Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting.

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.

Isolation and Screening of Zn (Zn) Solubilizing Rhizosphere Bacteria from Different Vegetations for Their Ability to Improve Growth, Zn Uptake, and Expression of Zn Transporter Genes in Tomato.

Zinc-solubilizing bacteria (ZSB) can convert insoluble zinc to an accessible form and increase Zn bioavailability in soil, which helps mitigate Zn deficiency in crops. In this study, different bacterial strains were screened for different Zn solubilization and plant growth promotion traits. Two bacterial strains, Acinetobacter pittii DJ55 and Stenotrophomonas maltophilia DJ24, were tested for their Zn-solubilizing potential on plate media, and both showed variable levels of Zn solubilization. The results showed that the bacterial strains applied to the plants in the pot experiment caused improvements in growth parameters compared to control conditions. DJ55, when applied with an insoluble source, enhanced plant height, leaf number, and leaf area compared to DJ24 and control conditions, while the maximum fruit weight was noticed in plants treated with ZnSO4. An increase in chlorophyll contents was noted in plants treated with ZnSO4, while maximum carotenoid contents were observed in plants treated with DJ55 + ZnO when compared with their controls. Plants supplemented with ZnO and DJ55 showed higher zinc content and iron content as compared to their respective controls. The expression patterns of the SLZIP5 and SLZIP4 genes were changed in the root and shoot. Application of ZnO stimulates both gene expression and protein synthesis in tomato roots and shoots. Inoculation of tomato plants with ZSB and insoluble ZnO reduced the expression of the SLZIP5 and SLZIP4 genes in the root and shoot. In conclusion, both strains can be considered as potential zinc-solubilizing bioinoculants to promote the growth and production yield of tomato.

Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.

Mutational Analysis of TYR, OCA2, SLC45A2, and TYRP1 Genes Identifies Novel and Reported Mutations in Chinese Families with Oculocutaneous Albinism.

Objective: This study aims to investigate the main types of oculocutaneous albinism (OCA) and the distribution characteristics of mutations in the Chinese population. Additionally, genetic diagnosis and prenatal diagnosis were conducted for Chinese OCA families. Methods: A total of 116 blood DNA samples were collected from 40 unrelated families with suspected albinism. OCA gene testing and mutation screening were performed to identify mutated genes and genotypes. The prenatal genetic diagnosis was conducted on 20 fetal DNA samples (17 amniotic fluid DNA samples, 2 villus DNA samples, and 1 umbilical cord blood DNA sample). Follow-up was conducted on the born fetuses, and the feasibility and accuracy of prenatal genetic diagnosis were assessed based on the clinical phenotype of the fetuses. Results: Analysis of 40 pedigrees led to a molecular diagnosis for the patients or their parents: 24 (60%) had OCA1, 12 (30%) had OCA2, 1 (2.5%) had OCA3, and 2 (5%) had OCA4. Furthermore, 2.5% of the patients harbored only one heterozygous mutation in OCA2. The most common form of albinism observed was OCA1, followed by OCA2, OCA4, and OCA3. Prenatal diagnosis was performed on 20 fetuses, and the clinical phenotype of the fetuses aligned with the predictions of prenatal genetic diagnosis after follow-up. Conclusions: The results of gene mutation analysis in 40 families with oculocutaneous albinism indicate that OCA1 is the predominant type of albinism in the Chinese population, with all four types of OCA identified. Further research is needed to expand the understanding of pathogenic mutations associated with different types of OCA. Prenatal genetic testing, based on determining the albinism type and genotype of the proband and their parents, proves to be the most accurate and least traumatic method in eugenics. This study provides valuable insights into identifying novel therapeutic targets.

Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale.

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

A Potential Nontraditional Approach To Combat tmexCD1-toprJ1-Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline.

The emergence of TMexCD1-TOprJ1, a novel transferable resistance-nodulation-division (RND)-type efflux pump conferring resistance to tigecycline, is now a serious public health issue in the world. Here, we found that melatonin synergistically enhanced the antibacterial efficacy of tigecycline against tmexCD1-toprJ1-positive Klebsiella pneumoniae by disrupting the proton driving force and efflux function to promote the accumulation of tigecycline into cells, damaging cell membrane integrity and causing the leakage of cell contents. The synergistic effect was further validated by a murine thigh infection model. The results revealed that the melatonin/tigecycline combination is a potential therapy to combat resistant bacteria carrying the tmexCD1-toprJ1 gene.

Two Permeases Associated with the Multifunctional CtaP Cysteine Transport System in Listeria monocytogenes Play Distinct Roles in Pathogenesis.

The soil-dwelling bacterium Listeria monocytogenes survives a multitude of conditions when residing in the outside environment and as a pathogen within host cells. Key to survival within the infected mammalian host is the expression of bacterial gene products necessary for nutrient acquisition. Similar to many bacteria, L. monocytogenes uses peptide import to acquire amino acids. Peptide transport systems play an important role in nutrient uptake as well as in additional functions that include bacterial quorum sensing and signal transduction, recycling of peptidoglycan fragments, adherence to eukaryotic cells, and alterations in antibiotic susceptibility. It has been previously described that CtaP, encoded by lmo0135, is a multifunctional protein associated with activities that include cysteine transport, resistance to acid, membrane integrity, and bacterial adherence to host cells. ctaP is located next to two genes predicted to encode membrane-bound permeases lmo0136 and lmo0137, termed CtpP1 and CtpP2, respectively. Here, we show that CtpP1 and CtpP2 are required for bacterial growth in the presence of low concentrations of cysteine and for virulence in mouse infection models. Taken together, the data identify distinct nonoverlapping roles for two related permeases that are important for the growth and survival of L. monocytogenes within host cells. IMPORTANCE Bacterial peptide transport systems are important for nutrient uptake and may additionally function in a variety of other roles, including bacterial communication, signal transduction, and bacterial adherence to eukaryotic cells. Peptide transport systems often consist of a substrate-binding protein associated with a membrane-spanning permease. The environmental bacterial pathogen Listeria monocytogenes uses the substrate-binding protein CtaP not only for cysteine transport but also for resistance to acid, maintenance of membrane integrity, and bacterial adherence to host cells. In this study, we demonstrate complementary yet distinct functional roles for two membrane permeases, CtpP1 and CtpP2, that are encoded by genes linked to ctaP and that contribute to bacterial growth, invasion, and pathogenicity.

Manganese uptake mediated by the NRAMP-type transporter MntH is required for acid tolerance in Listeria monocytogenes.

Listeria monocytogenes is a foodborne pathogen that is characterized by its ability to withstand mild stresses (i.e. cold, acid, salt) often encountered in food products or food processing environments. In the previous phenotypic and genotypic characterization of a collection of L. monocytogenes strains, we have identified one strain 1381, originally obtained from EURL-lm, as acid sensitive (reduced survival at pH 2.3) and extremely acid intolerant (no growth at pH 4.9, which supports the growth of most strains). In this study, we investigated the cause of acid intolerance in strain 1381 by isolating and sequencing reversion mutants that were capable of growth at low pH (pH 4.8) to a similar extent as another strain (1380) from the same MLST clonal complex (CC2). Whole genome sequencing showed that a truncation in mntH, which encodes a homologue of an NRAMP (Natural Resistance-Associated Macrophage Protein) type Mn2+ transporter, is responsible for the acid intolerance phenotype observed in strain 1381. However, the mntH truncation alone was not sufficient to explain the acid sensitivity of strain 1381 at lethal pH values as strain 1381R1 (a mntH+ revertant) exhibited similar acid survival to its parental strain at pH 2.3. Further growth experiments demonstrated that Mn2+ (but not Fe2+, Zn2+, Cu2+, Ca2+, or Mg2+) supplementation fully rescues the growth of strain 1381 under low pH conditions, suggesting that a Mn2+ limitation is the likely cause of growth arrest in the mntH- background. Consistent with the important role of Mn2+ in the acid stress response was the finding that mntH and mntB (both encoding Mn2+ transporters) had higher transcription levels following exposure to mild acid stress (pH 5). Taken together, these results provide evidence that MntH-mediated Mn2+ uptake is essential for the growth of L. monocytogenes under low pH conditions. Moreover, since strain 1381 was recommended for conducting food challenge studies by the European Union Reference Laboratory, the use of this strain in evaluating the growth of L. monocytogenes in low pH environments where Mn2+ is scarce should be reconsidered. Furthermore, since it is unknown when strain 1381 acquired the mntH frameshift mutation, the ability of the strains used for challenge studies to grow under food-related stresses needs to be routinely validated.

Normal Outcome With Prenatal Intervention for Riboflavin Transporter Defect.

BACKGROUND: Riboflavin transporter deficiency is a rare but severe neurometabolic disorder. METHODS: We report two siblings with pathogenic variants in SLC52A3 gene, resulting in riboflavin transporter 3 deficiency. RESULTS: The first sibling was diagnosed at age 11 months with severe respiratory compromise and regression of developmental milestones. His symptoms significantly improved with riboflavin supplementation therapy. The younger sibling was diagnosed by antenatal genetic analysis; riboflavin supplementation was initiated in utero and continued from birth. Now at age two years, he remains clinically asymptomatic despite genetic confirmation of riboflavin transporter deficiency. CONCLUSIONS: Antenatal riboflavin supplementation is a safe and effective treatment for the prevention of symptomatic manifestations of riboflavin transporter deficiency.

Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.

Genome-wide association studies (GWASs) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis that associates serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells strongly impairs choline metabolism due to the inhibition of choline import. Consistently, CRISPR-based genetic screens identified phospholipid synthesis and salvage machinery as synthetic lethal with FLVCR1 loss. Cells and mice lacking FLVCR1 exhibit structural defects in mitochondria and upregulate integrated stress response (ISR) through heme-regulated inhibitor (HRI) kinase. Finally, Flvcr1 knockout mice are embryonic lethal, which is partially rescued by choline supplementation. Altogether, our findings propose FLVCR1 as a major choline transporter in mammals and provide a platform to discover substrates for unknown metabolite transporters.

Genome-wide identification and expression analysis of SUT gene family members in sugar beet (Beta vulgaris L.).

Sucrose transporters (SUTs) play an important role in the transmembrane transport and distribution of sucrose, and their activity has an important impact on plant growth and crop yield. In this study, the SUT gene family was identified in the whole beet genome using bioinformatics methods, and gene characteristics, subcellular localization prediction, phylogenetic evolution, promoter cis-elements and expression patterns were systematically analyzed. A total of 9 SUT gene family members were identified from in beet genome and divided into 3 different groups (group 1, group 2, and Group 3), which were unevenly distributed on 4 chromosomes. Most SUT family members contained photoresponsive and hormone-regulated response elements. Subcellular localization prediction showed that the BvSUT genes are all located in the inner membrane, and most of the terms identified through GO enrichment analysis are classified as "membrane" related. The results of qRT-PCR showed that the expression level of the BvSUT gene was significantly higher in the tuber enlargement stage (100-140 d) than in other stages. This study is the first to analyze the BvSUT gene family in sugar beet, and it provides a theoretical basis for the functional exploration and application of SUT genes in crop improvement, especially in sugar crops.

Manganese Efflux Achieved by MetA and MetB Affects Oxidative Stress Resistance and Iron Homeostasis in Riemerella anatipestifer.

In bacteria, manganese homeostasis is controlled by import, regulation, and efflux. Here, we identified 2 Mn exporters, MetA and MetB (manganese efflux transporters A and B), in Riemerella anatipestifer CH-1, encoding a putative cation diffusion facilitator (CDF) protein and putative resistance-nodulation-division (RND) efflux pump, respectively. Compared with the wild type (WT), ΔmetA, ΔmetB, and ΔmetAΔmetB exhibited sensitivity to manganese, since they accumulated more intracellular Mn2+ than the WT under excess manganese conditions, while the amount of iron in the mutants was decreased. Moreover, ΔmetA, ΔmetB, and ΔmetAΔmetB were more sensitive to the oxidant NaOCl than the WT. Further study showed that supplementation with iron sources could alleviate manganese toxicity and that excess manganese inhibited bacterial cell division. RNA-Seq showed that manganese stress resulted in the perturbation of iron metabolism genes, further demonstrating that manganese efflux is critical for iron homeostasis. metA transcription was upregulated under excess manganese but was not activated by MetR, a DtxR family protein, although MetR was also involved in manganese detoxification, while metB transcription was downregulated under iron depletion conditions and in fur mutants. Finally, homologues of MetA and MetB were found to be mainly distributed in members of Flavobacteriaceae. Specifically, MetB represents a novel manganese exporter in Gram-negative bacteria. IMPORTANCE Manganese is required for the function of many proteins in bacteria, but in excess, manganese can mediate toxicity. Therefore, the intracellular levels of manganese must be tightly controlled. Manganese efflux transporters have been characterized in some other bacteria; however, their homologues could not be found in the genome of Riemerella anatipestifer through sequence comparison. This indicated that other types of manganese efflux transporters likely exist. In this study, we characterized 2 transporters, MetA and MetB, that mediate manganese efflux in R. anatipestifer in response to manganese overload. MetA encodes a putative cation diffusion facilitator (CDF) protein, which has been characterized as a manganese transporter in other bacteria, while this is the first observation of a putative resistance-nodulation-division (RND) transporter contributing to manganese export in Gram-negative bacteria. In addition, the mechanism of manganese toxicity was studied by observing morphological changes and by transcriptome sequencing. Taken together, these results are important for expanding our understanding of manganese transporters and revealing the mechanism of manganese toxicity.

Sugars and sucrose transporters in pollinia of Phalaenopsis aphrodite (Orchidaceae).

The pollen grains of Phalaenopsis orchids are clumped tightly together, packed in pollen dispersal units called pollinia. In this study, the morphology, cytology, biochemistry, and sucrose transporters in pollinia of Phalaenopsis orchids were investigated. Histochemical detection was used to characterize the distribution of sugars and callose at the different development stages of pollinia. Ultra-performance liquid chromatography-high resolution-tandem mass spectrometry data indicated that P. aphrodite accumulated abundant saccharides such as sucrose, galactinol, myo-inositol, and glucose, and trace amounts of raffinose and trehalose in mature pollinia. We found that galactinol synthase (PAXXG304680) and trehalose-6-phosphate phosphatase (PAXXG016120) genes were preferentially expressed in mature pollinia. The P. aphrodite genome was identified as having 11 sucrose transporters (SUTs). Our qRT-PCR confirmed that two SUTs (PAXXG030250 and PAXXG195390) were preferentially expressed in the pollinia. Pollinia germinated in pollen germination media (PGM) supplemented with 10% sucrose showed increased callose production and enhanced pollinia germination, but there was no callose or germination in PGM without sucrose. We show that P. aphrodite accumulates high levels of sugars in mature pollinia, providing nutrients and enhanced SUT gene expression for pollinia germination and tube growth.

Child Neurology: Infantile Biotin Thiamine Responsive Basal Ganglia Disease: Case Report and Brief Review.

Biotin thiamine responsive basal ganglia disease (BTRBGD) is an inherited autosomal recessive disorder that results from the inability of thiamine to cross the blood-brain barrier. It is considered a treatable condition if vitamin supplementation, most commonly with thiamine and biotin, is initiated early. BTRBGD can present as an infantile form, classical childhood form, or adult Wernicke-like encephalopathy. The infantile form is often the most severe and portends a worse prognosis with high mortality despite vitamin supplementation. We present a two-month-old who presented with irritability, opisthotonos, and abnormal eye movements who was found to have compound heterozygous variants in the SLC19A3 gene inherited in trans, including one known pathogenic intronic variant and a novel variant presumed to be pathogenic. She was therefore diagnosed with infantile BTRBGD. In this report, we discuss the differential for infantile BTRBGD, the clinical and radiologic features of BTRBGD, and describe a rapid, positive response to early vitamin supplementation in an infant with a likely pathogenic novel variant in SLC19A3.

Identification of a TonB-Dependent Receptor Involved in Lanthanide Switch by the Characterization of Laboratory-Adapted Methylosinus trichosporium OB3b.

Two methanol dehydrogenases (MDHs), MxaFI and XoxF, have been characterized in methylotrophic and methanotrophic bacteria. MxaFI contains a calcium ion in its active site, whereas XoxF contains a lanthanide ion. Importantly, the expression of MxaFI and XoxF is inversely regulated by lanthanide bioavailability, i.e., the "lanthanide switch." To reveal the genetic and environmental factors affecting the lanthanide switch, we focused on two Methylosinus trichosporium OB3b mutants isolated during routine cultivation. In these mutants, MxaF was constitutively expressed, but lanthanide-dependent XoxF1 was not, even in the presence of 25 µM cerium ions, which is sufficient for XoxF expression in the wild type. Genotyping showed that both mutants harbored a loss-of-function mutation in the CQW49_RS02145 gene, which encodes a TonB-dependent receptor. Gene disruption and complementation experiments demonstrated that CQW49_RS02145 was required for XoxF1 expression in the presence of 25 µM cerium ions. Phylogenetic analysis indicated that CQW49_RS02145 was homologous to the Methylorubrum extorquens AM1 lanthanide transporter gene (lutH). These findings suggest that CQW49_RS02145 is involved in lanthanide uptake across the outer membrane. Furthermore, we demonstrated that supplementation with cerium and glycerol caused severe growth arrest in the wild type. CQW49_RS02145 underwent adaptive laboratory evolution in the presence of cerium and glycerol ions, resulting in a mutation that partially mitigated the growth arrest. This finding implies that loss-of-function mutations in CQW49_RS02145 can be attributed to residual glycerol from the frozen stock. IMPORTANCE Lanthanides are widely used in many industrial applications, including catalysts, magnets, and polishing. Recently, lanthanide-dependent metabolism was characterized in methane-utilizing bacteria. Despite the global demand for lanthanides, few studies have investigated the mechanism of lanthanide uptake by these bacteria. In this study, we identify a lanthanide transporter in Methylosinus trichosporium OB3b and indicate the potential interaction between intracellular lanthanide and glycerol. Understanding the genetic and environmental factors affecting lanthanide uptake should not only help improve the use of lanthanides for the bioconversion of methane into valuable products like methanol but also be of value for developing biomining to extract lanthanides under neutral conditions.

Thiamine-Responsive Megaloblastic Anaemia With Hypothyroidism, A Puzzling Association.

Background: Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia, typically emerging subtly between infancy and adolescence. Administration of high-dose thiamine often yields improvements in anaemia and occasionally in diabetes. Uncommon manifestations include optic atrophy, congenital heart defects, short stature, and stroke. In this specific case, a 5-year-old diagnosed with insulin-dependent diabetes mellitus (IDDM) since the age of one presented with symptoms such as polyuria, fever, and vomiting, revealing an HbA1c of 10.64. Further examinations disclosed compromised hearing and vision. A negative antibody workup and a thyroid profile indicating hypothyroidism prompted additional investigations, including Brainstem Evoked Response Audiometry (BERA) and retinal examination, confirming bilateral sensorineural hearing loss and maculopathy, respectively. A comprehensive blood count unveiled megaloblastic anaemia. Genetic profiling confirmed a homozygous mutation in the SLC19A2 gene, thus diagnosing TRMA. An early diagnosis, coupled with genetic confirmation, enables timely intervention, with patients responding positively to high-dose thiamine. Genetic counselling plays a pivotal role in enlightening families about the disease and its inheritance patterns, fostering awareness and understanding.

Genome-Wide Identification of AMT2-Type Ammonium Transporters Reveal That CsAMT2.2 and CsAMT2.3 Potentially Regulate NH4+ Absorption among Three Different Cultivars of Camellia sinensis.

Ammonium (NH4+), as a major inorganic source of nitrogen (N) for tea plant growth, is transported and distributed across membranes by the proteins of ammonium transporters (AMTs). However, the AMT2-type AMTs from tea plants remain poorly understood. In this study, five CsAMT2 subfamily genes were identified in tea plant genomes, and their full-length coding sequences (CDS) were isolated from roots. Then, a NH4+ uptake kinetic comparison of Fudingdabaicha (FD), Huangdan (HD), and Maoxie (MX) showed that FD was a high N efficiency (HNE) cultivar that had a wide range of adaptability to NH4+, HD was a high N efficiency under high N conditions (HNEH) cultivar, in which it was easy to obtain higher yield in a high N environment, and MX was a high N efficiency under low N conditions (HNEL) cultivar, which had a higher affinity for NH4+ than the other two. Tissue-specific expression analysis suggested that CsAMT2.2 and CsAMT2.3 were highly expressed in the roots, indicating that these two members may be unique in the CsAMT2 subfamily. This is further supported by our findings from the temporal expression profiles in the roots among these three different N adaptation cultivars. Expression levels of CsAMT2.2 and CsAMT2.3 in FD and HD were upregulated by a short time (2 h) under high NH4+ treatment, while under low NH4+ treatment, CsAMT2.2 and CsAMT2.3 were highly expressed at 0 h and 2 h in the HNEL-type cultivar-MX. Furthermore, the functional analysis illustrated that CsAMT2.2 and CsAMT2.3 could make a functional complementation of NH4+-defective mutant yeast cells at low NH4+ levels, and the transport efficiency of CsAMT2.3 was higher than that of CsAMT2.2. Thus, we concluded that CsAMT2.2 and CsAMT2.3 might play roles in controlling the NH4+ uptake from the soil to the roots. These results will further the understanding of the NH4+ signal networks of AMT2-type proteins in tea plants.

Next-generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment.

Mitochondrial cytopathies, among which the Leigh syndrome (LS), are caused by variants either in the mitochondrial or the nuclear genome, affecting the oxidative phosphorylation process. The aim of the present study consisted in defining the molecular diagnosis of a group of Tunisian patients with LS. Six children, belonging to five Tunisian families, with clinical and imaging presentations suggestive of LS were recruited. Whole mitochondrial DNA and targeted next-generation sequencing of a panel of 281 nuclear genes involved in mitochondrial physiology were performed. Bioinformatic analyses were achieved in order to identify deleterious variations. A single m.10197G>A (p.Ala47Thr) variant was found in the mitochondrial MT-ND3 gene in one patient, while the others were related to autosomal homozygous variants: two c.1412delA (p.Gln471ArgfsTer42) and c.1264A>G (p.Thr422Ala) in SLC19A3, one c.454C>G (p.Pro152Ala) in SLC25A19 and one c.122G>A (p.Gly41Asp) in ETHE1. Our findings demonstrate the usefulness of genomic investigations to improve LS diagnosis in consanguineous populations and further allow for treating the patients harboring variants in SLC19A3 and SLC25A19 that contribute to thiamine transport, by thiamine and biotin supplementation. Considering the Tunisian genetic background, the newly identified variants could be screened in patients with similar clinical presentation in related populations.

Mitochondrial iron transporter (MIT) gene in potato (Solanum tuberosum): comparative bioinformatics, physiological and expression analyses in response to drought and salinity.

Mitochondrial iron transporter (MIT) genes are essential for mitochondrial acquisition/import of iron and vital to proper functioning of mitochondria. Unlike other organisms, research on the MITs in plants is limited. The present study provides comparative bioinformatics assays for the potato MIT gene (StMIT) as well as gene expression analyses. The phylogenetic analyses revealed monocots-dicot divergence in MIT proteins and it was also found clade specific motif diversity. In addition, docking analyses indicated that Asp172 and Gly100 residues to be identified as the closest residues binding to ferrous iron. The percentage of structure overlap of the StMIT 3D protein model with Arabidopsis, maize and rice MIT proteins was found between 80.18% and 85.71%. The transcript analyses exhibited that the expression of StMIT was triggered under drought and salinity stresses. The findings of the present study would provide valuable leads for further studies targeting specifically the MIT gene and generally the plant iron metabolism.