Specific Manner Research Articles

Grain filling in rice vis‐a‐vis ethylene production in the spikelets

AbstractRice being a staple food worldwide necessitates that its production be enhanced to meet the demands of the continuously increasing population. However, the productivity advantages associated with breeding programs have reached their maximum. The production plateau brought on is not due to a lack of genetic potential but rather is due to the inhibition of grain filling by ethylene produced in large quantities in the heavy‐panicle‐ and compact‐panicle‐type varieties developed thus far, as evidenced by the application of ethylene synthesis inhibitors and ethylene action blockers. The inhibition could be a result of the accumulation of HCN, a byproduct of ethylene biosynthesis. In addition, inhibition of grain filling by excessive amounts of ethylene may also be the result of enhanced synthesis/expression of rice starch regulator 1, an ethylene‐responsive element binding protein that inhibits expression of the genes encoding type I starch‐biosynthesizing enzymes. In the past decade, miRNAs have also been found to inhibit grain filling by targeting starch‐biosynthesizing enzymes and the transcription factors required for their expression. Hence, biotechnological interventions should be designed to (1) decrease ethylene production and CN− accumulation and (2) downregulate/knockdown the expression of miRNAs unfavorable to grain filling in a spikelet/seed‐specific manner to enhance rice production.

Engineering sequence-directed protein-RNA covalent linkages for compact RNA-labeling tools.

The HUH-endonuclease superfamily is a diverse group of nucleases that cleave single-stranded DNA (ssDNA) and covalently link to the substrate's newly exposed 5’ end in a sequence specific manner. These nucleases have been co-opted for use in biotechnology applications as sequence-directed protein-ssDNA bioconjugation fusion partners (HUH-tags) due to their modest size and tremendous reaction efficiency. Surprisingly, a minority of these nucleases can promiscuously interact with RNA, but with dramatically low efficiency in comparison to the cognate reaction with ssDNA. Here, we present the engineering, characterization, and example applications of a set of laboratory-evolved RNA-interacting HUH-endonucleases (rHUH-tags). Yeast surface display-based protein engineering campaigns have produced engineered rHUH-tag variants with dramatically enhanced reactivity towards non-cognate RNA substrates. We demonstrate that rHUH-tags are a robust means of sequence-directed protein-RNA covalent bioconjugation in vitro and highlight their potential applications through a variety of proof-of-concept RNA labeling experiments. Finally, we demonstrate their versatility through the development of a hyper-compact RNA-editing system dubbed ‘HUH-ADAR’, which is capable of converting adenosine bases to inosine in a sequence-specific manner on transcripts of interest.

Fluorite flotation separation from bastnaesite via an eco-friendly polymer as a depressant and insight into its mechanism of adsorption

Fluorite and bastnaesite are significant mineral resources, but they have comparable surface characteristics, making flotation separation challenging. An eco-friendly polymer depressant was used in this study, causticized cassava starch (CS), for flotation separation of fluorite and bastnaesite. Experimentation, molecular dynamics modeling, and characterization evaluation are used to identify the CS flotation adsorption process on minerals. These findings suggest that hydroxyl groups on CS branches can be weakly adsorbed on fluorite and bastnaesite surfaces by forming OH⋯F hydrogen bonds. CS belongs to causticized starch, which may adsorb on surfaces in a specific manner bastnaesite by developing the R′–CH2–O–Ce-R″ complex. Under the action of chemical adsorption and hydrogen bond adsorption, the adsorption energy of CS in bastnaesite is much larger than that in fluorite, which is −83.16 kJ/mol and −28.38 kJ/mol respectively. After a large amount of CS adsorption, the hydrophilicity of bastnaesite is awfully enhanced and the floatability is decreased. With intentionally mixed materials, flotation separation may provide a concentrate with 82.23 % CaF2 grading and 90.04 % CaF2 recovery. This study provides an idea for separating fluorite and rare earth by preferential flotation of fluorite and selective inhibition of bastnaesite.

Elucidating the structure of the HU-junction complex.

Histone-like protein (HU) is one of the most abundant proteins in the bacterial nucleoid with a multi-functional role in DNA packaging, recombination, replication, and repair. HU binds with high affinity and in a non-sequence specific manner to Holliday or DNA 4-Way Junctions (HJ), a central intermediate in recombination and repair. Current understanding of how HU binds and recognizes junctions, and its role in recombination is limited.

Abstract WMP109: Aged Maternal Biome Impairs Offspring Health

Background: The gut and its microbiome have become highlighted because of their holistic effect on the body in health and disease. The bi-directional communication of the gut-brain axis is highly involved in, among others, the immune response. Additionally, the maternal gut microbiome affects offspring brain, immune system, and gut microbiome formation and development. Therefore, an aged and unhealthy maternal biome that is may increase both stroke risk factors among offspring. Method: Young female C57B6 mice 3-month (M) of age had their host gut bacteria cleared via antibiotic treatment prior to recolonization via fecal microbiome transplants from 3M control, and 18M reproductively senescent female mice. The subsequent offspring was aged to 18 months, followed by behavioral tests, glucose tolerance, and blood pressure measurement, prior to a transient 90-minute middle cerebral artery occlusion (MCAO). Results: Compared to control females with 3M biome, females with an aged biome had decreased fecundity from 26.4 days to 54.75 days at the onset of breeding to birth of pups (p=0.0018). There was no change in estrus cycle between the groups. The offspring gut microbiome had been affected in a sex specific manner. Female pups from dysbiotic, aged, biome mothers differed significantly in terms of b-diversity compared to those from control mothers (p=0.009) with pathogenic increases to firmicutes shifting the F:B ratio. There was a less pronounced trend in male offspring (p=0.241). Interestingly, no weight differences were observed in offspring depending on the maternal biome. At 2M of age, a depressive phenotype in tail suspension test was noted for male(p=0.0001) and female (p=0.0059). However, at 6M and older, the depressive phenotype subsided. Male offspring at 18M demonstrated a significant change (p=0.0001) in Glucose tolerance test compared to age matched females. Conclusion: The maternal microbiome has a significant impact on offspring biome composition and health. Mice from mothers with aged microbiome exhibited early life depressive phenotypes, slower glucose metabolism, and a pathogenic gut microbiome composition. Therefore, maternal gut has transgenerational health effects which may be exacerbating stroke risk and potentially outcome.

Generalized extinction of fear memory depends on co-allocation of synaptic plasticity in dendrites

Memories can be modified by new experience in a specific or generalized manner. Changes in synaptic connections are crucial for memory storage, but it remains unknown how synaptic changes associated with different memories are distributed within neuronal circuits and how such distributions affect specific or generalized modification by novel experience. Here we show that fear conditioning with two different auditory stimuli (CS) and footshocks (US) induces dendritic spine elimination mainly on different dendritic branches of layer 5 pyramidal neurons in the mouse motor cortex. Subsequent fear extinction causes CS-specific spine formation and extinction of freezing behavior. In contrast, spine elimination induced by fear conditioning with >2 different CS-USs often co-exists on the same dendritic branches. Fear extinction induces CS-nonspecific spine formation and generalized fear extinction. Moreover, activation of somatostatin-expressing interneurons increases the occurrence of spine elimination induced by different CS-USs on the same dendritic branches and facilitates the generalization of fear extinction. These findings suggest that specific or generalized modification of existing memories by new experience depends on whether synaptic changes induced by previous experiences are segregated or co-exist at the level of individual dendritic branches.

Characterization and Detection of Cross-Router Covert Channels

In covert channel attacks, an adversary seeks various means to influence a tangible characteristic of a system, and then makes the systems leak information by measuring this characteristic. Covert channels are, by nature, very elusive. This makes it very difficult to identify them and defend against attacks that use these channels to leak sensitive information. Thus, they are a serious threat to the security of many systems.In this paper, we present two network timing covert channel attacks, and a defense mechanism against them. The purpose of the proposed attacks is to leak sensitive information between two logically separated (or isolated) networks that are hosted by a single router – one that is connected to the Internet, and another that is isolated and contains sensitive information. The attacks build on the fact that the response time of the router for a specific type of packet sent from a device that is connected to it is usually predictable, given the network topology. By interacting with the single shared router in a specific manner, an attacker can increase the router’s packet response time. The interaction is determined based on the information to be leaked, so the receiver (a computer located on the Internet-connected network) can measure the delayed packet response times and decode the sender’s signals (which operates from the isolated network) to receive classified information. The two classes of attacks presented in this work differ in the way that the delay is caused. In the cross-router covert channel (CRCC) attack, the sender overloads the router with control-plane packets; in the Wi-Fi micro-jamming attack, the sender uses a pre-installed implant to transmit single-tone signals in the 2.4GHz frequency range, disturbing the router’s packet transmissions. We showed that both attacks can influence a wide range of router brands and Wi-Fi capable devices and evaluated the optimal settings for both attacks when using different types of packets, transmission power, and data transmission rates.Our proposed defense mechanism is based on semi-supervised machine learning and deep learning algorithms, which are both used for novelty detection in network traffic. By detecting unusual traffic, we can identify the disturbances needed to leak the information. The system can then respond by blocking the suspicious devices that are involved in the attack. We evaluated the attacks in noisy and noise-free environments, successfully detecting both attacks in both environments. All the data and code, which includes the implementation of the attacks and the defense mechanism, is published as a benefit to the research community.

Controlled modulation of the dynamics of the Deinococcus grandis Dps N-terminal tails by divalent metals.

DNA-binding proteins from starved cells (Dps) are small multifunctional nanocages expressed by prokaryotes in acute oxidative stress conditions or during the starvation-induced stationary phase, as a bacterial defense mechanism. Dps proteins protect bacterial DNA from damage by either direct binding or by removing precursors of reactive oxygen species from solution. The DNA-binding properties of most Dps proteins studied so far are related to their unordered, flexible, N- and C-terminal extensions. In a previous work, we revealed that the N-terminal tails of Deinoccocus grandis Dps shift from an extended to a compact conformation depending on the ionic strength of the buffer and detected a novel high-spin ferrous iron center in the proximal ends of those tails. In this work, we further explore the conformational dynamics of the protein by probing the effect of divalent metals binding to the tail by comparing the metal-binding properties of the wild-type protein with a binding site-impaired D34A variant using size exclusion chromatography, dynamic light scattering, synchrotron radiation circular dichroism, and small-angle X-ray scattering. The N-terminal ferrous species was also characterized by Mössbauer spectroscopy. The results herein presented reveal that the conformation of the N-terminal tails is altered upon metal binding in a gradual, reversible, and specific manner. These observations may point towards the existence of a regulatory process for the DNA-binding properties of Dps proteins through metal binding to their N- and/or C-terminal extensions.

BDNF is altered in a brain-region specific manner and rescues deficits in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, dominantly inherited neurodegenerative disease caused by the expanded polyQ tract in the protein ATAXIN1 (ATXN1) and characterized by progressive motor and cognitive impairments. There are no disease-modifying treatments or cures for SCA1. Brain-derived neurotrophic factor (BDNF) plays important role in cerebellar physiology and has shown therapeutic potential for cerebellar pathology in the transgenic mouse model of SCA1, ATXN1[82Q] line that overexpress mutant ATXN1 under a cerebellar Purkinje-cell-specific promoter. Here we demonstrate decreased expression of brain derived neurotrophic factor (BDNF) in the cerebellum and medulla of patients with SCA1. Early stages of disease seem most amenable to therapy. Thus, we next quantified Bdnf expression in Atxn1154Q/2Q mice, a knock-in mouse model of SCA1, during the early symptomatic disease stage in four clinically relevant brain regions: cerebellum, medulla, hippocampus and motor cortex. We found that during the early stages of disease, Bdnf mRNA expression is reduced in the hippocampus and cerebellum, while it is increased in the cortex and brainstem. Importantly, we observed that pharmacological delivery of recombinant BDNF improved motor and cognitive performance, and mitigated pathology in the cerebellum and hippocampus of Atxn1154Q/2Q mice. Our findings demonstrate brain-region specific deficiency of BDNF in SCA1 and show that reversal of low BDNF levels offers the potential for meaningful treatment of motor and cognitive deficits in SCA1.

Pendidikan Berwawasan Multikultural

The concept of multiculturalism is not merely comprehended as an acceptance or acknowledgement of differences. Multiculturalism has come to the fore in philosophical discussionsemphasizing the importance of the acknowledgement of the other as a basis of individual and collective identity formation. And this formationcouldhavebeenpolitical,cultural,religiousinessence.Multiculturalism denotes several cultures exist in a society. It has to do with cultures, and it points out to a plurality of cultures and it refers to a specific manner to responding to that plurality.Dialogue then becomes day to day a Religion in action. It has been a human natural need ofequality and at the same time difference.We are unique not by “exclusion" but by “relation'". To be catholic means first of all to be multicultural and this beyond boundaries attitude has vigorously strengthening and promoting religion for human rights,justice, peace,and harmony.

Plasmonic sensor based on offset-splicing and waist-expanded taper using multicore fiber for detection of Aflatoxins B1 in critical sectors.

In this work, authors have developed a portable, sensitive, and quick-response fiber optic sensor that is capable of detection of Aflatoxins B1 (AFB1) quantitatively and qualitatively. Using multi-mode fiber (MMF) and multi-core fiber (MCF), the MMF-MCF-MCF-MMF fiber structure based on symmetric transverse offset splicing and waist-expanded taper is fabricated. The evanescent waves are enhanced to form a strong evanescent field by etching the fiber surface with hydrofluoric acid. To successfully excite the localized surface plasmon resonance phenomenon, gold nanoparticles are deposited on the optical fiber probe's surface. Further, to modify the fiber optic probes, Niobium carbide (Nb2CTx) MXene and AFB1 antibodies are functionalized. Nb2CTx MXene is employed to strengthen the biocompatibility of the sensor and increase the specific surface area of the fiber probe, while AFB1 antibody is used to identify AFB1 micro-biomolecules in a specific manner. The reproducibility, reusability, stability, and selectivity of the proposed fiber probe are tested and validated using various concentration of AFB1 solutions. Finally, the linear range, sensitivity, and limit of detection of the sensing probe are determined as 0 - 1000 nM, 11.7 nm/µM, and 26.41 nM, respectively. The sensor offers an indispensable technique, low-cost solution and portability for AFB1-specific detection in agricultural products and their byproducts with its novel optical fiber structure and superior detecting capability. It is also useful for marine species like fish and consequently affecting health of human body.

Site-Specific knockdown of microglia in the locus coeruleus regulates hypervigilant responses to social stress in female rats

BackgroundWomen are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. MethodsMicroglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3 μg/side, n = 5–6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25 μg/side, n = 13–14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. ResultsIntra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1β (IL-1β). Further, the efficacy and selectivity of microinjected m-CLD was fully characterized. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1β. Intra-central amygdala m-CLD had no effect on WS-evoked behavior. ConclusionsThese studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.

Low-Dose Lithium Supplementation Influences GSK3β Activity in a Brain Region Specific Manner in C57BL6 Male Mice.

Lithium, a commonly used treatment for bipolar disorder, has been shown to have neuroprotective effects for other conditions including Alzheimer's disease via the inhibition of the enzyme glycogen synthase kinase-3 (GSK3). However, dose-dependent adverse effects of lithium are well-documented, highlighting the need to determine if low doses of lithium can reliably reduce GSK3 activity. The purpose of this study was to evaluate the effects of a low-dose lithium supplementation on GSK3 activity in the brain of an early, diet-induced Alzheimer's disease model. Male C57BL/6J mice were divided into either a 6-week or 12-week study. In the 6-week study, mice were fed a chow diet or a chow diet with lithium-supplemented drinking water (10 mg/kg/day) for 6 weeks. Alternatively, in the 12-week study, mice were fed a chow diet, a high-fat diet (HFD), or a HFD with lithium-supplemented drinking water for 12 weeks. Prefrontal cortex and hippocampal tissues were collected for analysis. Results demonstrated reduced GSK3 activity in the prefrontal cortex as early as 6 weeks of lithium supplementation, in the absence of inhibitory phosphorylation changes. Further, lithium supplementation in an obese model reduced prefrontal cortex GSK3 activity as well as improved insulin sensitivity. Collectively, these data provide evidence for low-dose lithium supplementation to inhibit GSK3 activity in the brain. Moreover, these results indicate that GSK3 activity can be inhibited despite any changes in phosphorylation. These findings contribute to an overall greater understanding of low-dose lithium's ability to influence GSK3 activity in the brain and its potential as an Alzheimer's disease prophylactic.

Cucurbit[n]uril-based fluorescent indicator-displacement assays for sensing organic compounds.

The widespread conversion of synthetic receptors into luminescent sensors has been achieved via the use of fluorescent-indicator displacement assays (F-IDAs). Due to their rigid structures and efficient binding affinities, cucurbit[n]urils, combined with a variety of fluorescent guests, have gained extensive utilization in fluorescent-indicator displacement assays for sensing non-fluorescent or weakly fluorescent organic compounds (analytes) in a selective and specific manner. This mini-review summarizes recent advances in the design of cucurbit[n]uril-based fluorescent-indicator displacement assays and discusses the current challenges and future prospects in this area.

Engineered adhesion molecules drive synapse organization

In multicellular organisms, cell-adhesion molecules connect cells into tissues and mediate intercellular signaling between these cells. In vertebrate brains, synaptic cell-adhesion molecules (SAMs) guide the formation, specification, and plasticity of synapses. Some SAMs, when overexpressed in cultured neurons or in heterologous cells co-cultured with neurons, drive formation of synaptic specializations onto the overexpressing cells. However, genetic deletion of the same SAMs from neurons often has no effect on synapse numbers, but frequently severely impairs synaptic transmission, suggesting that most SAMs control the function and plasticity of synapses (i.e., organize synapses) instead of driving their initial establishment (i.e., make synapses). Since few SAMs were identified that mediate initial synapse formation, it is difficult to develop methods that enable experimental control of synaptic connections by targeted expression of these SAMs. To overcome this difficulty, we engineered novel SAMs from bacterial proteins with no eukaryotic homologues that drive synapse formation. We named these engineered adhesion proteins "Barnoligin" and "Starexin" because they were assembled from parts of Barnase and Neuroligin-1 or of Barstar and Neurexin3β, respectively. Barnoligin and Starexin robustly induce the formation of synaptic specializations in a specific and directional manner in cultured neurons. Synapse formation by Barnoligin and Starexin requires both their extracellular Barnase- and Barstar-derived interaction domains and their Neuroligin- and Neurexin-derived intracellular signaling domains. Our findings support a model of synapse formation whereby trans-synaptic interactions by SAMs drive synapse organization via adhesive interactions that activate signaling cascades.

Culture Protocol and Transcriptomic Analysis of Murine SVZ NPCs and OPCs.

The mammalian adult brain contains two neural stem and precursor (NPC) niches: the subventricular zone [SVZ] lining the lateral ventricles and the subgranular zone [SGZ] in the hippocampus. From these, SVZ NPCs represent the largest NPC pool. While SGZ NPCs typically only produce neurons and astrocytes, SVZ NPCs produce neurons, astrocytes and oligodendrocytes throughout life. Of particular importance is the generation and replacement of oligodendrocytes, the only myelinating cells of the central nervous system (CNS). SVZ NPCs contribute to myelination by regenerating the parenchymal oligodendrocyte precursor cell (OPC) pool and by differentiating into oligodendrocytes in the developing and demyelinated brain. The neurosphere assay has been widely adopted by the scientific community to facilitate the study of NPCs in vitro. Here, we present a streamlined protocol for culturing postnatal and adult SVZ NPCs and OPCs from primary neurosphere cells. We characterize the purity and differentiation potential as well as provide RNA-sequencing profiles of postnatal SVZ NPCs, postnatal SVZ OPCs and adult SVZ NPCs. We show that primary neurospheres cells generated from postnatal and adult SVZ differentiate into neurons, astrocytes and oligodendrocytes concurrently and at comparable levels. SVZ OPCs are generated by subjecting primary neurosphere cells to OPC growth factors fibroblast growth factor (FGF) and platelet-derived growth factor-AA (PDGF-AA). We further show SVZ OPCs can differentiate into oligodendrocytes in the absence and presence of thyroid hormone T3. Transcriptomic analysis confirmed the identities of each cell population and revealed novel immune and signalling pathways expressed in an age and cell type specific manner.

ArtinM Cytotoxicity in B Cells Derived from Non-Hodgkin's Lymphoma Depends on Syk and Src Family Kinases.

Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from Artocarpus heterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2/CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3γ N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T-cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkin’s lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cell incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell-lines sourced from non-Hodgkin’s lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM.

Oral administration of VDAC1-derived small molecule peptides increases circulating testosterone levels in male rats.

Cholesterol is the precursor of all steroid hormones, and the entry of cholesterol into the mitochondria is the rate-limiting step of steroidogenesis. Voltage-dependent anion channel (VDAC1) is an outer mitochondrial protein part of a multiprotein complex that imports cholesterol. We previously reported that intratesticular administration of a 25 amino acid peptide blocking the interaction between 14-3-3ϵ with VDAC1 increased circulating levels of testosterone. This fusion peptide was composed of a HIV-1 transactivator of transcription (TAT) protein transduction domain cell-penetrating peptide, a glycine linker, and amino acids 159-172 of VDAC1 (TV159-172). Here, we describe the development of a family of small molecules that increase circulating testosterone levels after an oral administration. We first characterized an animal model where TV159-172 was delivered subcutaneously. This subcutaneous model allowed us to study the interactions between TV159-172 and the hypothalamus-pituitary-gonadal axis (HPG) and identify the biologically active core of TV159-172. The core consisted of the tetrapeptide RVTQ, which we used as a platform to design synthetic peptide derivatives that can be administered orally. We developed a second animal model to test various derivatives of RVTQ and found 11 active compounds. Dose-response experiments identified 4 synthetic peptides that robustly increased androgen levels in a specific manner. We selected RdVTQ as the leading VDAC1-core derivative and profiled the response across the lifespan of Brown-Norway rats. In summary, we present the development of a new class of therapeutics that act within the HPG axis to increase testosterone levels specifically. This new class of small molecules self-regulates, preventing abuse.

Syntactic differences between adjectives and relative words in Setswana and isiZulu

The study investigates the syntactic differences between adjectives and relative words in Setswana and isiZulu. Setswana and isiZulu are from the same Bantu language family and both share certain general characteristics such as agglutinative morphology, but they differ in orthography, i.e. conjunctive and disjunctive orthography. The aim of the article is to show the differences between the adjective and relative words of isiZulu and Setswana in sentences. The intention is to display the possibility of comparing isiZulu and Setswana without comparing them to English. English is a valuable resource, but it should not be promoted at the expense of indigenous languages. The focus of this study is on the ordering and occurrence of the adjectives and to investigate whether Setswana and isiZulu adjectives and relatives do occur in a specific order when used attributively. A descriptive research design and qualitative approach are used to collect and analyse secondary data from the existing data to solve the research questions, such as: Do Setswana/isiZulu adjectives and relatives occur in a specific manner and can nouns and adjectives be conjoined in Setswana and isiZulu?

Sex-Gender-Based Differences in Metabolic Diseases.

Sexual dimorphism creates different biological and cellular activities and selective regulation mechanisms in males and females, thus generating differential responses in health and disease. In this scenario, the sex itself is a source of physiologic metabolic disparities that depend on constitutive genetic and epigenetic features that characterize in a specific manner one sex or the other. This has as a direct consequence a huge impact on the metabolic routes that drive the phenotype of an individual. The impact of sex is being clearly recognized also in disease, whereas male and females are more prone to the development of some disorders, or have selective responses to drugs and therapeutic treatments. Actually, very less is known regarding the probable differences guided by sex in the context of inherited metabolic disorders, owing to the scarce consideration of sex in such restricted field, accompanied by an intrinsic bias connected with the rarity of such diseases. Metabolomics technologies have been ultimately developed and adopted for being excellent tools for the investigation of metabolic mechanisms, for marker discovery or monitoring, and for supporting diagnostic procedures of metabolic disorders. Hence, metabolomic approaches can excellently embrace the discovery of sex differences, especially when associated to the outcome or the management of certain inborn errors of the metabolism.