Small Family Research Articles

Two new species of Machaerotidae from the Democratic Republic of the Congo, with some additional records of the family (Hemiptera: Cercopoidea)

Machaerotidae is a small family with a paleotropical distribution. Eight species are known from Africa. Labramachaerota luilaka sp. n. and Labramachaerota salonga sp. n. are described from Salonga National Park and along the Luilaka river in the buffer zone between the western and eastern sides of this National Park, situated in the Congo Basin in the Democratic Republic of the Congo. Enderleinia bispina Schmidt, 1907 is also recorded from the buffer zone of the Salonga National Park and several other locations, which are the first specified records of this species from the Democratic Republic of the Congo. Neuromachaerota discigutta Maa, 1963 is here recorded for the first time from the Democratic Republic of the Congo.

Rhes, a striatal enriched protein, regulates post-translational small-ubiquitin-like-modifier (SUMO) modification of nuclear proteins and alters gene expression

Rhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to cell via the formation of tunneling-like nanotubes (TNTs). However, the mechanisms by which Rhes mediates diverse functions remain unclear. Rhes is a small GTPase family member which contains a unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain that promotes SUMO post-translational modification of proteins (SUMOylation) by promoting “cross-SUMOylation” of the SUMO enzyme SUMO E1 (Aos1/Uba2) and SUMO E2 ligase (Ubc-9). Nevertheless, the identity of the SUMO substrates of Rhes remains largely unknown. Here, by combining high throughput interactome and SUMO proteomics, we report that Rhes regulates the SUMOylation of nuclear proteins that are involved in the regulation of gene expression. Rhes increased the SUMOylation of histone deacetylase 1 (HDAC1) and histone 2B, while decreasing SUMOylation of heterogeneous nuclear ribonucleoprotein M (HNRNPM), protein polybromo-1 (PBRM1) and E3 SUMO-protein ligase (PIASy). We also found that Rhes itself is SUMOylated at 6 different lysine residues (K32, K110, K114, K120, K124, and K245). Furthermore, Rhes regulated the expression of genes involved in cellular morphogenesis and differentiation in the striatum, in a SUMO-dependent manner. Our findings thus provide evidence for a previously undescribed role for Rhes in regulating the SUMOylation of nuclear targets and in orchestrating striatal gene expression via SUMOylation.

Demographic Characteristics of Members of Farmer Producer Organisations (FPOs) in Effectiveness of Group Dynamics and their Perceived Constraints in Lower Brahmaputra Valley Zone of Assam, India

The present study to investigate demographic profile of FPOs members in the effectiveness of group dynamics and their perceived constraints was conducted in Lower Brahmaputra Valley Zone (LBVZ) of Assam comprising six districts viz., Kamrup, Bongaigaon, Nalbari, Chirang, Barpeta and Goalpara. In doing so, it utilized the descriptive research design following an ex-post-facto approach to fulfil the objectives of the study. A total of eight FPOs promoted by Assam Agricultural University through CBBO-AAU and World Bank supported APART project were selected purposively. From each FPO, 15 active members were approached for data collection through personal interview method during 2022, which made 120 as final size of sample. The analysis of profile characteristics of the respondents revealed that majority of the respondents (FPOs members) in study areas were middle aged (66.67%) between 29 to 50 years with education level from high school to graduate/ above (80.83%), 64.17 percent were from small family size upto 4 members, 90.83 percent of the respondents had medium level of annual income (i.e. Rs 33190-379866.6), 46.67 percent had medium level of socio- political participation and 38.33 percent low and 35.83 percent high levels of material possession. The study also found that lack of co-ordination for different group activities, ineffective linkage and ineffective monitoring, lack of professional management, non-availability of timely credit and inadequate access to credit, weak financial position, absence of adequate market linkage, lack of storage facilities, distance from existing markets, lack of market information, lack of marketing knowledge and skills and difficulty in getting skilled labour were the perceived problems faced by FPO members in effective functioning of FPOs.

Recombinant biosensors for multiplex and super-resolution imaging of phosphoinositides.

Phosphoinositides are a small family of phospholipids that act as signaling hubs and key regulators of cellular function. Detecting their subcellular distribution is crucial to gain insights into membrane organization and is commonly done by the overexpression of biosensors. However, this leads to cellular perturbations and is challenging in systems that cannot be transfected. Here, we present a toolkit for the reliable, fast, multiplex, and super-resolution detection of phosphoinositides in fixed cells and tissue, based on recombinant biosensors with self-labeling SNAP tags. These are highly specific and reliably visualize the subcellular distributions of phosphoinositides across scales, from 2D or 3D cell culture to Drosophila tissue. Further, these probes enable super-resolution approaches, and using STED microscopy, we reveal the nanoscale organization of PI(3)P on endosomes and PI(4)P on the Golgi. Finally, multiplex staining reveals an unexpected presence of PI(3,5)P2-positive membranes in swollen lysosomes following PIKfyve inhibition. This approach enables the versatile, high-resolution visualization of multiple phosphoinositide species in an unprecedented manner.

THE RECEPTIVENESS PUZZLE: UNDERSTANDING WHY SMALL FAMILY BUSINESSES STRUGGLE WITH ACTIVITY-BASED COSTING ADOPTION

This study examines the challenges associated with the adoption of activity-based costing (ABC) in a small family business in a less developed country. Through a case study of PT XYZ, a logistic company, the study found that technical factors, including unpredictable customer requests, varying duration of activities, and uncertainty around distance and fuel consumption for each truck, make adopting the ABC method challenging. Organizational factors, such as a top-down hierarchy and the negative perception of the owner affecting the rest of the hierarchy, also contribute to the non-acceptance of ABC. Additionally, key agents within the company did not demonstrate enthusiasm toward changes. The cultural and contextual factors and unique characteristics of small family businesses further make them less receptive to adopting new ideas or changes, including the ABC method. This study offers practical implications for introducing changes, such as improving data collection processes, establishing better communication channels with family business owners, and seeking external expertise or advice from professionals with experience in family business management. The study expands the current discussion on ABC implementation and contributes to the family business literature by linking family business characteristics with the adoption of the ABC method.

INFLUENCE OF THE CHARACTERISTICS OF SMALL AND MEDIUM FAMILY BUSINESSES ON CRM IMPLEMENTATION: A CASE STUDY

Purpose: This paper aims to explore the customer relationship management (CRM) strategies adopted by Family Small and Medium Entreprises (SME), while highlighting the impact of their characteristics and their assets on the choice and the adoption of these CRM strategies. Methodology: Since the unique case study approach allows in-depth, multi-faceted explorations of complex issues, we opted for it as a research strategy in order to develop a detailed understanding of the problem. Therefore, an in-depth case study was carried out within a small and medium family business in Morocco. Findings: Through this study, we have highlighted causal links between the characteristics and specificities of the family SMEs and their impacts on the adoption and implementation of CRM tools and strategies. While some characteristics linked to the nature of family SMEs such as participatory management style, familiness, the desire to transmit the business to future generations and proximity to customers constitute assets for the implementation of CRM, other characteristics, such as the desire to maintain financial independence and recruitment policies that are most often in favor of family members despite their competence, can negatively influence the implementation of successful CRM projects. Implications for Theory and Practice: The results of the present paper allow the authors to draw conclusions that are relevant to both academics and practitioners. As for the theoretical implications, this study highlights the relationship between the characteristics of family SMEs and the choice and implementation of CRM strategies, while relying on their strengths. Furthermore, developing a good understanding of the specificity of CRM adoption and implementation approaches within family SMEs has important managerial implications for family SME decision-makers, as it can help them make better decisions regarding the choice of relevant CRM strategies and to optimize the deployment of available human, financial and technological resources, while relying on their socio-emotional wealth and their motivation to perpetuate the company. Originality: This paper is one of the first to explore CRM strategies adopted by family SMEs. The authors present a conceptual framework that can help researchers and practitioners better understand how the family business nature can influence decisions about CRM tools and strategies implementation.

Debt financing and growth of Ghanaian family-owned businesses: The dual role of family values

ABSTRACT This study investigates how family values can create finance and growth challenges for family-owned businesses in emerging economies. Specifically, it explores the interplay between family values, debt financing, and firm growth, while also considering the moderating role of self-enhancement and self-transcendence in this relationship. The paper uses Schwartz’s theory of human values to illustrate how incorporating indigenous ontologies based on Ubuntu can lead to sustainable growth in family businesses in Ghana and the African continent. A sample of 295 Small and Medium-sized family businesses in Accra, Ghana, was selected using purposive sampling, and multiple regression modeling was used to test the study’s hypotheses. The study employed Cronbach’s alpha and factor analysis to assess the reliability, validity, and variations between observed and correlated variables. The results suggest that family businesses with conservation, openness-to-change, and self-enhancement values may not be inclined to utilize debt financing, and conservation values have a negative effect on family business growth. The study also found that self-enhancement, conservation, and self-transcendence values positively moderated the relationship between debt financing and family business growth, with self-transcendence values playing a more significant role. These findings contribute to a better understanding of the complex relationship among family values, debt finance, and business growth in emerging economies, and lay a foundation for future research.

Biophysical Evidence for the Amyloid Formation of a Recombinant Rab2 Isoform of Leishmania donovani.

The most fatal form of Visceral leishmaniasis or kala-azar is caused by the intracellular protozoan parasite Leishmania donovani. The life cycle and the infection pathway of the parasite are regulated by the small GTPase family of Rab proteins. The involvement of Rab proteins in neurodegenerative amyloidosis is implicated in protein misfolding, secretion abnormalities and dysregulation. The inter and intra-cellular shuttlings of Rab proteins are proposed to be aggregation-prone. However, the biophysical unfolding and aggregation of protozoan Rab proteins is limited. Understanding the aggregation mechanisms of Rab protein will determine their physical impact on the disease pathogenesis and individual health. This work investigates the acidic pH-induced unfolding and aggregation of a recombinant Rab2 protein from L. donovani (rLdRab2) using multi-spectroscopic probes. The acidic unfolding of rLdRab2 is characterised by intrinsic fluorescence and ANS assay, while aggregation is determined by Thioflavin-T and 90⁰ light scattering assay. Circular dichroism determined the secondary structure of monomers and aggregates. The aggregate morphology was imaged by transmission electron microscopy. rLdRab2 was modelled to be a Rab2 isoform with loose globular packing. The acidinduced unfolding of the protein is a plausible non-two-state process. At pH 2.0, a partially folded intermediate (PFI) state characterised by ~ 30% structural loss and exposed hydrophobic core was found to accumulate. The PFI state slowly converted into well-developed protofibrils at high protein concentrations demonstrating its amyloidogenic nature. The native state of the protein was also observed to be aggregation-prone at high protein concentrations. However, it formed amorphous aggregation instead of fibrils. To our knowledge, this is the first study to report in vitro amyloid-like behaviour of Rab proteins in L donovani. This study provides a novel opportunity to understand the complete biophysical characteristics of Rab2 protein of the lower eukaryote, L. donovani.

CX3CL1 and its receptor CX3CR1 interact with RhoA signaling to induce paclitaxel resistance in gastric cancer

C-X3-C motif chemokine ligand 1 (CX3CL1) is a transmembrane protein, and the membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1/CX3CR1 axis induces many cellular responses relevant to cancer, such as proliferation, migration, invasion, and apoptosis resistance. Here we attempt to elucidate whether CX3CL1/CX3CR1 is associated with paclitaxel (PTX) resistance in gastric cancer (GC). The Gene Expression Omnibus database was queried to screen for differentially expressed genes in GC cells caused by drug resistance, and CX3CL1 was selected as a candidate. CX3CL1 was overexpressed in PTX-resistant cells and tissues. CX3CL1 loss sensitized GC cells to PTX, promoted apoptosis and DNA damage, and inhibited cell proliferation, migration, and invasion. CX3CR1 reversed the ameliorative effect of CX3CL1 silencing on PTX sensitivity in GC cells. The promotion of PTX resistance by CX3CL1/CX3CR1 was inhibited by impairment of the small GTPase Ras homolog gene family member A (RhoA) pathway in vitro and in vivo. These findings indicate that the CX3CL1/CX3CR1 expedites PTX resistance through the RhoA signaling in GC cells.

IJCM_326A: Access to Contraceptives for Migrants: Understanding how to improve family planning coverage in Brick Kiln in Northern India- A mixed methods study

Background: Family planning is a key means to achieving many of the Sustainable Development Goals. Lack of data in marginalized populations on knowledge, attitudes, and practices (KAP) hampers efforts to improve modern contraceptive practice. Objectives: To assess the knowledge, attitude and family planning practices and understand the facilitators and barriers for adopting family planning methods. Methodology: Cross-sectional study among men and women workers of reproductive age group and in-depth interviews (IDIs) in selected women worker of reproductive age group; were conducted. Qualitative data were described in proportions and compared using standard statistical tests. Qualitative data were coded and grouped and discussed using identified themes. Results: Among 85 migrant workers studied, more than two-third of the workers had no formal schooling. Only 38% were found to have practiced any Family Planning Methods (FPM), among the non-usage of any FPM, it has been found that 37% were never felt the need for FPM, 21% had no knowledge regarding any FPM. The facilitators identified for FPM were knowledge & practice about FPM, felt need for a small family, health system support, family support. As a migrant worker, they face multiple barriers like, difficulty in identifying the health facility, increased work time, difficulty in comprehending the local language and inaccessible frontline healthcare workers. Conclusion: The finding stresses the need to shift focus towards building intention, in addition to ensuring access of trained staff, and commodities drugs and equipment, and building capacities of health care providers

Sentiment Analysis: a Comparative Study of Online Booking Platforms Used for Spa Tourism in Northern Oltenia, Romania

Abstract: Purchasing a tourist package for a specific tourist destination has become extremely easy and transparent through the diversity and continuously upgraded online booking platforms. Their content provides information through the reviews among tourists and hospitality managers, being, at the same time, opened Big Data for researchers or policymakers. Mining the reviews of two global platforms (Booking and TripAdvisor) and a national one (Turistinfo) the study aims to an-alyze the tourists’ sentiments and emotions experienced in a balneary destination such as Northern Oltenia, Romania. The research addresses the overarching question of whether positive sentiments dominate in destinations led by spa tourism, and consequently, which emotions are definers? For this purpose, 10,945 online reviews, from 2018 to 2020 for 248 accommodation units of the studied area were collected and processed in Statistical Package for the Social Sciences (SPSS 17.0) and Geographical Information System (GIS). The key findings indicate that most travelers are satisfied with tourist destinations, sustained by the dominance of positive sentiments (82%) asso-ciated with a high rating score (8.9) and ‘joy’ and ‘trust’ emotions. Mostly positive sentiments are linked to the quality of five- and four-star accommodation units, but also to the intimacy of the small family’s business, the spatial framing in the landscape, and the friendship of the hosts. At the same time, the repulsive aspects draw attention to some problems of the state of the indoor or outdoor environment and the price-quality ratio. The research demonstrates the effectiveness of leveraging electronic word of mouth as a valuable resource for stakeholders in the tourism in-dustry. This approach enables a swift and sustainable assessment of tourist satisfaction, providing valuable insights for accommodation service providers to make informed decisions.

The Green Development in Saline–Alkali Lands: The Evolutionary Game Framework of Small Farmers, Family Farms, and Seed Industry Enterprises

Amid global climate change and population growth, the prevalence of saline–alkali lands significantly hampers sustainable agricultural development. This study employs theories of asymmetric information and bounded rationality to construct an evolutionary game model, analyzing the interactions among small farmers, family farms, and seed industry enterprises in the context of saline–alkali land management. It investigates the strategic choices and dynamics of these stakeholders under the influence of economic incentives and risk perceptions, with a focus on how government policies can foster green development. Utilizing Delay Differential Equations (DDEs) for simulations, this study highlights the risk of “market failure” without government intervention and underscores the need for government participation to stabilize and improve the efficiency of the green development process. The findings reveal that factors such as initial willingness to participate, the economic viability of salt-tolerant crops, seed pricing, research and development costs, and the design of incentive policies are crucial for sustainable land use. Accordingly, the paper proposes specific policy measures to enhance green development, including strengthening information dissemination and technical training, increasing the economic attractiveness of salt-tolerant crops, alleviating research and development pressures on seed companies, and optimizing economic incentives. This study provides a theoretical and policy framework for the sustainable management of saline–alkali lands, offering insights into the behavioral choices of agricultural stakeholders and supporting government strategies for agricultural and environmental protection.

HBO1/KAT7/MYST2 HAT complex regulates human adenovirus replicative cycle

Human adenoviruses (HAdV) belong to a small DNA tumor virus family that continues as valuable models in understanding the viral strategies of usurping cell growth regulation. A number of HAdV type 2/5 early viral gene products interact with a variety of cellular proteins to build a conducive environment that promotes viral replication. Here we show that HBO1 (Histone Acetyltransferase Binding to ORC1), a member of the MYST histone acetyltransferase (HAT) complex (also known as KAT7 and MYST2) that acetylates most of the histone H3 lysine 14, is essential for HAdV5 growth. HBO1/MYST2/KAT7 HAT complexes are critical for a variety of cellular processes including control of cell proliferation. In HBO1 downregulated human cells, HAdV5 infection results in reduced expression of E1A and other viral early genes, virus growth is also reduced significantly. Importantly, HBO1 downregulation reduced H3 lysine 14 acetylation at viral promoters during productive infection, likely driving reduced viral gene expression. HBO1 was also associated with viral promoters during infection and co-localized with viral replication centers in the nuclei of infected cells. In transiently transfected cells, overexpression of E1A along with HBO1 stimulated histone acetyltransferase activity of HBO1. E1A also co-immunoprecipitated with HBO1 in transiently transfected cells. In summary, our results demonstrate that HAdV recruits the HBO1 HAT complex to aid in viral replication.

Food: God’s Gift to All People. Case Study from Croatia

In the light of the biblical message, food is God’s gift to all people. Church’s documents emphasize that food is a natural human need, and every human has a natural right to food. This, however, presents new challenges to humanity today, because market-oriented agriculture often prevails, which does not focus so much on the quality and availability of food for all people, especially the poor, but puts profit at the center. The first part of paper attempts to concisely present the attitude of the Holy Scriptures towards food, which contribute to today’s reflection on solving the problem of production and availability of healthy food. The second part presents church’s guidelines, aimed to overcome today’s injustices in the world and provide everyone with access to food, and highlights the importance of producing healthy food for the protection of health. The third part of the paper deals with certain decrees on food production and control and the promotion of ecological production in the Republic of Croatia. Nevertheless, adopting the legislation of the European Union and accepting its guidelines on the development of agriculture has brought a certain shift in recent years. This legislative framework will contribute to the strengthening of the Croatian rural community, the encouragement of small family farms, and the increase of food production, especially healthy, ecologically grown food.

Sirtuins in clinical trials of approaches to the treatment of neurodegenerative diseases

Progressive decline in physiological functions during aging leads to various diseases that place a heavy burden on patients, their families and society as a whole. Due to the increasing average life expectancy, the problems of prevention and treatment of age-related diseases are becoming more and more relevant. As part of the research on the regulation of the aging program, considerable attention has been focused on a small family of NAD+-dependent deacetylases and deacylases called sirtuins. These proteins are involved in the regulation of numerous intracellular processes, and disruption of their functions plays an important role in the development of various diseases, such as metabolic disorders, pathologies of the cardiovascular system and other organs, musculoskeletal diseases, and neurodegeneration. It is interesting to note that the activity of sirtuins can be modulated to some extent under the influence of pharmacological agents, which makes them promising targets for age-related diseases prevention and therapy. The presented review will describe the influence of sirtuins on the development and pathogenesis of neurodegenerative diseases, as well as discuss recorded clinical trials focused on its therapy with pharmacological agents potentially affecting the activity of sirtuin proteins.

PdRabG3f interfered with gibberellin-mediated internode elongation and xylem developing in poplar

As a member of the small GTPases family, Rab GTPases play a key role in specifying transport pathways in the intracellular membrane trafficking system and are involved in plant growth and development. By quantitative trait locus (QTL) mapping, PdRabG3f was identified as a candidate gene associated with shoot height in a hybrid offspring of Populus deltoides ‘Danhong’ × Populus simonii ‘Tongliao1’. PdRabG3f localized to the nucleus, endoplasmic reticulum and tonoplast and was primarily expressed in the xylem and cambium. Overexpression of PdRabG3f in Populus alba × Populus glandulosa (84 K poplar) had inhibitory effects on vertical and radical growth. In the transgenic lines, there were evident changes in the levels of 15 gibberellin (GA) derivatives, and the application of exogenous GA3 partially restored the phenotypes mediated by GAs deficiency. The interaction between PdRabG3f and RIC4, which was the GA-responsive factor, provided additional explanation for PdRabG3f's inhibitory effect on poplar growth. RNA-seq analysis revealed differentially expressed genes (DEGs) associated with cell wall, xylem, and gibberellin response. PdRabG3f interfering endogenous GAs levels in poplar might involve the participation of MYBs and ultimately affected internode elongation and xylem development. This study provides a potential mechanism for gibberellin-mediated regulation of plant growth through Rab GTPases.

Abstract 4388: Tumor-associated RhoA mutants interact with effectors in both GDP- and GTP-bound states

Abstract RhoA is the founding member of the Ras-homology (Rho) small GTPase family and is a master regulator for multiple cell functions. Recurrent RhoA mutations have been identified in several human cancers, particularly in leukemia/lymphoma and gastric cancer. Intriguingly, both gain-of-function and loss-of-function mutations of RhoA are present, suggesting that RhoA GTPase may have a more sophisticated role in cancer and requires more rigorous investigations. Here, we have focused on two of the gain-of-function RhoA mutations identified in Adult T cell Leukemia/lymphoma (ATLL) at residue A161 (A161P and A161V) and aim to reveal the underlying mechanistic basis for their function by biochemical and structural analyses. We found that in contrast to conventional gain-of-function RhoA mutants such as RhoAG14V and RhoAQ63L which affect the GTP-hydrolysis activity, RhoAA161P and RhoAA161Vare both fast-cycling with drastically increased nucleotide dissociation and association rates, but only slightly reduced GTP-hydrolysis activity. We solved the crystal structures of GDP-bound RhoAA161P and RhoAA161V and saw that while RhoAA161P displays impaired solvent-mediated interactions to the bound nucleotide, RhoAA161V has a more exposed nucleotide binding pocket compared to RhoAWT and RhoAA161P. Interestingly, RhoAA161P and RhoAA161Vcan interact with effector targets in the GDP-bound states. Further 1H-15N HSQC NMR study provides evidence of the active population in GDP-bound RhoAA161V. Molecule dynamics (MD) simulations show that the dynamic properties of RhoA switch regions are affected differently by the two mutations. Thus, RhoAA161V and RhoAA161P are fast-cycling mutants with distinct mechanisms, and both likely endow their GDP-bound state towards an active conformation. These findings provide a better understanding of the oncogenic role of RhoA mutations in cancer and shine light on how changes in RhoA protein dynamic properties caused by mutations may affect its function. Citation Format: Yuan Lin, Theresa A. Ramelot, Simge Senyuz, Attila Gursoy, Hyunbum Jang, Ruth Nussinov, Ozlem Keskin, Yi Zheng. Tumor-associated RhoA mutants interact with effectors in both GDP- and GTP-bound states [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4388.

Abstract 4381: Role of Kindlin-2 in the regulation of integrins and TBR1 signaling in TNBC

Abstract Background: Kindlins are a small gene family of FERM domain-containing adaptor proteins that function as essential drivers of integrin activation. Kindlin-2 (K2) is the most widely expressed member of the Kindlin family; its homozygous deletion in mice is embryonically lethal, K2 expression is also dysregulated in several human cancers, including the breast. We established K2 as a major driver of TNBC tumors progression and metastasis through the regulation of several hallmarks of cancer. A well-established pathway whereby K2 regulates TNBC oncogenic behavior is through the regulation of integrin inside-out signaling by directly binding to the cytoplasmic tail of integrin β subunit. Interestingly, our recent studies found K2 to play a major role in activating the TGF-β-mediated regulation of the CSF1/EGF signaling through macrophage polarization to the M2 tumorigenic state and their increased tumor infiltration, as well as inhibiting tumor infiltration of cytotoxic lymphocytes, therefore, driving tumor immune evasion. Here we present novel findings involving K2 in the stabilization of the β1-Integrin:TβRI complexes by establishing a physical bridge that links β1-Integrin to TβRI. Loss of K2 results in the degradation of this protein complex and therefore, the inhibition of the oncogenic pathways downstream of these two major regulators of several hallmarks of cancer. Methods: We applied a combination of in vitro assays; CRISPR/Cas9 gene editing, cell migration, 3D tumor-sphere, solid binding, co-immunoprecipitation, cell adhesion and spreading, as well as western blot and flow cytometry analyses with MDA-MB-231 and 4T1 TNBC cell lines. We also used preclinical in vivo mouse models of TNBC tumor progression and metastasis to support or investigations. Results: We found that the K2/β1-Integrin direct interaction is mediated through the C-terminal F3 domain of K2, while the K2/TβRI direct interaction is mediated through the F2 domain of K2. Disruption of this bridge, via CRISPR/Cas9-mediated knockout of K2, leads to β1-Integrin and TβRI degradation, and inhibition of the oncogenic pathways downstream of both β1-Integrin and TβRI, and inhibited tumor growth and metastasis in levels comparable to loss of expression of either β1-Integrin and TβRI. Treatment of the K2-deficent cells with the proteasome inhibitor MG-132 restored expression of both β1-Integrin and TβRI, confirming that K2 is required for the stabilization of the β1-integrin/TβR1 complexes at the protein level. Rescue of K2 expression in the K2-KO cells restored their oncogenic activities both in vitro and in vivo. Conclusion: We identified K2 to play a novel and major in the stabilization of the β1-integrin/TβR1 complexes and the regulation of their downstream oncogenic signaling. These studies have a significant translational impact as they may identify new therapeutically targeted pathways that are desperately needed for the treatment of TNBC tumors. Citation Format: Neelum A. Yousaf Zai, Lamyae El Khalki, Wei Wang, Justin Szpendyk, Khalid Sossey-Alaoui. Role of Kindlin-2 in the regulation of integrins and TBR1 signaling in TNBC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4381.

Genome analysis and biogeographic distribution of the earliest divergent Frankia clade in the southern hemisphere.

Coriariaceae are a small plant family of 14-17 species and subspecies that currently have a global but disjunct distribution. All species can form root nodules in symbiosis with diazotrophic Frankia cluster-2 strains, which form the earliest divergent symbiotic clade within this bacterial genus. Studies on Frankia cluster-2 mostly have focused on strains occurring in the northern hemisphere. Except for one strain from Papua New Guinea, namely Candidatus Frankia meridionalis Cppng1, no complete genome of Frankia associated with Coriaria occurring in the southern hemisphere has been published thus far, yet the majority of the Coriariaceae species occur here. We present field sampling data of novel Frankia cluster-2 strains, representing two novel species, which are associated with Coriaria arborea and Coriaria sarmentosa in New Zealand, and with Coriaria ruscifolia in Patagonia (Argentina), in addition to identifying Ca. F. meridionalis present in New Zealand. The novel Frankia species were found to be closely related to both Ca. F. meridionalis, and a Frankia species occurring in the Philippines, Taiwan, and Japan. Our data suggest that the different Frankia cluster-2 species diverged early after becoming symbiotic circa 100 million years ago.

Unveiling ancient diversity of long-tailed wasps (Hymenoptera: Megalyridae): new taxa from Cretaceous Kachin and Taimyr ambers and their phylogenetic affinities

The Megalyridae are a small family of parasitoid wasps comprising eight extant genera (71 species) and six extinct genera (13 species). Here, we report eight new species from Late Cretaceous Kachin (Myanmar) and Taimyr (Russia) ambers; the family is recorded for the first time from the latter. †Cretolyra noijebumensisgen. et sp. nov., †Cretolyra shawigen. et sp. nov., †Genkyhag innebulagen. et sp. nov., †Megacoxa chandrahrasagen. et sp. nov., †Megacoxa janzenigen. et sp. nov., and †Megacoxa synchrotrongen. et sp. nov., are described from late Albian – early Cenomanian Kachin amber; †Kamyristi exfrigoregen. et sp. nov. and †Kamyristi yantardakhensisgen. et sp. nov. from Taimyr amber (Baikura, late Albian – early Cenomanian Ognevka Formation and Yantardakh, Santonian Kheta Formation, respectively). Phylogenetic analyses of the family are presented and the classification of the Megalyridae is revised accordingly. A new tribe, †Megalavinitrib. nov., is erected to accommodate †Cretolyragen. nov., †Genkyhaggen. nov., †Megacoxagen. nov. together with †Megalava Perrichot, 2009; †Megalavinitrib. nov. is characterized by the vein M fully pigmented and veins Rs+M and M+Cu aligned, the crenulate mesometapectal sulcus, and the pronotal spiracle not posteriorly surrounded by cuticle. This spiracular condition was previously only observed in †Megazar Perrichot, 2009, thus the subfamily †Megazarinae Perrichot, 2009 stat. nov. is proposed for the clade (†Megalavini + †Megazar), as sister to the remaining Megalyridae. The latter is defined as the Megalyrinae, with †Kamyristigen. nov. being retrieved as sister to all other genera except Rigel Shaw, 1987 under parsimony analyses. To align phylogeny with classification, three new tribes are erected (†Kamyristinitrib. nov., †Megallicinitrib. nov., and †Valaainitrib. nov.) and the †Cretodinapsini is synonymized under Megalyrini. A grouping [Rigel + Megalyridia] is supported under Bayesian analyses, which is the only specific conflict with the parsimony analyses, suggesting some degree of caution with respect to the internal relationships of the Megalyrinae. Finally, a revised key to the Megalyridae genera is provided.