimate self-disclosure and parasocial relationships, and subsequently, between parasocial relationships and purchase intentions.

Originality/value

This study brings fresh insights by pinpointing a boundary condition that dictates the influence of SMIs' intimate self-disclosure on purchase intentions via parasocial relationships. In doing so, this study provides a novel perspective in understanding the dynamics between SMIs and consumers in the rapidly evolving marketing landscape.
The role of letter knowledge acquisition ability on children's decoding and word identification: Evidence from an artificial orthography
Authors: Acha Joana , Rodriguez Nuria , Perea Manuel
Published: July 2023

Background

Letter knowledge is crucial in the first stages of reading development. It supports learning letter‐sound mappings and the identification of the letters that make up words. Previous studies have investigated the longitudinal impact of early letter knowledge on children's further word reading abilities. This study employed an artificial orthography learning paradigm to explore whether the rate of letter learning modulates children's reading and word identification skills.

Methods

In an initial training phase, 8‐year‐old Spanish children (N = 30) learned nine artificial letters and their corresponding sounds (two vowels and six consonants). The letter learning rate was set according to the number of attempts needed to name at least seven letters (i.e., 80% correct). These ranged from 1 to 4. In a second training phase, children visualized words made up of the trained letters while listening to their pronunciations. Some words included a context‐dependent syllable (i.e., leading to grapheme‐to‐phoneme inconsistency), and others had an inconsistent syllable (i.e., phoneme‐to‐grapheme inconsistency). The post‐test consisted of a reading aloud task and an orthographic‐choice task in which the target word was presented with a distractor equal to the target except for the substitution of a letter.

Results

Children showed a high accuracy rate in the post‐test tasks, regardless of whether words contained context‐dependent or inconsistent syllables. Critically, the letter learning rate predicted both reading aloud and identification accuracy of words in the artificial orthography.

Conclusions

We provide evidence for the vital role of letter knowledge acquisition ability in children's decoding and word identification skills. Training children on this ability facilitates serial letter‐sound mapping and word identification skills. Artificial orthography paradigms are optimal for exploring children's potential to achieve specific literacy skills.
Inequalities and content moderation
Authors: De Gregorio Giovanni , Stremlau Nicole
Published: July 2023

As the harms of hate speech, mis/disinformation and incitement to violence on social media have become increasingly apparent, calls for regulation have accelerated. Most of these debates have centred around the needs and concerns of large markets such as the EU and the United States, or the aggressive approach countries such as Russia and China adopt to regulate online content. Our focus in this article is with the rest, the smaller markets at the periphery of the advertising industry, and the deep inequalities that current approaches to content moderation perpetuate. We outline the depth of the unequal practice of moderation, particularly across Africa, and explore the underlying political and economic factors driving this gap. While recognizing content moderation has many limitations, we conclude by underlining potential approaches to increase oversight in content moderation.
Identification of predictive factors for early relapse in patients with unresectable stage III non‐small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy
Authors: Nam Jung Hyun , Yeo Chang Dong , Park Chan Kwon , Kim Sung Kyoung , Kim Ju Sang , Kim Yong Hyun , Kim Jin Woo , Kim Seung Joon , Lee Sang Haak , Kang Hye Seon
Published: July 2023

Background

Patients with locally advanced, unresectable, non‐small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation therapy (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance have not yet been identified.

Methods

The present study included the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from January 2018 to December 2021. A total of 51 NSCLC patients treated with durvalumab consolidation therapy after definitive CCRT were included in the analysis. Early relapse was defined as patients experiencing relapse within 6 months of starting initial durvalumab therapy.

Results

Among the 51 patients, 15 (29.4%) relapsed during the study period. Median time from initial therapy of durvalumab to progression was 451.00 ± 220.87 days (95% confidence interval [CI]: 18.10–883.90) in overall patients. In multivariate analysis, younger age (adjusted odds ratio [aOR], 0.792; 95% CI: 0.642–0.977; p = 0.030), higher pack‐years (aOR, 1.315; 95% CI: 1.058–1.635; p = 0.014), non‐COPD (aOR, 0.004; 95% CI: 0.000–0.828; p = 0.004) and anemia (aOR, 234.30; 95% CI: 1.212–45280.24; p = 0.042), were independent predictive factors for early relapse during durvalumab consolidation therapy.

Conclusion

Younger age, higher number of pack‐years, non‐COPD, and anemia were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high‐risk individuals.
Water conditions influence the detectability of Crossodactylus gaudichaudii (Anura, Hylodidae) in streams of the Atlantic Forest
Authors: Pereira‐Ribeiro Juliane , Linause Thais , Ferreguetti Átilla C. , Cozer Jonathan , Bergallo Helena G. , Rocha Carlos Frederico D.
Published: July 2023

Stream‐dwelling amphibians' occurrence, behaviour and reproductive success are strongly influenced by dynamic abiotic factors, for example, water flow and spray. These factors can disproportionately affect these frogs due to their dependency on specific favourable conditions for development and incapacity to disperse from unfavourable environments. We analysed the influence of environmental covariates on the detectability of Crossodactylus gaudichaudii, an amphibian species endemic to streams in the Brazilian Atlantic Forest. We conducted sampling in the streams of the Duas Bocas Biological Reserve, Brazil, and we measured air and water temperature, air humidity and pH of water on each sampling occasion. We estimated the effects of variables on the detectability of the species using single‐season occupancy models. Our results indicated that the detectability of the species increases on occasions with higher water temperatures (24–26°C) and lower pH (5.0–5.5). We investigated the influence of these covariates only on the detectability of adult frogs, but it is likely that the physiochemical properties of stream water are more important to aquatic larvae, and hence, the probability of their detection. Given this, further studies should examine the relevance of covariates on the detectability of adult frogs as well as larvae.
Risk factors of portal vein system thrombosis after splenectomy: a meta‐analysis
Authors: Lin Yu‐Kai , Cai Xin‐Ran , Hong Hai‐Jie , Chen Jiang‐Zhi , Chen Yan‐Ling , Du Qiang
Published: July 2023

Background

The primary aim of the present study was to explore risk factors for portal vein system thrombosis following splenectomy.

Methods

A systematic search of PubMed, Embase and Cochrane libraries was conducted to identify original studies that fulfilled the inclusion criteria. Raw data on potential risk factors for portal vein system thrombosis after splenectomy were extracted for meta‐analysis. Subsequently, a sensitivity analysis was conducted to verify the stability of the results.

Results

Eighteen studies with 626 thrombosis events from 1807 splenectomy met the inclusion criteria. Larger spleen volume (SMD 0.44, P = 0.000), broader splenic vein diameter (WMD 2.30, P = 0.000), broader portal vein diameter (WMD 2.08, P = 0.000), a lower velocity of portal blood flow (WMD −0.91, P = 0.001), decreased platelet count (WMD −5.14, P = 0.007), decreased white blood cell (WMD −0.40, P = 0.027), decreased haemoglobin (WMD −9.14, P = 0.002), ascites (OR 1.81, P = 0.003) and bleeding history before surgery (OR 1.88, P = 0.002) were identified to be factors that exacerbated the risk of portal vein system thrombosis after splenectomy. Sex, age, preoperative prothrombin time, postoperative platelet count, postoperative D‐dimer, operation time and intraoperative blood loss, did not increase the risk of thrombosis.

Conclusion

Larger spleen volume, broader splenic vein diameter, broader portal vein diameter, a lower velocity of portal blood flow, ascites, bleeding history before surgery, decreased platelet count, white blood cell and haemoglobin may increase the risk of portal vein system thrombosis.
Dual‐facing bridges and brokers: Diaspora politics and Chinese voluntary associations
Authors: Ho Elaine Lynn‐Ee
Published: July 2023

This commentary introduces the term ‘dual facing’ to describe the way that Chinese voluntary associations orientate themselves as collectives situated between the ancestral land (China) and their countries of settlement. The commentary uses examples of Chinese voluntary associations in Singapore and Myanmar to reflect on China's longstanding presence and expanding reach in Southeast Asia, including through its diaspora engagement with the Chinese abroad. It argues that such associations are embedded not only in the nation‐building efforts of their countries of settlement, but also the ancestral land. However, this dual‐facing orientation also means that they can become embroiled in conflictual domestic and foreign politics at both ends, potentially jeopardising how they are otherwise seen as bridges and brokers by China and in the countries where have settled.
Total gastrectomy as a risk factor for postoperative loss of skeletal muscle in minimally invasive surgery for patients with gastric cancer
Authors: Yoshida Shinya , Nishigori Tatsuto , Maekawa Hisatsugu , Hoshino Nobuaki , Hisamori Shigeo , Tsunoda Shigeru , Kobayashi Ami , Nobori Yukiko , Shide Kenichiro , Inagaki Nobuya , Obama Kazutaka
Published: July 2023

Purpose

Loss of skeletal muscle mass after gastrectomy for gastric cancer leads to decreased quality of life and poor postoperative survival. However, few studies have examined the postoperative loss of skeletal muscle mass following minimally invasive gastrectomy. This study investigated the impact of minimally invasive total gastrectomy (MI‐TG) on changes in skeletal muscle mass during the early postoperative period.

Methods

Patients who underwent MI‐TG or minimally invasive distal or proximal gastrectomy (MI‐nonTG) for cStage I‐III gastric cancer were retrospectively analyzed (n = 58 vs. 182). Their body composition was measured before surgery and 2 months after surgery. Multivariable linear regression analysis was performed to clarify the impact of the surgical procedure on skeletal muscle index changes using clinically relevant covariates.

Results

Skeletal muscle mass decreased more in the MI‐TG group than in the MI‐nonTG group (median [interquartile range]; −5.9% [−10.6, −3.7] vs −4.5% [−7.3, −1.9], P = 0.004). In multivariable linear regression analysis using clinically relevant covariates, MI‐TG was an independent risk factor for postoperative loss of skeletal muscle mass (coefficient − 2.6%, 95% CI −4.5 to −0.68, P = 0.008).

Conclusions

Total gastrectomy was a risk factor for loss of skeletal muscle mass during the early postoperative period. If oncologically feasible, proximal or distal gastrectomy with a small remnant stomach should be considered.
Isobutyric acid promotes colorectal cancer metastasis through activating RACK1
Authors: Chen Jinglian , Tang Jiali , Wang Han , Mei Jiale , Wei Xinjie , Qin Xiangqing , Lin Qiuhua , Huang Zhongnan , Tang Weizhong , Luo Tao
Published: July 2023

Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short‐chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC‐MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA–RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis.